Chong, Catherine D

Resting-state functional magnetic resonance imaging (rs-fMRI) is used to interrogate the functional connectivity and network organization amongst brain regions. Functional connectivity is determined by measuring the extent of synchronization in the spontaneous fluctuations of blood oxygenation level dependent (BOLD) signal. Here, we review current rs-fMRI studies in headache disorders including migraine, trigeminal autonomic cephalalgias, and medication overuse headache. We discuss (1) brain network alterations that are shared amongst the different headache disorders and (2) network abnormalities distinct to each headache disorder. In order to focus the section on migraine, the headache disorder that has been most extensively studied, we chose to include articles that interrogated functional connectivity: (i) during the attack phase; (ii) in migraine patients with aura compared to migraine patients without aura; and (iii) of regions within limbic, sensory, motor, executive and default mode networks and those which participate in multisensory integration. The results of this review show that headache disorders are associated with atypical functional connectivity of regions associated with pain processing as well as atypical functional connectivity of multiple core resting state networks such as the salience, sensorimotor, executive, attention, limbic, visual, and default mode networks.

Background Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). Methods This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. Results and Conclusions MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown “normalization” of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH.

Background This study used machine-learning techniques to develop discriminative brain-connectivity biomarkers from resting-state functional magnetic resonance neuroimaging ( rs-fMRI) data that distinguish between individual migraine patients and healthy controls. Methods This study included 58 migraine patients (mean age = 36.3 years; SD = 11.5) and 50 healthy controls (mean age = 35.9 years; SD = 11.0). The functional connections of 33 seeded pain-related regions were used as input for a brain classification algorithm that tested the accuracy of determining whether an individual brain MRI belongs to someone with migraine or to a healthy control. Results The best classification accuracy using a 10-fold cross-validation method was 86.1%. Resting functional connectivity of the right middle temporal, posterior insula, middle cingulate, left ventromedial prefrontal and bilateral amygdala regions best discriminated the migraine brain from that of a healthy control. Migraineurs with longer disease durations were classified more accurately (>14 years; 96.7% accuracy) compared to migraineurs with shorter disease durations (≤14 years; 82.1% accuracy). Conclusions Classification of migraine using rs-fMRI provides insights into pain circuits that are altered in migraine and could potentially contribute to the development of a new, noninvasive migraine biomarker. Migraineurs with longer disease burden were classified more accurately than migraineurs with shorter disease burden, potentially indicating that disease duration leads to reorganization of brain circuitry.

Background Migraine attacks manifest with hypersensitivities to light, sound, touch and odor. Some people with migraine have photosensitivity between migraine attacks, suggesting persistent alterations in the integrity of brain regions that process light. Although functional neuroimaging studies have shown visual stimulus induced “hyperactivation” of visual cortex regions in migraineurs between attacks, whether photosensitivity is associated with alterations in brain structure is unknown. Methods Levels of photosensitivity were evaluated using the Photosensitivity Assessment Questionnaire in 48 interictal migraineurs and 48 healthy controls. Vertex-by-vertex measurements of cortical thickness were assessed in 28 people with episodic migraine who had interictal photosensitivity (mean age = 35.0 years, SD = 12.1) and 20 episodic migraine patients without symptoms of interictal photosensitivity (mean age = 36.0 years, SD = 11.4) using a general linear model design. Results Migraineurs have greater levels of interictal photosensitivity relative to healthy controls. Relative to migraineurs without interictal photosensitivity, migraineurs with interictal photosensitivity have thicker cortex in several brain areas including the right lingual, isthmus cingulate and pericalcarine regions, and the left precentral, postcentral and supramarginal regions. Conclusion Episodic migraineurs with interictal photosensitivity have greater cortical thickness in the right parietal-occipital and left fronto-parietal regions, suggesting that persistent light sensitivity is associated with underlying structural alterations.

Background Specific white-matter tract alterations in migraine remain to be elucidated. Using diffusion tensor imaging (DTI), this study investigated whether the integrity of white-matter tracts that underlie regions of the “pain matrix” is altered in migraine and interrogated whether the number of years lived with migraine modifies fibertract structure. Methods Global probabilistic tractography was used to assess the anterior thalamic radiations, the corticospinal tracts and the inferior longitudinal fasciculi in 23 adults with migraine and 18 healthy controls. Results Migraine patients show greater mean diffusivity (MD) in the left and right anterior thalamic radiations, the left corticospinal tract, and the right inferior longitudinal fasciculus tract. Migraine patients also show greater radial diffusivity (RD) in the left anterior thalamic radiations, the left corticospinal tract as well as the left and right inferior longitudinal fasciculus tracts. No group fractional anisotropy (FA) differences were identified for any tracts. Migraineurs showed a positive correlation between years lived with migraine and MD in the right anterior thalamic radiations ( r = 0.517; p = 0.012) and the left corticospinal tract ( r = 0.468; p = 0.024). Conclusion Results indicate that white-matter integrity is altered in migraine and that longer migraine history is positively correlated with greater alterations in tract integrity.

Background/Objective Between attacks, migraine is associated with hypersensitivities to sensory stimuli. The objective of this study was to investigate hypersensitivity to pain in migraineurs between attacks. Methods Cutaneous heat pain thresholds were measured in 112 migraineurs, migraine free for ≥48 hours, and 75 healthy controls. Pain thresholds at the head and at the arm were compared between migraineurs and controls using two-tailed t-tests. Among migraineurs, correlations between heat pain thresholds and headache frequency, allodynia symptom severity, and time interval until next headache were calculated. Results Migraineurs had lower pain thresholds than controls at the head (43.9℃ ± 3.2℃ vs. 45.1℃ ± 3.0℃, p = 0.015) and arm (43.2℃ ± 3.4℃ vs. 44.8℃ ± 3.3℃, p < 0.001). There were not significant correlations between pain thresholds and headache frequency or allodynia symptom severity. For the 41 migraineurs for whom time to next headache was known, there were positive correlations between time to next headache and pain thresholds at the head ( r = 0.352, p = 0.024) and arm ( r = 0.312, p = 0.047). Conclusions This study provides evidence that migraineurs have low heat pain thresholds between migraine attacks. Mechanisms underlying these lower pain thresholds could also predispose migraineurs to their next migraine attack, a hypothesis supported by finding positive correlations between pain thresholds and time to next migraine attack.

Background Prior studies demonstrate reduced cortical thickness and volume in migraineurs. However, the effect of age on cortical thickness has not been assessed in migraineurs. In this study we investigated whether the process of aging on cortical thickness affects migraineurs differently compared to age-matched healthy controls, i.e. whether aging exacerbates cortical thinning in migraineurs. Methods Cortical thickness was estimated using a general linear model vertex-by-vertex approach for 32 healthy controls (mean age = 35.3 years; SD = 11.6) and 27 episodic migraine patients (mean age = 33.6 years; SD = 12.3). Results were modeled using a main effect analysis to estimate the effect of age on cortical thickness for each group separately, and an age-by-group analysis to estimate differences in age-related cortical thinning between migraine patients and normal controls. Results Although migraineurs and normal controls both have expected age-related thinning in many regions along the cortical mantle, migraineurs have age-related thinning of regions that do not thin in healthy controls, including: bilateral postcentral, right fusiform, and right temporal pole areas. Cortical thinning of these regions is more prominent with advancing age. Conclusion Results suggest that migraine is associated with atypical cortical aging, suggesting that the migraine disease process interacts with aging to affect cortical integrity.