DISRUPTION OF CENTRAL BRAINSTEM-CORTEX ANS EFFECTIVE CONNECTIVITY IN AUTONOMIC FAILURE OF PARKINSON’S DISEASE

In Parkinson’s disease (PD), α-synuclein-mediated damage to the autonomic nervous system (ANS) means failure to regulate blood pressure (BP) is a common comorbidity that is hard to treat, worsens quality-of-life and often precedes diagnosis. Central ANS dysfunction is still poorly understood in-vivo, but is crucial as α-synuclein accumulates in these regions long before overt symptoms. Here, we characterised function of a brainstem-cortical ANS network in relation to cardiovascular autonomic failure.
81 individuals with early-PD and 65 aged-matched healthy controls (HC) performed resting-state 3T fMRI, neurological assessments and a 3-minute standing test: lied down for 5-minutes, had BP measured, then stood-up and had BP measured every minute for 3-minutes. We used Dynamic Causal Modelling to investigate how drops in BP linked to effective connectivity in medullary and relay nuclei, hypothalamus, and cortical autonomic regions.
Drops in BP during the standing task, in patients, were associated with self-inhibition of the rostro-ventrolateral medulla (RVLM), a nucleus that regulates sympathetic increase of BP. Conversely, in HC, drops were associated with higher RVLM activity. Additionally, the patient model was dominated by bottom-up connectivity from medullary regions to relay and cortical ones, potentially pertaining to state-signalling to higher-order regions, given the decreased ability of medullary regions to regulate BP in patients.
Our findings are compatible with known PD pathophysiology and elucidate how in-vivo a baseline RVLM dysfunction may cause poor central ANS reactivity to orthostatic stimuli and predispose patients to BP drops. Finally, this study paves the way to further characterise central autonomic function in-vivo.