In the present study, we aimed to explore the brain function alterations specific to the comorbidity of migraine and depression using rs-fMRI in both migraine and MDD patients. Fourth major findings were reported. First, migraineurs with depression showed several areas with function alterations in the right precentral, right paracentral lobule, bilateral IOG, right lingual, bilateral calcarine, and left mPFC compared with HC. Second, intrinsic brain activity specific to migraine were mainly located in the right precentral, left thalamus, bilateral IOG, right lingual, bilateral calcarine, and left mPFC compared with HC. Third, a main effect of migraine was seen in the left IFG, triangular part; a interaction effect of migraine and depression was detected in the left calcarine. Fourth, the activity in the right paracentral lobule and left calcarine were significantly correlated with clinical variables (HAMD, HAMA, and BDI-II) in pooled migraine patients.
Migraineurs with comorbid depression showed significantly increased activity in the right precentral, the right paracentral lobule, the bilateral IOG, the right lingual, the bilateral calcarine; decreased activity in the left mPFC compared with the M-/D- subjects. Moreover, the interaction of migraine and depression was observed in the left calcarine. As the anterior node of the Default mode network (DMN), the mPFC was highly active at rest but inhibit activity mainly engaged in internally directed cognitions such as emotional processing and self-referential activity [31, 32]. A previous study investigated that migraine and depression jointly affected the development of the left mPFC, which may contribute to determining the common symptoms in migraine and depression . The precentral gyrus and paracentral lobule, thought to be part of Sensorimotor network (SMN) or PPN, related to detection and processing of sensory input (including pain) and preparation and execution of motor functions [34, 35]. The lingual, calcarine, and IOG were known as brain areas of VN, that was related visual perceptual processing and emotion . Mengmeng Ma, et al also demonstrated migraineurs with comorbid depression had different developmental trajectories in the right fusiform and thalamus, which were associated with transmitting, controlling and remembering pain and emotion . Taken together, the results presented here suggested that abnormalities in the DMN, PPN, and VN were profoundly involved in the neuropathological mechanism of co-occurrence of migraine and depression.
In this study, compared with HC, migraineurs without depression exhibited significantly increased activity in the right precentral, the bilateral IOG, the right lingual, the bilateral calcarine, the left thalamus; decreased activity in the left mPFC. Furthermore, the main effect of migraine was seen in the left IFG, triangular part. The IFG is part of the VAN, was suggested to be related to the stimulus-driven control attention . The thalamus, a region of PPN, is considered to play an important role in the transmission of nociceptive inputs to cortical pain related brain regions, including lateral pathway (somatic sensory area) and medial pathway (the PFC and limbic system) [37, 38]. Converging evidence suggested patients with migraine have multiple brain regions and networks alterations, and more than 20 FC were reported, which overlapped mostly with our results [13, 39]. Thus, the aberrant activity in the DMN, PPN, VN, and VAN may further suggest the impairment of sensory processing, visual perceptual processing and emotion, cognitive (attention, self-related) were associated with migraine patients.
When combing the findings for the comparing M+/D + group and M+/D- group with healthy controls, abnormalities in the right paracentral lobule were observed in the migraineurs with depression, but not in the migraineurs without depression. Interestingly, analysis of ROI demonstrated that the ALFF value in the paracentral lobule was positively correlated with the scores of HAMD and BDI-II, while the interaction effect of left calcarine gyrus was negatively correlated with the HAMD, HAMA, and BDI-II scores in the pooled migraine patients. The paracentral lobule and calcarine are the initial stage of brain information reception and processing from the periphery, has been linked to the further advanced emotion processing and response [40, 41]. HAMD, BDI-II, and HAMA reflected overall severity of depression and anxiety symptoms in our patients. This result highlighted the role of the right paracentral and left calcarine, which were associated with depression and anxiety symptoms in the migraineurs and even result in comorbidity.
There are several limitations that should be highlighted in this study. First, the sample size is relatively modest, which may limit the statistical power in detecting subtle brain alterations, such as the group difference between M-/D + group and HC group and the main effect of MDD. Second, we cannot absolutely rule out the influence of antidepressant medication and illness duration on our results, due to practical and ethical issues. Future studies are intended to test the reproducibility of our findings by using a larger sample of first-episode, medication-naïve patients. Finally, our cross-sectional design does not allow inference on causality. In the future, prospective longitudinal studies should be conduct whether these regional network alterations are a part of the pathogenesis or consequences of the comorbidity disorders.