Alterations in Effective Connectivity of the Hippocampus in Migraine without Aura

Abstract

Neuroimaging studies on migraine have revealed structural and functional alterations in the hippocampus, a region involved in pain processing and stress response. This study was designed to investigate whether effective connectivity of this region is disrupted in migraine and relates to chronicity of this disease. Patients and Methods: In 39 episodic migraine (EM) patients, 17 chronic migraine (CM) patients, and 35 healthy controls, we investigated differences in the directional influences between the hippocampus and the rest of the brain by combining resting-state functional magnetic resonance imaging and Granger causality analysis (GCA), with bilateral hippocampus as seed regions. The associations between directional influences and the clinical variables were also examined. Results: Comparing each patient group to the control group, we found increased and decreased negative influence on the hippocampus exerted by the bilateral visual areas and right dorsolateral prefrontal cortex (dlPFC), respectively. The hippocampus showed increased positive influence on the right posterior insula and medial prefrontal cortex (mPFC), as well as increased negative influence on the left cerebellum in CM patients relative to EM patients and healthy controls. Furthermore, across all patients, the migraine frequency exhibited a positive and negative association with causal influence from the hippocampus to mPFC and left cerebellum, respectively. Conclusion: Migraine patients have abnormal effective connectivity between the hippocampus and multiple brain regions involved in the sensory and cognitive processing of pain. Disrupted directional influences to the hippocampus exerted by dlPFC and bilateral visual areas were common features of EM and CM patients. Directional influences from the hippocampus to mPFC and left cerebellum may be useful imaging biomarkers for assessing migraine frequency.

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine

“…Here, we found that microgliosis, astrogliosis and neuronal loss were present in the cerebral cortex and hippocampus following dural IS stimulation (Fig. 4 ), which may account for the structural and functional alterations in the cerebral cortex and hippocampus of migraine patients previously observed in clinical neuroimaging studies [ 5 , 31 ]. These pathological changes were attenuated by pretreatment with BBG (Figs.…”

“…However, the role of P2X7R in migraine-related cognitive impairment has not been disclosed. Migraineurs frequently exhibited structural and functional abnormalities in the cerebral cortex and hippocampus, which is one of the possible mechanisms accounting for cognitive decline in migraineurs [ 5 , 31 ]. In the present study, we observed the elevated expression level of P2X7R in cerebral cortex and hippocampus, brain regions related to cognition, following repeated dural IS stimulation (Fig.…”

“…Evidence from clinical studies showed that cognitive symptoms of migraineurs may be associated with the structural and functional abnormalities in the cerebral cortex, hippocampus and white matter [ 5 , 31 , 32 ]. It has been shown that inflammasome activation can mediate cognitive decline in a mouse model of VaD by inducing gliosis, neuronal loss in the cerebral cortex and hippocampus, and white matter damage [ 27 ].…”

Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache

“…Previous studies have shown that migraineurs exhibited alterations in the rsFC of amygdala and hippocampus ( Hadjikhani et al, 2013 ; Zhu et al, 2021 ), and the two brain regions were associated with cognition and emotion ( Montagne et al, 2019 ; de Carvalho et al, 2021 ; Dogra et al, 2021 ; Duan et al, 2021 ; Mateus-Pinheiro et al, 2021 ; Nguyen et al, 2021 ). Considering the differences in neuropsychological performance between migraine and TTH ( Waldie et al, 2002 ; Gil-Gouveia et al, 2015 , 2016 ; Huang et al, 2017 ; Puledda et al, 2017 ; Karsan and Goadsby, 2018 ; Vuralli et al, 2018 ), we chose the bilateral amygdala and hippocampus as seed regions for rsFC analyses, to explore the potential rsFC features that may distinguish the two types of headache.…”

“…The amygdala and hippocampus are the key brain regions related to cognition and emotion ( Montagne et al, 2019 ; de Carvalho et al, 2021 ; Dogra et al, 2021 ; Duan et al, 2021 ; Mateus-Pinheiro et al, 2021 ; Nguyen et al, 2021 ). The alterations in rsFC of the two brain regions have been reported in migraineurs when compared to healthy controls (HCs) ( Hadjikhani et al, 2013 ; Zhu et al, 2021 ). However, there is a lack of studies to directly compare functional brain connectivity between migraine and TTH.…”