Evidence of central autonomic dysfunction in orthostatic hypotension of Parkinson's disease

INTRODUCTION: Autonomic dysfunction, particularly orthostatic hypotension (OH), is common and predicts poor outcomes in Parkinson's disease (PD). Brain contributions to autonomic failure in PD are suspected but understudied. METHODS: 31 PD participants underwent autonomic reflex testing and functional brain MRI. Region of interest (ROI) analyses were used to characterize intranetwork connectivity of salience network (implicated in sympathetic nervous system function) nodes. Seed-based connectivity of key Central Autonomic Network (CAN) (responsible for top-down autonomic control) ROIs was performed to confirm the specificity of these findings. Between-group differences in functional connectivity as well as associations of connectivity with clinical variables were investigated using ANOVA. All analyses were controlled for age and disease duration. RESULTS: 12/31 PD participants had OH. Functional connectivity between three clusters including the anterior cingulate cortex, bilateral anterior insula, rostral prefrontal cortex, and supramarginal gyrus were weaker in OH compared with no-OH. Blood pressure reduction measures and severity of self-completed assessment of autonomic dysfunction scores were associated with lower internode connectivity. No differences in intranetwork connectivity between PD with OH and those without were found in non-autonomic networks. CONCLUSION: Disrupted central sympathetic autonomic function through the salience network and the CAN is implicated in OH in PD. These findings identify potential novel targets for neuromodulation therapies in PD.