Habituation Of Visual Evoked Potentials Research Articles

Lack of habituation of visual-evoked potential in the interictal period is not a consistent neurophysiological marker of migraine: A cross-sectional analytical study

Objectives: Migraine is a frequent incapacitating neurovascular illness characterized by severe headache bouts. Individuals suffering from migraine appear to process auditory and visual information differently from those without migraine. The visual-evoked potential (VEP) is a commonly used standardized test to measure excitability in the occipital cortex. Patients with migraine exhibit amplification rather than habituation of stimulus-induced brain responses, between attacks. Our objective is to compare the amplitude of P100 and the latencies of N75, P100, and N145 (N and P represent negative and positive peaks, respectively, with average latency being subscripted with the alphabet) in the fourth block between migraine patients and controls and to determine the various clinical factors associated with the P100 mean amplitude and latency differences between the first and the fourth block in migraine patients. Materials and Methods: The study compared 20 migraine patients (with or without aura) and 20 apparently healthy subjects with no history of migraines or secondary headaches, focusing on the habituation of the VEP. Four blocks of 200 responses were recorded during the headache-free period, and the latencies and amplitudes of N75, P100, and N145 components were analyzed. Results: There was a statistically significant (P < 0.05) decrement in the P100 amplitude in the fourth block when compared to the first block in both eyes in the controls as well as migraine patients. In addition, there was no statistically significant difference between controls and migraine sufferers in the P100 amplitude of the fourth block in either eye. The N145 latency in the fourth block was shorter in both eyes in migraine patients compared to controls (P < 0.05). The mean P100 amplitude difference between the first and fourth block correlated negatively with age and positively with headache frequency, while there was a moderate negative correlation with headache duration. The mean P100 latency difference between the first and fourth block correlated positively with age and negatively with headache frequency, while there was a moderate positive correlation with headache duration. Conclusion: In our study, VEP habituation was not lacking in migraine patients which means that habituation of the P100 wave was noted in migraineurs. The VEP reveals neurological changes due to ischemia injury or neurotransmitter imbalances. Migraine alters cortical excitability, but it is unclear if these changes are due to altered excitatory connections, damaged inhibitory networks or subcortical pre-activation. Our findings suggest that at least during the interictal period, lack of habituation cannot be employed as a consistent neurophysiological marker of migraine across laboratories.

Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache.

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.

Revisiting the effects of transcranial direct current stimulation on pattern-reversal visual evoked potentials

Despite increasing growth of interest in transcranial direct current stimulation (tDCS), its underlying mechanisms are still unclear. With many claims based on the anodal-excitation and cathodal-inhibition dichotomy originally observed in the motor cortex, surprisingly few studies have examined these fundamental polarity-specific effects beyond the motor cortex. The after-effects of tDCS on the visual cortex are of particular interest because of their potential application to vision restoration and migraine treatment. Yet the limited studies revealed conflicting results. Here we investigated whether polarity-specific tDCS effects exist in the visual cortex. In a counterbalanced within-subject crossover design, 20 healthy subjects each completed three sessions of anodal, cathodal and sham tDCS (2 mA for 20 min) applied over the visual cortex. Pattern-reversal visual evoked potentials (VEP) and their habituation slopes were measured at five time-points immediately before, after and every 15 min following the end of tDCS. Compared to sham, we found no significant tDCS induced after-effects on VEP amplitudes or habituation slopes, supported by strong evidence from Bayesian statistics. Neither were there any after-effects of tDCS on EEG power of the frequency of stimulus presentation, theta or alpha band. In conclusion, our results challenge previous findings of robust polarity-dependent after-effects of tDCS over the visual cortex.

Evidence for associative plasticity in the human visual cortex

BackgroundRepetitive convergent inputs to a single post-synaptic neuron can induce long-term potentiation (LTP) or depression (LTD) of synaptic activity in a spike timing-dependent manner. ObjectiveHere we set a protocol of visual paired associative stimulation (vPAS) of the primary visual cortex (V1) in humans to induce persistent changes in the excitatory properties of V1 with a spike timing rule. MethodsWe provided convergent inputs to V1 by coupling transcranial magnetic stimulation (TMS) pulses of the occipital cortex with peripheral visual inputs, at four interstimulus intervals of −50/-25/+25/+50 ms relative to the visual evoked potential (VEP) P1 latency. We analysed VEP amplitude and delayed habituation before and up to 10 min after each vPAS protocol. ResultsVEP amplitude was reduced after vPAS+25. Delayed VEP habituation was increased after vPAS-25 while it was reduced after vPAS+25. ConclusionsWe provide evidence that associative bidirectional synaptic plasticity is a feature not only of the sensorimotor but also of the human visual system.

Neurophysiological correlates of clinical improvement after greater occipital nerve (GON) block in chronic migraine: relevance for chronic migraine pathophysiology

BackgroundTherapeutic management of Chronic Migraine (CM), often associated with Medication Overuse Headache (MOH), is chiefly empirical, as no biomarker predicting or correlating with clinical efficacy is available to address therapeutic choices. The present study searched for neurophysiological correlates of Greater Occipital Nerve Block (GON-B) effects in CM.MethodsWe recruited 17 CM women, of whom 12 with MOH, and 19 healthy volunteers (HV). Patients had no preventive treatment since at least 3 months. After a 30-day baseline, they received a bilateral betamethasone-lidocaine GON-B of which the therapeutic effect was assessed 1 month later. Habituation of visual evoked potentials (VEP) and intensity dependence of auditory evoked potentials (IDAP) were recorded before and 1 week after the GON-B.ResultsAt baseline, CM patients had a VEP habituation not different from HV, but a steeper IDAP value than HV (p = 0.01), suggestive of a lower serotonergic tone. GON-B significantly reduced the number of total headache days per month (− 34.9%; p = 0.003). Eight out 17CM patients reversed to episodic migraine and medication overuse resolved in 11 out of 12 patients. One week after the GON-B VEP habituation became lacking respect to baseline (p = 0.01) and to that of HV (p = 0.02) like in episodic migraine, while the IDAP slope significantly flattened (p < 0.0001). GON-B-induced reduction in headache days positively correlated with IDAP slope decrease (rho = 0.51, p = 0.03).ConclusionsGON-B may be effective in the treatment of CM, with or without MOH. The pre-treatment IDAP increase is compatible with a weak central serotonergic tone, which is strengthened after GON-B, suggesting that serotonergic mechanisms may play a role in CM and its reversion to episodic migraine. Since the degree of post-treatment IDAP decrease is correlated with clinical improvement, IDAP might be potentially useful as an early predictor of GON-B efficacy.

S105. Effect of change in pattern stimulation on the response latencies and amplitude of visual evoked potential in migraneurs and normal healthy adults

Visual Evoked Potentials (VEPs) are non- invasive studies which measure the electrophysiological activity at visual cortex. It represents the functional activity of optic pathway. It represents the functional activity of the optic pathway including anterior segment, retina, optic nerve, optic chiasm, lateral geniculate nucleus and visual cortex. The visual function in migraneurs differs from normal subjects and studies of VEP in migraneurs have yielded varied results. Several investigators did not find differences between migraneurs and healthy controls. while others reported changes of VEP amplitudes, latencies and habituation response. Thus present study is being conducted to see the variations in VEP latencies and amplitude with different spatial stimulation on pattern reversal VEP in migraineurs and healthy adults. A case control study is being conducted enrolling 250 migraine patients and 250 controls of either gender after having a written informed consent. VEP recording on a 6 channel EMG/EP measuring system of Nihon kohden is being done on all participants. Responses are recorded from scalp by electrodes placed according to the International 10/20 system. Visual stimulation is done with checkerboard pattern generated on the monitor consisting of black and white checks whose phase reverse with spatial frequency rates 0.5, 1, 2 and 4 cycles per degree and pattern size 16 × 16, 32 × 32, 64 × 64, 128 × 128, 256 × 256. 100 stimuli are given for each combination of pattern and frequency and an interval of at least 3 min is allowed between two patterns of stimulations. Preliminary analysis of data of 60 patients and 60 controls collected till now was analysed by clubbing the waveforms having the similar frequencies but different checkerboard size. It was seen that the onset latency, N75 was significantly different with smaller check size, i.e. 64 × 64 and 128 × 128 at all the frequencies 0.5,Hz,1 Hz, 2 Hz and 4 Hz. N75 latency was significantly different also at 4 Hz frequency and checkerboard 32 × 32. P100 latency showed significant differences only with smallest check size (128 × 128) at extremes of frequencies used i.e. 0.5 Hz and 4 Hz. While N145 latencies did not show any difference with any combinations of frequencies and checkerboard size. In the light of initial observations and preliminary analysis, it is prudent to include more participants in the study for increasing the power especially for the results which are showing borderline significance. This will assign more objectivity to finding. Probably migraineurs have different response to extreme visual stimuli than non-migraineurs thus we plan to summarize the data with mean as measure of central tendency and standard deviation as measure of dispersion. The clubbed data will be compared for specified latency and amplitude by applying the repeated measure ANOVA (RANOVA). In the next step we intend to do a linkage analysis for two groups for identifying the pattern (if any).

23. Effects of visual paired associative stimulation on visual evoked potentials in healthy volunteers

Associative stimulation of peripheral afferents paired with low-frequency transcranial magnetic stimulation (LF-TMS) over the motor area (PAS) at an interstimulus interval (ISI) slightly shorter or longer than the time needed for the afferent inputs to reach the cerebral cortex, can decrease or increase the excitability of the motor system. None has proven whether the same time-dependent plasticity rules may also be valid for the visual system. In 12 healthy subjects, we performed a visual PAS (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with LF-TMS pulses over the occipital cortex at 4 ISIs in separate sessions chosen by subtracting or adding 25/50 ms to the visual evoked potential (VEP) P1 latency. We recorded VEPs (600 sweeps) before, after, and 10-min later each vPAS session. VEPs were partitioned in 6 blocks of 100 sweeps. We analyzed VEP N1-P1 first amplitude and delayed habituation. VEP amplitude of the first block was reduced immediately after PAS+25, while it remained unchanged after the other vPAS protocols. Delayed VEP habituation significantly increased after PAS−25, and decreased after PAS+25. Associative bidirectional synaptic plasticity is not confined to the corticomotor system, but can also be a feature of the visual system.

Sunlight irradiance and habituation of visual evoked potentials in migraine: The environment makes its mark.

Background Migraine is a complex multifactorial disease that arises from the interaction between a genetic predisposition and an enabling environment. Habituation is considered as a fundamental adaptive behaviour of the nervous system that is often impaired in migraine populations. Given that migraineurs are hypersensitive to light, and that light deprivation is able to induce functional changes in the visual cortex recognizable through visual evoked potentials habituation testing, we hypothesized that regional sunlight irradiance levels could influence the results of visual evoked potentials habituation studies performed in different locations worldwide. Methods We searched the literature for visual evoked potentials habituation studies comparing healthy volunteers and episodic migraine patients and correlated their results with levels of local solar radiation. Results After reviewing the literature, 26 studies involving 1291 participants matched our inclusion criteria. Deficient visual evoked potentials habituation in episodic migraine patients was reported in 19 studies. Mean yearly sunlight irradiance was significantly higher in locations of studies reporting deficient habituation. Correlation analyses suggested that visual evoked potentials habituation decreases with increasing sunlight irradiance in migraine without aura patients. Conclusion Results from this hypothesis generating analysis suggest that variations in sunlight irradiance may induce adaptive modifications in visual processing systems that could be reflected in visual evoked potentials habituation, and thus partially account for the difference in results between studies performed in geographically distant centers. Other causal factors such as genetic differences could also play a role, and therefore well-designed prospective trials are warranted.

Familial history of migraine influences habituation of visual evoked potentials.

Background Lack of habituation of visual evoked potentials (VEP) is a common finding in migraine patients between attacks. Previous studies have suggested an electrophysiological familial aggregation pattern associated with migraine. The aim of this study was to evaluate the influence of a positive familial history of migraine on VEP amplitude and habituation. Methods We recorded six blocks of 100 VEP during continuous pattern-reversal stimulation in 30 patients with migraine between attacks (MO) and in 30 healthy volunteers, of whom 15 had a first-degree relative suffering from migraine (HVm) and 15 had not (HV). Results Both MO and HVm had a significant deficit of VEP habituation and similarly reduced N1-P1 first block amplitudes, compared to HV (habituation slope: MO = 0.033, HVm = 0.021, HV = -0.025, HV vs. MO p = 0.002, HV vs. HVm p = 0.036; mean N1-P1 amplitude in the first block: MO = 9.08 µV, HVm = 9.29 µV, HV = 12.19 µV. HV vs. MO p = 0.041, HV vs. HVm p = 0.076). The first block N1-P1 amplitude was negatively correlated with the habituation slope for both MO (ρ = -.44, p = 0.015) and HVm (ρ = -.56, p = 0.031) while no significant correlation was found in HV (ρ = .17, p = 0.53). There were no differences in VEP latencies between the groups. Conclusions Our study suggests that lack of habituation of visual evoked potentials is probably a genetically determined endophenotypic trait that is associated with both migraine and migraine susceptibility. We hypothesize that genetic diversity of populations could account for some of the discrepancies between electrophysiological studies performed in migraine and for interindividual variations among the subgroups.

Visual and auditory cortical evoked potentials in interictal episodic migraine: An audit on 624 patients from three centres.

Background Many studies report a habituation deficit of visual evoked potentials (VEP) and/or increased intensity dependence of auditory evoked cortical potentials (IDAP) in episodic migraine patients between attacks. These findings have a pathophysiological interest, but their diagnostic utility is not known. Aims To perform an audit on a large database of interictal VEP and IDAP recordings in episodic migraine patients and evaluate their diagnostic accuracy. Methods We pooled data for VEP habituation and IDAP measured in 624 episodic migraineurs (EM) and 360 healthy volunteers (HV) from three centers. Thresholds were calculated by Receiver Operating Curve analysis and used to calculate sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and the accuracy of each test, using ICHD diagnostic criteria as the gold standard. Results In EM, VEP habituation was significantly lower than in HV, and IDAP slopes were significantly steeper. VEP (five blocks of 50 responses), VEP (six blocks of 100 responses) and IDAP had respectively 61.0%, 61.4% and 45.7% sensitivity, and 77.9%, 77.9% and 87.2% specificity. Their positive (LR+) and negative (LR-) likelihood ratios were respectively 2.760, 2.778, 3.570 and 0.500, 0.495, 0.623, with diagnostic accuracies of 65.3%, 69.0% and 54.3%. In combined VEP + IDAP recordings, an abnormality of at least one test had 83.4% sensitivity, 66.7% specificity, 2.504 LR+, 0.249 LR- and 81.1% accuracy. Conclusions In this large database, VEP habituation is significantly reduced and IDAP increased in episodic migraine patients between attacks. Taken alone, neither VEP nor IDAP has sufficient diagnostic accuracy. However, when both tests are performed in the same patient, an abnormality of at least one of them is highly predictive of interictal episodic migraine.

Reliability and repeatability of testing visual evoked potential habituation in migraine: A blinded case-control study.

Background Many studies have shown that migraine patients have an interictal habituation deficit of visual evoked potentials (VEPs). Some discordant results were attributed to non-blinded analyses and a lack of repeatability. Aims In this study, we compared blinded and non-blinded analyses of the same recordings and assessed test-retest repeatability. Methods VEP recordings of 25 healthy volunteers (HVs) and 78 episodic migraine patients (EMs; 52 interictal, 26 ictal) were analysed by two investigators, one of whom was blinded to diagnosis and headache phase. Twelve HVs and nine EMs had two recordings for test repeatability. Results In both blinded and non-blinded analyses, VEP habituation was normal in HVs and EMs during an attack, but deficient in EMs interictally. Intra-individual habituation percentages were highly correlated in two recordings separated by ≥7 days. Conclusions The studies showing a VEP habituation deficit in migraineurs between attacks are unlikely to be biased by non-blinding analysis or poor repeatability.

Test-retest reliability of visual-evoked potential habituation.

Habituation of visual-evoked potentials (VEPs) is typically described as deficient interictally in migraine patients, supposedly indicating altered cortical excitability. Use of this parameter for monitoring changes over time, e.g. under treatment, requires demonstration of test-retest reliability. VEPs were recorded interictally in 41 episodic migraine patients and 40 controls. N75-P100 amplitudes were measured over six consecutive blocks of 75 VEPs each. Amplitude regression slopes and block ratios were used to quantify VEP habituation. Test-retest reliability was assessed over 15 minutes and two to three weeks. Controls showed significantly more negative VEP habituation slopes than migraine patients (-0.21 ± 0.40 vs. 0.04 ± 0.46 µV/block, p < 0.05). Results were similar for block ratios, though, in the migraine group, VEP habituation significantly increased from test to two- to three-week retest (p < 0.05). In addition, VEP habituation test-retest correlations were mostly poor both in migraine patients and controls (intraclass correlation coefficients, 15 minutes: -0.13 to 0.30, two to three weeks: 0.07 to 0.59). Deficient VEP habituation in migraine was confirmed. However, the test-retest reliability of VEP habituation was rather weak. Therefore, we suggest that VEP habituation should be used for evaluation of cortical excitability under treatment only at the group level and only when a control group with sham treatment is included.

Correlation between habituation of visual-evoked potentials and magnetophosphene thresholds in migraine: A case-control study.

In migraine most studies report an interictal deficit of habituation of visual-evoked potentials (VEP-hab) and reduced thresholds for phosphene induction (PT) by transcranial magnetic stimulation (TMS). We searched for a possible correlation between VEP-hab and PT in migraine patients and healthy controls to test whether they reflect the same pathophysiological abnormality. We assessed PT and VEP-hab measured as the percentage change of N1/P1 amplitude over six blocks of 100 responses in 15 healthy volunteers (HV) and in 13 episodic migraineurs without aura (MO) between attacks. Results were compared using Mann-Whitney U test. Interrelationships were examined using Spearman's correlation. In MO patients VEP-hab was reduced compared to HV (p = 0.001), while PT were not significantly different between HV and MO. There was no correlation between PT and VEP-hab in either group of participants. We confirm that in interictal migraine VEP habituation is deficient, but magnetophosphene threshold normal. VEP-hab and PT were not correlated with each other in healthy controls or in migraineurs. This finding suggests that they index different facets of cortical excitability in migraine, i.e. a punctual normal measure of the cortical activation threshold for PT and a dynamic response pattern to repeated stimuli for VEP habituation.

Visual evoked potentials in migraine: Is the “neurophysiological hallmark” concept still valid?

ObjectiveLack of habituation is considered a neurophysiological hallmark of migraine. However, the results of visual evoked potential (VEP) studies have been discrepant, possibly because of different stimulation parameters and lack of blinding. Hence, there is a need for independent confirmation of lack of VEP habituation in migraine. In this blinded study we applied 16′ checks to supplement our previous findings with 8′, 31′, 62′ and 65′ checks. MethodsVEPs in 41 interictal migraineurs and 30 controls were compared. VEPs were recorded in six blocks of 100 single responses. Linear N70-P100 amplitude change over blocks (habituation slope) was compared with an independent samples Student’s t-test. ResultsAmplitude decline over blocks was observed in both groups. Habituation slope was not significantly different between controls (−0.43±0.54μV/block) and migraineurs (−0.29±0.35μV/block) (p=0.33). ConclusionVEP habituation with 16′ checks did not differ in migraineurs and controls. This is in agreement with previous findings with other stimulation parameters. It is therefore unlikely that use of different stimulation parameters could explain the discrepant results of previous studies. No studies that applied blinding during recording of VEP have found lack of habituation in migraineurs. SignificanceLack of VEP habituation cannot be considered a reliable neurophysiological hallmark in migraine.

Correlation between Habituation of Visual Evoked Potentials and Magnetophosphene thresholds in migraine

Event Abstract Back to Event Correlation between Habituation of Visual Evoked Potentials and Magnetophosphene thresholds in migraine Anna Ambrosini1*, Aliaksei Kisialiou2, Ennio Iezzi1, Armando Perrotta1, Andrea Nardella1, Alfredo Berardelli3, Francesco Pierelli3 and Jean Schoenen4 1 IRCCS Neuromed, Pozzilli (Isernia), Italy, Italy 2 University of Glasgow, United Kingdom 3 University "La Sapienza", Italy 4 CHR CItadelle - University of Liège, Belgium Introduction: An interictal habituation deficit of visual evoked potentials (VEP) and a reduced threshold (PT) of magnetophosphenes have been reported in migraine in separate studies. While the habituation deficit was attributed to reduced preactivation level of the visual coretx, the reduced PT likely indicates cortical hyperexcitability. Both phenomena have not yet been explored in the same patients. Methods: We assessed PT by transcranial magnetic stimulation (TMS) in 15 healthy volunteers (HV) and in 13 episodic migraineurs without aura between attacks (MO), whereafter we recorded pattern-reversal VEP (6 blocks of 100 responses) and measured habituation. Results were compared using Mann-Whitney U test. Interrelationships were examined using Spearman’s correlation. Results: Phosphene thresholds was not significantly different between HV and MO. By contrast, MO patients had a reduced VEP habituation compared to HV (p=0.001). There was no correlation between PT and habituation in neither group of subjects . Conclusion: this study confirmed that migraineurs present interictally a deficit of VEP habituation, but failed to find decreased PT in these patients. VEP habituation and phosphene threshold values are not reciprocally correlated in healthy volunteers or in migraine patients, which suggest that they index different aspects of cortical excitability, i.e. a punctual measure of cortical activation threshold for PT, as opposed to a dynamic response pattern to repeated stimuli for VEP habituation. Keywords: Migraine Disorders, migraine pathophysiology, Evoked Potentials, Visual, transcranial magnetic stimulation cortical, phosphene threshold Conference: Belgian Brain Council 2014 MODULATING THE BRAIN: FACTS, FICTION, FUTURE, Ghent, Belgium, 4 Oct - 4 Oct, 2014. Presentation Type: Poster Presentation Topic: Clinical Neuroscience Citation: Ambrosini A, Kisialiou A, Iezzi E, Perrotta A, Nardella A, Berardelli A, Pierelli F and Schoenen J (2014). Correlation between Habituation of Visual Evoked Potentials and Magnetophosphene thresholds in migraine. Conference Abstract: Belgian Brain Council 2014 MODULATING THE BRAIN: FACTS, FICTION, FUTURE. doi: 10.3389/conf.fnhum.2014.214.00071 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Jul 2014; Published Online: 16 Aug 2014. * Correspondence: Dr. Anna Ambrosini, IRCCS Neuromed, Pozzilli (Isernia), Italy, Pozzilli, Isernia, Italy, anna.ambrosini@neuromed.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anna Ambrosini Aliaksei Kisialiou Ennio Iezzi Armando Perrotta Andrea Nardella Alfredo Berardelli Francesco Pierelli Jean Schoenen Google Anna Ambrosini Aliaksei Kisialiou Ennio Iezzi Armando Perrotta Andrea Nardella Alfredo Berardelli Francesco Pierelli Jean Schoenen Google Scholar Anna Ambrosini Aliaksei Kisialiou Ennio Iezzi Armando Perrotta Andrea Nardella Alfredo Berardelli Francesco Pierelli Jean Schoenen PubMed Anna Ambrosini Aliaksei Kisialiou Ennio Iezzi Armando Perrotta Andrea Nardella Alfredo Berardelli Francesco Pierelli Jean Schoenen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Does habituation depend on cortical inhibition? Results of a rTMS study in healthy subjects

Habituation, i.e. the decremental response to repeated sensorial stimulation, is studied in humans through evoked potential stimulation. Mechanisms underlying habituation are not yet cleared, even if inhibitory circuits are supposed to play an important role. Light deprivation (LD) increases visual cortical excitability likely through down-regulation of GABA circuits. We previously found that high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) can revert these facilitatory effects likely restoring the activity of inhibitory circuits. Here, we studied the effects of LD and rTMS on habituation of visual evoked potentials (VEPs). The hypothesis was that if the inhibitory circuits have a role in habituation, then LD that downregulates GABA circuits, should impair habituation that in turn should be restored by hf-rTMS. Fifteen healthy subjects underwent VEPs recording in baseline (without LD), in LD alone (without rTMS), in LD and 1Hz rTMS and in LD and 10Hz rTMS. Habituation observed in baseline (without LD) was significantly impaired after LD; 10Hz but not 1Hz rTMS was able to restore normal habituation phenomena. VEPs habituation is impaired by LD but it could be restored if hf-rTMS is given during LD. As LD acts reducing GABA circuits activity and hf-rTMS likely upregulates such circuits, these data give support to the hypothesis that cortical inhibition can play a relevant role in mechanisms underlying habituation.

Changes in visual-evoked potential habituation induced by hyperventilation in migraine

Hyperventilation is often associated with stress, an established trigger factor for migraine. Between attacks, migraine is associated with a deficit in habituation to visual-evoked potentials (VEP) that worsens just before the attack. Hyperventilation slows electroencephalographic (EEG) activity and decreases the functional response in the occipital cortex during visual stimulation. The neural mechanisms underlying deficient-evoked potential habituation in migraineurs remain unclear. To find out whether hyperventilation alters VEP habituation, we recorded VEPs before and after experimentally induced hyperventilation lasting 3 min in 18 healthy subjects and 18 migraine patients between attacks. We measured VEP P100 amplitudes in six sequential blocks of 100 sweeps and habituation as the change in amplitude over the six blocks. In healthy subjects, hyperventilation decreased VEP amplitude in block 1 and abolished the normal VEP habituation. In migraine patients, hyperventilation further decreased the already low block 1 amplitude and worsened the interictal habituation deficit. Hyperventilation worsens the habituation deficit in migraineurs possibly by increasing dysrhythmia in the brainstem-thalamo-cortical network.

Tonic Pain Abolishes Cortical Habituation of Visual Evoked Potentials in Healthy Subjects

We investigated changes in visual cortex excitability by analyzing visual evoked potential (VEP) habituation in healthy subjects during tonic pain evoked by the cold-pressor test (CPT). We tested VEP amplitude habituation (slope of the linear regression line for N1-P1 amplitude from the 1st to 6th block of 100 sweeps) in 19 healthy volunteers during 4 experimental conditions: baseline; no-pain (hand held in warm water, 25 degrees C); pain (hand held in cold water, 2-4 degrees C); and the after-effects of tonic pain. During baseline and no-pain sessions, VEPs habituated normally across the 6 consecutive blocks (mean slope -.28 and -.18%), whereas during pain and its after-effects they failed to decrease (0%, and -.11%). Tonic pain induced by the CPT abolishes normal VEP habituation and the lack of habituation persists after the CPT is stopped. Tonic pain probably abolishes VEP habituation by acting on brainstem neural structures which modulate thalamo-cortical activation thereby changing visual cortex excitability. This study shows that tonic pain alters visual cortex excitability, a brain region unrelated to pain processing. These changes probably reflect defensive strategies against pain. Extending the study from healthy volunteers to patients with migraine between attacks would offer the opportunity to investigate visual cortical excitability under conditions when baseline habituation is absent.

Lack of cold pressor test-induced effect on visual-evoked potentials in migraine

In patients with migraine, the various sensory stimulation modalities, including visual stimuli, invariably fail to elicit the normal response habituation. Whether this lack of habituation depends on abnormal activity in the sub-cortical structures responsible for processing incoming information as well as nociception and antinociception or on abnormal cortical excitability per se remains debateable. To find out whether inducing tonic pain in the hand by cold pressure test (CPT) alters the lack of visual-evoked potential (VEP) habituation in migraineurs without aura studied between attacks we recorded VEPs in 19 healthy subjects and in 12 migraine patients during four experimental conditions: baseline; no-pain (hand held in warm water, 25°C); pain (hand held in cold water, 2–4°C); and after-effects. We measured P100 amplitudes from six blocks of 100 sweeps, and assessed habituation from amplitude changes between the six sequential blocks. In healthy subjects, the CPT decreased block 1 VEP amplitude and abolished the normal VEP habituation (amplitude decrease to repeated stimulation) in patients with migraine studied between attacks; it left block 1 VEP amplitude and abnormal VEP habituation unchanged. These findings suggest that the interictal cortical dysfunction induced by migraine prevents the cortical changes induced by tonic painful stimulation both during pain and after pain ends. Because such cortical changes presumably reflect plasticity mechanisms in the stimulated cortex, our study suggests altered plasticity of sensory cortices in migraine. Whether this abnormality reflects abnormal functional activity in the subcortical structures subserving tonic pain activation remains conjectural.

Nitroglycerin sensitises in healthy subjects CNS structures involved in migraine pathophysiology: Evidence from a study of nociceptive blink reflexes and visual evoked potentials

Nitroglycerin (NTG), a NO donor, induces an attack in migraine patients approximately 4–6h after administration. The causative mechanisms are not known, but the long delay leaves room for a central effect, such as a change in neuronal excitability and synaptic transmission of various CNS areas involved in pain and behaviour including trigeminal nucleus caudalis and monoaminergic brain stem nuclei. To explore the central action of NTG, we have studied its effects on amplitude and habituation of the nociceptive blink reflex (nBR) and the visual evoked potential (VEP) before, 1h and 4h after administration of NTG (1.2mg sublingual) or placebo (vehicle sublingual) in two groups of 10 healthy volunteers. We found a significant decrease in nBR pain and reflex thresholds both 1 and 4h post-NTG. At the 4h time point R2 latency was shorter (p=0.04) and R2 response area increased (p<0.01) after NTG but not after placebo. Habituation tended to become more pronounced after both NTG and placebo administration. There was a significant amplitude increase in the 5th VEP block (p=0.03) at 1h after NTG and in the 1st block (p=0.04) at 4h. VEP habituation was replaced by potentiation at both delays after NTG; the change in habituation slope was significant at 1h (p=0.02). There were no significant VEP changes in subjects who received sublingual placebo. In conclusion, we found that in healthy subjects sublingual NTG, but not its vehicle, induces changes in a trigeminal nociceptive reflex and an evoked cortical response which are comparable to those found immediately before and during an attack of migraine. These changes could be relevant for the attack-triggering effect of NTG in migraineurs.