White Matter Dysfunction and Neurotransmitter Basis Underlying the Freezing of Gait in Parkinson's Disease

Abstract

ABSTRACT Freezing of gait (FOG) is a severe and refractory motor complication in Parkinson's disease (PD). Although structural changes of white matter (WM) associated with FOG have been extensively studied, the functional alterations of WM remain unclear. This study aims to investigate WM dysfunction and the neurotransmitter basis underlying FOG in PD. The study compared the WM function among 29 PD with FOG patients (FOG), 31 PD without FOG patients (nFOG), and 31 healthy controls (HC) using amplitude of low‐frequency fluctuations (ALFF). Then, functional connectivity (FC) analysis was performed to examine connectivity patterns related to ALFF changes. Finally, correlations were explored between ALFF and FC findings and neurotransmitter receptors/transporters. We found decreased ALFF in the left superior longitudinal fasciculus, right corticospinal tract, and forceps major in FOG patients compared with nFOG and HC. The forceps major cluster showed increased FC with the insular, putamen, and prefrontal cortex in FOG patients. Although both metrics were significantly correlated with mGluR5 and GABA, the FC abnormalities were additionally correlated with dopamine, VAChT, and 5‐HT systems. This study reveals imaging dysfunction of WM and its neurotransmitter basis, offering a novel perspective on the neural mechanisms underlying the pathophysiology of FOG.

Affiliated Institutions

• Anhui Medical University CN
• First Affiliated Hospital of Anhui Medical University CN
• Second Hospital of Anhui Medical University CN
• Anhui Mental Health Center CN

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