Functional connectivity compensation in Parkinson's disease with freezing of gait

Abstract Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole‐brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD‐FOG) and 8 without FOG (PD‐nFOG), and 10 healthy controls were enrolled. High‐resolution 3D T1‐weighted and resting‐state functional MRI (rs‐fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs‐fMRI FC using seed‐based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs‐fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = −0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD‐nFOG group. PD‐FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD‐nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD‐FOG and distinguishing between PD subtypes.