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Among painful disorders, migraine is distinguishable by its chronic pathology and episodic clinical manifestation. Only a small percentage of patients with migraine progress to a chronic form of migraine. Both peripheral and central portions of the trigeminal system are involved in the pathophysiology of migraine pain, as they are involved in the processes of peripheral and central sensitization, alongside various subcortical and cortical brain structures. This review focuses on clinical, neurophysiological, and neuroimaging data underscoring cortical pain processing in migraine. Data obtained from quantitative sensory testings are inconclusive and support the involvement of the peripheral portion of the trigeminovascular system as indirect evidence of peripheral sensitization, solely during the headache phase. The assessment of subjective pain intensity in response to several painful modalities has not been conclusive for the clear state of central sensitization in between migraine attacks but for the subclinical allodynia state that defines the boundary between behavioural responses and an irritable nervous state. Modulation of the brainstem and midbrain pain pathways, in conjunction with the thalamic and thalamocortical pathways, may be critical for the initiation and maintenance of migraine attacks. Several studies using different neuroimaging techniques have demonstrated that brains experiencing migraine undergo plastic changes in both microstructure and macrostructure and in the functioning of cortical networks, which may manifest early in the life of a patient with migraine. Further studies are required to understand how specific these results are to migraine relative to other painful disorders.

Objective: The findings of resting-state functional MRI studies have suggested that abnormal functional integration between interconnected cortical networks characterises the brain of patients with migraine. The aim of this study was to investigate the functional connectivity between the hypothalamus, brainstem, considered as the migraine generator, and the following areas/networks that are reportedly involved in the pathophysiology of migraine: default mode network (DMN), executive control network, dorsal attention system, and primary and dorsoventral visual networks., Methods: Twenty patients with chronic migraine (CM) without medication overuse and 20 healthy controls (HCs) were prospectively recruited. All study participants underwent 3-T MRI scans using a 7.5-min resting-state protocol. Using a seed-based approach, we performed a ROI-to-ROI analysis selecting the hypothalamus as the seed., Results: Compared to HCs, patients with CM showed significantly increased neural connectivity between the hypothalamus and brain areas belonging to the DMN and dorsal visual network. We did not detect any connectivity abnormalities between the hypothalamus and the brainstem. The correlation analysis showed that the severity of the migraine headache was positively correlated with the connectivity strength of the hypothalamus and negatively with the connectivity strength of the medial prefrontal cortex, which belongs to the DMN., Conclusion: These data provide evidence for hypothalamic involvement in large-scale reorganisation at the functional-network level in CM and in proportion with the perceived severity of the migraine pain.

Background Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode network (DMN) with the insula. Here, we investigated seed-based resting state DMN-insula connectivity during acute migraine headaches. Methods Thirteen migraine without aura patients (MI) underwent 3 T MRI scans during the initial six hours of a spontaneous migraine attack, and were compared to a group of 19 healthy volunteers (HV). We evaluated headache intensity with a visual analogue scale and collected seed-based MRI resting state data in the four core regions of the DMN: Medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs), as well as in bilateral insula. Results Compared to HV, MI patients showed stronger functional connectivity between MPFC and PCC, and between MPFC and bilateral insula. During migraine attacks, the strength of MPFC-to-insula connectivity was negatively correlated with pain intensity. Conclusion We show that greater subjective intensity of pain during a migraine attack is associated with proportionally weaker DMN-insula connectivity. This is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain.

Background: To date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM., Methods: Twenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients' clinical features and GM maps were regressed., Results: Initially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month., Conclusion: No gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage.

Background: Resting 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., Methods: Eighteen 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., Results: In 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., Conclusions: The 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.

Objective: We used MRI to search for changes in thalamo-cortical networks and thalamic microstructure during spontaneous migraine attacks by studying at the same time structure with diffusion tensor imaging and resting state function in interconnected brain networks with independent component analysis., Methods: Thirteen patients with untreated migraine without aura (MI) underwent 3T MRI scans during an attack and were compared to a group of 19 healthy controls (HC). We collected resting state data in 2 selected networks identified using group independent component (IC) analysis. Fractional anisotropy (FA) values of bilateral thalami were calculated in the same participants and correlated with resting state IC z scores., Results: Functional connectivity between the executive and the dorso-ventral attention networks was reduced in MI compared to HC. In HC, but not in MI, the higher the IC24 z score, encompassing interconnected areas of the dorso-ventral attention system, the lower the bilateral thalamic FA values. In patients, the higher the executive control network z scores, the lower the number of monthly migraine days., Conclusions: These results provide evidence for abnormal connectivity between the thalamus and attentional cerebral networks at rest during migraine attacks. This abnormality could subtend the known ictal impairment of cognitive performance and suggests that the latter might worsen with increasing attack frequency., (© 2016 American Academy of Neurology.)

Background: We searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom. Methods: 3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores. Results: As compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs. Conclusions: The present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC). Methods: Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi's FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values. Results: CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS. Conclusions: FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack. [ABSTRACT FROM AUTHOR]