Exploration of intrinsic brain activity in migraine with and without comorbid depression.

BACKGROUND: Major depressive disorder is a common comorbidity in migraineurs. Depression may affect the progression and prognosis of migraine. Few studies have examined the brain function in migraineurs that may cause this comorbidity. Here, we aimed to explore depression-related abnormalities in the intrinsic brain activity of interictal migraineurs with comorbid depression using resting-state functional magnetic resonance imaging. RESULTS: Significant main effects of migraine and depression provided evidence that migraine and depression jointly affected the left medial prefrontal cortex, which was thought to be the neural basis of self-referential mental activity in previous studies. Abnormalities in this region may contribute to determining the common symptoms of migraine and depression and even result in comorbidity. Additionally, migraineurs with comorbid depression had different developmental trajectories in the right thalamus and fusiform, which were associated with recognizing, transmitting, controlling and remembering pain and emotion. CONCLUSIONS: Based on our findings, the abnormal mPFC which may contribute to determining the common symptoms in migraine and depression and may be a therapeutic target for migraineurs comorbid depression. The different developmental trajectory in thalamus and fusiform indicates that the comorbidity may arise through a specific mechanism rather than simple superposition of migraine and depression.

Altered resting-state ascending/descending pathways associated with the posterior thalamus in migraine without aura.

This study aimed to investigate the dysfunctional ascending/descending pain pathways at the thalamic level in patients with migraine without aura (MWoA) using the effective connectivity analysis of the resting-state functional MRI. Twenty MWoA and 25 matched healthy controls participated in the resting-state functional MRI scans. The directional interactions between the posterior thalamus (PTH) and other brain regions were investigated using the Granger causality analysis and choosing bilateral PTH as two individual seeds. Pearson's correlation analysis was carried out between the abnormal effective connectivity and the headache duration and pain intensity of MWoA. Compared with healthy controls, MWoA showed decreased inflows to the bilateral PTH from the ventromedial prefrontal cortex and the left precuneus/posterior cingulate cortex, decreased outflow from the left PTH to the ipsilateral dorsomedial prefrontal cortex, and increased inflow to the right PTH from the ipsilateral dorsolateral prefrontal cortex. In addition, the abnormal inflows to the right PTH from the ventromedial prefrontal cortex and the right dorsolateral prefrontal cortex correlated positively with the headache duration and pain intensity, respectively. The abnormal ascending/descending pain pathways between the thalamus and these cortical regions indicate a disrupted pain modulation in affective and sensory domains, which suggests a disequilibrium of pain inhibition and facilitation in MWoA. These findings may help to shed light on the pathophysiologic mechanisms of migraine.

Functional alterations of pain processing pathway in migraine patients with cutaneous allodynia.

OBJECTIVE: Cutaneous allodynia (CA) is a characteristic of central sensitization, predicting migraine progression, and poor response to therapy. The present study aimed to find out the cerebral functional alterations related to the establishment of central sensitization in migraineurs using functional magnetic resonance imaging (fMRI). DESIGN: The experiment was performed in 15 migraineurs with Cutaneous allodynia (MWCA) and 19 patients without Cutaneous allodynia (MWoCA) in the interictal phase, and 20 matched healthy controls. Blood oxygen level dependent-fMRI was applied in all subjects when they were given transcutaneous electrical nerve stimulation at the left medial forearm, achieving to a predetermined level of pain sensation (i.e., visual analogue scale [VAS] = 40). Contrast images were then produced to determine whether this disorders present functional changes in the brain during pain processing. RESULTS: Demographic and headache characteristics were balanced between groups. The contrast images of both migraine groups comparing to healthy controls exhibited weaker activation of various brain regions (e.g., cerebellum and insulae), which might be relevant to the pathophysiological procedure of migraine. The direct comparison between the two migraine groups revealed that activation in the dorsal pons and contralateral (right) inferior parietal lobule of MWCA subjects were significantly lower than it in MWoCA ones. CONCLUSIONS: The interictal dysfunction of pain processing pathway may be responsible for (at least relevant to) central sensitization in migraine patients, via abnormal modulations of nociceptive transmission.

Altered effective connectivity of posterior thalamus in migraine with cutaneous allodynia: a resting-state fMRI study with Granger causality analysis.

BACKGROUND: Most migraineurs develop cutaneous allodynia (CA) during migraine, and the underlying mechanism of CA in migraine is thought to be sensitization of the third-order trigeminovascular neurons in the posterior thalamic nuclei. This study aimed to investigate whether the ascending/descending pathway associated with the thalamus is disturbed in migraineurs with CA (MWCA) using effective connectivity analysis of resting-state functional magnetic resonance imaging. METHODS: Thirty four migraineurs without aura (14 MWCA and 20 migraineurs without CA (MWoCA)) and 25 matched healthy controls (HC) were recruited in the study. The effective connectivity pathways associated with the posterior thalamus (PTH) were investigated using the Granger causality analysis. We chose bilateral PTH as two individual seeds, and compared MWCA with MWoCA and HC, respectively. Spearman correlation analysis was performed to test the correlation between the abnormal effective connectivity and the allodynia severity of MWCA. RESULTS: Compared with MWoCA, MWCA showed decreased inflows from the left limbic regions and dorsal medial prefrontal cortex (dmPFC) to the ipsilateral PTH, as well as increased inflow from the right ventral medial prefrontal cortex (vmPFC) to the ipsilateral PTH; no significantly different outflows from the bilateral PTH to other regions were found. Compared with HC, MWCA showed increased outflows from the left PTH to the bilateral vmPFC, decreased outflows from the right PTH to the bilateral temporoparietal areas, decreased inflow from the left parietooccipital area to the ipsilateral PTH, and increased inflows from the right dorsolateral prefrontal cortex and the bilateral temporoparietal areas to the right PTH. Correlation analyses revealed that the disturbed connectivities between PTH and cuneus, as well as PTH and middle frontal gyrus were associated with the allodynia severity of MWCA. CONCLUSIONS: MWCA demonstrated disrupted effective connection pathways between the PTH and other cortical or subcortical regions that participated in multi-dimentional pain processing. Our findings highlight the dysfunctional ascending and descending pain network at the thalamic-level and may help to illuminate the possible pathophysiologic mechanisms of CA.

High-field magnetic resonance imaging of suicidality in patients with major depressive disorder.

OBJECTIVE: Suicide is a major social and public health problem, but its neurobiology in major depressive disorder is poorly understood. The purpose of this study was to use magnetic resonance diffusion tensor imaging to characterize abnormalities of white matter integrity in major depressive disorder patients with and without a history of suicide attempts. METHOD: Participants were 52 patients with major depressive disorder, with (N=16) and without (N=36) a history of suicide attempts, and 52 healthy comparison subjects matched for age, gender, education, and ethnicity. Diffusion tensor imaging in a 3.0 Tesla magnetic resonance scanner was performed. Whole-brain voxel-based analysis was used to compare fractional anisotropy across the three groups and analyze the correlation with symptom severity. A region-of-interest analysis was applied to the bilateral hippocampus, thalamus, and lentiform nucleus RESULTS: Fractional anisotropy was decreased in the left anterior limb of the internal capsule in suicide attempters relative to both nonattempters and healthy comparison subjects, in the right frontal lobe relative to comparison subjects only, and in the right lentiform nucleus relative to nonattempters only. There was no significant correlation with symptom severity. CONCLUSIONS: Decreased fractional anisotropy in the left anterior limb of the internal capsule appears to characterize patients with major depressive disorder who have a history of attempting suicide. Longitudinal studies are required to validate this as a potential marker that may inform the development of strategies for reducing suicide.