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

Abstract

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.

Neuroimaging abnormalities in individuals exhibiting Parkinson's disease risk markers

“…In keeping with the suggested white matter changes in motor regions of the brain including those surrounding the thalamus in our study, a recent resting-state fMRI study revealed reduced intra-and interhemispheric functional connectivity in a striatothalamo-pallidal network in patients with either isolated hyposmia or isolated RBD. 52 This further corroborates the notion that degenerative changes may be preferentially observed in patients at PD risk with hyposmia (and/or RBD). By including participants with a reduced smell sense into our study we may thus have artificially selected participants that are not only at risk for PD but, more important, are also at risk for a more rapid decline and a higher tendency to more advanced neurodegeneration.…”

Update of the MDS research criteria for prodromal Parkinson's disease

“…35 Promising techniques include 11 C-donepezil PET/CT (cholinergic (parasympathetic) gut innervation), 123 I-metaiodobenzylguanidine scintigraphy (cardiac sympathetic denervation), 36 susceptibility-weighted and neuromelanin-sensitive MRI (dorsal nigral hyperintensity; integrity of pigmented neurons of the locus coeruleus), 11 Cmethylreboxetine PET (noradrenergic nerve terminals originating in the locus coeruleus), structural connectivity and functional MRI (striatal or whole-brain function). 35,[37][38][39] However, for the establishment of prodromal (neuro)imaging markers consensus on specific methods and analyses is needed. 3.…”