Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson's disease

Although the diagnosis of Parkinson's disease (PD) remains anchored around the cardinal motor symptoms of bradykinesia, rest tremor, rigidity and postural instability, it is becoming increasingly clear that the clinical phase of the disease is preceded by a long period of neurodegeneration, which is not readily evident in terms of motor dysfunction. The neurobiological mechanisms that underpin this prodromal phase of PD remain poorly understood. Based on converging evidence of basal ganglia (BG) dysfunction in early PD, we set out to establish whether the prodromal phase of the disease is characterized by alterations in functional communication within the input and output structures of the BG. We analyzed resting-state functional MRI data collected from patients with REM sleep behavior disorder (RBD) and/or hyposmia, two of the strongest markers of prodromal PD, in comparison to age-matched controls. Relative to controls, subjects in the prodromal group showed reduced intra- and interhemispheric functional connectivity in a striato-thalamo-pallidal network. Functional connectivity alterations were restricted to the BG and did not extend to functional connections with the cortex. The data suggest that local interactions between input and output BG structures may be disrupted already in the prodromal phase of PD.