Disrupted hypothalamic functional connectivity in patients with PD and autonomic dysfunction

Objective To test whether symptoms of autonomic dysfunction in Parkinson disease (PD) are associated with alterations in intrinsic hypothalamic functional connectivity, given the regulatory role of the hypothalamus (HTH) in the autonomic nervous system. Methods Resting-state fMRI scans from patients with PD were analyzed, comparing patients with the highest (n = 24) and lowest (n = 28) quartile scores in a questionnaire assessing autonomic dysfunction in PD (Scales for Outcomes in Parkinson's Disease-Autonomic [SCOPA-AUT]), obtained from a larger pool of patients (n = 93). Higher scores on the SCOPA-AUT indicate more severe symptoms. Seed-based functional connectivity maps, based on a seed region in the left and right HTH, were computed for each patient and compared by use of a general linear model, with false discovery rate correction for multiple comparisons. Partial correlation tests were additionally performed to test whether the associations between SCOPA-AUT scores and hypothalamic functional connectivity were independent of motor dysfunction, disease duration, cognitive function, and age. Results Relative to patients with PD with lower SCOPA-AUT scores, patients with higher scores displayed significantly reduced functional connectivity between the HTH and the striatum (caudate, putamen) and thalamus. The significant association between striato-thalamohypothalamic functional connectivity and SCOPA-AUT scores was retained after controlling for each patient's corresponding Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, age, disease duration, and cognitive function. Conclusions Patients with PD with symptoms of autonomic dysfunction show disrupted thalamo-striatohypothalamic functional connectivity independently of overall motor dysfunction, disease duration, age and cognitive function. These findings suggest that symptoms of autonomic dysfunction in PD are accompanied by central deficits in the neural circuits that regulate autonomic function and their interaction with the basal ganglia.