Interictal Migraine Research Articles

Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls.

Calcitonin gene-related peptide (CGRP) released from trigeminal nerve fibres indicates trigeminal activation and has a key role in migraine pathophysiology. The trigeminal nerve directly innervates the eye. Therefore, in this study, we compared Calcitonin gene-related peptide in tear fluid of migraine patients and healthy controls. Calcitonin gene-related peptide concentrations in tear fluid and plasma of 48 episodic and 45 chronic migraine patients and 48 controls were assessed using ELISA. Calcitonin gene-related peptide levels in tear fluid (0.94 ± 1.11 ng/ml) were ∼140 times higher than plasma concentrations (6.81 ± 4.12 pg/ml). Tear fluid CGRP concentrations were elevated in interictal migraine patients (1.10 ± 1.27 ng/ml, n = 49) compared to controls (0.75 ± 0.80 ng/ml, p = 0.022). There was no difference in tear fluid CGRP levels between interictal episodic and chronic migraine patients (episodic: 1.09 ± 1.47 ng/ml, n = 30 and chronic: 1.10 ± 0.89 ng/ml, n = 19) and no correlation of tear fluid CGRP levels with headache frequency in interictal patients (rho = 0.062, p = 0.674). Unmedicated ictal migraine patients had even more elevated tear fluid CGRP levels than interictal migraine patients (1.92 ± 1.84 ng/ml, n = 13, p = 0.102), while medicated ictal migraine patients had lower levels (0.56 ± 0.47 ng/ml, n = 25, p = 0.011 compared to interictal patients), which were undistinguishable from controls (p = 0.609). In contrast to tear fluid, no significant group differences were found in plasma CGRP levels. To the best of our knowledge, this study shows, for the first time, increased CGRP tear fluid levels in migraine patients compared to healthy subjects. Detection of calcitonin gene-related peptide in tear fluid is non-invasive, and likely allows a more direct access to CGRP released from the trigeminal nerve than plasma sampling.

Volume of Hypothalamus as a Diagnostic Biomarker of Chronic Migraine.

It is believed than hypothalamus (HTH) might be involved in generation of migraine, and evidence from high resolution fMRI reported that the more anterior part of HTH seemed to play an important role in migraine chronification. The current study was aimed to identify the alteration of morphology and resting-state functional connectivity (FC) of the hypothalamus (HTH) in interictal episodic migraine (EM) and chronic migraine (CM). High-resolution structural and resting-state functional magnetic resonance images were acquired in 18 EM patients, 16 CM patients, and 21 normal controls (NC). The volume of HTH was calculated and voxel-based morphometry (VBM) was performed over the whole HTH. Receiver operating characteristics (ROC) curve analysis was applied to evaluate the diagnostic efficacy of HTH volume. Correlation analyses with clinical variables were performed and FC maps were generated for positive HTH regions according to VBM comparison. The volume of the HTH significantly decreased in both EM and CM patients compared with NC. The cut-off volume of HTH as 1.429 ml had a good diagnostic accuracy for CM with sensitivity of 81.25% and specificity of 100%. VBM analyses identified volume reduction of posterior HTH in EM vs. NC which was negatively correlated with headache frequency. The posterior HTH presented decreased FC with the left inferior temporal gyrus (Brodmann area 20) in EM. Decreased volume of anterior HTH was identified in CM vs. NC and CM vs. EM which was positively correlated with headache frequency in CM. The anterior HTH presented increased FC with the right anterior orbital gyrus (AOrG) (Brodmann area 11) in CM compared with NC and increased FC with the right medial orbital gyrus (MOrG) (Brodmann area 11) in CM compared with EM. Our study provided evidence of structural plasticity and FC changes of HTH in the pathogensis of migraine generation and chronification, supporting potential therapeutic target toward the HTH and its peptide.

Abnormal thalamocortical network dynamics in migraine.

To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity. We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model. Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC. Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Functional connectivity of hypothalamus in chronic migraine with medication overuse.

To investigate the functional connectivity of the hypothalamus in chronic migraine compared to interictal episodic migraine in order to improve our understanding of migraine chronification. Using task-free fMRI and ROI-to-ROI analysis, we compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n = 25) to age- and sex-matched patients with episodic migraine in the interictal phase (n = 22). We also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. All patients with chronic migraine had medication overuse. We found a significant connectivity (T = 2.08, p = 0.024) between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these two regions were not connected in the episodic group. The strength of connectivity was not correlated with pain intensity (rho: 0.09, p = 0.655). In the seed-to-voxel analysis, three regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei (MNI coordinate x = 2, y = -44, z = -62), the right dorsal anterior insula (MNI coordinate x = 10, y = 10, z = 18), and the right caudate (MNI coordinate x = 12, y = 28, z = 6). However, these correlations were no longer significant after whole brain FWE correction. An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase.

Low-frequency facial hemodynamic oscillations distinguish migraineurs from non-headache controls.

Surface imaging is a promising, noninvasive approach to assess regional perfusion in craniovascular disorders such as migraine. We used optical imaging to examine differences in facial blood volume at baseline and in response to ammonia inhalation (a noxious stimulus), as well as standardized measures of cardiovascular autonomic function, in healthy, non-headache controls (n = 43) and in interictal migraine subjects (n = 22). Resting facial cutaneous oscillation (FCO) frequency was significantly different in migraine compared to healthy controls. Following ammonia inhalation, healthy controls showed a significant increase in resting FCO frequency, whereas this response was not significant in the migraine group. Standardized autonomic reflex parameters did not differ significantly between study groups, and facial cutaneous activity did not correlate with standardized cardiovascular autonomic reflex parameters, suggesting potentially different regulation. This approach to the assessment of craniofacial hemodynamic function appears to exhibit differing mechanisms from previously available techniques, and represents a promising new physiological biomarker for the study of craniofacial vascular function in migraine and potentially other craniovascular disorders.

Altered short-term visual paired associative plasticity in migraine patients between attacks

In healthy volunteers (HVs), we recently observed that the rules of the time-dependent paired-associative plasticity found in the sensorimotor system are valid also for the visual system. With the latter method, here, we have tested whether dysfunctioning associative plasticity might characterize the visual system in patients with episodic migraine without aura (MO), where abnormalities in both inhibitory and excitatory paired-associative sensorimotor plasticity have been observed between attacks (1). In 11 MO between attacks and in 14 HVs, we performed a visual paired associative stimulation (vPAS) protocol by coupling 90 black-and-white checkerboard reversals with low-frequency TMS pulses over the occipital cortex at 2 interstimulus intervals in separate sessions by subtracting or adding 25 ms to the visual evoked potential (VEP) P100 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 analysed VEP N1-P1 first block amplitude and delayed habituation. While vPAS-25 significantly enhanced and vPAS + 25 reduced VEP amplitude habituation in HVs, they both did not significantly change VEP amplitude habituation in MO between attacks. We provide evidence for lack of excitability depressing and enhancing short-term associative plasticity mechanisms within the visual system in interictal migraine.

Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study.

Studies in interictal migraine show either normal or impaired pain modulation, at the psychophysical level. To date, pain modulation in migraineurs has yet to be explored concurrent with imaging methods. We aimed to investigate brain activity associated with endogenous analgesia by functional magnetic resonance imaging in attack-free migraineurs. Thirty-nine episodic migraineurs and 35 controls participated. Endogenous analgesia efficiency was assessed by the conditioned pain modulation (CPM) paradigm during functional magnetic resonance imaging. Conditioned pain modulation included 4 stimulation sequences of either test stimulus (noxious contact heat at forearm) given stand alone (Ts_alone) or concomitant to contralateral foot immersion in cold water (Ts_conditioned). The psychophysical CPM (Ts_conditioned minus Ts_alone; 0-10 numerical rating scale) and related brain activity were examined. No group differences were found in the psychophysical CPM (controls: -0.52 ± 0.80; migraineurs: -0.20 ± 0.88; repeated-measures analysis of variance: P = 0.110) or related brain activity (family wise error [P < 0.05] correction at the voxel level). Within groups, controls showed a significant CPM effect (Ts_alone: 6.15 ± 2.03 vs Ts_conditioned: 5.63 ± 1.97; P < 0.001), whereas migraineurs did not (Ts_alone: 5.60 ± 1.92 vs Ts_conditioned: 5.39 ± 2.30; P = 0.153); yet, both groups showed significant CPM-related decreased deactivation in prefrontal areas including the superior frontal gyrus and parietal regions including precuneus. The change in brain activity seems related to task demands rather than to pain reduction. The lack of group difference between migraineurs and controls in CPM and its related brain activity may result from (1) the specific CPM methodology used in this study, since migraineurs are reported to show various pain modulation efficiency for different test paradigms and/or (2) pathophysiological diversity of patients with migraine.

Evidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials

BackgroundMigraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers.MethodsTwenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups.ResultsThe mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann’s areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers.ConclusionThis study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology.This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata.

The cold pressor test in interictal migraine patients \u2013 different parasympathetic pupillary response indicates dysbalance of the cranial autonomic nervous system

BackgroundData on autonomic nervous system (ANS) activations in migraine patients are quite controversial, with previous studies reporting over- and underactivation of the sympathetic as well as parasympathetic nervous system. In the present study, we explicitly aimed to assess the cranial ANS in migraine patients compared to healthy controls by applying the cold pressor test to a cohort of migraine patients in the interictal phase and measuring the pupillary response.MethodsIn this prospective observational study, a strong sympathetic stimulus was applied to 20 patients with episodic migraine in the interictal phase and 20 matched controls without migraine, whereby each participant dipped the left hand into ice-cold (4 °C) water for a maximum of 5 min (cold pressor test). At baseline, 2, and 5 min during the cold pressor test, infrared monocular pupillometry was applied to quantify pupil diameter and light reflex parameters. Simultaneously, heart rate and blood pressure were measured by the external brachial RR-method at distinct time intervals to look for at least clinically relevant changes of the cardiovascular ANS.ResultsThere were no significant differences between the migraine patients and controls at baseline and after 2 min of sympathetic stimulation in all the measured pupillary and cardio-vascular parameters. However, at 5 min, pupillary light reflex (PLR) constriction velocity was significantly higher in migraineurs than in controls (5.59 ± 0.73 mm/s vs. 5.16 ± 0.53 mm/s; unpaired t-test p < 0.05), while both cardiovascular parameters and PLR dilatation velocity were similar in both groups at this time point.ConclusionsOur findings of an increased PLR constriction velocity after sustained sympathetic stimulation in interictal migraine patients suggest an exaggerated parasympathetic response of the cranial ANS. This indicates that brainstem parasympathetic dysregulation might play a significant role in migraine pathophysiology. More dedicated examination of the ANS in migraine patients might be of value for a deeper understanding of its pathophysiology.

Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings.

Pain interventions with no active ingredient, placebo, are sometimes effective in treating chronic pain conditions. Prior studies on the neurobiological underpinnings of placebo analgesia indicate endogenous opioid release and changes in brain responses and functional connectivity during pain anticipation and pain experience in healthy subjects. Here, we investigated placebo analgesia in healthy subjects and in interictal migraine patients (n = 9) and matched healthy controls (n = 9) using 11C-diprenoprhine Positron Emission Tomography (PET) and simultaneous functional Magnetic Resonance Imaging (fMRI). Intravenous saline injections (the placebo) led to lower pain ratings, but we did not find evidence for an altered placebo response in interictal migraine subjects as compared to healthy subjects.

Structural differences in interictal migraine attack after epilepsy: A diffusion tensor imaging analysis

ObjectivePatients with epilepsy (PWE) are more likely to suffer from migraine attack, and aberrant white matter (WM) organization may be the mechanism underlying this phenomenon. This study aimed to use diffusion tensor imaging (DTI) technique to quantify WM structural differences in PWE with interictal migraine. MethodsDiffusion tensor imaging data were acquired in 13 PWE with migraine and 12 PWE without migraine. Diffusion metrics were analyzed using tract-atlas-based spatial statistics analysis. Atlas-based and tract-based spatial statistical analyses were conducted for robustness analysis. Correlation was explored between altered DTI metrics and clinical parameters. ResultsThe main results are as follows: (i) Axonal damage plays a key role in PWE with interictal migraine. (ii) Significant diffusing alterations included higher fractional anisotropy (FA) in the fornix, higher mean diffusivity (MD) in the middle cerebellar peduncle (CP), left superior CP, and right uncinate fasciculus, and higher axial diffusivity (AD) in the middle CP and right medial lemniscus. (iii) Diffusion tensor imaging metrics has the tendency of correlation with seizure/migraine type and duration. ConclusionResults indicate that characteristic structural impairments exist in PWE with interictal migraine. Epilepsy may contribute to migraine by altering WMs in the brain stem. White matter tracts in the fornix and right uncinate fasciculus also mediate migraine after epilepsy. This finding may improve our understanding of the pathological mechanisms underlying migraine attack after epilepsy.

Low 5-HT1B receptor binding in the migraine brain: A PET study.

Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding in interictal migraine patients without aura compared to controls. Methods Eighteen migraine patients, who had been migraine free for >48 hours, and 16 controls were scanned after injection of the 5-HT1B receptor specific radioligand [11C]AZ10419369 for quantification of cerebral 5-HT1B receptor binding. Patients who reported migraine <48 hours after the PET examination were excluded from the final analysis. We defined seven brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results Our data support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor binding in the dorsal raphe and in the midbrain. Conclusion We report here for the first time that migraine patients have low 5-HT1B receptor binding in pain modulating regions, reflecting decreased receptor density. This is either a primary constitutive trait of the migraine brain or secondary to repeated exposure to migraine attacks. We also provide indirect support for the dorsal raphe 5-HT1B receptors being temporarily downregulated during the migraine attack, presumably in response to higher cerebral serotonin levels in the ictal phase.

1. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: A multimodal evoked potentials study

A ketogenic diet (KD) – a drastic restriction in carbohydrate and lipid intake promoting fat metabolism and ketone body synthesis – has a role in preventing migraine. Here, we aim to identify cortical neurophysiological correlates of responsiveness to short-lasting preventive intervention with KD in migraine. Thus, we recorded visual (VEPs) and median nerve somatosensory (SSEPs) evoked potentials in 18 interictal migraine patients before and after 1 month of KD during ketogenesis. We measured VEP N1-P1 and SSEP N20-P25 amplitudes respectively in 6 and in 2 sequential blocks of 100 sweeps as well as habituation as the slope of the linear regression between block 1 and 6 for VEPs or between 1 and 2 for SSEPs. After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P < 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly induced normalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequent blocks. KD could restore normal EPs habituation curves during stimulus repetition without significantly changing the early amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balance between excitation and inhibition at the cortical level.

Thalamo-cortical network activity between migraine attacks: Insights from MRI-based microstructural and functional resting-state network correlation analysis.

BackgroundResting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks.MethodsEighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores.ResultsIn comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally.ConclusionsThe present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology.

Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis.

Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

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.

Highlights in migraine electrophysiology: are controversies just reflecting disease heterogeneity?

In migraine, the brain is 'hyperresponsive', which refers to a deficit of habituation to repeated sensory stimuli between attacks. This deficit normalizes in peri-ictal and ictal phases. A decreased cortical preactivation of thalamo-cortical origin and an impaired intracortical inhibition are probably involved in its pathophysiology. The reality of a habituation deficit of visual evoked potentials, a neurophysiological 'hallmark' of interictal migraine, has been questioned. Blinding may be an issue, but some genetic, environmental, or behavioural differences could also exist between populations. A habituation deficit is found interictally in other sensory modalities, and strongly depends on the time of the recordings within the migraine cycle. An impaired thalamocortical drive is demonstrated in interictal phase, and normalizes in ictal phase as well as in chronic migraine, where a strength enhancement of primary cortical activation is observed. An interictal dysexcitability, of subcortical or primary cortical origin, is suggested by magnetic stimulation. These phenomena could occur in varying degrees depending on patients and on the migraine cycle, and account for the heterogeneity of electrophysiological results. Finding a reliable electrophysiological biomarker for such a multifaceted and cycling disease as migraine is still a challenge. A better standardization of protocols would be worthwhile.

51. Hand somatosensory Functional Source Separation (FSS) analysis reveals hypoactive sub-cortical source signals in migraine interictally

Recent morpho-functional evidences pointed out that abnormalities in the thalamus could play a major role in the expression of migraine neurophysiological and clinical correlates. To this aim, we used Functional Source Separation algorithm to extract, from EEG signals, the activity of different neuronal pools recruited at different latencies along the somatosensory pathway in interictal migraine without aura (MO) patients. Twenty MO patients and twenty healthy volunteers (HV) underwent EEG recording. Four functional sources, two sub-cortical (FS14 at brainstem and FS16 at thalamic level) and two cortical (FS20 radial and FS22 tangential parietal), were extracted along the somatosensory pathway in response to the median nerve stimulation. High-frequency oscillatory (HFO) was extracted using band-pass digital filter (450–750 Hz) from the broadband EEG signal. Significant HFO reduction in the sub-cortical FS14 and FS16 were observed for the MO patients compared to the HV. No significant differences were reached, instead, for the cortical ones. Reduced sub-cortical brainstem and thalamic HFO activations play an important role in MO patients. Present results are the first neurophysiological evidence supporting the hypothesis that a functional disconnection of the thalamus from the subcortical monoaminergic system may underline the interictal cortical abnormal information processing in migraine.

Sequential brief neuropsychological evaluation of migraineurs is identical to controls.

Evidence of attack-related cognitive dysfunction in migraine is growing. Controversy exists on whether cognitive dysfunction, mainly executive, may persist between attacks. Measuring the impact of cognitive function is gaining importance in clinical and research settings in migraine. To compare the performance of interictal migraine patients to controls in an assembled neuropsychological battery focused on executive functions and to study the practice effect of its repeated applications. Assembly of the battery that was then applied twice within 6weeks to interictal migraineurs and matched healthy controls. Migraine patients (n=24) and controls (n=24) had similar performance in both applications of the battery. There was a slight practice effect between the first and second evaluation, significant in Stroop Interference test (P=0.002, multiplicity corrected); a meaningful score change was determined for each raw test scores. Interictal migraineurs and controls performance is identical in a brief cognitive battery focused on executive functions. Repeated applications produced a practice effect that was quantified.

O027. Sub-cortical sources of the somatosensory pathway are hypoactive in migraine interictally: a Functional Source Separation analysis.

Background: Recent morpho-functional evidence pointed out that abnormalities in the thalamus could play a major role in the expression of migraine neurophysiological and clinical correlates. Whether this phenomenon is primary or secondary to its functional disconnection from the brainstem remains to be determined. We used a Functional Source Separation algorithm of EEG signal to extract the activity of the different neuronal pools recruited at different latencies along the somatosensory pathway in interictal migraine without aura (MO) patients. Methods: Twenty MO patients and 20 healthy volunteers (HV) underwent EEG recording. Four ad-hoc functional constraints, two sub-cortical (FS14 at brainstem and FS16 at thalamic level) and two cortical (FS20 radial and FS22 tangential parietal sources), were used to extract the activity of successive stages of somatosensory information processing in response to the separate left and right median nerve electric stimulation. A band-pass digital filter (450-750 Hz) was applied offline in order to extract high-frequency oscillatory (HFO) activity from the broadband EEG signal. Results: In both stimulated sides, significant reduced sub-cortical brainstem (FS14) and thalamic (FS16) HFO activations characterized MO patients when compared with HV. No difference emerged in the two cortical HFO activations between the two groups. Conclusions: Present results are the first neurophysiological evidence supporting the hypothesis that a functional disconnection of the thalamus from the subcortical monoaminergic system may underline the interictal cortical abnormal information processing in migraine. Further studies are needed to investigate the precise directional connectivity across the entire primary subcortical and cortical somatosensory pathway in interictal MO. Written informed consent to publication was obtained from the patient(s).