Directional Functional Influence of the Locus Coeruleus on the Whole Brain in Tremor-dominant and Akinetic-Rigid Parkinson’s Disease

Objective The involvement of locus coeruleus (LC) in Parkinson's disease (PD) motor dysfunction remains unclear.This study aims to investigate LC's directional influence on the whole-brain in tremor-dominant (TD) and akinetic-rigid (AR) PD.Methods Forty-nine PD patients (20 TD and 29 AR) and 20 healthy controls (HCs) from a single center were retrospectively analyzed.The contrast-to-noise ratio (CNR) of LC was assessed using Neuromelanin-sensitive MRI.Effective connectivity (EC) of the LC was analyzed using seed-based Granger Causality analysis to examine the inflow and outflow of the LC's directional influence using functional MRI, corrected by Gaussian random field at voxel level (P<0.01) and cluster level (P<0.05).Pearson's analysis assessed the correlation between EC results and MDS-UPDRS III (P<0.05,Bonferroni corrected). ResultsThe CNRLC was significantly lower in both PD subgroups than in HCs, with TD-PD showing higher CNRLC than AR-PD.Compared to HCs, TD-PD exhibited enhanced EC from the LC to the cerebellum and inferior temporal gyrus; and from the cerebellum to the LC.AR-PD exhibited enhanced EC from the LC to the inferior temporal gyrus and cerebellum.Compared to TD-PD, AR-PD exhibited stronger EC from the LC to the middle frontal, inferior frontal, and middle occipital gyri, and from the cerebellum to the LC.LC-EC correlated significantly with MDS-UPDRS III in TD-PD and AR-PD (R = -0.487 to 0.682, P = 0.001 to 0.007). ConclusionOur results highlight the LC's directional influence in TD-PD and AR-PD, providing insights into motor dysfunction that could inform LC-noradrenaline-based therapy for personalized intervention.