Aberrant inter-network functional connectivity in drug-naive Parkinson’s disease patients with tremor dominant and postural instability and gait difficulty

Background: Insight into neural mechanisms of tremor dominant (TD) and postural instability and gait disorder (PIGD) subtypes in Parkinson’s disease (PD) is vital for understanding pathophysiological hypotheses underlying this phenotype. However, network disturbances and their correlation with motor subtypes of PD remain unclear. We aimed to investigate the alterations of intra- and inter-network functional connectivity (FC) in drug-naive PD patients with different motor subtypes. Methods: Resting-state functional magnetic resonance imaging was performed on 25 drug-naive PD patients with TD (PD-TD) and 40 drug-naive PD patients with PIGD (PD-PIGD), and 37 healthy controls (HCs) underwent. The following networks were extracted using independent component analysis: sensorimotor network (SMN), left executive control network (LECN), right executive control network, anterior salience network (aSN), posterior salience network (pSN), ventral attention network (VAN), dorsal attention network (DAN), default mode network (DMN), visual network, and auditory network (AN). We measured FC values within and between these networks. Results: There were no detectable variations in intra-network FC. PD-PIGD group demonstrated lower FC between aSN and pSN, as well as between VAN and DMN, in contrast to PD-TD group. Particularly, the FC strength between VAN and DMN was positively correlated with TD and tremor scores, and the best fitting classification models of TD and PIGD subtypes were based on the FC between aSN and pSN. Compared with HCs, both PD-TD and PD-PIGD patients displayed decreased FC between two SMN subnetworks, while PD-TD patients exhibited increased FC between the SMN subnetwork and pSN, and between LECN and VAN. Furthermore, PD-PIGD patients demonstrated decreased FC between the SMN subnetwork and AN. Conclusions: The altered FC between aSN and pSN can be an imaging marker to distinguish PD-TD from PD-PIGD. We for the first time disclosed that the PD-TD patients compensated by increasing attention resources and the PD-PIGD patients displayed reduced FC between SMN and AN. Our findings provide a basis for identification and precision treatment of PD motor subtypes.