Autonomic disorders in Parkinson disease: Disrupted hypothalamic connectivity as revealed from resting-state functional magnetic resonance imaging

Converging evidence from diverse methodologies implicate the hypothalamus in the pathophysiology of Parkinson's disease (PD). Pathology in the hypothalamus and in hypothalamic pathways has been linked primarily to autonomic dysfunction, routinely experienced by individuals with PD throughout the course of the disease, sometimes predating onset of motor symptoms. Postmortem and molecular imaging studies have delineated pathologic changes in the hypothalamus and demonstrated alterations in neurotransmitter systems within this structure and associated pathways, which track the progression of the disease. More recently, functional interactions between the hypothalamus, thalamus, and striatum, as assessed using resting-state functional magnetic resonance imaging, were shown to be reduced in PD patients with high in comparison to those with low autonomic symptom burden. These functional changes may relate to micro- and macrostructural alterations which are also observed in PD. An examination of the hypothalamus and hypothalamic pathways can also shed light on atypical parkinsonian disorders and their distinct pathophysiologic characteristics relative to idiopathic PD. Altogether, the current state of knowledge on the involvement of the hypothalamus in PD is profound, yet emerging methodological advances are likely to move our understanding of hypothalamic pathology in PD significantly forward.