The Functional Connectivity Study On The Brainstem-Cortical/Subcortical Structures In Responders Following Cervical Vagus Nerve Stimulation

Background Cervical vagus nerve stimulation (VNS) is an effective neuromodulation therapy for patients with drug-resistant epilepsy (DRE). The previous studies reported that VNS may reduce seizures by regulating the functional connectivity (FC) between cortical and subcortical regions. However, no studies on brainstem have been done in responders who achieved >= 50% seizure reduction following VNS. Methods Eight healthy controls and eight patients who became responders after 3 months of operation were enrolled in this study. Resting-state functional MRI (rs-fMRI) was performed, and two sample and paired samplettest were, respectively, used to detect altered FC between brainstem and cortical/subcortical regions between controls and patients, between preoperative and postoperative patients. Results In the control group, regions with highest FC to brainstem included bilateral anterior cingulate gyri, left basal ganglia, left insula, left cuneus, right precuneus, and bilateral cerebellum. In preoperative patients, right frontal middle gyrus, bilateral basal ganglia, and right cerebellum were showed highest FC to brainstem. Compared with the controls, preoperative patients exhibited increased FC in bilateral inferior frontal gyri, right temporal cortex, while decreased FC in left insula, left postcentral gyrus, right posterior cingulate gyrus, right precuneus, and left superior parietal gyrus. In postoperative patients, regions with increased FC to brainstem were left insula, left precuneus and left cuneus, and those with decreased FC were right inferior occipital gyrus and right cerebellum. Conclusions Recurrent seizures caused disturbances in brainstem-cortical/subcortical FC, especially in motor executive function related regions and default mode network. VNS could reorganize the altered FC between brainstem and insula, precuneus, and cerebellum in responders.