More Than Just Static: Dynamic Functional Connectivity Changes of the Thalamic Nuclei to Cortex in Parkinson's Disease With Freezing of Gait

Abstract

Background: The thalamus is not only a key relay node of the thalamocortical circuit but also a hub in the regulation of gait. Previous studies of resting-state functional magnetic resonance imaging (fMRI) have shown static functional connectivity (FC) between the thalamus and the cortex are disrupted in Parkinson's disease (PD) patients with freezing of gait (FOG). However, temporal dynamic FC between the thalamus and the cortex has not yet been characterized in these patients. Methods: Fifty PD patients, including 25 PD patients with FOG (PD-FOG) and 25 PD patients without FOG (PD-NFOG), and 25 healthy controls (HC) underwent resting-state fMRI. Seed-voxel-wise static and dynamic FC were calculated between each thalamic nuclei and other voxels across the brain using the 14 thalamic nuclei in both hemispheres as regions of interest. Associations between altered thalamic FC based on significant inter-group differences and severity of FOG symptoms were also examined in PD-FOG. Results: Both PD-FOG and PD-NFOG showed lower static FC between the right lateral posterior thalamic nuclei and right inferior parietal lobule (IPL) compared with HC. Altered FC dynamics between the thalamic nuclei and several cortical areas were identified in PD-FOG, as shown by temporal dynamic FC analyses. Specifically, relative to PD-NFOG or HC, PD-FOG showed greater fluctuations in FC between the left intralaminar (IL) nuclei and right IPL and between the left medial geniculate and left postcentral gyrus. Furthermore, the dynamics of FC between the left pulvinar anterior nuclei and left inferior frontal gyrus were upregulated in both PD-FOG and PD-NFOG. The dynamics of FC between the right ventral lateral nuclei and left paracentral lobule were elevated in PD-NFOG but were maintained in PD-FOG and HC. The quantitative variability of FC between the left IL nuclei and right IPL was positively correlated with the clinical scales scores in PD-FOG. Conclusions: Dynamic FC between the thalamic nuclei and relevant associative cortical areas involved in sensorimotor integration or cognitive function was disrupted in PD-FOG, which was reflected by greater temporal fluctuations. Abnormal dynamic FC between the left IL nuclei of the thalamus and right IPL was related to the severity of FOG.

Keywords: Parkinson's disease; freezing of gait; functional connectivity; resting-state fMRI; thalamus.