Divergent amygdala function in proposed brain-first and body-first Parkinson's disease: a resting-state functional...

The newly proposed α-Synuclein Origin and Connectome (SOC) Model classifies Parkinson's disease (PD) patients into brain-first and body-first subtypes. In brain-first patients, α-synuclein may originate in the amygdala of one cerebral hemisphere and disseminate ipsilaterally via the neural connectome. This study aimed to investigate the differences in clinical characteristics and amygdala function between these two subtypes and to evaluate whether amygdala function could serve as a marker for subtype distinctions.

Resting-state functional MRI data of 66 early-stage PD patients and 17 healthy controls (HC) were retrieved from the Parkinson's Progression Markers Initiative database. PD patients with REM Sleep Behavior Disorder (RBD) were classified as the body-first subtype, while those without RBD were classified as the brain-first subtype.

We found that body-first patients had a longer disease duration and more severe autonomic dysfunction compared to brain-first patients. Amygdala-related FC in brain-first patients was similar to that in the HC group, with both groups showing stronger FC between the bilateral amygdala and the right postcentral gyrus than body-first patients. Importantly, the abnormal amygdala-related FC was negatively correlated with SCOPA-Aut scores (r = -0.361, P = 0.002) in PD patients. ROC analysis indicated that the area under the curve for the FC was 0.834.

Our findings suggest that the amygdala-related FC may serve as an effective indicator to differentiate brain-first and body-first subtypes. Moreover, functional abnormalities in the amygdala contribute to autonomic dysfunction, rather than depression or anxiety in early-stage PD patients. Further validation of these findings in trials with larger cohorts is needed.