Magnetic Therapy Migraine Headache – Pulsed Electromagnetic Field Therapy PEMF / rTMS Bibliography

Pulsed magnetic fields beneficially affect migraine’s abnormal brain electrophysiology and that is present to one extent or another in headache syndromes of all types. 10% of U.S. males and 20% of U.S. females experience migraine headache at least once per 3 months. 2% of the worlds population experience headache 15 days per month. With such widespread populations you’d think that a simple, non-invasive non pharmacological solution like rTMS/pulsed electromagnetic field therapy would have garnered more interest by the media, but then, they’re controlled by the big-pharma cartel, so no wonder you don’t know about it.

We believe beneficial effects of pulsed electromagnetic fields / rTMS is attributable to MoreATP, which explains the healing effects of frequency specific pulsed electromagnetic fields (PEMF) therapy. Particularly where pulse repetition rate approximates 10 Hz. While we are fairly sure most pulsed electromagnetic therapies lead to enhanced cellular energy parameters through some heretofore undisclosed mechanism, where pulse repetition rate is within 1 Hz and 15 Hz nearly all reported effects are simply due to enhanced organic ATP production.

“When the solution is simple…God is answering” ~ Albert Einstein

Magnetic Therapy Migraine Headache – Pulsed Electromagnetic Field Therapy Bibliography

To read the original source, use Pubmed and search for Title of the citation

Clin Neurophysiol. 2014 Oct;125(10):2090-9. doi: 10.1016/j.clinph.2014.01.028. Epub 2014 Feb 14.
Modulation of visual evoked potentials by high-frequency repetitive transcranial magnetic stimulation in migraineurs.
Omland PM1, Uglem M2, Engstrøm M3, Linde M3, Hagen K3, Sand T3.

This one is surprising particularly since it was done at 10 Hz and we’ve had such good success with migrain sufferors. Perhaps do to so much field amplitude at 80% motor threshold (about 10-15 times our current v.5 maximum setting). We don’t care why you buy your EP, you’ve got a 90 days money back satisfaction guarantee.

J Clin Diagn Res. 2014 Sep;8(9):MM01-2. doi: 10.7860/JCDR/2014/9377.4886. Epub 2014 Sep 20.
Poor Tolerance of Motor Cortex rTMS in Chronic Migraine.
Teo WP1, Kannan A2, Loh PK3, Chew E4, Sharma VK5, Chan YC5.

Cephalalgia. 2014 May;34(6):464-72. doi: 10.1177/0333102413515340. Epub 2013 Dec 10.
Randomized, proof-of-principle clinical trial of active transcranial magnetic stimulation in chronic migraine.
Conforto AB1, Amaro E Jr, Gonçalves AL, Mercante JP, Guendler VZ, Ferreira JR, Kirschner CC, Peres MF.

J Neurol. 2013 Nov;260(11):2793-801. doi: 10.1007/s00415-013-7072-2. Epub 2013 Aug 21.
High-rate repetitive transcranial magnetic stimulation in migraine prophylaxis: a randomized, placebo-controlled study.
Misra UK1, Kalita J, Bhoi SK.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for pain but there is no class 1 study on its role in migraine prophylaxis. In this study we report the efficacy and safety of high-rate rTMS in migraine prophylaxis. Adult migraine patients having >4 attacks/month were randomized to high-rate rTMS or sham stimulation. Stimulation in the form of 10 Hz rTMS, 600 pulses in 10 trains were delivered to the hot spot of the right abductor digiti minimi in 412 s. Three sessions were delivered on alternate days. The outcome was defined at 1 month. The primary outcome measures were reduction in headache frequency and severity >50 % as assessed by the Visual Analogue Scale (VAS). The secondary outcome measures were functional disability, rescue medication and adverse events. Fifty patients each were randomized to rTMS or sham stimulation. The baseline characteristics of rTMS and sham stimulation groups were similar. At 1 month, headache frequency (78.7 vs. 33.3 %; P = 0.0001) and VAS score (76.6 vs. 27.1 %; P = 0.0001) improved significantly in the patients receiving rTMS compared to those in the sham stimulation group. Functional disability also improved significantly in rTMS group (P = 0.0001). Only one patient following rTMS developed transient drowsiness and was withdrawn from the study. This study provides evidence of the efficacy and safety of 10 Hz rTMS in migraine prophylaxis.

Neurol Sci. 2013 May;34 Suppl 1:S109-12. doi: 10.1007/s10072-013-1385-x.
Refractory migraine: the role of the physician in assessment and treatment of a problematic disease.
Colombo B, Dalla Libera D, Dalla Costa G, Comi G.

Cephalalgia. 2013 Apr;33(5):316-22. doi: 10.1177/0333102412473372. Epub 2013 Jan 11.
Is β endorphin related to migraine headache and its relief?
Misra UK, Kalita J, Tripathi GM, Bhoi SK.

Neurol Res. 2012 Jul;34(6):547-51. doi: 10.1179/1743132812Y.0000000045. Epub 2012 Jun 20.
High frequency repetitive transcranial magnetic stimulation (rTMS) is effective in migraine prophylaxis: an open labeled study. Misra UK, Kalita J, Bhoi SK.

Effects of repetitive transcranial magnetic stimulation on somatosensory evoked potentials and high frequency oscillations in migraine. Coppola G, De Pasqua V, Pierelli F, Schoenen J.


To evaluate the effect of high rate repetitive transcranial magnetic stimulation (rTMS) in migraineprophylaxis in medically refractory patients.
Migraine patients above 15 years of age, having more than 7 attacks/month and refractory to at least two prophylactic drugs were included. The patients were evaluated for migraine frequency, severity, functional disability, number of rescue medications and migraine index. Three sessions of alternate day 10 Hz rTMS comprising of 600 pulses in 10 trains were delivered to left frontal cortex. The response was evaluated at the end of session and weekly for 4 weeks.
Fifty-one patients aged 16-61 years and 45 females were treated. Fifty (98%) patients had more than 50% reduction of headache frequency at the end and 1 week after rTMS and the improvement persisted till the fourth week in 80.4% patients. The headache frequency, severity, functional disability,migraine index, and rescue medications significantly reduced at all time points, but the maximum benefit was observed in the first 2 weeks. There were no serious adverse events.
High rate rTMS in left frontal cortex is effective and well tolerated for migraine prophylaxis.

Cephalalgia. 2012 Jul;32(9):700-9. doi: 10.1177/0333102412446313. Epub 2012 May 31. Headache. 2010 Jul;50(7):1153-63. Epub 2010 Jun 10.
Transcranial magnetic stimulation for migraine: a safety review.
Dodick DW, Schembri CT, Helmuth M, Aurora SK.
Mayo Clinic, Phoenix, AZ, USA.

Cephalalgia. 2010 Jan;30(1):46-52.
High-frequency transcranial magnetic stimulation on motor cortex of patients affected by migraine with aura: a way to restore normal cortical excitability?
Brighina F, Palermo A, Daniele O, Aloisio A, Fierro B.
Dipartimento Universitario di Neuroscienze Cliniche, University of Palermo, Palermo, Italy. 

Neurotherapeutics. 2010 Apr;7(2):204-12.
Transcranial magnetic simulation in the treatment of migraine.
Lipton RB, Pearlman SH.
Department of Neurology, Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA

CNS Spectr. 2007 Dec;12(12):921-5.
Unexpected reduction in migraine and psychogenic headaches following rTMS treatment for major depression: a report of two cases.
O’Reardon JP, Fontecha JF, Cristancho MA, Newman S.
University of Pennsylvania, Transcranial Magnetic Stimulation Laboratory, Philadelphia, PA, USA. 

Cereb Cortex. 2008 Mar 27. [Epub ahead of print]  
Homeostatic Metaplasticity of the Motor Cortex is Altered during Headache-Free Intervals in Migraine with Aura.
Antal A, Lang N, Boros K, Nitsche M, Siebner HR, Paulus W.
Department of Clinical Neurophysiology, Georg-August University, 37073 Göttingen, Germany.

Preconditioning of the human primary motor cortex (M1) with transcranial direct current stimulation (tDCS) can shape the magnitude and direction of excitability changes induced by a subsequent session of repetitive transcranial magnetic stimulation (rTMS). Here, we examined this form of metaplasticity in migraine patients with visual aura and healthy controls. In both groups, facilitatory preconditioning of left M1 with anodal tDCS increased the mean amplitudes of motor-evoked potentials (MEPs) elicited in the contralateral hand, whereas inhibitory preconditioning with cathodal tDCS produced a decrease in amplitude. Following cathodal tDCS, a short train of low-intensity 5-Hz rTMS antagonized the suppression of the mean MEP amplitude in both groups. In contrast, the homeostatic effects of 5-Hz rTMS differed between groups when rTMS was given after anodal tDCS. In controls 5-Hz rTMS induced a marked decrease in MEP amplitudes, whereas in migraineurs rTMS induced only a modest decrease in MEP amplitudes, which were still facilitated after rTMS when compared with baseline amplitudes. These findings indicate that short-term homeostatic plasticity is altered in patients with visual aura between the attacks.

PMID: 18372292 [PubMed – as supplied by publisher]

Clin Neurophysiol. 2008 Mar;119(3):504-32. Epub 2007 Dec 11. 
The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee.
Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, Mills K, Rösler KM,Triggs WJ, Ugawa Y, Ziemann U.
Division of Neurology, Toronto Western Research Institute, University of Toronto, 7MC411, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ont., Canada M5T 2S8. robert.chen[@]

The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer’s disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.

PMID: 18063409

Schmerz. 2008 Feb;22 Suppl 1:17-21. 
[Cortical dysbalance in the brain in migraineurs–hyperexcitability as the result of sensitisation?]
[Article in German]
Stankewitz A, May A.

Institut für systemische Neurowissenschaften, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

A cortical dysbalance has a pivotal role in the pathophysiology of migraine. Numerous electrophysiological and transcranial magnetic stimulation (TMS) studies have investigated the interictal excitability level in migraineurs and have shown a consistent lack of habituation during repetitive stimulation. There is some controversy in the current literature over whether this deficit is based on a lowered or an elevated preactivation level. However, the current discussion may be misguided. It seems that multiple external and intrinsic factors influence the level of cortical excitability and the frequency and intensity of attacks: Habituation is specific neither to migraine nor even to pain; the same phenomenon is found in tinnitus patients, for example. Cortical hyperexcitability is presumably the result of chronicity and the concomitant central sensitisation process.

PMID: 18228046

J Neurol Sci. 2008 Jan 15;264(1-2):93-6. Epub 2007 Aug 27. 
Clinical correlates of phosphene perception in migraine without aura: an Asian study.
Lo YL, Lum SY, Fook-Chong S, Cui SL, Siow HC.
Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. lo.yew.long[@]

INTRODUCTION: Although controversy exists with regard to the presence of hypoexcitability versus hyperexcitability of the visual cortex in migraine patients, there remain a group who do not perceive phosphenes (P-). However, its clinical implications have not been systematically addressed. In this study, we hypothesize that P- patients classified as migraine without aura (MO) have distinct clinical features. METHODS: Twenty-nine Asian MO patients (7 men; mean age: 44; median: 45; range: 25 to 65) were consecutively entered into the study. Visual cortex transcranial magnetic stimulation (TMS) was performed in the migraine interictum. RESULTS: Of the 19 patients, 19 (66%) were able to perceive phosphenes (P+), while 10 (34%) were not able to after repeated TMS (P-). P- patients had significantly higher headache frequency (p=0.008) and pain score (p=0.002) compared with P+ patients. In addition, there was significant positive correlation of phosphene threshold with pain score (r=0.52, p=0.02) in P+ patients. There was no significant difference between P+ and P- patients in terms of age (t-test, p=0.6). CONCLUSIONS: Our study is inkeeping with the hypothesis that interictal visual cortex excitability is reduced in relation to the severity of migraine in Asian MO patients, and lack of phosphene perception may be related to significantly elevated thresholds beyond the output of TMS stimulators.

PMID: 17720202

CNS Spectr. 2007 Dec;12(12):921-5.
Unexpected reduction in migraine and psychogenic headaches following rTMS treatment for major depression: a report of two cases.
O’Reardon JP, Fontecha JF, Cristancho MA, Newman S.
University of Pennsylvania, Transcranial Magnetic Stimulation Laboratory, Philadelphia, PA, USA. oreardon[@]

Our objective is to report a coincident reduction in headache pain in patients treated with repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD). Two patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, non-responsive to prior antidepressant treatment who were enrolled in a sham-controlled, double-blind study of rTMS for MDD. After the study, it was revealed that both were in the active-treatment arm. Both patients suffered from near daily headaches and kept logs of headache frequency and severity before, during, and after the study. Headache pain was significantly reduced under double-blind conditions with rTMS treatment, but returned to baseline following cessation of rTMS treatment. Ultimately, when receiving rTMS post-study as a maintenance intervention for MDD (approximately 2 rTMS sessions/week), the positive effects on headache amelioration were sustained. Headache pain is frequently comorbid with mood disorders and has been reported as the most common side effect with rTMS. In these subjects, rTMS was, in fact, associated with relief of depressive symptoms and preexisting headache pain. This indicates that rTMS may be beneficial for both disorders in some patients.

PMID: 18163038

Pain. 2007 Nov;132(1-2):124-31. Epub 2007 Jun 14. 
Shortened cortical silent period in facial muscles of patients with migraine.
Curra A, Pierelli F, Coppola G, Barbanti P, Buzzi MG, Galeotti F, Serrao M, Truini A, Casali C, Pauri F, Cruccu G.
Department of Neurological Sciences, La Sapienza University, Rome, Italy. antonio.curra[@]

Despite intensive neurophysiological research, evidence is lacking to show whether abnormal cortical excitability in migraine reflects a primary cortical disturbance or reduced control by thalamo-cortical loops. One way to contribute to the scientific discussion on this topic is to deliver transcranial magnetic stimulation (TMS) and test the cortical silent period (SP) recorded in facial muscles. The facial-muscle SP is a purely cortical phenomenon that reflects the excitability of inhibitory interneurons, and can disclose changes in cortical inhibition even in patients without documented primary lesions of the motor cortices. To test the interictal excitability of cortical motor inhibitory interneurons in migraine, we investigated the facial-SP in patients with migraine with and without aura between attacks. In 26 patients and 15 age-matched controls, high-intensity magnetic stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction. Electromyographic responses were recorded from surface electrodes placed over the subjects’ perioral muscles. Facial SPs were significantly shorter in patients than in controls. The SP shortening provides neurophysiological evidence showing hypoexcitability of cortical inhibitory neurons in patients with migraine between attacks. Despite a possible primary deficit of cortical inhibitory interneurons in migraine, we favor the interpretation of a secondary disfacilitation by hypoactive thalamo-cortical loops. Based on this interpretation, the interictal reduced cortical inhibition documented by the shortened SP could be considered the motor counterpart of the reduced preactivation excitability level in the sensory cortices purported to explain why cortical evoked responses habituate poorly in patients with migraine.

PMID: 17574759

Brain Nerve. 2007 Sep;59(9):961-70.
[Neurophysiology of visual aura in migraine]
[Article in Japanese]
Shibata K.
Department of Medicine, Tokyo Women’s Medical University, Medical Center East, 2-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.

Visual processing in migraine has been targeted because the visual symptoms that are commonly associated with attack, either in the form of aura or other more subtle symptoms, indicate that the visual pathways are involved in migrainous pathophysiology. The visual aura of the migraine attack has been explained by the cortical spreading depression (CSD) of Leão, neuroelectric event beginning in the occipital cortex and propagating into contiguous brain region. Clinical observations suggest that hyperexcitability occurs not only during the attack, typically in the form of photophobia, but also between attacks. Numerous human neuroimaging, neurophysiological and psychophysical studies have identified differences in cortical visual processing in migraine. The possibility of imaging the typical visual aura with BOLD functional MRI has revealed multiple neurovascular events in the occipital cortex within a single attack that closely resemble CSD. As transient synchronized neuronal excitation precedes CSD, changes in cortical excitability underlie the migraine attack. Independent evidence for altered neuronal excitability in migraineurs between attacks emerges from visual evoked potentials (VEPs) and transcranial magnetic stimulation (TMS), recordings of cortical potentials and psychophysics. Recently, both TMS and psycho-physical studies measuring visual performance in migraineurs have used measures which presumably measure primary visual (V1) and visual association cortex. Our VEP and blink reflex study showed that migraine patients exhibiting allodynia might show central sensitization of braistem trigeminal neuron and had contrast modulation dysfunction during the cortical visual processing of V1 and visual association cortex in-between attacks. In pathophysiology of migraine, these neurophysiological and psychophysical studies indicate that abnormal visual and trigeminal hyperexcitability might persist between migraine attacks. The influence of migraine on cortical neural processing is likely to extend beyond V1 and abnormal cortical activity might lead to CSD when enhanced activation coincides with other factors.

PMID: 17886478

Cephalalgia. 2007 Jul;27(7):833-9. Epub 2007 May 10. 
Transcranial direct current stimulation reveals inhibitory deficiency in migraine.
Chadaide Z, Arlt S, Antal A, Nitsche MA, Lang N, Paulus W.
Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany.

The issue of interictal excitability of cortical neurons in migraine patients is controversial: some studies have reported hypo-, others hyperexcitability. The aim of the present study was to observe the dynamics of this basic interictal state by further modulating the excitability level of the visual cortex using transcranial direct current stimulation (tDCS) in migraineurs with and without aura. In healthy subjects anodal tDCS decreases, cathodal stimulation increases transcranial magnetic stimulation (TMS)-elicited phosphene thresholds (PT), which is suggested as a representative value of visual cortex excitability. Compared with healthy controls, migraine patients tended to show lower baseline PT values, but this decrease failed to reach statistical significance. Anodal stimulation decreased phosphene threshold in migraineurs similarly to controls, having a larger effect in migraineurs with aura. Cathodal stimulation had no significant effect in the patient groups. This result strengthens the notion of deficient inhibitory processes in the cortex of migraineurs, which is selectively revealed by activity-modulating cortical input.

PMID: 17498207

Headache. 2007 Jul-Aug;47(7):996-1003; discussion 1004-7 
Brainstem dysfunction in chronic migraine as evidenced by neurophysiological and positron emission tomography studies.
Aurora SK, Barrodale PM, Tipton RL, Khodavirdi A.
Swedish Headache Center, 1101 Madison #200, Seattle, WA 98104, USA.

BACKGROUND: The pathophysiology of chronic migraine (CM) is not fully understood. We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical excitability in patients with CM and also performed PET studies to ascertain if there were any areas of activation and inhibition for possible correlation. METHODS: Excitability of the cortex was assessed by a reliable parameter of magnetic suppression of perceptual accuracy (MSPA) profiles using transcranial magnetic stimulation in 25 patients with CM. Of these 10 patients were also studied with ((18)F-FDG PET) scans. RESULTS: MSPA demonstrated decreased inhibition in CM compared to normal controls and episodic migraine. The percentage of letters reported correct at 100 ms was 84.37 for CM compared to 19.14 for normal controls and 57.41 for episodic migraine. The PET evaluation in 10 subjects demonstrated increased cerebral metabolism in areas of in the brainstem compared to the global flow. There were also decreased areas of cerebral metabolism in the medial frontal and parietal as well as the somatosensory cortex. CONCLUSIONS: Patients with CM appear to be characterized by reduced visual suppression correlating with high cortical excitability. In a cohort of these subjects there was brainstem activation and inhibition in certain areas of the cortex suggesting a potential dysfunction in the inhibitory pathways.

PMID: 17635590

Brain Res Bull. 2007 May 30;72(4-6):208-14. Epub 2007 Jan 24. 
Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients.
Poreisz C, Boros K, Antal A, Paulus W.
Department of Clinical Neurophysiology, Georg-August University, Robert Koch Strasse 40, 37075 Göttingen, Germany. csaba.poreisz[@]

Cortical excitability changes induced by tDCS and revealed by TMS, are increasingly being used as an index of neuronal plasticity in the human cortex. The aim of this paper is to summarize the partially adverse effects of 567 tDCS sessions over motor and non-motor cortical areas (occipital, temporal, parietal) from the last 2 years, on work performed in our laboratories. One-hundred and two of our subjects who participated in our tDCS studies completed a questionnaire. The questionnaire contained rating scales regarding the presence and severity of headache, difficulties in concentrating, acute mood changes, visual perceptual changes and any discomforting sensation like pain, tingling, itching or burning under the electrodes, during and after tDCS. Participants were healthy subjects (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus patients (9.8%). During tDCS a mild tingling sensation was the most common reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the subjects, whereas a light itching sensation under the stimulation electrodes occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and insomnia (0.98%) were reported, but fairly infrequently. In addition, the incidence of the itching sensation (p=0.02) and the intensity of tingling sensation (p=0.02) were significantly higher during tDCS in the group of the healthy subjects, in comparison to patients; whereas the occurrence of headache was significantly higher in the patient group (p=0.03) after the stimulation. Our results suggest that tDCS applied to motor and non-motor areas according to the present tDCS safety guidelines, is associated with relatively minor adverse effects in healthy humans and patients with varying neurological disorders.

PMID: 17452283

Headache. 2007 Mar;47(3):364-70.  
Intracortical inhibition and facilitation in migraine–a transcranial magnetic stimulation study.
Siniatchkin M, Kröner-Herwig B, Kocabiyik E, Rothenberger A.
Department of Child Neurology, University of Kiel, Kiel, Germany.

OBJECTIVE: Migraine is a disease of altered cortical excitability between attacks. However, the mechanisms of abnormal excitability in migraine are insufficiently investigated. Hence, the aim of the study was to investigate intracortical inhibition/facilitation of the motor circuit in migraine. METHODS: Sixteen women suffering from migraine without aura and 15 healthy women were investigated using a suprathreshold transcranial magnetic stimulation (TMS) in the paired-pulse paradigm with long interstimulus intervals (ISI = 20, 60, 120 ms) and measurement of the cortical silent period. RESULTS: We found no differences for the cortical silent period and for the long intracortical inhibition between the groups. Concerning intracortical facilitation, this ability was significantly more pronounced in patients suffering from migraine compared with healthy controls. CONCLUSION: Migraineurs produce an increased intracortical facilitation. The results may be discussed in line of glutamatergic mechanisms in migraine, which could be related to altered facilitation.

PMID: 17371353

J Headache Pain. 2006 Oct;7(5):341-6. Epub 2006 Oct 25.
Transcranial magnetic stimulation for migraine: clinical effects.
Clarke BM, Upton AR, Kamath MV, Al-Harbi T, Castellanos CM.
Division of Neurology, McMaster University, Hamilton, Ontario, Canada.

Acta Neurol Belg. 2003 Sep;103(3):144-54.
Transcranial magnetic stimulation in migraine: a review of facts and controversies.
Fumal A, Bohotin V, Vandenheede M, Schoenen J.
Departments of Neurology and Neuroanatomy, University of Liège, B-4000 Liège, Belgium.

Med Hypotheses. 2002 Dec;59(6):703-5. 
Cellular telephones and effects on the brain: the head as an antenna and brain tissue as a radio receiver. 
Weinberger Z, Richter ED. 
Jerusalem College of Technology, Jerusalem, Israel. 
Headache and other neuropsychological symptoms occur in users of cellular telephones, and controversy exists concerning risks for brain cancer. We hypothesize these effects result from the head serving as an antenna and brain tissue as a radio receiver.

Adv Ther. 2001 May-Jun;18(3):101-9. 
Impulse magnetic-field therapy for migraine and other headaches: a double-blind, placebo-controlled study. 
Pelka RB, Jaenicke C, Gruenwald J. 
Universitat der Bundeswehr Munchen Munich, Germany.

Headache. 1999 Sep;39(8):567-75. 
Treatment of migraine with pulsing electromagnetic fields: a double-blind, placebo-controlled study. 
Sherman RA, Acosta NM, Robson L. 
Orthopedic Surgery Service, Madigan Army Medical Center, Tacoma, WA 98431, USA.

Headache. 1998 Mar;38(3):208-13. 
Initial exploration of pulsing electromagnetic fields for treatment of migraine. 
Sherman RA, Robson L, Marden LA. 
Service of Orthopedic Surgery, Madigan Army Medical Center, Tacoma, Wash. 98431, USA. 

Ambrosini A, Schoenen J. The electrophysiology of migraine.  
Curr Opin Neurol. 2003 Jun;16(3):327-31. Review.  
PMID: 12858069

Schoenen J, Ambrosini A, Sandor PS, Maertens de Noordhout A. Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance.  
Clin Neurophysiol. 2003 Jun;114(6):955-72. Review.  
PMID: 12804664

Bohotin V, Fumal A, Vandenheede M, Bohotin C, Schoenen J. Excitability of visual V1-V2 and motor cortices to single transcranial magnetic stimuli in migraine: a reappraisal using a figure-of-eight coil.  
Cephalalgia. 2003 May;23(4):264-70.  
PMID: 12716343

Aurora SK, Welch KM, Al-Sayed F. The threshold for phosphenes is lower in migraine.  
Cephalalgia. 2003 May;23(4):258-63.  
PMID: 12716342

Ambrosini A, de Noordhout AM, Sandor PS, Schoenen J. Electrophysiological studies in migraine: a comprehensive review of their interest and limitations.  
Cephalalgia. 2003;23 Suppl 1:13-31. Review.  
PMID: 12699456

Mulleners W, Chronicle E, Vredeveld J, Koehler P. Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS.  
Headache. 2003 Mar;43(3):304.  
PMID: 12603670 [PubMed – as supplied by publisher]

Ozturk V, Cakmur R, Donmez B, Yener GG, Kursad F, Idiman F. Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study.  
J Neurol. 2002 Sep;249(9):1268-71.  
PMID: 12242552

Brighina F, Piazza A, Daniele O, Fierro B. Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation.  
Exp Brain Res. 2002 Jul;145(2):177-81. Epub 2002 May 09.  
PMID: 12110957

Battelli L, Black KR, Wray SH. Transcranial magnetic stimulation of visual area V5 in migraine.  
Neurology. 2002 Apr 9;58(7):1066-9.  
PMID: 11940694

Bohotin V, Fumal A, Vandenheede M, Gerard P, Bohotin C, Maertens de Noordhout A, Schoenen J. Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine.  
Brain. 2002 Apr;125(Pt 4):912-22.  
PMID: 11912123

Mulleners WM, Chronicle EP, Vredeveld JW, Koehler PJ. Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS.  
Eur J Neurol. 2002 Jan;9(1):35-40.  
PMID: 11784374

 Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW. Visual cortex excitability in migraine with and without aura.  
Headache. 2001 Jun;41(6):565-72.  
PMID: 11437892

Aurora SK, Cao Y, Bowyer SM, Welch KM. The occipital cortex is hyperexcitable in migraine: experimental evidence.  
Headache. 1999 Jul-Aug;39(7):469-76.  
PMID: 11279929

Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW. Suppression of perception in migraine: evidence for reduced inhibition in the visual cortex.  
Neurology. 2001 Jan 23;56(2):178-83.  
PMID: 11160952

Cutrer FM, O’Donnell A, Sanchez del Rio M. Functional neuroimaging: enhanced understanding of migraine pathophysiology.  
Neurology. 2000;55(9 Suppl 2):S36-45. Review.  
PMID: 11089518

Werhahn KJ, Wiseman K, Herzog J, Forderreuther S, Dichgans M, Straube A. Motor cortex excitability in patients with migraine with aura and hemiplegic migraine.  
Cephalalgia. 2000 Feb;20(1):45-50.  
PMID: 10817446

Afra J, Ambrosini A, Genicot R, Albert A, Schoenen J. Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers.  
Headache. 2000 Jan;40(1):36-40.  
PMID: 10759901

Maertens de Noordhout A, Schoenen J. Transcranial magnetic stimulation in migraine.  
Electroencephalogr Clin Neurophysiol Suppl. 1999;51:260-4. Review. No abstract available.  
PMID: 10590958

Aurora SK, al-Sayeed F, Welch KM. The cortical silent period is shortened in migraine with aura.  
Cephalalgia. 1999 Oct;19(8):708-12.  
PMID: 10570724

Cutrer FM, O’Donnell A. Recent advances in functional neuroimaging.  
Curr Opin Neurol. 1999 Jun;12(3):255-9. Review.  
PMID: 10499170

Curr Opin Neurol. 2003 Jun;16(3):327-31. 
The electrophysiology of migraine. 
Ambrosini A, Schoenen J. 
Headache Clinic, INM Neuromed, IRCCS, Pozzilli, Isernia, Italy. 

PURPOSE OF REVIEW: The pathophysiology of migraine is far from being understood. Electrophysiological methods are useful to investigate peripheral and central mechanisms underlying this disorder. The purpose of this review is to highlight the results of electrophysiological studies published during the last year and to examine their added value to our previous knowledge.

RECENT FINDINGS: Studies by visual and auditory evoked potentials and event-related responses suggested that lack of habituation is the principal interictal abnormality of sensory processing in migraineurs. Recently confirmed for somatosensory and laser-evoked cortical potentials and for brainstem responses, it is also responsible for the increased intensity dependence of auditory evoked potentials. This abnormality is possibly caused by a reduced cortical preactivation level due to hypofunctioning subcortico-cortical aminergic pathways. Although studies of cortical excitability by transcranial magnetic stimulation have yielded conflicting results, results obtained using habituation of pattern-reversal visual evoked potentials to explore cortical excitability changes induced by repetitive transcranial magnetic stimulation strongly favour the hypothesis that migraine is characterized by a decreased level of preactivation excitability. With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during the attack, and may even persist interictally.

SUMMARY: Scientific publications over the last year confirmed that electrophysiological methods are particularly suited to unravelling some of the pathophysiological mechanisms of migraine. To improve their future contribution, they need to be better standardized and to be correlated with behavioural, metabolic and genetic studies. 

PMID: 12858069 [PubMed – in process]

Cephalalgia. 2003;23 Suppl 1:13-31. 
Electrophysiological studies in migraine: a comprehensive review of their interest and limitations. 
Ambrosini A, de Noordhout AM, Sandor PS, Schoenen J. 
Headache Clinic, INM Neuromed, IRCCS, Pozzilli (Isernia),Italy. 

Electrophysiological methods may help to unravel some of the pathophysiological mechanisms of migraine. Lack of habituation is the principal and most reproducible interictal abnormality in sensory processing in migraineurs. It is found in evoked potential (EP) studies for every stimulation modality including nociceptive stimuli, and it is likely to be responsible for the increased intensity dependence of EP. We have hypothesized that deficient EP habituation in migraine could be due to a reduced preactivation level of sensory cortices because of hypofunctioning subcortico-cortical aminergic pathways. This is not in keeping with simple hyperexcitability of the cortex, which has been suggested by some, but not all, studies of transcranial magnetic stimulation (TMS). A recent study of the effects of repetitive TMS on visual EP strongly supports the hypothesis that migraine is characterized by interictal cortical hypoexcitability. With regard to pain mechanisms in migraine, electrophysiological studies of trigeminal pathways using nociceptive blink and corneal reflexes have confirmed that sensitization of central trigeminal nociceptors occurs during migraine attacks.

PMID: 12699456

Clin Neurophysiol. 2003 Jun;114(6):955-72.
Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance. 
Schoenen J, Ambrosini A, Sandor PS, Maertens de Noordhout A. 
University Department of Neurology, CHR Citadelle, Blvd du XIIemede Ligne, 1-B-4000, Liege, Belgium. jean.schoenen[@]

Migraine is a disorder in which central nervous sytem dysfunction might play a pivotal role. Electroneurophysiology seems thus particularly suited to study its pathophysiology. We have extensively reviewed evoked potential and transcranial magnetic stimulation studies performed in migraineurs in order to identify their pathophysiologic significance. Publications available to us were completed by a Medline search. Retrieved and personal data were compared with respect to methodology and interpreted according to present knowledge on cortical information processing. Results are in part contradictory which appears to be method-, patient- and disease- related. Nonetheless, both evoked potential and transcranial magnetic stimulation studies demonstrate that the cerebral cortex, and possibly subcortical structures, are dysfunctioning interictally in both migraine with and without aura. These electrophysiologic abnormalities tend to normalise just before and during an attack and some of them seem to have a clear familial and predisposing character. Besides the studies of magnetophosphenes which have yielded contrasting results, chiefly because the method is not sufficiently reliable, most recent electrophysiologic investigations of cortical activities in migraine favour deficient habituation and decreased preactivation cortical excitability as the predominant interictal dysfunctions. We propose that the former is a consequence of the latter and that it could favour both interictal cognitive disturbances as well as a cerebral metabolic disequilibrium that may play a role in migraine pathogenesis. To summarize, electrophysiologic studies demonstrate in migraine between attacks a cortical, and possibly subcortical, dysfunction of which the hallmark is deficient habituation. 

PMID: 12804664 [PubMed – in process]

Curr Opin Neurol. 2002 Jun;15(3):303-9. 
The electrophysiology of migraine. 
Giffin NJ, Kaube H. 
Headache Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK. 

Migraine is currently regarded as a neurovascular disorder of trigeminal sensory processing, generated centrally, probably at the level of the brainstem. In the past, electrophysiological techniques have drawn no definite conclusions on either interictal or ictal changes in migraineurs compared with controls, largely because of methodological differences. Recently, two findings have been shown consistently: an interictal increasing lack of habituation of evoked potentials with a normalization at the start of the attack and strong intensity dependence of auditory evoked potentials. These findings substantiate migraine sufferers as having an abnormal trait interictally, with the attack characterized by a change in the state of central processing. Exploitation of these differences may be a useful tool to study the mechanism of action of drugs used for the treatment of migraine. 

PMID: 12045729

Cephalalgia. 2000 Oct;20(8):714-9. 
Habituation of visual and intensity dependence of auditory evoked cortical potentials tends to normalize just before and during the migraine attack. 
Judit A, Sandor PS, Schoenen J. 
Department of Neurology, Semmelweis University of Medicine, Budapest, Hungary. 

Between attacks, migraine with (MO) or without aura (MA) patients show deficient habituation of pattern-reversal visual evoked potentials (PR-VEP) and a strong intensity dependence of auditory evoked cortical potentials (IDAP). Clinical observations of migraine prodromes and previously published electrophysiological studies suggest that cortical information processing may vary in close temporal relationship to the attack. We studied PR-VEP and IDAP just before (11 MO pts), during (23 MO, 3 MA), 1 day following (27 MO, 1 MA) and 2 days following (14 MO) a migraine attack. The results were compared with a large group of MO patients recorded at a distance of at least 3 days from an attack (n = 66 for IDAP; n = 39 for VEP). Patients recorded the day before the attack had on average an habituation of -13.6+/-20.5% (mean +/- SD) between the 5th and 1st block of 100 averaged VEP responses and a flat (0.38+/-1.06 microV/10 dB) amplitude-stimulus intensity function (ASF) slope of the auditory evoked cortical potential. Both values were significantly different from those obtained in the attack interval (P=0.003; P=0.020). During the attack, VEP habituation was less pronounced (-0.17+/-26.2%) and ASF slopes remained flat (0.32+/-1.44 microV/10 dB; P=0.002 compared to interval). During the 2 days following the attack, VEP habituation was replaced by potentiation (+0.09+/-29.1% the 1st day; 19.5+/-45.7% the 2nd day) and ASF slopes increased markedly (0.87+/-1.39 and 1.14+/-1.12 microV/10 dB). The normalization of evoked cortical responses just before and during the attack, might reflect an increase in the cortical preactivation level due to enhanced activity in raphe-cortical serotonergic pathways. 

PMID: 11167900

Clin Neurosci. 1998;5(1):10-7. 
Cortical electrophysiology in migraine and possible pathogenetic implications. 
Schoenen J. 
Department of Neurology, University of Liege, CHR Citadelle, Liege, Belgium. Schoenen.J[@] 

According to recent evoked potential studies a fundamental, probably protective, feature of cortical information processing, i.e., response habituation during stimulus repetition, is abnormal in migraine between attacks. The deficient habituation is found for different sensory modalities and experimental paradigms: pattern-reversal visual evoked potentials (same stimulus at a constant intensity), cortical auditory evoked potentials (same stimulus at increasing intensities), and auditory event-related potential obtained in a passive “oddball” paradigm (novel stimulus). The abnormal information processing is an interictal cortical dysfunction most likely due to inadequate control by the so-called “state-setting, chemically-addressed pathways” originating in the brain stem, in particular by the serotonergic pathway, leading to a low preactivation level of sensory cortices. We propose that it may play a pivotal role in migraine pathogenesis in conjunction with the reported decrease of brain mitochondrial energy reserve, by favouring a rupture of metabolic homeostasis and biochemical shifts capable of activating the trigeminovascular system and, thus, of producing a migraine attack. We postulate that both the deficient habituation in information processing and the deranged oxygen metabolism may have behavioral correlates. Which of these abnormalities are inherited, acquired, or both remains to be determined.

PMID: 9523052

Biomed Pharmacother. 1996;50(2):71-8. 
Deficient habituation of evoked cortical potentials in migraine: a link between brain biology, behavior and trigeminovascular activation? 
Schoenen J. 
Department of Neurology, University of Liege, Belgium. 

According to recent evoked potential studies, a fundamental, probably protective, feature of cortical information processing, ie, response habituation during stimulus repetition, is abnormal in migraine between attacks. The deficient habituation is found for different sensory modalities and experimental paradigms: pattern-reversal visual evoked potentials (same stimulus at a constant intensity), cortical auditory evoked potentials (same stimulus at increasing intensities) and auditory event-related potentials obtained in a passive “oddball” paradigm (novel stimulus). The abnormal information processing is an interictal cortical dysfunction most likely due to inadequate control by the so-called “state-setting, chemically-addressed pathways” originating in the brain stem, in particular by the serotonergic pathway, leading to a low preactivation level of sensory cortices. We suggest that it may play a pivotal role in migraine pathogenesis in conjunction with the reported decrease of brain mitochondrial energy reserve, by favouring a rupture of metabolic homeostasis and biochemical shifts capable of activating the trigeminovascular system and thus capable of producing a migraine attack. We postulate that both the deficient habituation in information processing and the deranged oxygen metabolism may have behavioral correlates. Which of these abnormalities are inherited, acquired or both remains to be determined. 

PMID: 8761712

Clin Neurophysiol. 2000 Jun;111(6):1124-9. 
Comparison of visual and auditory evoked cortical potentials in migraine patients between attacks. 
Afra J, Proietti Cecchini A, Sandor PS, Schoenen J. 
Department of Neurology Semmelweis University of Medicine, Budapest, Hungary. 

OBJECTIVE: As both habituation of pattern reversal visual evoked potentials (PR-VEP) (Schoenen J, Wang W, Albert A, Delwaide PJ. Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks. Eur J Neurol 1995;2:115-122) and intensity dependence of auditory evoked cortical potentials (IDAP) (Wang W, Timsit-Berthier M, Schoenen J. Intensity dependence of auditory evoked potentials in migraine: an indication of cortical potentiation and low serotonergic neurotransmission? Neurology 1996;46:1404-1409) were found abnormal in migraine between attacks, we have searched for intraindividual correlations between both tests in 59 migraine patients (22 with aura [MA], 37 without aura [MO]) and in 23 healthy volunteers (HV). METHODS: Amplitude change of the PR-VEP N1-P1 was measured between the 1st and 5th block of 50 sequential averagings during continuous stimulation at 3.1 Hz. IDAP was computed from N1-P2 amplitudes of 100 averagings during stimulations at 40, 50, 60 and 70 dB SL. Amplitude-stimulus intensity function (ASF) slopes and amplitude changes between 40 and 70 dB were calculated. MO and MA differed from HV in PR-VEP amplitude change (P=0.007) and IDAP slope (P = 0.0004). RESULTS: There was no significant correlation between VEP amplitude changes and IDAP slopes, nor between the latter two and attack frequency or disease duration. A negative correlation was found between the amplitude of the first block of averaged responses and potentiation of VEP in all subject groups (P = 0.03) as well as between the amplitude of the auditory evoked potential, at 40 dB, and the percentage of amplitude increase between 40 and 70 dB in MO (P = 0.004) and MA (P = 0.007). ASF slopes and 40 dB amplitudes were significantly correlated only in the MA group (P = 0.002). These results confirm the interictal deficit of habituation in cortical processing of repetitive visual and auditory information in migraine. Since there is no intraindividual correlation between the cortical responses to these sensory modalities they are complementary tools for the study of migraine and may help to identify subgroups of patients with distinct pathophysiological mechanisms. CONCLUSIONS: The strong negative correlation between the initial amplitude of evoked potentials and their amplitude increase during subsequent averaging confirms that the response potentiation in migraine is likely to be due to a reduced preactivation level of sensory cortices. 

PMID: 10825720

Brain. 2002 Apr;125(Pt 4):912-22. 
Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine. 
Bohotin V, Fumal A, Vandenheede M, Gerard P, Bohotin C, Maertens de Noordhout A, Schoenen J. 
Department of Neurology, University of Liege, Liege, Belgium.

Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical excitability. We have studied the changes in visual cortex excitability by recording pattern-reversal visual evoked potentials (PR-VEP) after low- and high-frequency repetitive transcranial magnetic stimulation (rTMS), known respectively for their inhibitory and excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was set to the phosphene threshold or to 110% of the motor threshold if no phosphenes were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy volunteers, PR-VEP amplitude was significantly decreased in the first block after 1 Hz rTMS and the habituation normally found in successive blocks after sustained stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was followed by a significant increase of first block PR-VEP amplitude and by a reversal to normal habituation of the potentiation (or dishabituation) characteristic of the disorder. This effect was similar in both forms of migraine and lasted for at least 9 min. There were no significant changes of PR-VEP amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy volunteers, nor after sham stimulation. The recovery of a normal PR-VEP habituation pattern after high-frequency rTMS is probably due to activation of the visual cortex and the dishabituation in healthy volunteers to cortical inhibition. We conclude, therefore, that the deficient interictal PR-VEP habituation in migraine is due to a reduced, and not to an increased, pre-activation excitability level of the visual cortex. 

PMID: 11912123

Brain. 2003 Jun 23 [Epub ahead of print]. 
Lack of habituation causes high intensity dependence of auditory evoked cortical potentials in migraine. 
Ambrosini A, Rossi P, De Pasqua V, Pierelli F, Schoenen J. 
Headache Clinic, INM Neuromed, Pozzilli (Isernia), Italy. 

Migraineurs are characterized interictally by lack of habituation, or even potentiation, of cortical evoked potentials during repetitive stimulation and by a strong intensity dependence of auditory evoked potentials (IDAP). To determine whether these two features of sensory processing are interrelated, we have studied them simultaneously on the same recordings of auditory evoked potentials (AEPs). AEPs were obtained at four different stimulation intensities in 14 patients suffering from migraine without aura (MO) and 14 healthy volunteers (HV). For each intensity, 120 trials were averaged off-line globally and over four sequential blocks of 30 trials. IDAP was expressed by the amplitude/stimulus intensity function (ASF slope) for global and block averages. Habituation was calculated as the percentage amplitude variation between the first and fourth blocks for each stimulus intensity. The IDAP slope for global averages was higher in MO (1.05 +/- 0.27 micro V/10 dB) than in HV (0.64 +/- 0.45 micro V/10 dB) (P = 0.008), but IDAP slopes for block averages were greater in MO only at the fourth block (P = 0.048). First block amplitudes tended to be lower in MO, except at 80 dB. There was a potentiation of AEP amplitudes at every stimulus intensity in MO, contrasting with habituation in HV. IDAP slopes were negatively correlated with mean habituation percentages in pooled data from patients and controls (r = -0.610; P = 0.0006). This study confirms that IDAP is higher in migraineurs than in healthy controls. It also shows that the AEP habituation is replaced by potentiation at all stimulus intensities. The negative correlation found between IDAP and habituation suggests that the latter is able to have a strong influence on the former and perhaps even lead to it. In migraine, the habituation deficit amplifies the IDAP and may thus be the causal functional abnormality. We propose that it is due to a decreased pre-activation level of sensory cortices, a hypothesis also supported in this study by the lower amplitude of first AEP blocks in patients. 

PMID: 12821515 [PubMed – as supplied by publisher]

Neurosci Lett. 2001 Jun 22;306(1-2):132-4. 
Reduced gating of middle-latency auditory evoked potentials (P50) in migraine patients: another indication of abnormal sensory processing? 
Ambrosini A, De Pasqua V, Afra J, Sandor PS, Schoenen J. 
Headache Clinics – IRCCS Neuromed via Atinense, 18, I-86077 , Pozzilli (Isernia), Italy. 

Habituation of cortical evoked responses to repetitive stimuli is reduced in migraine between attacks. To explore another aspect of information processing, we measured auditory sensory gating. The amplitude of the P50 response to the second of two homologous stimuli was significantly less reduced in migraineurs than in healthy volunteers. This lack of auditory sensory gating may be due to a hypofunction of monoaminergic subcortico-cortical pathways, which is also supposed to cause the interictal deficit of cortical habituation to repetitive stimuli. 

PMID: 11403975

Neurology. 1996 May;46(5):1404-9. 
Intensity dependence of auditory evoked potentials is pronounced in migraine: an indication of cortical potentiation and low serotonergic neurotransmission? 
Wang W, Timsit-Berthier M, Schoenen J. 
Department of Neurology, University of Liege, Belgium. 

Migraine is associated with stimulus hypersensitivity, increased evoked cortical responses, and abnormal 5-HT levels in peripheral blood. We studied cortical auditory evoked potentials (AEPs) between attacks in 35 patients suffering from migraine without aura (MO, n = 25) or with aura (MA, n = 10) and in 25 healthy volunteers. Binaural tones were delivered at 40, 50, 60, and 70 dB sensation level (SL) in a pseudorandomized order. The intensity dependence of the auditory N1-P2 component was significantly greater in MO (p = 0.003) and MA (p = 0.02) patients than in healthy controls, resulting in a much steeper amplitude/stimulus intensity function slope. When three sequential blocks of 40 averaged responses were analyzed at the 40- and 70-dB SL intensities, N1-P2 amplitude decreased in second and third blocks at both intensities in controls, but increased in migraineurs, a difference that was significant in both blocks for the 70-dB SL stimulus. The strong interictal dependence of AEPs on stimulus intensity may thus be due to potentiation (instead of habituation) of the response during repetition of the high-intensity stimulation. In concordance with previous studies of visual evoked potentials, these results confirm that migraine is characterized between attacks by an abnormality of cortical information processing, which might be a consequence of low 5-HT transmission and favor cortical energy demands. 

PMID: 8628490

Cephalalgia. 2000 Nov;20(9):804-20. 
Visual, long-latency auditory and brainstem auditory evoked potentials in migraine: relation to pattern size, stimulus intensity, sound and light discomfort thresholds and pre-attack state. 
Sand T, Vingen JV. 
Department of Clinical Neurosciences, Trondheim University Hospital, Norwegian University of Science and Technology. trond.sand[@] 

We aimed to estimate primary sensory evoked potential (EP) amplitude, amplitude-intensity functions and habituation in migraine patients compared with healthy control subjects and to investigate the possible relation to check size, sound and light discomfort thresholds, and the time to the next attack. Amplitudes of cortical visual evoked potentials (VEP, check size 8′ and 33′), cortical long latency auditory evoked potential (AEP NIP1; 40, 55 and 70 dB SL tones) and brainstem auditory evoked potential (BAEP wave IV-V; 40, 55 and 65 dB SL clicks) were recorded and analysed in a blind and balanced design. The difference between the response to the first and the second half of the stimulus sequence was used as a measure of habituation. Twenty-one migraine patients (16 women and five men, mean age 39.3 years, six with aura, 15 without aura) and 22 sex- and age-matched healthy control subjects were studied (18 women and four men, mean age 39.5 years). Low sound discomfort threshold correlated significantly with low levels of BAEP wave IV-V amplitude habituation (r = -0.30, P = 0.05). VEP an AEP amplitudes, habituation, and amplitude-intensity function (ASF) slopes did not differ between groups when ANOVA main factors were considered. Control group VEP habituation was found for small check stimuli (P = 0.04), while potentiation was observed for medium sized checks (P = 0.02). The eight migraine patients who experienced headache within 24 h after the test tended to have increased BAEP wave IV-V ASF slopes (P = 0.08). This subgroup did also have a significant VEP habituation to small checks (P = 0.04). No correlation was found between different modalities. These results suggest that: (i) VEP habituation/potentiation state and brainstem activatio state may depend on the attack-interval cycle in migraine; (ii) VEP habituation/ potentiation may depend on spatial stimulus frequency; (iii) phonophobia (and possibly photophobia) may depend more on subcortical (brainstem) function than on cortical mechanisms; (iv) low cortical preactivation in migraine could not be confirmed; (v) EP habituation and ASF analysis may reflect sensory modality-specific, not generalized, central nervous system states in migraine and healthy control subjects. 

PMID: 11167910

Headache. 2000 Jan;40(1):30-5. 
Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials. 
Sandor PS, Afra J, Ambrosini A, Schoenen J. 
Neurology Department, CHR Citadelle, University of Liege, Belgium. 

OBJECTIVE: To investigate the influence of different pharmacological treatments on the intensity dependence of auditory evoked cortical potentials in migraineurs.

BACKGROUND: Between attacks, patients with migraine show abnormalities in cortical information processing and decreased brain mitochondrial energy reserve. Both are most probably relevant for migraine pathogenesis, and they could be differentially modified by prophylactic drug therapy. Design.-The intensity dependence of the auditory evoked cortical potentials is, on average, increased in migraine. We have studied this intensity dependence in 26 patients before and after a 4-month period of prophylaxis with beta-blockers (n = 11, all migraine without aura; metoprolol or bisoprolol) or riboflavin (n = 15, migraine without aura: 13, migraine with aura: 2). Recordings were performed at least 3 days before or after an attack.

RESULTS: After the treatment with beta-blockers, the intensity dependence of the auditory evoked cortical potentials was significantly decreased (before: 1.66+/-1.02 microV/10 dB; after: 0.79+/-1.06 microV/10 dB, P=.02). The decrease in intensity dependence was correlated significantly with clinical improvement (r = .69, P = .02). There was no change in intensity dependence after riboflavin treatment (before: 1.80+/-0.81 microV/10 dB; after: 1.56+/-0.83 microV/10 dB, P = .39), although the majority of patients showed improvement.

CONCLUSIONS: These results confirm that beta-blockers and riboflavin act on two distinct pathophysiological mechanisms. Combining both treatments might enhance their efficacy without increasing central nervous system side effects. 

PMID: 10759900

Eur J Neurol. 2002 May;9(3):227-32. 
Median nerve somatosensory evoked potentials in migraine. 
Ozkul Y, Uckardes A. 
Department of Neurology, Faculty of Medicine, University of Harran, Sanliurfa, Turkey. yasarozkul[@] 

In visual evoked potential studies, habituation during stimulus repetition with the same stimulus at a constant intensity has been found to be abnormal in migraineurs between attacks. The purpose of this study was to investigate habituation of somatosensory evoked potentials (SEPs) and the effects of migraine on them. Eighty-five subjects were included in the study: 30 healthy volunteers (HVs) and 55 migraineurs [30 with migraine without aura (MO), 25 with migraine with aura (MA)]. During continuous stimulation at 3 Hz, four blocks of 100 responses were sequentially averaged of Erb’s point (N9), cervical (N13), and cortical (N20) median nerve SEPs. Mean amplitude changes in the second, third and fourth blocks are expressed as percentages of the first block. There was habituation to N13 and N20 in the second, third and fourth blocks in HVs. In the migraine groups, there was no habituation; on the contrary, potentiation was found. This potentiation was statistically significant only in the second blocks for N13 (MO P=0.007, MA P=0.01 versus HVs). However, in both migraineur groups, the rate of N20 potentiations was statistically significant versus that in HVs for all blocks (all P < 0.05). It is concluded that whilst physiological habituation occurs in HVs for cervical and cortical SEPs, in migraine patients there is an interictal deficit of habituation of this sensory modality. 

PMID: 11985630

Neuroreport. 1999 Apr 26;10(6):1235-8.
Familial influences on cortical evoked potentials in migraine. 
Sandor PS, Afra J, Proietti-Cecchini A, Albert A, Schoenen J. 
Neurology Department, University of Zurich, Switzerland

Cortical information processing in migraine patients is impaired between attacks, showing deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. We investigated VEP habituation and IDAP in 20 pairs of migraineurs made up of parents and their children. Using a Monte-Carlo statistical method, we selectively assessed vertical familial influences. VEP habituation and IDAP were abnormal in both parents and children. However, similarity was far more pronounced between related pairs than between unrelated pairs. Familial influences are highly significant in determinants of cortical information processing in migraineurs, hence supporting the important role of genetic factors. 

PMID: 10363931

Headache. 2000 Jan;40(1):36-40. 
Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers. 
Afra J, Ambrosini A, Genicot R, Albert A, Schoenen J. 
Department of Neurology, Semmelweis University of Medicine, Budapest, Hungary. 

OBJECTIVE: To investigate whether colored glasses influence the habituation of visual evoked potentials.

BACKGROUND: We have previously shown that during pattern-reversal stimulations lasting 2 minutes the amplitude of the visual evoked potential increases in migraine with and without aura between attacks, whereas it decreases in healthy volunteers. Red light was found to increase visually evoked EEG fast activity only in children with migraine with aura. Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel with a reduction of the visually evoked EEG fast activity.

METHODS: We compared the change in amplitude of the visual evoked potential using five different tinted glasses in 12 patients with migraine with aura and in 10 healthy volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses were sequentially averaged using red, yellow, green, blue, and grey glasses and without glasses in a random order and analyzed in terms of latencies and N1-P1 amplitudes. Amplitude changes were calculated for each block by comparison with the first block in every condition and analyzed statistically using Zerbe’s method.

RESULTS: In healthy volunteers, the visual evoked potential amplitude increased with red glasses compared to without glasses (P = .05) or with green glasses (P = .03). In patients with migraine with aura, no significant difference was detected using colored glasses. Our findings in healthy volunteers are in line with earlier reports of increased excitability of the human visual cortex when exposed to red light. The lack of such a pattern in patients with migraine with aura suggests that the visual cortex is interictally hypoexcitable rather than hyperexcitable, which is consistent with studies of transcranial magnetic stimulation.

PMID: 10759901

Headache. 2002 Jul-Aug;42(7):582-7. 
Effects of fluoxetine on habituation of pattern reversal visually evoked potentials in migraine prophylaxis. 
Ozkul Y, Bozlar S. 
University of Harran, Faculty of Medicine, Department of Neurology, Sanliurfa, Turkey. 

OBJECTIVE: To investigate the effects of fluoxetine in migraine prophylaxis on habituation of visually evoked potentials.

BACKGROUND: Habituation of pattern reversal visually evoked potentials was found to be abnormal in migraine between attack, and this abnormality was most likely due to serotonergic pathway dysfunction in the brain stem.

METHODS: One hundred nineteen subjects were included in the study: 40 healthy volunteers and 79 migraineurs not taking any prophylactic migraine medication (44 without aura and 35 with aura). Visually evoked potentials in migraineurs were recorded in the headache-free interval. Amplitude change of the visually evoked potentials (N1-P1) was measured between the first and fifth block of 50 sequential averagings during continuous stimulation at 3.1 Hz. All migraineurs were placed on fluoxetine 20 mg/day for prophylaxis of migraine. One month later, visually evoked potentials were recorded again.

RESULTS: Mean amplitude changes in the fifth block expressed as percentages of the first block were -13.4% +/- 19.2% in healthy volunteers, 9.8% +/- 23.3% in migraine without aura, and 4.4% +/- 8.7% in migraine with aura during the baseline period. The difference was significant between migraineurs and healthy volunteers (both P= 0.0001), but not between migraineur groups. After treatment, amplitude changes were -9.3% +/- 14.5% in migraine without aura and -10.1% +/- 11.5% in migraine with aura. Habituation pattern tended to normalize with prophylactic treatment, and mean amplitude changes were not significant between migraineurs and healthy volunteers (both P = 0.4).

CONCLUSIONS: We concluded that the fluoxetine prophylaxis corrects the interictal deficit of habituation in migraineurs. 

PMID: 12482209

Brain. 1998 Feb;121 ( Pt 2):233-41. 
Visual evoked potentials during long periods of pattern-reversal stimulation in migraine. 
Afra J, Cecchini AP, De Pasqua V, Albert A, Schoenen J. 
Department of Neurology, University of Liege, Belgium.

We have previously shown that during repetitive pattern-reversal stimulation, lasting 2 min, the amplitude of the visual evoked potential (PR-VEP) increases in migraineurs when tested interictally whereas it decreases in healthy control subjects. According to Sappey-Marinier et al. (J Cereb Blood Flow Metab 1992; 12: 584-92) habituation of the PR-VEP in normal subjects is maxima after 12 min, at a time when there is a decrease of stimulation-enhanced lactate levels in the occipital cortex. We have therefore compared PR-VEP during long periods of repetitive stimulation in healthy control subjects (n = 25) and in patients suffering from migraine without (n = 25) and with aura (n = 15) between attacks. During uninterrupted stimulation at 3.1 Hz VEPs were sequentially averaged in blocks of 100 responses for a total duration of 15 min and analysed in terms of latencies and peak-to-peak amplitudes of N1-P1 and P1-N2 peaks. Amplitude changes from the baseline were calculated for each block, by comparison with the first block, and analysed statistically using Zerbe’s method. The N1-P1 and P1-N2 amplitudes in the first block tended to be lower in migraineurs than in healthy control subjects. During the 15 min of stimulation, amplitudes of both components progressively decreased in control subjects, but remained stable in both groups of patients. The difference between patients and control subjects proved to be significant (P < 0.05). The neurophysiological data were not correlated with clinical features such as attack frequency or duration of illness. These results are yet another demonstration in migraine of an interictal habituation deficit in cortical information processing, which might favour lactate accumulation in sensory cortices during sustained activation. 

PMID: 9549502

Cephalalgia. 2002 Feb;22(1):48-53. 
A neural network model of sensitization of evoked cortical responses in migraine. 
Thomas E, Sandor PS, Ambrosini A, Schoenen J. 
Research Center for Cellular and Molecular Neurobiology, University of Liege, Belgium. ethomas[@] 
Migraine patients show abnormalities of cerebral electrophysiology that manifest themselves mainly during the attack interval. Cortical-evoked potentials of migraineurs fail to habituate to repetitive presentations of visual stimuli, and the amplitude of components of their auditory cortical-evoked potentials have a higher dependence on the stimulus intensities than in healthy subjects. A computer model of a neural hetwork has been developed that is able to reproduce both these neurophysiological dysfunctions. It predicts a positive correlation between the magnitudes of both these dysfunctions. The model also offers an explanation of why mutations in the same ion channel gene with opposite consequences on channel function, e.g. P/Q Ca2+ channels in migraine, may lead to similar electrophysiological abnormalities. 

PMID: 11993613

Funct Neurol. 2000;15 Suppl 3:68-72.
From neurophysiology to genetics: cortical information processing in migraine underlies familial influences–a novel approach. 
Sandor PS, Afra J, Proietti Cecchini AP, Albert A, Schoenen J. 
Department of Neurology, CHR Citadelle, University of Liege, Belgium. 

Migraine patients show impaired cortical information processing between attacks with deficient habituation of pattern-reversal visual evoked potentials (VEP), and strong intensity dependence of auditory cortical evoked potentials (IDAP). This could be a genetic trait as certain genetic patterns are known for evoked potentials in healthy subjects. VEP-habituation and IDAP were studied in 40 migraine patients, i.e. pairs of 20 parents and their children. We developed a novel approach based on Monte Carlo statistics to selectively assess vertical familial influences. Both groups, parents and children, were characterized by abnormal VEP-habituation and IDAP. However, similarity between related pairs was far more pronounced than similarity between unrelated pairs. Assessed with a novel statistical approach, familial influences proved to be highly significant in determining cortical information processing in migraineurs, thus supporting the important role of genetic factors. 

PMID: 11200803

Cephalalgia. 1998 Jun;18(5):261-5; discussion 241. 
Interictal potentiation of passive “oddball” auditory event-related potentials in migraine. 
Wang W, Schoenen J. 
Department of Neurology, University of Liege, Belgium. 

We have studied habituation of the P3a component of the passive “oddball” auditory event-related potential which reflects automatic processing of a “novel” stimulus in 24 patients suffering from migraine without aura and in 21 healthy volunteers. Three blocks of responses to 160 standard and to 40 novel tones were sequentially averaged at Cz and analyzed for latencies and peak-to-peak amplitudes. Latencies of components N1 and P2 elicited by standard tones and of components N1, P2, N2, and P3a elicited by novel tones were not significantly different between sequential blocks or between subject groups, nor were mean N1-P2 amplitudes. The N2-P3a amplitude tended to be lower in migraine, but not significantly so. The most striking result in migraineurs was a significant potentiation of N2-P3a in successive blocks, contrasting with an habituation in controls. Our previous evoked- and event-related potential studies and the present one suggest that deficient habituation, or even potentiation, represents interictally a fundamental dysfunction of cortical information processing in migraine, which might increase energy demands and play a role in etiopathogenesis. 

PMID: 9673805

Rev Neurol (Paris). 2001 Apr;157(4):365-75. 
[Clinical and pathophysiological contribution of event-related potentials used to study migraine headache] 
[Article in French] 
Legrain V, Janne P, Laloux P, Ossemann M, Dupuis M, Reynaert C. 
Departement de psychologie clinique, Faculte de Psychologie et des Sciences de l’Education, Universite Catholique de Louvain, Louvain-la-Neuve. legrain[@] 

Event-related potentials are electric brain manifestations evoked by mental activities. This neurophysiological technique is able to describe temporal succession of cognitive processing and allows to measure the neurobiological correlates of each cognitive activity. The evoked potentials of the oddball paradigm and the Contingent Negative Variation (CNV) are also concerned by clinical applications in neuropsychiatry, in neurology and in psychopharmacology. In the case of migraine, the studies with CNV recorded between migraine attacks are characterized by two major phenomena, cerebral hyperreactivity and lack of habituation to repetitive stimuli. From cognitive point of view, this can be interpreted as a difficulty from migraine sufferers to adapt their information-processing to environmental constraints. From neurological point of view, this trouble is related with dysregulation of norepinephrin and serotonin ascending pathways. Studies with the oddball paradigm potentials remain non consistent. The mismatch between different methodologies could explain such a lack of consistency. The neurophysiological studies have contributed to new physiopathological hypothesis of migraine. Those hypothesis reveal that a shift in the brain metabolic homeostasis could be the common factor of migraine attacks. The clinical contribution of event-related potentials is of little use in the diagnosis of migraine. But two purposes have been suggested: the differential diagnosis between common migraine and tension-type headaches and the monitoring of beta-blocking agents prophylaxis. 

PMID: 11398007

Cephalalgia. 2000 Sep;20(7):621-31. 
Olfactory and trigeminal event-related potentials in migraine. 
Grosser K, Oelkers R, Hummel T, Geisslinger G, Brune K, Kobal G, Lotsch J. 
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen Nurnberg, Erlangen, Germany. 

BACKGROUND: Trigeminal/neuronal hyperexcitability and spreading depression activating the trigemino-vascular system are discussed in migraine-pathophysiology. This study investigated trigeminal and olfactory event-related potentials in migraineurs.

METHODS: Nasal chemosensitivity was assessed in 19 female migraineurs with or without aura > 72 h before or after an attack and in 19 healthy females employing event-related cortical potentials (ERPs) after specific trigeminal stimulation of nasal nociceptors with short pulses of CO2, and specific olfactory stimulation with H2S. Odour thresholds and odour identification performance were also tested.

RESULTS: Migraineurs exhibited greater responses to trigeminal stimulation, indicated by significantly larger ERP amplitudes N1. In contrast, olfactory ERP amplitudes P1N1 were significantly smaller in migraineurs. A leave-one-out classification procedure on the basis of these two parameters assigned 76.3% cases correctly. The olfactory ERP amplitude discriminated better between groups than trigeminal ERPs (71.1 vs. 68.4% correct classification).

CONCLUSIONS: Our data suggest trigeminal hyperexcitability in migraineurs. A general increase of nasal chemosensitivity is not supported because of smaller olfactory ERP amplitudes in migraineurs. Olfactory ERPs discriminate better than trigeminal ERPs between migraineurs and controls, emphasizing the significance of the olfactory system in migraine. 

PMID: 11128819

Brain. 1999 Jun;122 ( Pt 6):1147-55. 
Visual evoked potentials in migraine patients: alterations depend on pattern spatial frequency. 
Oelkers R, Grosser K, Lang E, Geisslinger G, Kobal G, Brune K, Lotsch J. 
Department of Experimental and Clinical Pharmacology, University of Erlangen-Nurnberg, Germany. rieke_oelkers[@] 

Visual information is conducted by two parallel pathways (luminance- and contour-processing pathways) which are thought to be differentially affected in migraine and can be investigated by means of pattern-reversal visual evoked potentials (VEPs). Components and habituation of VEPs at four spatial frequencies were compared between 26 migraineurs (13 without aura, MO; 13 with aura, MA) and 28 healthy volunteers. Migraineurs were recorded in the headache-free interval (at least 72 h before and after an attack). Five blocks of 50 responses to chequerboards of 0.5, 1, 2 and 4 cycles per degree (c.p.d.) were sequentially averaged and analysed for latency and amplitude. Differences in VEPs were dependent on spatial frequency. Only when small checks were presented, i.e. at high spatial frequency (2 and 4 c.p.d.), was the latency of N2 significantly prolonged in MA and did it tend to be delayed in MO subjects. Habituation behaviour was not significantly different between groups under the stimulating conditions employed. Prolonged N2 latency might be explained by the lack or attenuation of a contour-specific component N130 in migraineurs, indicating an imbalance of the two visual pathways with relative predominance of the luminance-processing Y system. These results reflect an interictally persisting dysfunction of precortical visual processing which might be relevant in the pathophysiology of migraine. 

PMID: 10356066

Exp Brain Res. 2002 Jul;145(2):177-81. Epub 2002 May 09.
Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation. 
Brighina F, Piazza A, Daniele O, Fierro B. 
Istituto di Neuropsichiatria, Universita di Palermo, via G. La Loggia 1, 90129 Palermo, Italy. 

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS. 

PMID: 12110957

Patol Fiziol Eksp Ter. 1996 Apr-Jun;(2):3-6. 
[Multimodal evoked potentials and central mechanisms of afferentation in trigeminal neuralgia] 
[Article in Russian] 
Meizerov EE, Reshetniak VK, Koroleva MV, Grachev IuV. 

Multimodal evoked potentials in patients with trigeminal neuralgia are analyzed in the paper. The comprehensive studies of cortical trigeminal somatosensory evoked potentials, visual evoked potentials, and brainstem auditory evoked potentials have revealed their changes that are indicative of the impaired central mechanisms of afferentation in patients with trigeminal abnormality. The findings are discussed in the light of the theory of generator mechanisms of neuropathological pain syndromes. 

PMID: 8754133

J Neurol Sci. 1996 Jul;139(1):106-10. 
Interictal cortical hyperexcitability in migraine patients demonstrated with transcranial magnetic stimulation. 
van der Kamp W, Maassen VanDenBrink A, Ferrari MD, van Dijk JG. 
Department of Neurology and Clinical Neurophysiology, University Hospital Leiden, Netherlands. 

Cortical excitability to magnetic stimulation was investigated interictally in 10 patients with migraine with aura, 10 with migraine without aura and in 10 healthy volunteers. Thresholds, latencies and amplitudes of the magnetic-evoked potentials (MEPs) were measured from threshold to 100% stimulus intensity in 10% steps. Compound motor action potentials (CMAPs) evoked with supramaximal electrical stimulation of the ulnar nerve were used to calculate MEP/CMAP amplitude ratios. Thresholds and latencies of MEPs did not differ between patients and controls. MEP/CMAP amplitude ratios were significantly increased at all intensities in patients with migraine with aura (RM-ANOVA, p < 0.01) and without aura (p < 0.05) compared with controls. In migraine patients, MEP amplitudes and MEP/CMAP amplitude ratios were positively related to the frequency of migraine attacks (Spearman’s r = 0.47, p < 0.01 and r = 0.56, p < 0.002, respectively). MEP parameters were not related to the side of the headache nor the aura, in either type of migraine, implying that both hemispheres are equally involved in migraine. Migraine with aura and, to a lesser extent, migraine without aura, are associated with increased interictal cortical excitability. 

PMID: 8836980

Cephalalgia. 1985 May;5 Suppl 2:53-8. 
Visual evoked potentials and brainstem auditory evoked potentials in migraine and transient ischemic attacks. 
Benna P, Bianco C, Costa P, Piazza D, Bergamasco B. 

A study of brainstem auditory evoked potentials (BAEPs) and pattern reversal visual evoked potentials (VEPs), recorded in intercritical phase, was carried out in 20 subjects (10 suffering from common migraine and 10 suffering from vertebrobasilar TIA) in order to obtain a comparative evaluation of cortical-subcortical functions. The data we obtained demonstrate the presence of BAEPs alterations in patients with previous vertebrobasilar TIA: no abnormalities were found in the migraine group. VEPs parameters are normal in both groups. Our data show that the study of the so-called “stimulus-related” potentials, such as BAEPs and pattern reversal VEPs, is useful in evaluating the damage produced by any noxa, while it cannot clearly emphasize individual factors predisposing to a specific pathology, as the absence of specific alterations in migraine patients demonstrates.
PMID: 4016942

Ann Neurol. 1998 Aug;44(2):209-15. 
Interictal cortical excitability in migraine: a study using transcranial magnetic stimulation of motor and visual cortices. 
Afra J, Mascia A, Gerard P, Maertens de Noordhout A, Schoenen J. 
Department of Neurology, CHR Citadelle, University of Liege, Belgium. 

We performed transcranial magnetic stimulations of the motor and visual cortices in healthy controls (n = 27) and in patients suffering from migraine without (n = 33) or with (n = 25) aura between attacks. By using a 13-cm circular coil placed over the vertex and recordings of the first dorsal interosseus muscle, we measured thresholds (at rest and during contraction), amplitudes of motor evoked potentials and cortical silent periods. Paired stimulations with short (1-20 msec) interstimulus intervals were performed to assess intracortical inhibition. The visual cortex was stimulated with the same coil placed over the occipital scalp (7 cm above the inion) and the prevalence and threshold of phosphene production was determined. In patients with migraine with aura, motor thresholds during isometric contraction were significantly higher, whereas the prevalence of stimulation-induced phosphene production was lower compared with healthy controls. These changes were not correlated with attack frequency or disease duration. No differences were found between subject groups in thresholds at rest, motor evoked potential amplitudes, cortical silent periods, or response curves after paired stimuli. These results are in favor of cortical hypoexcitability rather than hyperexcitability in patients with migraine with aura between attacks. 

PMID: 9708543

Neurology. 2002 Apr 9;58(7):1066-9. 
Transcranial magnetic stimulation of visual area V5 in migraine. 
Battelli L, Black KR, Wray SH. 
Department of Psychology, Harvard University, Cambridge, MA 02138, USA. Battelli[@] 

OBJECTIVE: To examine visual cortical excitability in persons with migraine using transcranial magnetic stimulation (TMS) over an extrastriate area of the brain, area V5.

BACKGROUND: Previous studies found that persons with migraine have a lower phosphene threshold than healthy control subjects with TMS delivered over the primary visual cortical area V1. The result suggests that the occipital cortex in migraineurs between migraine attacks is hyperexcitable. However, it is not known whether interictal cortical hyperexcitability is also present in areas of the association visual cortex.

METHOD: To investigate this, single-pulse TMS was delivered over visual area V5, the motion cortex, to 16 persons with migraine and visual aura, nine migraineurs without visual aura, and 16 healthy control subjects. TMS was delivered at intensities ranging from 30 to 100% of maximum stimulator output or until the participant reported seeing phosphenes (visual illusions characterized by flashes of light). Thresholds to phosphenes were obtained for each participant using a staircase procedure.

RESULT: Significantly lower phosphene thresholds for TMS delivered over V5 were found in migraineurs as compared with control subjects. Qualitatively, the migraineurs’ experience of phosphenes were more vivid, florid, and sustained compared with that of control subjects.

CONCLUSION: Results of this study indicate that hyperexcitability of the visual cortex in migraine goes beyond visual area V1 and demonstrates for the first time a significant difference in threshold for excitability of visual area V5 in persons with migraine. 

PMID: 11940694

Exp Brain Res. 2003 Jun;150(3):332-40. Epub 2003 Apr 16.
Effects of repetitive transcranial magnetic stimulation on visual evoked potentials: new insights in healthy subjects. 
Fumal A, Bohotin V, Vandenheede M, Seidel L, de Pasqua V, de Noordhout AM, Schoenen J. 
University Department of Neurology, CHR Citadelle Hospital, 4000 Liege, Belgium. 

In a previous comparative study with migraineurs, we found in 24 normal subjects that the amplitude of the pattern-reversal visual evoked potential (PR-VEP) in the first block of 100 responses and its habituation over 6 sequential blocks were significantly decreased after 1 Hz repetitive transcranial magnetic stimulation (rTMS), while 10 Hz rTMS had no significant effect. We report here our results on the reproducibility of the rTMS effect studied in ten of these subjects by repeating the recordings for each frequency three times on different days. We have also reanalysed the data obtained in 24 normal subjects, looking separately at the results in those stimulated at an intensity equal to phosphene threshold (group 1; n=14) and those stimulated at 110% of motor threshold because of unelicitable phosphenes (group 2; n=10). We finally determined the precise duration of the rTMS effect. Despite some interindividual variability, the effects of both rTMS frequencies on first block amplitude, habituation between first and sixth block and habituation slope over the six blocks were highly reproducible. The only difference between the two groups of subjects was the effect of 1 Hz rTMS on the second measured PR-VEP component. Whereas first block amplitude of the first P1-N1 component and habituation were decreased in both groups, such a decrease was found for the second P1-N2 component only in group 1 stimulated at phosphene threshold. The dishabituation of the N1-P1 component after 1 Hz rTMS was maximal at 15 min, but lasted up to 33 min, while that of P1-N2 disappeared after 3 min. There was a non-significant trend ( p=0.06) for a reduction of first block amplitude after 10 Hz rTMS in the total group of subjects, but no effect on habituation. The inhibitory effect of 1 Hz rTMS, which reduces in healthy controls both first block PR-VEP amplitude and habituation, probably by decreasing the preactivation excitability level of the underlying visual cortex, is thus reproducible and long lasting. Long trains of 10 Hz rTMS tend to attenuate reproducibly the cortical preactivation level in normal subjects, but they do not affect habituation at all, which contrasts with their effect in migraineurs, in whom, as previously reported, they significantly correct the habituation deficit. The absence of an effect of 1 Hz rTMS on PR-VEP P1-N2 in subjects stimulated at 110% of motor threshold may be explained by the deeper anatomical location of the cortical generators of this component and the lower stimulation intensity used. Taken together our results confirm that the effect of rTMS on the underlying cortex depends on several variables such as frequency, intensity and level of cortical preactivation. 

PMID: 12698314 [PubMed – in process]

Cephalalgia. 2001 Jun;21(5):611-6. 
Altered cerebrovascular response pattern in interictal migraine during visual stimulation. 
Backer M, Sander D, Hammes MG, Funke D, Deppe M, Conrad B, Tolle TR. 
Department of Neurology, Technical University of Munich, Munich, Germany. 

A dysbalance of the cerebrovascular response during functional activation of the brain has been postulated as a factor in the pathophysiology of migraine. To determine the dynamic pattern of the cerebrovascular response in migraineurs compared with a control group, changes of the cerebral perfusion during cerebral activation were studied with high temporal resolution by functional transcranial Doppler sonography (fTCD). The cerebral blood flow velocity (CBFV) in the right posterior cerebral artery (PCA) and the left middle cerebral artery (MCA) was measured simultaneously during visual stimulation in 19 interictal migraineurs and in 19 age- and sex-matched control subjects. Data were analysed with a previously validated technique based on automated stimulus-related averaging of the CBFV. The MCA migraineurs exhibited a steady increase of CBFV during the stimulation, while normal subjects showed a habituation of the CBFV response. The lack of habituation in migraineurs was significantly (P < or = 0.05) more pronounced across patients with a high attack frequency (> or = 4 per month) compared with migraineurs with a low attack frequency (< 4 per month). In the PCA, compared with normal subjects, migraineurs showed significantly (P < or = 0.05) stronger CBFV changes at the beginning and after the end of stimulation, with a slower decline to baseline. Data are in accordance with electrophysiological findings in migraineurs. It is assumed that a lack of habituation of the cerebrovascular response in migraineurs might contribute to a disturbance of the metabolic homeostasis of the brain that might induce migraine attacks.

PMID: 11472388

Headache. 2003 Mar;43(3):303. 
Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex. 
De Tommaso M, Murasecco D, Libro G, Guido M, Sciruicchio V, Specchio L, Gallai V, Puca F. 
Int J Psychophysiol. 2002 Jun;44(3):239-249

The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine. Comment: Further physiologic and functional evidence for the interictal hyperexcitability of neurons in patients with migraine, in this case trigeminal neurons involved in the blink reflex. SJT 

PMID: 12603665 [PubMed – as supplied by publisher]

Curr Opin Neurol. 1998 Jun;11(3):205-9. 
Brain excitability in migraine: evidence from transcranial magnetic stimulation studies. 
Aurora SK, Welch KM. 
Henry Ford Hospital and Health Sciences Center, Department of Neurology, Detroit, Michigan, USA. 

Central neuronal hyperexcitability is proposed to be the putative basis for the physiologic disturbances in migraine. Because there are no structural disturbances in migraine, only physiologic studies can provide insight into the underlying mechanisms. Recently, transcranial magnetic stimulation has been developed as a valuable research tool and can be used to study brain function noninvasively. This article is a review of the studies done in migraine using transcranial magnetic stimulation. 

PMID: 9642537

No To Shinkei. 1998 Apr;50(4):361-5. 
[Superficial siderosis of the central nervous system: an electrophysiological study] 
[Article in Japanese] 
Shimo Y, Nohara C, Hotta M, Miwa H, Mizuno Y. 
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. 

Superficial siderosis of the central nervous system (SS) is a rare neurological disorder characterized by symptoms such as neurosensory hearing loss, ataxic gait, and spastic paraparesis. Recently, magnetic resonance imaging (MRI) enables us to make a clinical diagnosis. However, the exact pathophysiological mechanism underlying this disorder remains uncertain. Although iron chelation therapy has been attempted experimentally, it has not been successful and there is no effective medical treatment available. Towards the better understanding of the pathophysiological mechanism underlying SS, we performed electrophysiological studies, in which multiple evoked potential studies were included, in 3 patients with SS. Somatosensory evoked potentials (SEPs) evoked by median nerve stimulation were all normal, but those evoked by the posterior tibial nerve stimulation showed a significant delay of the latency of P40. In the auditory brainstem response (ABR) studies, there were no reproducible responses of the brainstem origin. In the blink reflex studies, R2 latency was delayed in one patient. In visual evoked potential (VEP) studies, the latency of P100 was delayed in two of three patients, unless all the patients clinically showed no visual symptom. The nerve conduction velocity studies performed in peripheral nerves of upper and lower extremities were all normal. The abnormal findings of ABR and SEP may suggest that the acoustic nerve and the posterior funiculus of the spinal cord are involved, respectively. These findings are also in a good agreement with pathological findings of SS reported in the literature. In SS, the hemosiderine accumulation is usually less severe in the visual tract; however, the delay of VEPs may suggest the latent dysfunctioning of the visual system in SS. It is suggested that multiple evoked potential study is useful for clinical evaluation of SS. 

PMID: 9592826

Curr Opin Neurol. 2000 Jun;13(3):273-6. 
Migraine: imaging the aura. 
Aurora SK, Welch KM. 
Neurophysiology Laboratory, Henry Ford Hospital, Detroit, Michigan 48202, USA. sheaur[@] 

We currently conceive of a migraine attack as originating in the brain. Triggers of an attack initiate a depolarizing neuroelectric and metabolic event likened to the spreading depression of Leao. This event activates the headache and associated features of the attack by mechanisms that remain to be determined, but appear to involve either peripheral trigeminovascular or brainstem pathways, or both. The excitability of cell membranes, perhaps partly genetically determined, is the brain’s susceptibility to attacks. Factors that increase or decrease neuronal excitability constitute the threshold for triggering attacks. Using a model of visual stress-induced migraine or by studying spontaneous attacks and applying advanced imaging and neurophysiological methods, results have been obtained that support spreading neuronal inhibition as the basis of aura. This neuroelectric event is accompanied by hyperoxia of the brain, possibly associated with vasodilation. Evidence has also been obtained that the spreading cortical event can activate the subcortical centers possibly involved in nociception and associated symptoms of the migraine attack. Susceptibility to migraine attacks appears to be related to brain hyperexcitability. These newer techniques of functional neuroimaging have confirmed the primary neural basis of the migraine attack with secondary vascular changes, reconciling previous theories into a neurovascular mechanism. 

PMID: 10871250

Curr Opin Neurol. 2003 Feb;16(1):5-13. 
Migrainous vertigo: development of a pathogenetic model and structured diagnostic interview. 
Furman JM, Marcus DA, Balaban CD. 
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. furman[@] 

PURPOSE OF REVIEW: Vestibular symptoms occur frequently in patients with migraine. This review refines recently proposed diagnostic criteria for migraine-related vestibular symptoms, and develops a pathophysiological model for the interface between migraine and the vestibular system.

RECENT FINDINGS: The epidemiological link between migraine and vestibular symptoms and signs suggests shared pathogenetic mechanisms. between the vestibular nuclei, the trigeminal system, and thalamocortical processing centers provide the basis for the development of a pathophysiological model of migraine-related vertigo. During the last year, several studies have increased understanding of the relationship between migraine and vestibular symptoms. A study of motion sickness and allodynia in migraine patients supports the importance of central mechanisms of sensitization for migraine-related vestibular symptoms. A study has demonstrated effective treatment of vertigo with migraine therapy. The identification of migrainous vertigo, however, is hampered by a lack of standardized assessment criteria for both clinical and research practices. The application of published criteria for the diagnosis of migrainous vertigo allows the development of a standardized, structured assessment interview.

SUMMARY: An understanding of the relationship between migraine and the vestibular system increases knowledge of the pathogenesis of both migraine and vertigo. In addition, studies have identified successful treatment, with standard migraine therapies, of vestibular symptoms in patients with both migraine and vertigo. The use of a standardized assessment tool to identify this unique population of patients will help future studies to test both the pathological model and effective treatment options. 

PMID: 12544852

Funct Neurol. 1986 Oct-Dec;1(4):357-61. 
Bulbo-cortical pathways and their possible relevance to migraine and epilepsy. 
Lance JW, Adams RW, Lambert GA. 

Facilitation of the visual evoked response from the reticular formation in the cat has been shown to depend on nicotinic cholinergic receptors distinct from the muscarinic cholinergic receptors responsible for the arousal reaction. An increase in the amplitude of visual evoked responses in migraineurs does not therefore imply any change in reticulocortical activity of relevance to epilepsy. Stimulation of locus ceruleus and nucleus raphe dorsalis exerted comparatively minor effects on the visual evoked response and did not alter the discharge rate of cortical neurons in the resting state. It is concluded that the changes in cerebral blood flow previously reported to result from stimulation of these monoaminergic brainstem nuclei, which resemble those observed in migraine, must be exerted directly on the cortical microcirculation and not simply follow the metabolic demand of cortical neurons. There is thus a place in the management of migraine for pharmaceutical agents acting on cerebral vessels even if the neural hypothesis for the mechanism of migraine proves to be correct. 

PMID: 3609865

Electromyogr Clin Neurophysiol. 2002 Apr-May;42(3):175-9. 
Visual evoked potential & brainstem auditory evoked potentials in acute attack & after the attack of migraine. 
Kochar K, Srivastava T, Maurya RK, Jain R, Aggarwal P. 
Department of Medicine, S.P. Medical College, Bikaner-334003, Rajasthan, India. 

PURPOSE: To study the effect on visual evoked potential (VEP) and brainstem auditory evoked potential (BAEP) at time of acute attack and after 7 days of the attack of migraine.

MATERIAL AND METHODS: We studied BAEP and pattern reversal VEP in 25 patients during acute attack and after 7 days of the attack. The diagnosis of migraine was established according to criteria given by international headache society (IHS). Peak and interpeak latencies (IPL’s) of BAEP and P100 latency of VEP were the main criteria to judge abnormalities.

RESULTS: There were prolonged peak and interpeak latencies in BAEP and prolonged peak latency (P100) in VEP at the time of acute attack of migraine. The data of these abnormal recording were highly significant. After 7 days when the attack was over, we recorded the BAEP and VEP again. The observation obtained at this time was comparable to normal values.

CONCLUSIONS: From the observation of this study we can safely conclude that in acute attacks of migraine there may be some pathological changes in different areas of brain and brainstem, producing changes in evoked potential which are statistically highly significant. However, these changes are reversible, as the values of BAEP & VEP on 7th day after the attack were comparable to those observed in normal healthy control. 

PMID: 11977431

Pain. 2000 Mar;85(1-2):247-54. 
Intensity dependence of auditory evoked cortical potentials in migraine families. 
Siniatchkin M, Kropp P, Neumann M, Gerber W, Stephani U. 
Institute of Medical Psychology, University of Kiel, Niemannsweg 147, D-24105, Kiel, Germany. siniatchkin[@] 

Intensity dependence of auditory evoked cortical potentials is abnormal in migraine. This study investigated intensity dependence in migraine and healthy families using group comparisons and analysis of individual differences. Migraineurs were characterized by a steeper amplitude/stimulus function slope and more pronounced difference between the amplitudes of N1-P2 on the more and the less intensive tones than healthy age matched subjects. Apart from migraine, the age of the participants was an important predictive variable of intensity dependence. Analysis of individual differences revealed low sensitivity and moderate specificity of intensity dependence for migraine. Familial prevalence of intensity dependence among first-degree relatives in migraine families was equal to that in healthy families. These findings support the assumption that high-intensity dependence reflects a functional CNS trait which is more pronounced and prevalent in migraine, but may also be found in healthy individuals and in other neuropsychiatric disorders. Increased intensity dependence is only one of several factors contributing to the risk for this form of headache. 

PMID: 10692625

Cephalalgia. 1999 Apr;19(3):137-46. 
Clinical neurophysiology in childhood headache. 
Puca F, de Tommaso M. 
Clinica Neurologica I, Universita di Bari, Italy. 

Electrophysiological studies in childhood headache are of interest because of the need to make a clinical diagnosis and also because of the efficacy of physiopathological studies in juvenile age attributable to the recent outcome of the illness, with less clinical modification by environmental factors or drug use. Electrophysiological studies in childhood headache are concerned with migraine and electroencephalographic (EEG) evaluations; evoked potentials, event-related potentials and, less often, electromyographic studies are also reported. Visual analysis of EEG suggests an association between migraine and epilepsy; quantitative EEG, visual and event-related evoked potentials show fluctuating abnormalities, depending on the occurrence of the migraine attacks and permanent anomalous patterns related to the basic mechanisms underlying the disease. Blink reflex studies might suggest a primary dysfunction of the nociceptive control central system in children affected by tension-type headache and migraine. The use of neurophysiological procedures in juvenile migraine is considered limited in clinical practice and of particular interest in neurophysiological studies of headache.

PMID: 10234460

J Neurol. 2002 Sep;249(9):1268-71. 
Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study. 
Ozturk V, Cakmur R, Donmez B, Yener GG, Kursad F, Idiman F. 
Dokuz Eylul University, Medical School, Department of Neurology, 35340, Izmir, Turkey. vesile.ozturk[@] 

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes. 

PMID: 12242552

Rev Neurol. 1997 Oct;25(146):1611-6. 
[Neurophysiological studies of headaches] 
[Article in Spanish] 
Munoz-Farjas E. 
Servicio de Neurologia, Hospital Clinico Universitario de Zaragoza, Espana. 

INTRODUCTION AND OBJECTIVE: The diagnosis of headache is based on the clinical criteria suggested by the IHS in 1988. The neurophysiological examinations often used in the study of headache may support the clinical diagnosis and give information as to the prognosis. The objective of this paper is to review the neurophysiological examinations most often used in the clinical and pathological investigation of headache.

DEVELOPMENT: As shown by recent studies, the EEG is of little value in the routine evaluation of a patient with headache. However, it may be useful as an exploratory test for underlying pathology in atypical headache or when intra-cranial pathology is suspected. Evoked potentials, when used to study migraine, show absence of Habituation (or Potentiation) in migraine patients. This finding may represent abnormality in the processing of information at a cortical level in these patients. There is a tendency to unify the theory of neurone hypoxia and the absence of Habituation in Migraine as a single hypothesis of pathogenesis. Negative Contingent Variation has proved to be clinically useful to optimize treatment in Migraine. The electromyogram and Muscle Reflexes have been used in the study of Tension Type Headaches, ES2 changes, showing brainstem antinociceptive reflexes support the participation of a central factor in the origin of chronic Tension Headache.

CONCLUSION: Neurophysiological tests may be useful in investigation of the pathology of headache since they permit a functional study of many neurone paths and the action of drugs on the central nervous system. 

PMID: 9462993

Neurology. 1997 May;48(5):1462-4. 
Interictal cortical excitability to magnetic stimulation in familial hemiplegic migraine. 
van der Kamp W, MaassenVanDenBrink A, Ferrari MD, van Dijk JG. 
Department of Neurology and Clinical Neurophysiology, Leiden University Hospital, the Netherlands. 

We studied interictal cortical excitability with magnetic stimulation in controls, in patients with migraine with aura, and in patients with familial hemiplegic migraine (FHM), in which ictal hemiparesis occurs. Amplitudes (p < 0.05) and amplitude ratios (p < 0.01) revealed heightened excitability in migraine with aura when compared to controls. In patients with FHM, mean thresholds were higher (p < 0.001) and conduction times longer (p < 0.01) than in controls. In FHM, amplitudes were lower on the ictally paretic side of the body than on the other (p < 0.05). Patients with FHM may have increased interictal cortical excitability, complicated by decreased excitability of the affected side. 

PMID: 9153495

Can J Neurol Sci. 1999 Nov;26 Suppl 3:S12-9. 
Pathophysiology of migraine–new insights. 
Hargreaves RJ, Shepheard SL. 
Merck Research Laboratories, West Point PA 9486, USA. 

Current theories propose that the primary dysfunction in migraine occurs within the CNS and that this evokes changes in blood vessels within pain-producing intracranial meningeal structures that give rise to headache pain. Migraine is now thought of as a neurovascular disorder. It has been proposed that genetic abnormalities may be responsible for altering the response threshold to migraine specific trigger factors in the brain of a migraineur compared to a normal individual. The exact nature of the central dysfunction that is produced in migraineurs is still not clear and may involve spreading depression-like phenomena and activation of brain stem monoaminergic nuclei that are part of the central autonomic, vascular and pain control centers. It is generally thought that local vasodilatation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous pain pathways is a key mechanism underlying the generation of headache pain associated with migraine. This activation of the ‘trigeminovascular system’ is thought to cause the release of vasoactive sensory neuropeptides, especially CGRP, that increase the pain response. The activated trigeminal nerves convey nociceptive information to central neurons in the brain stem trigeminal sensory nuclei that in turn relay the pain signals to higher centers where headache pain is perceived. It has been hypothesized that these central neurons may become sensitized as a migraine attack progresses. The ‘triptan’ anti-migraine agents (e.g. sumatriptan, rizatriptan, zolmitriptan naratriptan) are serotonergic agonists that have been shown to act selectively by causing vasoconstriction through 5-HT1B receptors that are expressed in human intracranial arteries and by inhibiting nociceptive transmission through an action at 5-HT1D receptors on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brain stem sensory nuclei. These three complementary sites of action underlie the clinical effectiveness of the 5-HT1B/1D agonists against migraine headache pain and its associated symptoms. 

PMID: 10563228

Neurology. 2002 Apr 23;58(8):1234-8. 
Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus? 
Kaube H, Katsarava Z, Przywara S, Drepper J, Ellrich J, Diener HC. 
Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK. holgerk[@] 

OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine using a novel “nociception-specific” blink reflex.

METHODS: Seventeen patients with unilateral migraine headache were studied within 6 hours of onset. Blink reflexes were elicited with a standard stimulating electrode (standard blink reflex) and concentric stimulating electrode (nociception-specific blink reflex) during the acute migraine attack, after treatment with IV lysine acetylsalicylate (1,000 mg) or oral zolmitriptan (5 mg) and interictally.

RESULTS: After standard stimulation, no differences were detected for the R1 and R2 onset latencies and areas under the curve (AUC) between the different time points and the headache and nonheadache side. Nociception-specific stimulation revealed a shortening of R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for nonheadache side) during the acute migraine attack compared with the headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on the headache side by 680% and on the nonheadache side by 230% compared with the headache-free interval. Drug treatment parallel to pain relief increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%).

CONCLUSION: The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks. 

PMID: 11971092

Pain. 1999 Mar;80(1-2):191-200. 
Electrophysiological testing of the trigeminofacial system: aid in the diagnosis of atypical facial pain. 
Jaaskelainen SK, Forssell H, Tenovuo O. 
Department of Clinical Neurophysiology, Turku University Central Hospital, Finland. satu.jaaskelainen[@] 

The aim of this study was to evaluate the yield of objective electrophysiological testing of the trigeminofacial system in atypical facial pain (AFP). In addition to the clinical neurological examination, two brainstem reflexes covering both the peripheral parts and the central connections of the trigeminal and the facial nerves, the blink and jaw reflexes (BR and JR), were recorded in 17 AFP patients. The control group consisted of 18 healthy volunteers with no history of facial pain or chronic headache. The AFP patients could be divided into three distinct groups on the basis of the clinical and electrophysiological findings. (1) Major trigeminal neuropathy. Four patients had clinical and electrophysiological signs of trigeminal neuropathy (three patients with an afferent pattern of abnormal BR, and one with absent JR on the clinically affected side) despite normal findings in the MRI-scans of the brain. Thus, electrophysiological testing may be more sensitive than MRI in demonstrating pathology in some of the AFP patients. (2) Minor trigeminal neuropathy. Seven patients had signs of increased excitability of the BR in the form of uni- or bilaterally abnormal (diminished or absent) habituation of the R2 component of the BR; two of these patients also showed clinical signs of trigeminal dysfunction, but the MRI-scans were all normal. This deficient habituation of the BR indicates increased excitability of the BR at brainstem level in nearly 50% of our AFP patients. (3) ‘Idiopathic’, no signs of trigeminal neuropathy. Five patients had normal findings both in the brainstem reflex recordings and in the clinical examinations. Additionally, one patient had abnormal BAEP and EEG recordings. On the group level, the AFP patients had significantly higher thresholds of the tactile R1 component of the BR than the control subjects. Electrophysiological testing may offer a valuable tool for both the clinical evaluation, and the scientific study of AFP. 

PMID: 10204731

Pain. 2003 Jan;101(1-2):25-32. 
Abnormal brain processing of cutaneous pain in patients with chronic migraine. 
de Tommaso M, Valeriani M, Guido M, Libro G, Specchio LM, Tonali P, Puca F. 
Department of Psychiatric and Neurological Sciences, University of Bari, Bari, Italy. m.detommaso[@] 

Syndromes with chronic daily headache include chronic migraine (CM). The reason for the transformation of migraine into chronic daily headache is still unknown. In this study, we aimed to evaluate heat pain thresholds and event-related potentials following CO(2)-laser thermal stimulation (LEPS) in hand and facial regions in patients with CM, to show changes in nociceptive brain responses related to dysfunction of pain elaboration at the cortical level. The results were compared with findings from normal control subjects and from subjects who suffer from migraine without aura. The effects of stimulus intensity, subjective pain perception and attention were monitored and compared with features of the LEPS. Twenty-five CM patients, 15 subjects suffering from migraine without aura and 15 normal control subjects were enrolled in the study. LEPS amplitude variation was reduced in CM patients with respect to the perceived stimulus intensity, in comparison with migraine without aura patients and control subjects. In both headache groups, the distraction from the painful laser stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in comparison with control subjects. These results suggest an abnormal cortical processing of nociceptive input in CM patients, which could lead to the chronic state of pain. In both headache groups, an inability to reduce pain elaboration during an alternative cognitive task emerged as an abnormal behaviour probably predisposing to migraine. 

PMID: 12507697

Neurosci Lett. 2001 Sep 7;310(1):37-40. 
The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man. 
de Tommaso M, Libro G, Guido M, Sciruicchio V, Puca F. 
Interuniversity Center for the Study of Headache and Neurotransmitter Disorders of the Central Nervous System, Perugia, Roma, Sassari, Bari, Napoli, Firenze, Italy. m.detommaso[@] 

Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers. 

PMID: 11524152

Electroencephalogr Clin Neurophysiol. 1989 Oct;73(4):285-94. 
Difference of steady-state visual evoked potentials in classic and common migraine. 
Nyrke T, Kangasniemi P, Lang AH. 
Department of Clinical Neurophysiology, University Central Hospital, Turku, Finland. 

The present study was designed to find evidence for the neural hypothesis of migraine and to evaluate possible interictal differences in the two varieties of migraine by electrophysiological means. Steady-state visual evoked potentials (SVEPs) in response to sinusoidally modulated light were measured in 20 patients with classic migraine and compared with those of 30 common migraineurs and 49 reference subjects. SVEPs to stimuli at 10-24 Hz were recorded occipitally from a pair of midline electrodes and, in classic migraineurs and controls, additionally from left and right occipital areas. The response was processed by the Fast Fourier Transform and automatically analysed. The fundamental component of the midline response to medium frequency stimuli (16-22 Hz) appeared normal in patients with classic migraine, contrary to an augmented response in common migraineurs (ANOVA between groups, P = 0.006). In classic migraine the 2nd harmonic component was attenuated (P less than 0.01 at 18-20 Hz) and the amount of strong interhemispheric f1 asymmetries was increased in about half of the patients. The groups also diverged significantly in the SVEP dynamics during stimulation. The results support the hypothesis of a primary neural disorder in both types of migraine. Different sites and mechanisms of brain dysfunction in classic and common migraine are suggested. Hypothetical neuroanatomical correlates for the abnormalities are presented. 

PMID: 2477215

Neurology. 2000;55(9 Suppl 2):S36-45. 
Functional neuroimaging: enhanced understanding of migraine pathophysiology. 
Cutrer FM, O’Donnell A, Sanchez del Rio M. 
Partners Headache Center, Department of Neurology, Massachusetts General Hospital, Boston, 02129, USA. 

Research into migraine pathophysiology has been hampered by the episodic nature and unpredictable onset of migraine attacks. Recently, newer imaging techniques have been providing noninvasive methods of studying metabolism and hemodynamics in the brains of migraineurs during and between acute attacks. 133Xe blood flow techniques, transcranial Doppler, and SPECT have all been employed to investigate hemodynamic changes during migraine aura. PET has been useful in the study of migraine without aura, with findings of increased blood flow related to pain in cortical areas and in the medial brainstem. Currently, three functional MRI imaging techniques are being used in migraine research. Diffusion-weighted imaging has shown normal findings in measures of the ability of neurons to maintain osmotic gradients. Studies using perfusion-weighted imaging have shown alterations in relative cerebral blood flow (CBF), relative cerebral blood volume, and mean transit time during migraine visual aura. The blood oxygen level-dependent technique can supply information related to neuronal activation during acute migraine aura. MRS has been used with mixed success to look for evidence of abnormal energy metabolism in the brains of migraineurs. Magnetoencephalography studies support the presence of a spreading depression-like phenomenon in migraine with aura. Two groups have used transcranial magnetic stimulation to assess whether neurons in the occipital cortex are hyperexcitable, predisposing patients to develop aura symptoms. Despite conflicting findings, migraine with visual aura appears to be generally associated with transient decreases in regional CBF. 

PMID: 11089518

Indian J Physiol Pharmacol. 1998 Apr;42(2):172-88. 
Average evoked potentials–clinical applications of short latency responses. 
Tandon OP. 
Department of Physiology, University College of Medical Sciences, Shahdar, Delhi. 

Many clinical neurophysiology laboratories have added average evoked potential studies to their routine procedures as evoked potential recording methods are non invasive, highly objective and informative. Indeed, short latency brainstem auditory evoked potentials as well as short and intermediate latency cortical evoked potentials, lately have proved to be valuable clinical tools for objectively testing afferent functions in patients with neurological and sensory disorders. The averaged evoked potential responses (EPR) have been widely used in clinical practice to record the changes in the electrical potentials that occur within the central nervous system (CNS) of the patient in response to an external stimulus. Two types of evoked potentials are usually recorded. 1-Stimulus related, short latency evoked potentials, which represent an obligate neuronal response to a given stimulus and both the amplitudes and latencies of these depend on the physical characteristics of the eliciting stimulus. In this category brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs), have normal values for latencies, amplitudes of waves and characteristic wave form. Any abnormality of these reflects excitation, conduction block in the specific pathways in the CNS. Certain abnormalities in EPR reflect subclinical involvement of CNS even before the disease clinically manifests. Abnormality in BAEPs can in addition, depict the exact site of lesion in the brainstem auditory pathways. Same is true for SEPs where abnormalities in far-field or near-field components, reflect lesions at the plexus, spinal cord, brainstem or thalamo-cortical regions respectively. 2- The event related potentials (ERPs) can be recorded in response to an external stimulus to which person is attentive or an event requiring cognition, discrimination, or reaction to the target stimulus. P300 is one such ERP, helpful in distinguishing between disorders such as dementia and depression. This first review gives a bird’s eyeview of the essentials, methods, interpretation and clinical applications of stimulus evoked short latency (brainstem auditory, visual and somatosensory) responses in human beings. 

PMID: 10225045

Semin Neurol. 1997;17(4):335-41. 
Pathogenesis of migraine. 
Welch KM. 
Department of Neurology, Henry Ford Hospital and Health Sciences Center, Detroit, Michigan 48202, USA. 

Prevailing hypotheses for the mechanisms of migraine are reviewed. Models of aura mechanisms include transient cerebral ischemia and spreading depression. Models of headache involve trigeminovascular and brainstem mechanisms. The ability to trigger an attack may depend on a threshold of brain excitability. Mitochondrial disorder, magnesium deficiency, and abnormality of presynaptic calcium channels may be responsible for neuronal hyperexcitability between attacks. It remains to be determined whether cortical or brainstem centers generate the attack. 

PMID: 9474713

Acta Neurol Scand. 2001 Nov;104(5):301-7. 
Asymmetric scalp distribution of pattern visual evoked potentials during interictal phases in migraine. 
Logi F, Bonfiglio L, Orlandi G, Bonanni E, Iudice A, Sartucci F. 
Department of Neuroscience, Institute of Neurology, University of Pisa, Italy. 

The N70 and P100 components of transient pattern visual evoked potentials (P-VEPs) were measured in migraine patients, with and without aura, and in normal subjects in order to evaluate their latency, amplitude and occipital scalp distribution. The aim was to find any typical electrophysiological abnormalities in migraine. P-VEP N70 and P100 were analyzed in 59 patients without any known visual field defect. Mean latency and amplitude values were within normal ranges for either N70 and P100 all over the occipital scalp; the only significant abnormality we found was related to the absolute right-left amplitude ratio either for N70 and P100 waves, providing an asymmetry in P-VEP scalp distribution; this finding was detected in 78.9% of patients with aura and 72.5% without aura. Our results show that in migraine patients, both P-VEP waves N70 and P100, have an asymmetric topographic distribution, even during interictal phases, that can be explained by a cortical disturbance in agreement with the neural hypothesis of headache. 
PMID: 11696025

Clin Neurophysiol. 2003 May;114(5):889-93. 
Decreased habituation of the R2 component of the blink reflex in migraine patients. 
De Marinis M, Pujia A, Natale L, D’arcangelo E, Accornero N. 
Department of Neurological Sciences, La Sapienza University, Viale dell’ Universita 30, 00185 Rome, Italy. milena.demarinis[@] 

OBJECTIVE: Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects.

METHODS: An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides, and to randomly repeat the stimulations at different time intervals in order to induce habituation.

RESULTS: Whereas the R1 and R2 latencies, amplitudes and areas in the basal assessment were similar in patients and control subjects, the blink reflex habituation responses were markedly reduced in migraine patients who had a migraine attack within 72 h after testing (group A). In these patients, the differences between the R2 areas, obtained when stimuli were delivered at subsequent time intervals ranging between 10-5, 5-4, 4-3 and 3-2 s, were statistically different (P<0.001) from those of the patients who had a migraine attack after a longer time interval (group B) and control subjects.

CONCLUSIONS: Our data suggest that the brainstem pathways involved in the blink reflex may be activated in the premonitory phase of migraine attacks, probably through mechanisms that involve dopaminergic function. 

PMID: 12738435

J Neurol Sci. 2001 Mar 1;184(2):139-41. 
Visual evoked potential changes in migraine. Influence of migraine attack and aura. 
Yilmaz M, Bayazit YA, Erbagci I, Pence S. 
Department of Neurology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep, Turkey. 

OBJECTIVE: To assess the visual evoked potential (VEP) changes in migraines with and without aura.

STUDY DESIGN: A clinical study in which the VEP results of 45 migraineurs (study group) and 22 healthy volunteers (control group) were compared. Of 45 migraineurs, 29 had migraine with aura (MA) and 16 had migraine without aura (MOA), and they were examined both during and between the migraine attacks.

METHODS: The patients and healthy controls underwent VEP assessment. On VEP recording, mono-ocular stimulation was performed by means of the pattern reversal check board. The latencies of N1, P1 and N2, and the N1–P1 amplitude were noted. The following comparisons were made between NI, P1 and N2 latencies and N1–P1 amplitudes of the migraine and control groups; during and between attack the VEP results of the patients with MA and MOA.

RESULTS: The VEP results of the migraineurs and healthy controls were similar (P>0.05). The during attack results of MA, during and between attack results of MOA, and the results of the control group were also similar (P>0.05). N2 latency significantly elongated in patients with MA in the attack free period than it was during the attack (P=0.01), and was also longer than it was in the control group (P=0.01).

CONCLUSIONS: There is involvement of the visual pathway in MA rather than MOA, and differentiation between these subtypes of the migraine disease may be performed on the basis of VEP findings manifesting by the prolongation of the N2 wave latency. This contention should be confirmed by further studies. 
Publication Types: 
* Clinical Trial

PMID: 11239947

Int J Psychophysiol. 2002 Jun;44(3):239-49. 
Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex. 
de Tommaso M, Murasecco D, Libro G, Guido M, Sciruicchio V, Specchio LM, Gallai V, Puca F. 
Clinical Neurologica I Policlinico, Piazza G. Cesare II, 70124, Bari, Italy. m.detommaso[@] 

The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.

PMID: 12031298

J Neurol Neurosurg Psychiatry. 1988 Jan;51(1):43-9. 
Argon laser induced single cortical responses: a new method to quantify pre-pain and pain perceptions. 
Bjerring P, Arendt-Nielsen L. 
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark. 

The shape (amplitude and latency) of single cortical responses to argon laser stimulation was found to match six perceptual classes: three pre-pain and three pain. The amplitude of the pain related single cortical responses correlated with the perceived feeling of pain. Easy detectable responses were obtained because habituation to the stimuli was reduced and a high degree of attention was given to each stimulus. Single cortical responses to argon laser stimuli are suggested as a new quantitative technique with application in the assessment of function in the thermal and nociceptive pathways. 

PMID: 3351530

Headache. 2001 Jun;41(6):565-72. 
Visual cortex excitability in migraine with and without aura. 
Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW. 
Departments of Neurology, Atrium Medical Center, Heerlen, The Netherlands. 

OBJECTIVES: Previous research using transcranial magnetic stimulation has produced equivocal findings concerning thresholds for the generation of visual phosphenes in migraine with aura. These studies were methodologically varied and did not systematically address cortical excitability in migraine without aura. We therefore studied magnetophosphene thresholds in both migraine with aura and migraine without aura compared with headache-free controls.

METHODS: Sixteen subjects with migraine with aura and 12 subjects with migraine without aura were studied and compared with 16 sex- and age-matched controls. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the threshold stimulation intensity at which subjects just perceived phosphenes via a method of alternating course and fine-tuning of stimulator output.

RESULTS: There were no significant differences across groups in the proportion of subjects seeing phosphenes. However, the mean threshold at which phosphenes were reported was significantly lower in both migraine groups (migraine with aura=47%, migraine without aura=46%) than in controls (66%). Moreover, there was no significant correlation between individual phosphene threshold and the time interval to the closest migraine attack.

CONCLUSION: Our findings confirm that the occipital cortex is hyperexcitable in the migraine interictum, both in migraine with and without aura. 

PMID: 11437892

Can J Neurol Sci. 1984 Feb;11(1):60-3. 
Electrophysiological studies in five cases of abetalipoproteinemia. 
Lowry NJ, Taylor MJ, Belknapp W, Logan WJ. 

Auditory brainstem responses (ABRs), visual and somatosensory evoked responses (VEPs and SEPs) and nerve conduction studies were conducted in 5 patients with abetalipoproteinemia. The ABRs were normal in all cases. The VEPs were of normal amplitude but of increased latencies in two patients. The four eldest patients had delayed cortical SEPs but normal peripheral sensory nerve conduction studies. The peripheral motor conduction velocities were normal in all cases. The peripheral sensory studies showed normal velocity when a response was seen; however, the amplitude of the response was often reduced or it was absent. The electrophysiological studies reported here support a model of axonal loss of large myelinated fibres with secondary demyelination in abetalipoproteinemia. 

PMID: 6704795

Muscle Nerve. 1999 Apr;22(4):508-16. 
Assessment of trigeminal small-fiber function: brain and reflex responses evoked by CO2-laser stimulation. 
Cruccu G, Romaniello A, Amantini A, Lombardi M, Innocenti P, Manfredi M. 
Dipartimento Scienze Neurologiche, Viale Universita 30, Roma, Italy. 

Laser pulses selectively excite mechano-thermal nociceptors and evoke brain potentials that may reveal small-fiber dysfunction. We applied CO2-laser pulses to the perioral and supraorbital regions and recorded the scalp laser-evoked potentials (LEPs) and reflex responses in the orbicularis oculi, masticatory, and neck muscles in 30 controls and 10 patients with facial sensory disturbances. Low-intensity pulses readily evoked scalp potentials consisting of a negative component with a latency of 165 ms followed by a positive component at 250 ms. In vertex recordings, the amplitude of LEPs exceeded 30 microV. Although only high-intensity pulses evoked reflex responses, some subjects showed–even to low-intensity pulses–an orbicularis oculi (blink-like) response that markedly contaminated the scalp recording. Scalp LEPs were abnormal in patients with hypalgesia and normal trigeminal reflexes and normal in patients with normal pain sensitivity and abnormal trigeminal reflexes. Possibly because of the high receptor density in this area and the short conduction distance, laser stimulation of the trigeminal territory yields low-threshold and large LEPs, which are useful for detecting dysfunction in peripheral and central pain pathways. 

PMID: 10204787

Headache. 1992 Jul;32(7):345-7. 
Menstrual migraine without aura: cortical excitability to magnetic stimulation. 
Bettucci D, Cantello R, Gianelli M, Naldi P, Mutani R. 
Department of Neurology, University School of Medicine of Novara, Italy. 

The purpose of the present study was the evaluation of the excitability threshold and the central motor conduction time (CCT) studied by means of electromagnetic cortical stimulation in ten subjects affected by menstrual migraine without aura, both in the ictal and the interictal period. The patients were chosen from among a group of 254 outpatients affected by migraine, diagnosed according to the International Headache Society criteria. The control group consisted of ten healthy female subjects. As far as CCTs were concerned no differences emerged between patients and controls. However in the patient group we found a significant increase in the excitability threshold values, both in the ictal and the interictal period, and in both hemispheres. If confirmed, the increased excitability threshold may be a useful neurophysiological correlate of migraine without aura. 

PMID: 1526765

Cephalalgia. 1999 Jun;19(5):485-91.
Dynamic changes of cognitive habituation and serotonin metabolism during the migraine interval. 
Evers S, Quibeldey F, Grotemeyer KH, Suhr B, Husstedt IW. 
Department of Neurology, University of Munster, Germany. everss[@] 

Migraine patients show a specific cognitive processing with a loss of habituation in the interval and a normal habituation in the attack as measured by event-related potentials (ERPs). It is unknown whether the loss of habituation changes during the migraine interval or is a stable state. Serotonin (5HT) metabolism is involved in the pathophysiology of migraine and also in the generation of ERPs. We enrolled 14 patients with regular migraine attacks in order to measure visually evoked ERPs repetitively during the migraine interval and in the migraine attack. Cognitive habituation was evaluated by analysis of P3 latency. Platelet serotonin content and free serotonin plasma level were measured at the same time points. The loss of habituation increased continuously during the migraine interval and abruptly normalized in the migraine attack (p < 0.05, time series analysis). The platelet 5HT content decreased significantly in the migraine attack (p < 0.03) and was at its maximum in the middle of the interval. The P3 latency was significantly increased in the attack (p < 0.01) and was significantly inversely correlated with the platelet 5HT content (r = -0.44, p < 0.001). Free 5HT plasma levels did not show any significant change. Our findings suggest that loss of cognitive habituation continuously increases during the migraine interval until its normalization in the migraine attack. This phenomenon cannot be attributed to serotonergic transmission. In patients with regular changes of cognitive habituation before the migraine attack, it might be possible to predict the attack by analysing ERPs. 

PMID: 10403063

Cephalalgia. 1990 Dec;10(6):317-29. 
Event-related slow potentials and associated catecholamine function in migraine. 
Nagel-Leiby S, Welch KM, D’Andrea G, Grunfeld S, Brown E. 
Department of Neurology, Henry Ford Hospital, Detroit, MI 48202. 

Plasma norepinephrine and dopamine and event-related slow potentials were measured at menses and ovulation in migraine with and without aura relative to normal subjects. The results indicated that at menses, but not ovulation, plasma dopamine was increased and norepinephrine was decreased relative to normal. This catecholamine imbalance was greater in migraine without aura than in migraine with aura. Conversely, event-related slow potentials measured over the posterior cortex at ovulation but not at the menses was altered relative to normal. Early epoch negativity was reduced in migraine with aura, whereas late epoch negativity was reduced in migraine without aura. The results suggested that (a) migraine without aura may involve dynamic shifts in the function of both norepinephrine and dopamine responsive neurons; (b) pathophysiology of migraine with aura is less dependent on catecholamine imbalance (norepinephrine alone affected); (c) these pathophysiological mechanisms are most prevalent in or restricted to posterior cortical regions but may be modulated by brainstem mechanisms. 
PMID: 2289233

J Physiol. 2002 Apr 15;540(Pt 2):623-33. 
Modulation of human corticomotor excitability by somatosensory input. 
Kaelin-Lang A, Luft AR, Sawaki L, Burstein AH, Sohn YH, Cohen LG. 
Human Cortical Physiology Section, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. 

In humans, somatosensory stimulation results in increased corticomotoneuronal excitability to the stimulated body parts. The purpose of this study was to investigate the underlying mechanisms. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) from abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles. MEP amplitudes, recruitment curves (RC), intracortical inhibition (ICI), intracortical facilitation (ICF), resting (rMT) and active motor thresholds (aMT) were recorded before and after a 2-h period of ulnar nerve electrical stimulation at the wrist. Somatosensory input was monitored by recording somatosensory evoked potentials. To differentiate excitability changes at cortical vs. subcortical sites, we recorded supramaximal peripheral M-responses and MEPs to brainstem electrical stimulation (BES). In order to investigate the involvement of GABAergic mechanisms, we studied the influence of lorazepam (LZ) (a GABA(A) receptor agonist) relative to that of dextromethorphan (DM) (an NMDA receptor antagonist) and placebo in a double-blind design. We found that somatosensory stimulation increased MEP amplitudes to TMS only in the ADM, confirming a previous report. This effect was blocked by LZ but not by either DM or placebo and lasted between 8 and 20 min in the absence of (i) changes in MEPs elicited by BES, (ii) amplitudes of early somatosensory-evoked potentials or (iii) M-responses. We conclude that somatosensory stimulation elicited a focal increase in corticomotoneuronal excitability that outlasts the stimulation period and probably occurs at cortical sites. The antagonistic effect of LZ supports the hypothesis of GABAergic involvement as an operating mechanism. 

PMID: 11956348

Neurology. 1999 Mar 23;52(5):1044-9. 
Physiology of perception: cortical stimulation and recording in humans. 
Ray PG, Meador KJ, Smith JR, Wheless JW, Sittenfeld M, Clifton GL. 
Department of Neurology, Medical College of Georgia, Augusta 30912, USA. 

OBJECTIVES: 1) To determine the effect of stimulus train duration (TD) on sensory perception using direct stimulation of somatosensory and visual cortices. 2) To investigate the occurrence of evoked potentials in response to stimulation that is subthreshold for perception.

BACKGROUND: Studies of the mechanisms of conscious perception using direct cortical stimulation and recording techniques are rare. The clinical necessity to implant subdural electrode grids in epilepsy patients undergoing evaluation for surgery offers an opportunity to examine the role of stimulus parameters and evoked potentials in conscious perception.

METHODS: Subjects included epilepsy patients with grids over somatosensory or occipital cortex. Single pulses (100 microseconds) and stimulus trains were applied to electrodes, and thresholds for perception were found. Evoked potentials were recorded in response to peripheral stimulation at intensities at, above, and below sensory threshold.

RESULTS: During cortical stimulation, sensory threshold changed little for stimulus trains of 250 milliseconds and longer, but increased sharply as TD decreased below this level. Primary evoked activity was recorded in response to peripheral stimulations that were subthreshold for conscious perception.

CONCLUSIONS: The results confirm a previous report of the effects of stimulus TD on sensory threshold. However, no motor responses occurred following somatosensory stimulation with short trains, as previously reported. The TD threshold pattern was similar in visual cortex. In agreement with the previous report, early components of the primary evoked response were not correlated with conscious sensory awareness. 
PMID: 10102426

J Clin Neurophysiol. 2002 Aug;19(4):294-306. 
Transcranial magnetic stimulation and epilepsy. 
Macdonell RA, Curatolo JM, Berkovic SF. 
Department of Neurology, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia. rmac[@] 

Transcranial magnetic stimulation has been used to study generalized and focal epilepsies for more than a decade. The technique appears safe and has yielded important information about the mechanisms underlying epilepsy. Transcranial magnetic stimulation findings differ depending on the epilepsy syndrome, lending support to the concept that there are distinct pathophysiologies underlying each condition. In most studies of generalized epilepsies, transcranial magnetic stimulation has indicated a state of relative hyperexcitability of excitatory cortical interneurons and possibly inhibitory interneurons as well, which can be reversed through the actions of anticonvulsant medications. Transcranial magnetic stimulation studies in patients with a seizure focus in the motor cortex indicate increased cortical excitability and reduced inhibition, but in patients with seizure foci located elsewhere the findings are similar to those in generalized epilepsies. Transcranial magnetic stimulation has also been used to study the mode of action of anticonvulsants and may prove to be a useful means of testing the potential for new drugs to act as anticonvulsants. Repetitive transcranial magnetic stimulation may prove to have a therapeutic role by producing long-lasting cortical inhibition after a train of impulses. 

PMID: 12436086

Appl Psychophysiol Biofeedback. 2002 Sep;27(3):203-13. 
On the pathophysiology of migraine– for “empirically based treatment” with neurofeedback. 
Kropp P, Siniatchkin M, Gerber WD. 
Institute of Medical Psychology, University of Kiel, Niemannsweg 147, D-24105 Kiel, Germany. kropp[@] 

Psychophysiological data support the concept that migraine is the result of cortical hypersensitivity, hyperactivity, and a lack of habituation. There is evidence that this is a brain-stem related information processing dysfunction. This cortical activity reflects a periodicity between 2 migraine attacks and it may be due to endogenous or exogenous factors. In the few days preceding the next attack slow cortical potentials are highest and habituation delay experimentally recorded during contingent negative variation is at a maximum. These striking features of slow cortical potentials are predictors of the next attack. The pronounced negativity can be fed back to the patient. The data support the hypothesis that a change in amplitudes of slow cortical potentials is caused by altered habituation during the recording session. This kind of neurofeedback can be characterized as “empirically based” because it improves habituation and it proves to be clinically efficient. 

PMID: 12206051

Cephalalgia. 1999 Oct;19(8):718-24; discussion 697-8. 
Personality and response to repeated visual stimulation in migraine and tension-type headaches. 
Wang W, Wang GP, Ding XL, Wang YH. 
Anhui Institute of Stereotactic Neurosurgery, Hefei, China. wang_wei[@] 

Migraine sufferers potentiate their visual evoked potentials (VEPs) from a short period of 2 min to a longer period of 15 min. As a lack of habituation is linked to higher level arousal, we thus hypothesized that short-term VEP potentiation might be correlated with an arousal-related personality trait. We therefore carried out short-term VEPs, Plutchik-van Praag’s Depression Inventory, Zuckerman’s Sensation-Seeking Scales (Form V), and Zuckerman-Kuhlman’s Personality Questionnaire in 26 healthy subjects, 22 patients suffering from migraine without aura between attacks, 13 episodic and 20 chronic tension-type headaches. The chronic tension-type headache sufferers showed increased depression compared with other groups, which might be a consequence of the headache itself. Migraines, however, showed steeper habituation slopes of N1-P1 and P1-N2, decreased thrill and adventure-seeking, and general sensation-seeking than healthy controls; in addition, the habituation slope of P1-N2 was positively correlated with experience-seeking in migraine. The short-term VEP potentiation and the decreased thrill and adventure-seeking and general sensation-seeking in migraine might be related to a high level of cortical arousal and a low 5HT neurotransmission. In compliance with the long-term VEP study, the positive correlation between the P1-N2 habituation slope and experience-seeking in migraine suggests a continuous metabolic overload for the brain interictally, which can trigger the activation of a migraine attack. 

PMID: 10570726

J Neurol Neurosurg Psychiatry. 1987 Apr;50(4):416-22. 
Laterality of pain in migraine distinguished by interictal rates of habituation of electrodermal responses to visual and auditory stimuli. 
Gruzelier JH, Nicolaou T, Connolly JF, Peatfield RC, Davies PT, Clifford-Rose F. 

Support is provided for a primary neural factor in migraine by studies in autonomic responsiveness to sensory stimuli in relation to the laterality of pain. Migraineurs with consistently lateralised headaches were found in two studies to exhibit extremes of autonomic responsiveness to sensory stimuli during the interictal phase. The direction of responsiveness was predictive of the laterality of pain; left-sided pain was associated with under-responsiveness and fast habituation, right-sided pain with over-responsiveness and slow habituation. Bipolarity in rate of habituation is consistent with a defect in a regulatory mechanism that controls regional cerebral activation such as the diffuse thalamic projection system. 

PMID: 3585352

Brain Res Cogn Brain Res. 2003 May;16(3):488-91. 
Reductions in CI amplitude after repetitive transcranial magnetic stimulation (rTMS) over the striate cortex. 
Schutter DJ, van Honk J. 
Affective Neuroscience Section, Helmholtz Research Institute, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands. d.schutter[@] 

Slow repetitive transcranial magnetic stimulation (rTMS) is a method capable of transiently inhibiting cortical excitability and disrupting information processing in the visual system. This method can be used to topographically map the functional contribution of different cortical brain areas in visual processing. An early electrophysiological component, the CI is argued to reflect early visual processing. In addition, source-localization studies have provided evidence for the assumption that the striate cortex is the underlying neural generator of CI. In the present placebo-controlled, crossover study, slow rTMS was applied in order to further investigate the relationship between the striate cortex and the CI component. Based on the inhibitory effects of slow rTMS, a reduction in CI amplitude and an increase in latency were expected. Compared to placebo stimulation, slow rTMS over the striate cortex resulted in significant decreases of the CI amplitude, but did not affect latency. The present study provides causal evidence for the involvement of the striate cortex in generating the CI component. 

PMID: 12706228

Electromyogr Clin Neurophysiol. 1995 Jun-Jul;35(4):251-6. 
Effects of visual and auditory stimuli on median nerve somatosensory evoked potentials in man. 
Okajima Y, Chino N, Takahashi M, Kimura A. 
Department of Rehabilitation Medicine, Keio University School of Medicine, Tokyo, Japan. 

To demonstrate electrophysiological evidence of neural connections of somatosensory with visual and auditory pathways, interactions of median nerve somatosensory evoked potentials (SEPs) with visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were analyzed in 12 healthy subjects. In Experiment I (SEP vs. VEP), three patterns of stimulation, namely, electric stimulation of left median nerve, binocular LED flash, and simultaneous electric and flash stimulation, were applied with random interstimulus intervals of 2-4 sec until more than 100 responses had been obtained and averaged for each pattern of stimulation. Simultaneous electric and visual responses were subtracted from arithmetical sums of SEPs and VEPs to show interactions between somatosensory and visual responses. In Experiment II (SEP vs. AEP), binaural short-duration tone bursis instead of LED flashes were used in the same manner as in Experiment I, and interactions between somatosensory and auditory responses were analyzed. Results indicated that the effects of both visual and auditory interaction on SEPs were significant around 120-130 msec of latency. In other words, cross-modal sensory interaction occurred in the late phase of sensory processing. 

PMID: 7555931

Neurosci Lett. 2000 Feb 4;279(3):153-6. 
Different generators in human temporal-parasylvian cortex account for subdural laser-evoked potentials, auditory-evoked potentials, and event-related potentials. 
Lenz FA, Krauss G, Treede RD, Lee JL, Boatman D, Crone N, Minahan R, Port J, Rios M. 
Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD 21287-7713, USA. fal[@] 

In order to localize cortical areas mediating pain we now report subdural cortical potentials evoked by auditory stimulation (auditory-evoked potentials – AEPs) and by cutaneous stimulation with a laser (laser-evoked potentials – LEPs). Stimulation with the laser evokes a pure pain sensation by selective activation of nociceptors. LEPs were maximal over the inferior aspect of the central sulcus and had the same polarity on either side of the sylvian fissure. AEPs were maximal posterior to the LEP maximum and had opposite polarity on opposite sides of the sylvian fissure, consistent with the location of a known generator in the temporal operculum. Auditory P3 (event-related) potentials were maximal over the temporal base. These findings demonstrate that the LEP generator is not in secondary somatosensory cortex on the parietal operculum and is different from the P3 generator. 

PMID: 10688052

Rev Neurol. 1998 Dec;27(160):955-63. 
[Electrophysiological characteristics of asymptomatic relatives of patients with type 2 spinocerebellar ataxia] 
[Article in Spanish] 
Velazquez L, Medina EE. 
Laboratorio de Neurofisiologia Clinica, Hospital Docente Provincial Vladimir Ilich Lenin, Holguin, Cuba. 

INTRODUCTION: Electrophysiological studies have been shown to be useful in hereditary ataxia, but only a small number of patients have been studied, and the duration of the illness, serial studies and molecular definition have not been taken into account.

OBJECTIVE: We proposed, by means of electrophysiological techniques, to characterize the functional evolutionary state of the afferent and efferent systems in asymptomatic relations of patients with type 2 spinocerebellar ataxia (SCA2). Patients and methods. A 10 year longitudinal, prospective study was made of 59 children of patients with SCA2. The sequence included four studies: 1986, 1991, 1994 and 1996, all with informed consent for the investigation. The control group consisted of 108 volunteers. The electrophysiological studies recorded were: conduction studies in peripheral nerves and multimodal evoked potentials. For statistical analysis multivariate methods were used with a confidence interval of 95% (alpha = 0.05).

RESULTS: Electrophysiological alterations were observed even in the absence of clinical signs, such as reduced amplitude of sensory potentials, morphological changes and prolonged latency of the central components of somatosensory evoked potentials, and of brain stem auditory evoked potentials, whilst the visual evoked potentials remained normal. Of 79 relations studied during the 10 year investigation, 17 had clinical signs and were considered to be patients with SCA2.

CONCLUSIONS: Four stages of the illness were defined: ‘healthy’, presymptomatic, and patients with and without nerve conduction block. These characterized the degenerative mechanisms of the afferent and efferent systems of the relations of patients with SCA2 who became ill themselves. 

PMID: 9951012

Headache. 2001 Sep;41(8):792-7. 
Spectral analysis of visual potentials evoked by pattern-reversal checkerboard in juvenile patients with headache. 
Marrelli A, Tozzi E, Porto C, Cimini N, Aloisi P, Valenti M. 
Unita Operativa di Neurofisiopatologia, Ospedale S. Salvatore-Coppito; Clinica Pediatrica, Universita di L’Aquila, L’Aquila, Italy. 

Changes in visual evoked potentials, mainly affecting the amplitude of the major positive wave, are referred to by many authors and are related to the pathophysiological basis of primary headache. We performed both transient pattern-reversal visual evoked potentials and spectral analysis by means of fast Fourier transform of 8-Hz steady-state pattern-reversal visual evoked potentials in 34 children affected with migraine (14 with aura, 20 without aura), and compared them with 14 patients with tension-type headache and 10 healthy subjects. The amplitude of the response to the transient stimulation (P100) was higher and the latency shorter in the patients with headache compared with the controls, but the difference was not statistically significant. The absolute power of the first harmonic (1F) obtained by the spectral analysis of the steady-state stimulation was increased in all the patients with headache compared with the controls, and the increase was significant in patients with migraine. These data seem to confirm the hypothesis of abnormal processing of visual input in migraineurs and could be interpreted as neurophysiological support for the theory that different headache types are related conditions. Furthermore, the spectral analysis of steady-state pattern-reversal visual evoked potentials could be proposed as a test to diagnose migraine. 

PMID: 11576204

Muscle Nerve. 2000 Mar;23(3):321-35. 
Electrophysiological studies of myoclonus. 
Shibasaki H. 
Departments of Neurology and Brain Pathophysiology, Kyoto University School of Medicine, Shogoin, Sakyo, Kyoto, 606-8507 Japan. 

As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification and about its generator mechanisms. The EEG-EMG polygraph provides the most essential information about the myoclonus of interest. Jerk-locked back averaging and evoked potential studies combined with recording of the long latency, long loop reflexes are useful to further investigate the pathophysiology of myoclonus, especially that of cortical myoclonus. A recent advance in magnetoencephalographic techniques has contributed significantly to the elucidation of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in each individual patient is important for selecting the most appropriate treatment of choice. Copyright 2000 American Association of Electrodiagnostic Medicine. 

PMID: 10679708

Klin Wochenschr. 1988;66 Suppl 14:1-10. 
[Evoked potentials and intravenous anesthetics] 
[Article in German] 
Kochs E, Schulte am Esch J. 
Abteilung fur Anasthesiologie, Universitatskrankenhaus Eppendorf, Hamburg. 

In contrast to the electroencephalogram, which is a collection of the spontaneous brain electrical potentials generated by the cerebral cortex, evoked potentials are the electrical signals generated by the nervous system in response to brief extrinsic sensory stimuli. They can be used to establish objective evidence of an abnormality when clinical signs and symptoms are equivocal. Moreover they prove useful to define the anatomical level of lesions in the afferent pathway tested. They have been successfully applied during anesthesia and operations when pathways amenable to evoked potential recording were at risk. The most practical techniques in common intraoperative evoked response monitoring involve stimulation of visual, auditory and somatosensory pathways. As could be clearly demonstrated alterations of evoked responses can not only be found with diminished regional blood flow but in a graded manner depend on the used anesthetics as well. The potential application of evoked responses to monitor depth of anesthesia has been demonstrated by several groups. In contrast to visual, auditory and somatosensory cortical evoked potentials which show a large inter- and intraindividual variance acoustical evoked brainstem and somatosensory evoked subcortical potentials are very robust under general anesthesia. Drug-induced effects on shape, amplitude and latencies of evoked responses during balanced anesthesia must be well documented in order to establish evoked responses as sensitive indicators of systemic problems that may threaten the viability of the central nervous system. There is evidence that the effects on evoked responses during deep anesthetic states can be mimicked by several life-threatening conditions (e.g.: hypoxia, ischemia). This review describes the effects of intravenously used anesthetic drugs on visual, auditory and somatosensory evoked potentials and the alterations in evoked responses by abnormal systemic conditions as seen under hypotension, hypoxia, ischemia. 

PMID: 3292821

Brain. 2001 Nov;124(Pt 11):2310-8. 
Increased visual after-effects following pattern adaptation in migraine: a lack of intracortical excitation? 
Shepherd AJ. 
School of Psychology, Birkbeck College, London, UK. a.shepaerd[@] 

Much research on visual function in migraine has examined early aspects of visual processing, often using detection or discrimination measures and stimuli reported to trigger an attack, e.g. striped patterns or flickering lights. Differences between people with and without migraine have been attributed to abnormal cortical processing in migraine, variously described by interictal hyperexcitability, heightened responsiveness, a lack of habituation and/or a lack of intra-cortical inhibition. Here, two experiments are presented that explore a uniquely cortical phenomenon, pattern or contrast adaptation, one using the motion after-effect, one the tilt after-effect. Pattern adaptation reflects specific interactions between groups of neurones and is therefore ideally suited to address proposed models of cortical function in migraine. These models lead to specific predictions in an adaptation study: there should be smaller effects in people with migraine than in people without. The results from both adaptation experiments, however, revealed larger effects in migraine sufferers than in headache-free control subjects. There were no differences between migraine subgroups classified according to the presence or absence of aura. These results are discussed in terms of models of cortical function in migraine. 

PMID: 11673331

Neurolog. 2001 Sep;7(5):279-86. 
The pathophysiology of migraine. 
Tepper SJ, Rapoport A, Sheftell F. 
New England Center for Headache, Stamford, Connecticut, Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, and Department of Psychiatry, New York Medical College, New York, New York E-mail: sjtepper[@] 

BACKGROUND: Migraine results from episodic changes in central nervous system physiologic function in hyperexcitable brain manifested by abnormal energy metabolism, lowered threshold for phosphene generation, and increased contingent negative variation. Human functional magnetic resonance imaging and magnetoencepholography data strongly suggest that aura is caused by cortical spreading depression.

REVIEW SUMMARY: Brain hyperexcitability may be caused by low magnesium levels, mitochondrial abnormalities with abnormal phosphorylation of adenosine 5′-diphosphate, a dysfunction related to nitric oxide, or calcium channelopathy. Low magnesium can result in opening of calcium channels, increased intracellular calcium, glutamate release, and increased extracellular potassium, which may in turn trigger cortical spreading depression. Mitochondrial dysfunction has been suggested by a low phosphocreatine:Pi ratio and a possible response by migraine patients to riboflavin prophylaxis. Nitroglycerine administration results in a delayed migraine-like headache in migraine patients but not in control patients, and a nonspecific nitric oxide synthase inhibitor aborted migraine at 2 hours in the majority of tested migraine patients compared to controls. Many patients with familial hemiplegic migraine have a missense mutation in the P/Q calcium channel, so that this form of migraine, at least, is associated with a demonstrable calcium channelopathy.

CONCLUSIONS: The generation of migraine occurs centrally in the brain stem, sometimes preceded by cortical spreading depression and aura. Activation of the trigeminovascular system stimulates perivascular trigeminal sensory afferent nerves with release of vasoactive neuropeptides, resulting in vasodilation and transduction of central nociceptive information. There is then a relay of pain impulses to central second- and third-order neurons and activation of brain stem autonomic nuclei to induce associated symptoms. 

PMID: 12803669 [PubMed]

Neuroscience. 2003;119(2):597-609. 
Electrophysiological evidence for the existence of a posterior cortical-prefrontal-basal forebrain circuitry in modulating sensory responses in visual and somatosensory rat cortical areas. 
Golmayo L, Nunez A, Zaborszky L. 
Department of Morphology, School of Medicine, Autonomous University of Madrid, Madrid, Spain. 

The prefrontal cortex (PFC) receives input from sensory neocortical regions and sends projections to the basal forebrain (BF). The present study tested the possibility that pathways from sensory cortical regions via the PFC-BF and from the BF back to specific sensory cortical areas could modulate sensory responses. Two prefrontal areas that responded to stimulation of the primary somatosensory and visual cortices were delineated: an area encompassing the rostral part of the cingulate cortex that responded to visual cortex stimulation, and a region dorso-lateral to the first in the precentral-motor association area that reacted to somatosensory cortex stimulation. Moreover, BF neurons responded to PFC electrical stimulation. They were located in the ventral pallidum, substantia innominata and the horizontal limb of the diagonal-band areas. Of the responsive BF neurons 42% reacted only to stimulation of ‘visually-responsive,’ 33% responded only to the ‘somatosensory-responsive’ prefrontal sites and the remaining neurons reacted to both prefrontal cortical areas. The effect of BF and PFC stimulations on somatosensory and visual-evoked potentials was tested. BF stimulation increased the amplitude of both sensory-evoked potentials. However, stimulation of the ‘somatosensory-responsive’ prefrontal area increased only somatosensory-evoked potentials while ‘visually-responsive’ prefrontal-area stimulation increased only visual-evoked potentials. Atropine blocked both facilitatory effects.The proposed cortico-prefronto-basalo-cortical circuitry may have an important role in cortical plasticity and selective attention. 

PMID: 12770572 [PubMed – in process]

Crit Rev Oral Biol Med. 2000;11(1):57-91. 
Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. 
Sessle BJ. 
Faculty of Dentistry, University of Toronto, Ontario, Canada. 

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC. 

PMID: 10682901

Brain. 1998 Feb;121 ( Pt 2):281-91. 
Somatosensory-evoked blink response: investigation of the physiological mechanisms. 
Miwa H, Nohara C, Hotta M, Shimo Y, Amemiya K. 
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. 

The somatosensory-evoked blink response (SBR) is a newly identified blink reflex elicited by electrical stimulation of peripheral nerves. The present study was performed to investigate the physiological mechanism underlying the SBR elicited by median nerve stimulation in normal subjects. The peripheral afferents responsible for the SBR included low-threshold cutaneous fibres. In the SBR-positive subjects, the late (R2) component of the blink reflex elicited by supraorbital nerve stimulation and the SBR facilitated each other when both responses were induced at the same time, but they each caused long-lasting inhibition in the other when one stimulus was given as a conditioning stimulus. The extent of inhibition was correlated with the size of the preceding SBR. In the SBR-negative subjects, simultaneous inhibition of R2 was observed when median nerve stimulation was applied as a conditioning stimulus. Brainstem excitability, as evaluated by blink-reflex recovery studies, did not differ between SBR-positive and SBR-negative subjects. Therefore, based on anatomical and physiological findings, it appears that the reflex pathways of the SBR and R2 converge within the brainstem and compete with each other, presumably by presynaptic inhibition at the premotor level, before entering the common blink-reflex pathway. The influence of median nerve stimulation upon tonic contraction of the orbicularis oculi muscle was studied to detect the latent SBR. There was not only a facilitatory period corresponding to the SBR but also an active inhibitory period (exteroceptive suppression), suggesting that the mechanism generating the SBR is not only influenced by blink-reflex volleys but also by active exteroceptive suppression. Thus, the SBR may appear as a result of integration of facilitatory and inhibitory mechanisms within the brainstem. 

PMID: 9549506

J Urol. 1991 Jul;146(1):118-23. 
Cortical evoked potentials by stimulation of the vesicourethral junction: clinical value and neurophysiological considerations. 
Ganzer H, Madersbacher H, Rumpl E. 
Division of Urology and Neurology, University Hospital, Innsbruck, Austria. 

In 21 healthy volunteers and 42 patients with either neurogenic bladder dysfunction (24), partial peripheral denervation of the bladder (12) or nonneurogenic bladder dysfunction (6) scalp-derived evoked potentials after stimulation of the vesicourethral junction (cortical evoked potentials) were recorded. In addition, evoked potentials from the posterior tibial nerve (tibial somatosensory evoked potentials) and from the pudendal nerve (pudendal somatosensory evoked potentials) were evaluated. The results obtained in normal subjects were reproducible and comparable to those reported in previous studies. Cortical evoked potentials of vesicourethral junction consisted of a prominent negativity with a mean latency of 95 msec. Tibial and pudendal somatosensory evoked potentials were similar and showed a typical W-shaped complex. In normal subjects stimulation of the vesicourethral junction was described as a stimulus-synchronous pulsation combined with a continuous burning feeling and sometimes with a desire to void. In 4 normal subjects no cortical evoked potentials of the vesicourethral junction could be obtained because of a decreased pain threshold. In regard to clinical value, the results demonstrate that in patients with lesions of the central nervous system (in the group with cauda equina and conus medullaris lesions, and in the group with suprasacral spinal cord lesions) the results of cortical evoked potentials of the vesicourethral junction and pudendal somatosensory evoked potentials widely correlate due to similar afferent nervous pathways within the central nervous system. However, in patients with partial peripheral denervation of the bladder with suspected additional secondary local detrusor damage the results of cortical evoked potentials obtained by stimulation of the vesicourethral junction differ mostly from the results of somatosensory evoked potentials obtained by stimulation of the pudendal nerve. The pattern obtained (increased sensory and pain threshold, normal cortical evoked potentials of the vesicourethral junction with normal latencies and normal or increased amplitude) is indicative of local detrusor damage. In 21 patients the ability to detect cortical evoked potentials of the vesicourethral junction was combined with the sensation of stimulus-synchronous pulsation, whereas in the other 21 patients the absence of this sensation during stimulation was combined with the absence of cortical evoked potentials. On the other hand, no correlation was found between the ability of obtaining cortical evoked potentials of the vesicourethral junction and the stimulus-induced sensation of pain and/or desire to void.(ABSTRACT TRUNCATED AT 400 WORDS) 

PMID: 2056569

J Neurol Sci. 1997 Feb 12;145(2):177-81. 
Pattern reversal visual evoked potentials in classic and common migraine. 
Shibata K, Osawa M, Iwata M. 
Department of Neurology, Neurological Institute, Tokyo Women’s Medical College, Japan. 

Pattern reversal visual evoked potentials (PVEPs) to transient checkerboard were recorded in 19 patients with migraine with visual aura (i.e., classic migraine), 14 patients with migraine without aura (i.e., common migraine) in the interictal period and 43 normal subjects. Latencies and amplitudes of PVEPs in each group were analyzed. In classic migraine patients, P100 amplitude was significantly higher than in normal subjects (p < 0.01), whereas latencies of PVEPs did not significantly differ. There were no significant differences between the common migraine and normal subjects, nor within the classic and common migraine groups in latencies and amplitudes of PVEP. Four patients with classic migraine underwent PVEPs during or 1-2 h immediately after their migraine attacks. Two of these patients who underwent PVEPs 1.5-2 h after their attacks showed abnormally increased PVEP amplitudes. These results suggest that there are different pathophysiologies in the visual pathway between classic and common migraine and furthermore, classic migraine patients in interictal periods may have hyperexcitability in the visual pathway and that the increased amplitude of PVEPs after attacks may be due to cortical spreading depression. 

PMID: 9094046

J Neurol Neurosurg Psychiatry. 2000 Oct;69(4):507-11. 
Long term decline of P100 amplitude in migraine with aura. 
Khalil NM, Legg NJ, Anderson DJ. 
Department of Neurology, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. 

OBJECTIVES: To investigate visual function in migraine using visual evoked potentials.

METHODS: Electroretinograms (ERGs) and visual evoked potentials (VEPs) to single flash (SF) and pattern reversal (PR) stimuli were studied in 92 migraine subjects and 62 controls. RESULTS: In subjects with migraine, ERGs to single flash were normal. Mean latencies of the P1 and P2 waves in the SFVEP were increased at the occiput by 6% and 4% respectively, but normal at the vertex. Mean latency of the P100 wave in the PRVEP was increased by 5%. These increases were not related to the presence or absence of an aura or to the duration of migraine. P100 amplitude showed a more complex abnormality. It was increased in migraine without aura by 23% compared with controls, regardless of duration of migraine. In migraine with aura it was similarly increased, by 23%, in cases of short duration, but in addition it showed a sharp decline with duration. In cases with a duration of 30 or more years it was 36% less than in cases of short duration, and 21% less than in controls.

CONCLUSIONS: Subjects with migraine have constitutionally prolonged VEP latencies and increased P100 amplitude, but the latter declines to below normal in cases with a long history of migraine with aura. This decline may reflect subtle neuronal damage within the visual system from repeated transient ischaemia experienced during the aura. Future electrophysiological and other studies will need to be controlled for duration of migraine history. 

PMID: 10990512

Headache. 1997 Jun;37(6):383-5. 
Visual evoked potentials and serum magnesium levels in juvenile migraine patients. 
Aloisi P, Marrelli A, Porto C, Tozzi E, Cerone G. 
Servizio di Neurofisiopatologia, University of L’Aquila, Italy. 

Changes in visual evoked potentials and decreased intracellular magnesium levels have been separately described in patients affected by migraine both during the attacks and in the interictal periods. An inverse correlation between increased P100 amplitude and lowered serum magnesium levels was found in children suffering from migraine with and without aura in a headache-free period. A 20-day treatment with oral magnesium pidolate seemed to normalize the magnesium balance in 90% of patients. After treatment, the reduced P100 amplitude confirmed the inverse correlation with the serum magnesium level. These data seem to suggest the hypothesis that higher visual evoked potential amplitude and low brain magnesium level can both be an expression of neuronal hyperexcitability of the visual pathways related to a lowered threshold for migraine attacks. 

PMID: 9237412

Arch Neurol. 1997 May;54(5):619-24. 
Influence of peripheral nerve stimulation on human motor cortical excitability in patients with ventrolateral thalamic lesion. 
Hirashima F, Yokota T. 
Department of Neurology, Tokyo Medical and Dental University, Tokyo, Japan. 

OBJECTIVE: To determine the peripheral afferent pathways that influence the activities of the motor cortex by examining the effects of peripheral nerve stimulation on motor cortical excitability.

PATIENTS AND METHODS: We examined 12 healthy volunteers and 4 patients with localized brain lesions caused by cerebrovascular attack. Of the 4 patients, 1 patient had pontine infarction, including medial lemniscus, and severe sensory deficit and 3 had small localized lesions in the lateral part of the thalamus and neither sensory impairment nor abnormal N20 waves on somatosensory evoked potential recordings. Central motor tract excitability was examined by measuring a change in the motor evoked potential (MEP), using transcranial magnetic stimulation of the motor cortex after peripheral nerve stimulation at the wrist significantly increased MEP response in the controls at long conditioning-test intervals of 28 to 60 milliseconds, as well as at short intervals of 0 to 6 milliseconds. A late MEP potentiation was not observed on the affected side in all patients.

CONCLUSIONS: The loss of late MEP potentiation in patients with pontine and thalamic lesions indicates that this potentiation is caused by the alternation of the motor cortical excitability. Furthermore, the results in the patients with thalamic lesions suggest that the lateral nuclei of the thalamus, other than the ventral posterolateral nucleus and probably including the ventrolateral nucleus, have an important function in the processing of peripheral sensory input for tuning motor cortical excitability. 

PMID: 9152119

Rinsho Byori. 1995 Sep;43(9):965-70. 
[Excitability of motor cortex with transcranial magnetic double stimulation in the intact man] 
[Article in Japanese] 
Yoshino A, Yokota T. 
Department of Medical Technology, Tokyo Medical and Dental University. 

To evaluate the excitability of central motor tract, we studied a transcranial magnetic double stimulation with short conditioning-test (C-T) interval of 1-10ms in eight normal volunteers. In addition, H-reflex of the forearm muscle was used to study the effect of the magnetic cortical conditioning stimulus on alpha-motoneuron, and the test response evoked by electrical cortical stimulation was also used to examine the effect of the magnetic cortical conditioning stimulus. The subthreshold conditioning and suprathreshold test stimuli were applied, and compound muscle responses were recorded in the relaxed abductor pollicis brevis muscle. There was a decrease of the test response size by the conditioning stimulus at C-T interval of 1-5ms. This attenuation was probably caused by intracortical inhibition. Because the identical magnetic cortical conditioning stimulus produced increase in H-reflex size. Moreover, the test response evoked by electrical cortical stimulus was not suppressed by the magnetic cortical conditioning stimulus; whereas, response evoked by the magnetic cortical test stimulus was suppressed at C-T intervals of 2ms. With the technique of transcranial magnetic double stimulation, therefore, it is possible to evaluate the inhibitory function in the motor cortex. The technique may be of use for pathophysiology, diagnosis and estimation of treatment in the diseases. 

PMID: 7474462

J Neurol Neurosurg Psychiatry. 1986 Nov;49(11):1280-7. 
Visual evoked cortical potentials and pattern electroretinograms in Parkinson’s disease and control subjects. 
Nightingale S, Mitchell KW, Howe JW. 

Parkinson’s disease patients have been shown to have abnormal visually evoked cortical potentials (VEPs) to pattern stimulation. Whereas dopamine is not an important neurotransmitter in the central visual pathways, the retina is rich in dopamine and, together with previous animal and human studies, this suggests that the abnormal VEPs in Parkinson’s disease patients may be due to a biochemical and electrophysiological disorder in the retina. This hypothesis has been examined by studying the VEPs and pattern electroretinogram (PERG) of Parkinson’s disease patients and matched control subjects. The amplitudes of the cortical and retinal evoked potentials were significantly reduced in Parkinson’s disease patients compared with the control subjects and this could not be attributed to any particular feature of the disease or its treatment. There was a significant relationship between the VEP P100 latency and the PERG amplitude. Moreover for those subjects in whom there was an interocular difference in both cortical and retinal evoked potentials, the abnormality was more commonly found in the potentials from the same eye. These findings suggest that the abnormality of the VEP in Parkinson’s disease patients is, at least in part, secondary to an abnormality of the retina itself. 

PMID: 3794734

Headache. 1999 Jul-Aug;39(7):469-76. 
The occipital cortex is hyperexcitable in migraine: experimental evidence. 
Aurora SK, Cao Y, Bowyer SM, Welch KM. 
Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202-2689, USA. 

OBJECTIVES: Threshold for generation of magnetophosphenes has been reported to be lower in migraine. We compared the threshold for eliciting phosphenes by transcranial magnetic stimulation and the ability to visually trigger headache in a select group of individuals with migraine with and without aura to normal controls.

METHODS: Transcranial magnetic stimulation was performed using the Cadwell MES-10 stimulator. A circular coil, 9.5 cm in diameter, was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulator intensity was then fine-tuned to determine the threshold at which phosphenes were seen. In the same subjects, visual stimulation was given in 3.0 T MRI and if a headache occurred the response was recorded.

RESULTS: Fifteen subjects with migraine were compared to 8 controls. A significant proportion of the migraineurs (86.7%) developed phosphenes compared to the controls (25%) (P = .006). The probability of triggering a headache was also higher in the migraineurs (53%); no headache was triggered in the controls (P = .019). A significant correlation was found between the threshold for phosphenes on transcranial magnetic stimulation and visually triggered headache (P = .002). When only migraine was considered, there was again a significant trend (P = .084).

CONCLUSIONS: There is a difference in threshold for excitability of occipital cortex in migraineurs and controls. The hyperexcitable visual cortex in migraine is predisposed to visually triggered headache. 

PMID: 11279929

Nervenarzt. 2002 Apr;73(4):332-5. 
[Modulation of cortical excitability by transcranial direct current stimulation] 
[Article in German] 
Nitsche MA, Liebetanz D, Tergau F, Paulus W. 
Abteilung Klinische Neurophysiolgie, Georg-August-Universitat Gottingen. mnitsch1[@] 

Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients’ cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed. 

PMID: 12040980

Acta Psiquiatr Psicol Am Lat. 1986 Mar;32(1):11-25. 
[Electrophysiological contributions to the study of attention] 
[Article in Spanish] 
Lolas F. 

A selective review of electrophysiological studies of attention and attentional behavior is presented. The emphasis is placed on the contribution of cerebral event-related potentials (ERP) (evoked potentials) to the clarification of major issues, such as the role of peripheral versus central mechanisms and testing of hypotheses regarding selective attention. A number of clinical studies dealing mostly with diagnostic applications and therapeutic trials is discussed. The difficulties of interpretation and integration with other sources of knowledge on behavioral physiology are briefly discussed. 

PMID: 3751641

Brain Dev. 1995 May-Jun;17(3):175-81. 
Neurophysiological study in Pelizaeus-Merzbacher disease. 
Nezu A. 
Department of Pediatrics, Yokohama City University, School of Medicine, Japan. 

The Neurophysiological characteristics of Pelizaeus-Marzbacher disease (PMD) were studied in four Japanese patients aged between 5 and 13 years. Pendular spontaneous nystagmus was always recorded with a frequency between 2.5 and 4 Hz, and abnormal saccades with an almost twofold prolongation in onset time and 50% decrease in velocity were noted. Brainstem auditory evoked potentials consistently demonstrated severely altered waves II to V, following a normal wave I, despite normal hearing acuity. Somatosensory evoked potentials (SEPs) were always absent between brainstem components and early cortical responses. Late cortical components of SEPs and visual evoked potentials with significantly prolonged latencies were recorded in the three younger cases having normal sensory and visual acuity (N35 of SEP, 73.1 +/- 2.1 ms; N75 of VEP, 129.0 +/- 12.7 ms; mean +/- S.D.), while these peaks were absent in the oldest case having the most severe handicap. In motor evoked potentials (MEPs), R1 of blink reflex with significantly prolonged latency (14.9 +/- 1.48ms) was always obtained, and no subsequent R2 was elicited. Magnetic transcortical stimulation elicited no MEPs of the thenar even in the facilitating condition on voluntary contraction despite mild weakness of the thenar, while normal MEPs were always elicited on cervical stimulation. These electrophysiological findings were consistent with extensive conduction slowing involving the brainstem to the cerebrum, which seemed to be accompanied by conduction block in motor systems rather than sensory systems. Although each of the results was not specific, in combination they suggested the characteristics of diffuse brain dysmyelination in PMD. 

PMID: 7573756

J Clin Neurophysiol. 2000 Mar;17(2):201-11. 
Somatosensory, auditory, and visual evoked magnetic fields in patients with brain diseases. 
Nakasato N, Yoshimoto T. 
Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan. 

The features of somatosensory (SEFs), auditory (AEFs), and visual evoked fields (VEFs) in healthy subjects and patients with brain diseases provide the basis for clinical investigations using magnetoencephalography (MEG). The SEFs provide clinically useful information to identify the central sulcus and somatotopic organization of the primary somatosensory cortex. Localization accuracy of the SEFs can be tested by cortical stimulation during surgery. Functional reorganization suggested by SEF studies must be verified by other modalities. The AEFs can localize the auditory cortex in the bilateral temporal lobes. Separation of bilateral activities is much clearer in AEFs than in auditory evoked potentials. Modulation of the interhemispheric differences of latency, amplitude, and source localization of AEFs can be used to evaluate auditory function in patients with intracranial lesions. Pattern reversal VEFs provide stable localization of the primary visual function. Separation of bihemispherical activities is the advantage of VEFs over visual evoked potentials. Investigation of VEFs provides objective evaluation of visual field deficits such as homonymous or bitemporal hemianopsia in patients with intracranial lesions. Evoked magnetic fields can provide useful diagnostic information. Such clinical findings, in turn, provides the opportunity to test the source estimation accuracy of MEG. 

PMID: 10831111

Muscle Nerve. 1996 Dec;19(12):1586-95. 
Reduced brain stem excitability in mitochondrial myopathy: evidence for early detection with blink reflex habituation studies. 
Koutroumanidis M, Papadimitriou A, Bouzas E, Avramidis T, Papathanassopoulos P, Howard RS, Papapetropoulos T. 
Department of Clinical Neurophysiology and Epilepsies, St Thomas’ Hospital, London, United Kingdom. 

Blink reflex (BR) was studied in 17 patients with histochemically and genetically confirmed mitochondrial myopathy (MM). Fourteen patients had chronic progressive external ophthalmoplegia (CPEO) associated with a mild to moderate craniosomatic myopathy without any symptoms or signs of central nervous system (CNS) involvement, 2 myoclonic epilepsy with ragged red fibers syndrome, and 1 Kearns-Sayre syndrome. The mean latencies of the early (R1) and late (R2) responses were prolonged (P < 0.01 and P < 0.001, respectively), and the corresponding amplitudes decreased (P < 0.001). Increased habituation of the reflex was clearly observed in 10 out of 14 patients tested (71.4%), 9 of whom presented CPEO. These findings suggest that the brain stem reticular network is in a state of basal inhibition which is presumably due to a subclinical impairment of the cerebral cellular metabolism. Multimodal evoked potentials revealed abnormalities suggestive of CNS involvement in 7 out of 17 patients (41.2%), 4 of whom had CPEO. These observations document the validity of BR in detecting clinically silent brain stem impairment in patients with apparently pure MM and provide important clues for a further understanding of the underlying pathophysiology. 

PMID: 8941273

Neurosci Lett. 2002 Nov 15;333(1):29-32. 
Abnormal brain processing of cutaneous pain in migraine patients during the attack. 
de Tommaso M, Guido M, Libro G, Losito L, Sciruicchio V, Monetti C, Puca F. 
First Neurologic Clinic, University of Bari, Policlinico, Piazza G Cesare 11, 70124 Bari, Italy. m.detommaso[@] 

We examined cutaneous pain thresholds using CO(2) laser stimuli during migraine attacks, and defined the evoked cortical potential characteristics. Ten patients without aura were studied during attacks and for at least 72 h subsequently. Pain stimuli were generated on the dorsum of both hands and the right and left supraorbital zones, using pulses from a CO(2) laser. Absolute latencies of scalp potentials were measured at the highest peak of each response component, and the peak-to-peak amplitudes of N2a-P2 components were recorded. Cutaneous pain thresholds were significantly reduced on both the symptomatic and non-symptomatic sides during the attack, in comparison with the headache-free phase. The N2a-P2 complexes also increased in amplitude during attacks in comparison with the pain-free side. Thus, cutaneous hyperalgesia occurs during migraine attack, and is subtended by central sensitization phenomena, probably involving the cortex. Copyright 2002 Elsevier Science Ireland Ltd. 

PMID: 12401553

Electroencephalogr Clin Neurophysiol. 1981 Oct;52(4):283-97. 
Visual, auditory and somatosensory pathway involvement in hereditary cerebellar ataxia, Friedreich’s ataxia and familial spastic paraplegia. 
Pedersen L, Trojaborg W. 

Pattern-reversal visual, auditory and somatosensory evoked potentials were recorded from 11 patients with hereditary cerebellar ataxia, 13 with familial spastic paraplegia and 7 with Friedreich’s ataxia. In all the 31 patients the conduction velocity along the median and tibial nerves to the level of the spinal cord was normal. Five of the 7 patients with Friedreich’s ataxia had reduced sural nerve sensory potentials. There was electrophysiological evidence of malfunction along one or several pathways within the CNS in 8 of the 11 patients with cerebellar ataxia, 4 of the 13 with familial spastic paraplegia, and in all 7 cases of Friedreich’s ataxia. The increase in latency of visual, auditory and somatosensory evoked cortical potentials is attributed to nerve fibre loss in the central pathways with associated slowing of conduction. 

PMID: 6169505

J Neurol Sci. 1996 Oct;142(1-2):45-53. 
Autosomal dominant cerebellar ataxia type I: multimodal electrophysiological study and comparison between SCA1 and SCA2 patients. 
Perretti A, Santoro L, Lanzillo B, Filla A, De Michele G, Barbieri F, Martino G, Ragno M, Cocozza S, Caruso G. 
Department of Clinical Neurophysiology, Universita degli studi di Napoli “Federico II”, Italy. 

A multimodal electrophysiological study was performed on 41 patients from 24 families with autosomal dominant cerebellar ataxia type I (ADCA I). Upper- and lower-limb motor evoked potentials (MEPs) to transcranial magnetic stimulation, median and tibial nerve somatosensory evoked potentials (Mn and Tn-SSEPs), orthodromic sensory (SCV) and motor conduction (MCV) velocity along median and tibial nerve, brainstem auditory evoked potentials (BAEPs), and visual evoked potentials (VEPs) were examined. Molecular analysis showed 2 SCA1 families and 2 families linked to the SCA2 locus. A sural nerve biopsy was performed in 5 patients. Brainstem damage of the auditory pathway was observed in 79% of patients examined. VEP abnormalities possibly of central origin were found in 52% of patients. MEP and SSEP abnormalities were differently distributed along the pathways examined: the longer the pathway, the higher the occurrence and severity of impairment. Peripheral dying-back neuropathy (confirmed by nerve bioptic data) was a frequent finding (56%). A progressive degenerative process involving first the longest tracts of the central motor and central and peripheral branches of somatosensory pathways is hypothesized in ADCA I. MEP abnormalities were more frequent in SCA1, and the sensory-motor neuropathy was more severe in SCA2. 

PMID: 8902719

Headache. 1992 Jul;32(7):360-5. 
Bilateral occipital lobe infarction in acute migraine: clinical, neurophysiological, and neuroradiological study. 
Ganji S, Williams W, Furlow J. 
EEG and Evoked Potential Labs, Terrebonne General Medical Center, Houma, Louisiana 70361. 

A woman having common migraine attacks coincident with an asymmetrical bilateral occipital lobe infarction that spared the brainstem and cerebellum underwent these studies: serial electroencephalography, brainstem auditory, visual and somatosensory evoked potentials, magnetic resonance imaging of the brain and cerebral arteriography. The patient’s vision improved greatly during a one-year follow-up. The absence of risk factors for stroke suggested that migraine caused the infarction in the posterior circulation network. The pathophysiological mechanisms of stroke in migraine remains speculative. 
PMID: 1526769

End pulsed electromagnetic field therapy for migraine headache bibliography


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