Task-dependent changes in effective connectivity from limbic to cognitive networks during motor imagery of freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that has been related to abnormal functional connectivity across motor, cognitive, and limbic networks. However, it remains unclear how directional (i.e., effective) connectivity between various networks is altered by an actual FOG-related motor imagery task. Twenty-four individuals with PD (11 freezers and 13 non-freezers) and 15 healthy controls underwent functional MRI. Participants performed a motor imagery task while observing two videos: (1) a person with PD engaged in typical walking, and (2) a person with PD experiencing a FOG-episode. We performed between-group comparisons of the task-related changes using dynamic causal modeling (DCM) analysis and the parametric empirical Bayes framework, followed by correlation analysis. DCM analysis revealed that task-dependent changes in effective connectivity during FOG imagery differed significantly in two limbic to cognitive network connections in freezers compared with non-freezers. Specifically, freezers showed greater changes in connectivity from the hippocampus to anterior part of middle frontal gyrus (posterior probability > 0.95), which was associated with a higher freezing ratio (Spearman's rho = 0.952, p < 0.01). We also found lower changes in connectivity from anterior insula to supramarginal gyrus (posterior probability > 0.95), which was not correlated with FOG measures. Motor imagery of FOG altered effective connectivity from limbic to cognitive regions in freezers versus non-freezers. The positive modulatory effects on connectivity from the hippocampus to middle frontal gyrus in freezers could represent a greater limbic FOG-related episodic memory response or a failed suppression of these responses in freezers.