Globus pallidus externus correlates with arousal in disorders of consciousness: a resting-state functional MRI study

IntroductionThe “Mesocircuit” model explains consciousness loss and recovery following severe brain injury as disconnection of cortical-subcortical circuits. Excessive inhibition of prefrontal cortex/thalamus by internal globus pallidus (GPi) is proposed as key to disorders of consciousness (DoC). However, recent research found external globus pallidus (GPe) crucial for arousal in DoC patients.MethodsTo investigate the relationship between GPe and arousal, this study enrolled 50 patients with DoC who were admitted to the Department of Neurosurgery, Shaanxi Provincial People’s Hospital, from November 2022 to November 2024. Patients were stratified into coma, UWS and MCS groups based on behavioral assessments (GCS/CRS-R) and underwent resting-state functional MRI (rs-fMRI). Whole-brain functional connectivity (FC) was analyzed with GPe as seed regions. Comparison and correlation analysis of FC strength between GPe and brain regions of subjects in two groups, with relation to arousal, were conducted.ResultsIn the FC analysis, Coma group showed weakened FC between GPe and left middle frontal gyrus, middle temporal gyrus, superior frontal gyrus, precuneus, and right precentral gyrus. Coma group demonstrated enhanced FC between GPe and thalamus: Central lateral (left CL and right CL). Correlation analysis revealed these abnormally weakened FC positively correlated with patients’ arousal state, among which GPe-left superior frontal gyrus FC (rs = 0.61, P < 0.001) and GPe-left CL FC (rs = 0.86, P < 0.001) showed strongest correlation with arousal.ConclusionOur findings provide neuroimaging evidence of disrupted functional connectivity between GPe and distributed cortical regions, including the left middle frontal gyrus, middle temporal gyrus, superior frontal gyrus, precuneus, CL, and right precentral gyrus, CL. These connectivity abnormalities spanning executive control, default mode, and primary motor networks suggest their coordinated role in consciousness impairment. Notably, arousal levels positively correlated with FC between GPe and cortical regions, specifically the left superior frontal gyrus, while negatively correlating with FC between GPe and CL. This suggests that altered GPe-cortical and GPe-thalamic FC may underlie the neural substrate for arousal regulation in patients with DoC.