Cortex In Migraine Research Articles

Bi-sinusoidal light stimulation reveals an enhanced response power and reduced phase coherence at the visual cortex in migraine.

Migraine is associated with enhanced visual sensitivity during and outside attacks. Processing of visual information is a highly non-linear process involving complex interactions across (sub)cortical networks. In this exploratory study, we combined electroencephalography with bi-sinusoidal light stimulation to assess non-linear features of visual processing in participants with migraine. Twenty participants with migraine (10 with aura, 10 without aura) and ten non-headache controls were measured (outside attacks). Participants received bi-sinusoidal 13 + 23 Hz red light visual stimulation. Electroencephalography spectral power and multi-spectral phase coherence were compared between groups at the driving stimulation frequencies together with multiples and combinations of these frequencies (harmonic and intermodulation frequencies) caused by non-linearities. Only at the driving frequency of 13 Hz higher spectral power was found in migraine with aura participants compared with those with migraine without aura and controls. Differences in phase coherence were present for 2nd, 4th, and 5th-order non-linearities in those with migraine (migraine with and without aura) compared with controls. Bi-sinusoidal light stimulation revealed evident non-linearities in the brain's electroencephalography response up to the 5th order with reduced phase coherence for higher order interactions in interictal participants with migraine. Insight into interictal non-linear visual processing may help understand brain dynamics underlying migraine attack susceptibility. Future research is needed to determine the clinical value of the results.

Functional brain alterations in migraine patients: an activation likelihood estimation study

ABSTRACT Background Previous functional magnetic resonance imaging (fMRI) studies reported inconsistent results for comparison in brain activation between migraine patients and healthy controls (HC). Thus, activation likelihood estimation (ALE) method, a powerful voxel-based technique, was used to explore the concordant functional brain changes in migraine patients. Methods Studies published before October 2022 were searched in the following databases (PubMed, Web of Science and Google Scholar). Results Migraine without aura (MWoA) patients showed reduced amplitude of low-frequency fluctuations (ALFF) in right lingual gyrus, the left posterior cingulate and the right precuneus (PCUN), compared to HC. Migraine patients showed increased ALFF in the right claustrum, the left caudate, the left insula and the right parahippocampal gyrus, compared to HC. MWoA patients showed reduced regional homogeneity (ReHo) in the right culmen, compared to HC. In addition, migraine patients showed increased ReHo in the bilateral thalamus, compared to HC. MWoA patients showed reduced whole-brain functional connectivity (FC) in the left middle occipital gyrus and the right superior parietal lobule, compared to HC. In addition, migraine patients showed increased whole-brain FC in the left middle temporal gyrus (MTG), the right inferior frontal gyrus, the right superior temporal gyrus (STG) and the left inferior temporal gyrus, compared to HC. Conclusions ALE analysis identified consistent functional changes in widespread regions, especially in cingulate gyrus, basal ganglia region and frontal cortex in migraine. These regions involve in pain processing, cognitive dysfunction and emotional problems. These results may provide important clues for clarifying the pathophysiology of migraine.

Cortical mechanisms in migraine.

Migraine is the second most prevalent disorder in the world; yet, its underlying mechanisms are still poorly understood. Cumulative studies have revealed pivotal roles of cerebral cortex in the initiation, propagation, and termination of migraine attacks as well as the interictal phase. Investigation of basic mechanisms of the cortex in migraine not only brings insight into the underlying pathophysiology but also provides the basis for designing novel treatments. We aim to summarize the current research literatures and give a brief overview of the cortex and its role in migraine, including the basic structure and function; structural, functional, and biochemical neuroimaging; migraine-related genes; and theories related to cortex in migraine pathophysiology. We propose that long-term plasticity of synaptic transmission in the cortex encodes migraine.

Altered resting-state functional connectivity between subregions in the thalamus and cortex in migraine without aura.

Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes. A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed-based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions. The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R-IPL) and right middle frontal gyrus. Furthermore, the FC Z-scores between the VPN and R-IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z-scores between the VPN and R-IPL. These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R-IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity.

Disrupted functional connectivity between sub-regions in the sensorimotor areas and cortex in migraine without aura

BackgroundMigraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation.MethodsForty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions.ResultsWe found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities.ConclusionIn patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.

Effectiveness of cathodal tDCS of the primary motor or sensory cortex in migraine: A randomized controlled trial

ObjectivesTranscranial Direct Current Stimulation (tDCS) is a new technology that is extensively used for migraine treatment. The present study aims to examine the effectiveness of cathodal-tDCS (c-tDCS) in decreasing migraine pain frequency, duration, and intensity at the right primary motor cortex (M1) or sensory cortex (S1) in individuals with episodic or chronic migraine. MethodsThe present study has a randomized, single-blind, and sham-controlled design. It tests the effectiveness of 22 sessions of c-tDCS (20min/1000 μA) in 45 migraine patients (episodic = 35; chronic = 10/with aura = 28; without aura = 17). Spread over 10 consecutive weeks, the sessions started with three sessions per week and ended with one session per week. Participants were tested at the baseline, at the end of intervention, and at 12-month follow-up. The migraine diagnosis was based on criteria set by International Headache Society (IHS) and patients were allocated to two experimental (nm1 = 15; ns1 = 15) and a sham intervention group (nc = 15). ResultsThe results of a series of MANCOVAs showed a significant reduction (p < 0.05) in all hypothesized symptoms of migraine pain in both experimental groups compared to the sham intervention group at the posttest and follow-up. ConclusionThe application of c-tDCS to M1 or S1 can be used as a technological intervention for the prophylactic and therapeutic treatment of episodic or chronic migraine. Ethical committee registration numberIr.mums.fm.rec.1396.362.

Temporal instability of salience network activity in migraine with aura

This study aims to investigate whether intranetwork dynamic functional connectivity and causal interactions of the salience network is altered in the interictal term of migraine. Thirty-two healthy controls, 37 migraineurs without aura, and 20 migraineurs with aura were recruited. Participants underwent a T1-weighted scan and resting-state fMRI protocol inside a 1.5T MR scanner. We obtained average spatial maps of resting-state networks using group independent component analysis, which yielded subject-specific time series through a dual regression approach. Salience network regions of interest (bilateral insulae and prefrontal cortices, dorsal anterior cingulate cortex) were obtained from the group average map through cluster-based thresholding. To describe intranetwork connectivity, average and dynamic conditional correlation was calculated. Causal interactions between the default-mode, dorsal attention, and salience network were characterised by spectral Granger's causality. Time-averaged correlation was lower between the right insula and prefrontal cortex in migraine without aura vs with aura and healthy controls (P < 0.038, P < 0.037). Variance of dynamic conditional correlation was higher in migraine with aura vs healthy controls and migraine with aura vs without aura between the right insula and dorsal anterior cingulate cortex (P < 0.011, P < 0.026), and in migraine with aura vs healthy controls between the dorsal anterior cingulate and left prefrontal cortex (P < 0.021). Causality was weaker in the <0.05 Hz frequency range between the salience and dorsal attention networks in migraine with aura (P < 0.032). Overall, migraineurs with aura exhibit more fluctuating connections in the salience network, which also affect network interactions, and could be connected to altered cortical excitability and increased sensory gain.

Impaired intrinsic functional connectivity between the thalamus and visual cortex in migraine without aura

BackgroundResting-state functional magnetic resonance imaging (fMRI) has confirmed disrupted visual network connectivity in migraine without aura (MwoA). The thalamus plays a pivotal role in a number of pain conditions, including migraine. However, the significance of altered thalamo-visual functional connectivity (FC) in migraine remains unknown. The goal of this study was to explore thalamo-visual FC integrity in patients with MwoA and investigate its clinical significance.MethodsResting-state fMRI data were acquired from 33 patients with MwoA and 22 well-matched healthy controls. After identifying the visual network by independent component analysis, we compared neural activation in the visual network and thalamo-visual FC and assessed whether these changes were linked to clinical characteristics. We used voxel-based morphometry to determine whether functional differences were dependent on structural differences.ResultsThe visual network exhibited significant differences in regions (bilateral cunei, right lingual gyrus and left calcarine sulcus) by inter-group comparison. The patients with MwoA showed significantly increased FC between the left thalami and bilateral cunei and between the right thalamus and the contralateral calcarine sulcus and right cuneus. Furthermore, the neural activation of the left calcarine sulcus was positively correlated with visual analogue scale scores (r = 0.319, p = 0.043), and enhanced FC between the left thalamus and right cuneus in migraine patients was negatively correlated with Generalized Anxiety Disorder scores (r = − 0.617, p = 0.005).ConclusionOur data suggest that migraine distress is exacerbated by aberrant feedback projections to the visual network, playing a crucial role in migraine physiological mechanisms. The current study provides further insights into the complex scenario of migraine mechanisms.

Current understanding of cortical structure and function in migraine.

ObjectiveTo review and discuss the literature on the role of cortical structure and function in migraine.DiscussionStructural and functional findings suggest that changes in cortical morphology and function contribute to migraine susceptibility by modulating dynamic interactions across cortical and subcortical networks. The involvement of the cortex in migraine is well established for the aura phase with the underlying phenomenon of cortical spreading depolarization, while increasing evidence suggests an important role for the cortex in perception of head pain and associated sensations. As part of trigeminovascular pain and sensory processing networks, cortical dysfunction is likely to also affect initiation of attacks.ConclusionMorphological and functional changes identified across cortical regions are likely to contribute to initiation, cyclic recurrence and chronification of migraine. Future studies are needed to address underlying mechanisms, including interactions between cortical and subcortical regions and effects of internal (e.g. genetics, gender) and external (e.g. sensory inputs, stress) modifying factors, as well as possible clinical and therapeutic implications.

Different mean thickness implicates involvement of the cortex in migraine.

The results of neuroimaging studies on migraines have shown that the functions and functional connectivity networks of some brain regions are altered in migraine patients, and different brain structure volumes have also been observed in recent years. However, it is still not known whether the mean thickness of the cortex is different in migraine patients.A total of 48 migraine without aura (MWoA) patients in interictal phase and 48 healthy controls were enrolled in this study. All subjects received neurological and magnetic resonance imaging (MRI) examinations. Automatic segmentation processing of high-resolution MRI structure images was performed using FreeSurfer software.The mean cortical thickness of many brain regions in the frontal lobe, temporal lobe, occipital lobe, parietal lobe, and insula in the migraine patient group was significantly decreased compared with that in the healthy control group. The mean cortical thickness of the insula anterior was positively correlated with the duration of the disease course, while the mean cortical thickness of insula superior and insula inferior was negatively correlated with the duration of the disease course.The results showed that MWoA results from a complex interactive reaction involving many brain regions and many brain network systems together. However, it is still not clear whether the difference in the brain structure of migraine patients is the result or the cause of headache, which is a topic that must be better elucidated. Therefore, longitudinal neuroimaging studies on migraine patients with large samples sizes should be performed using more advanced neuroimaging techniques.

Altered neurochemical coupling in the occipital cortex in migraine with visual aura.

Visual aura is present in about one-third of migraine patients and triggering by bright or flickering lights is frequently reported. Using migraine with visual aura patients, we investigated the neurochemical profile of the visual cortex using magnetic resonance spectroscopy. Specifically, glutamate/creatine and GABA/creatine ratios were quantified in the occipital cortex of female migraine patients. GABA levels in the occipital cortex of migraine patients were lower than that of controls. Glutamate levels in migraine patients, but not controls, correlated with the blood-oxygenation-level-dependent (BOLD) signal in the primary visual cortex during visual stimulation. Migraine with visual aura appears to disrupt the excitation-inhibition coupling in the occipital cortex.

Thickening of the somatosensory cortex in migraine without aura.

We aimed to explore cortical thickness abnormalities in a homogeneous group of patients with migraine without aura and to delineate possible relationships between cortical thickness changes and clinical variables. Fifty-six female migraine patients without aura and T2-visible white matter hyperintensities and 34 female controls were scanned on a 3T magnetic resonance imager. Cortical thickness was estimated and compared between patients and controls using a whole-brain vertex-by-vertex analysis. Correlation analysis was conducted between cortical thickness of significant clusters and clinical variables. Compared to controls, migraine patients had cortical thickening in left rostral middle frontal gyrus and bilateral post-central gyri. Region-of-interest analysis revealed cortical thickening of bilateral post-central gyri in migraine patients relative to controls. The average thickness of bilateral post-central gyri positively correlated with disease duration as well as estimated lifetime headache frequency. We have provided evidence for interictal cortical abnormalities of thickened prefrontal cortex and somatosensory cortex in female migraine patients without aura. Our findings of greater thickening of the somatosensory cortex in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time may lead to structural changes of the somatosensory cortex through increased noxious afferent input within the trigemino-thalamo-cortical pathway in migraine.

The missing link: Enhanced functional connectivity between amygdala and visceroceptive cortex in migraine

Migraine is a neurovascular disorder in which altered functional connectivity between pain-modulating circuits and the limbic system may play a role. Cortical spreading depression (CSD), which underlies migraine aura (MWA), induces C-fos expression in the amygdala. The role of CSD and amygdala connectivity in migraine without aura (MwoA) is less clear and may differentiate migraine from other chronic pain disorders. Using resting-state functional MRI, we compared functional connectivity between the amygdala and the cortex in MWA and MWoA patients as well as in healthy subjects and in two other chronic pain conditions not associated with CSD: trigeminal neuralgia (TGN) and carpal tunnel syndrome (CTS). Amygdala connectivity in both MWA and MWoA was increased to the visceroceptive insula relative to all other groups examined. The observed increased connectivity within the limbic/viscerosensory network, present only in migraineurs, adds to the evidence of a neurolimbic pain network dysfunction and may reflect repetitive episodes of CSD leading to the development of migraine pain.

Novel techniques and developments in migraine research

Advancing our understanding of the pathophysiology of migraine is one of the key ways that researchers can help provide answers to the many questions that migraineurs have. More importantly it is the only way that tailored therapeutics can be developed that can provide relief to all sufferers, not just those that are lucky enough to respond to existing therapies. It is therefore crucial that we in headache research continue in our efforts to find these answers, through continued development of our methods and providing open-minded thinking to embrace new techniques and ideas into our field. There is much important research in migraine being conducted throughout the world at this time, research that will hopefully help us to find some of these answers. It is the aim and focus of this teaching session to try to introduce the audience to some of the more recent findings and developments in migraine research, and some of the novel approaches researchers are trying to take to understand the dynamics of the migraine pain experience, from a fully translational point of view. Dr. Akerman will provide an introduction to the topics that will be highlighted and briefly discuss our current understanding of the pathophysiology of migraine and how this may drive migrainous symptoms. It is well known that migraine involves activation of the trigeminovascular system, but it is what and how other areas of the brain and periphery may drive this activation in patients to impact migraine that still requires further investigation. These areas may include the peripheral meningeal nociceptors, the brainstem and the diencephalon, but also interaction of these areas with the cortex, and the respective importance of both the neuronal and vascular components. We know that thalamocortical function is very important in the processing of nociceptive information. Altered cortical function has long been thought to be at the root of migraine aura, and maybe even trigeminovascular activation. Dr. Holland will use preclinical data to discuss how alteration of normal cortical function can result in symptoms such as migraine aura, but also how uncoupling of the normal neurovascular relationship in the cortex, thought to drive aura, can also impact other symptomatic aspects of migraine that results in migraine as a global brain disorder. Dr. Sprenger will discuss this issue of cortical function from a clinical perspective. He will try to address how imaging is helping us understand the role of the cortex in migraine, and how migraineurs may present cortical function that is different from the non-migrainous brain. Another very important issue for the headache researcher is in actually understanding the dynamics of the pain experienced by the migraineur. Other forms of pain research, away from the head, have for a long time relied on animal behavioural models to observe nociceptive behaviours as a marker of pain. These models are used to study, preclinically, the different dynamics of pain that may be experienced in the clinic and also to test pharmacological agents for therapeutic efficacy. It is only recently that headache research has begun to embrace these techniques. Dr. Romero will discuss some of the methods and techniques that can be used to assess pain in the head and facial region in migraine. She will address the importance of measuring spontaneous (non-evoked) nociceptive behaviours in animals, something which the migraine patient complains of mostly, and how one can do this. Also, as we have seen in our understanding of migraine pathophysiology and the role of sensitisation, how this physiology can be interpreted in the measurement of evoked behaviours in animals. Finally, for a clinician, understanding the pain experienced by their patients is of the utmost importance in diagnosing and treating them, as well as aiding us in understanding the pathophysiology. Therefore, having the tools available to understand this is crucial. Dr. Geber, using this clinical approach, and his skills and experience in allodynia and sensory testing in experimental pain models and pain patients, will describe how these techniques can be used in patients to understand the quality of the pain symptoms related to the headache and facial region. Also, how they can be used experimentally as a research tool to aid us in understanding more about the pathophysiology of migraine and other head pain disorders.

Motion processing deficits in migraine are related to contrast sensitivity

There are conflicting reports concerning the ability of people with migraine to detect and discriminate visual motion. Previous studies used different displays and none adequately assessed other parameters that could affect performance, such as those that could indicate precortical dysfunction. Motion-direction detection, discrimination and relative motion thresholds were compared from participants with and without migraine. Potentially relevant visual covariates were included (contrast sensitivity; acuity; stereopsis; visual discomfort, stress, triggers; dyslexia). For each task, migraine participants were less accurate than a control group and had impaired contrast sensitivity, greater visual discomfort, visual stress and visual triggers. Only contrast sensitivity correlated with performance on each motion task; it also mediated performance. Impaired performance on certain motion tasks can be attributed to impaired contrast sensitivity early in the visual system rather than a deficit in cortical motion processing per se. There were, however, additional differences for global and relative motion thresholds embedded in noise, suggesting changes in extrastriate cortex in migraine. Tasks to study the effects of noise on performance at different levels of the visual system and across modalities are recommended. A battery of standard visual tests should be included in any future work on the visual system and migraine.

Impaired Glutamatergic Neurotransmission in Migraine With Aura? Evidence by an Input–Output Curves Transcranial Magnetic Stimulation Study

An imbalance between activity of inhibitory and facilitatory intracortical circuits could play a central role in migraine etiology. We used input-output curves to achieve further information about intracortical excitability of motor cortex in migraine with aura. Input-output curves were measured in the right abductor pollicis brevis muscle at rest in 12 patients suffering from migraine with aura and 8 healthy subjects. Stimuli were delivered at intensity ranging from 100% to 160% of resting motor threshold with 10-second inter-stimulus intervals. Seven patients were studied before and during treatment with levetiracetam. Results showed a greater motor-evoked potential amplitude in response to increasing intensity of stimuli in patients compared to controls (P < .02). This increased facilitatory effect was abolished by levetiracetam (P < .005). Our findings support the hypothesis of an interictal cortical hyper-responsivity in migraine patients that appears to be normalized by levetiracetam. This effect could support the potential therapeutic role of levetiracetam in migraine with aura prevention.

Differential activation of the middle-temporal complex to visual stimulation in migraineurs

Differences between people with and without migraine on various measures of visual perception have been attributed to abnormal cortical processing due to the disease. The aim of the present study was to explore the dynamics of the basic interictal state with regard to the extrastriate, motion-responsive middle temporal area (MT-complex) with functional magnetic resonance imaging (fMRI) at 3 tesla using coherent/incoherent moving dot stimuli. Twenty-four migraine patients (12 with aura [MwA], 12 without aura [MwoA]) and 12 healthy subjects participated in the study. The individual cortical folding pattern was accounted for by using a cortical matching approach. In the inferior-posterior portion of the MT-complex, most likely representing MT, control subjects showed stronger bilateral activation compared to MwA and MwoA patients. Compared with healthy controls MwoA and MwA patients showed significantly stronger activation mainly at the left side in response to visual stimulation in the superior-anterior portion of the MT-complex, representing the medial-superior temporal area (MST). Our findings strengthen the hypothesis that hyperresponsiveness of the visual cortex in migraine goes beyond early visual areas, even in the interictal period.

Migraine: an overview.

The pathophysiology of migraine is not completely understood and continues to be investigated. The complexity of interactions taking place in the sensory neuronal network with the mediation of all different neurotransmitters involved gives the measure of the extreme difficulty connected with the knowledge of migraine pathogenesis and in particular of its cardinal sign. Neuronal components are relevant in migraine pathophysiology: there could be a generalized interictal abnormal excitability of the cerebral cortex in migraine, possibly favoring the occurrence of spreading depression with consequent activation of the trigeminal system. Many theories have been formulated in these last sixty years about the pathogenesis of migraine and other forms of primary headache, but the problem is still far to be fully clarified. The present review is focused on the description of different theories on the migraine pathogenesis. This review is dedicated to the memory of Prof. Alfredo Bianchi.

Cortical inhibition and habituation to evoked potentials: relevance for pathophysiology of migraine

Dysfunction of neuronal cortical excitability has been supposed to play an important role in etiopathogenesis of migraine. Neurophysiological techniques like evoked potentials (EP) and in the last years non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation gave important contribution to understanding of such issue highlighting possible mechanisms of cortical dysfunctions in migraine. EP studies showed impaired habituation to repeated sensorial stimulation and this abnormality was confirmed across all sensorial modalities, making defective habituation a neurophysiological hallmark of the disease. TMS was employed to test more directly cortical excitability in visual cortex and then also in motor cortex. Contradictory results have been reported pointing towards hyperexcitability or on the contrary to reduced preactivation of sensory cortex in migraine. Other experimental evidence speaks in favour of impairment of inhibitory circuits and analogies have been proposed between migraine and conditions of sensory deafferentation in which down-regulation of GABA circuits is considered the more relevant pathophysiological mechanism. Whatever the mechanism involved, it has been found that repeated sessions of high-frequency rTMS trains that have been shown to up-regulate inhibitory circuits could persistently normalize habituation in migraine. This could give interesting insight into pathophysiology establishing a link between cortical inhibition and habituation and opening also new treatment strategies in migraine.

Orientation Discrimination and Contrast Detection Thresholds in Migraine for Cardinal and Oblique Angles

To determine whether orientation discrimination deficits in migraine, which have been found to depend on the spatial frequency of the stimulus, are due to precortical dysfunction or to abnormal patterns of orientation tuning at cortical loci. Further, to assess whether any cortical involvement is restricted to the striate cortex or whether higher cortical areas are also involved. Orientation-specific abnormalities would provide evidence of cortical dysfunction. Orientation-discrimination and contrast-detection thresholds were assessed at cardinal (0 degrees) and oblique (45 degrees) orientations using explicit lines defined by Gabor patches. To test for extrastriate dysfunction, participants made orientation judgments using virtual lines defined by two widely spaced circles. Migraine history, migraine triggers, and pattern sensitivity were also assessed. Twenty migraineurs (10 with visual aura, 10 without) and 20 control participants were tested. Orientation-discrimination thresholds were lower for discriminations made about the cardinal axis than for discriminations made about the oblique axis, a well-documented phenomenon known as the oblique effect. Relative to the control group, the migraine group exhibited orientation-specific sensitivity losses on explicit and virtual judgments. Orientation-discrimination thresholds about the oblique axis were significantly elevated in the migraine group. In contrast, the migraine and control groups' detection thresholds did not differ. These findings reflect abnormal function of striate and extrastriate cortex in migraine. In addition, the discrimination data are consistent with wider orientation-tuning curves for orientation-sensitive cells in migraine, whereas the detection data suggest peak sensitivity does not differ between the groups.