Thalamic-limbic circuit dysfunction and white matter topological alteration in Parkinson's disease are correlated with gait disturbance.

ABSTRACT

Background: Limbic structures have recently garnered increased attention in Parkinson's disease (PD) research. This study aims to explore changes at the whole-brain level in the structural network, specifically the white matter fibres connecting the thalamus and limbic system, and their correlation with the clinical characteristics of patients with PD. Methods: Between December 2020 and November 2021, we prospectively enrolled 42 patients with PD and healthy controls at the movement disorder centre. All participants underwent diffusion tensor imaging (DTI), 3D T1-weighted imaging (3D-T1WI), and routine brain magnetic resonance imaging on a 3.0 T MR scanner. We employed the tract-based spatial statistical (TBSS) analytic approach, examined structural network properties, and conducted probabilistic fibre tractography to identify alterations in white matter pathways and the topological organisation associated with PD. Results: In patients with PD, significant changes were observed in the fibrous tracts of the prefrontal lobe, corpus callosum, and thalamus. Notably, the fibrous tracts in the prefrontal lobe and corpus callosum showed a moderate negative correlation with the Freezing of Gait Questionnaire (FOG-Q) scores (r = -0.423, p = 0.011). The hippocampus and orbitofrontal gyrus exhibited more fibre bundle parameter changes than other limbic structures. The mean streamline length between the thalamus and the orbitofrontal gyrus demonstrated a moderate negative correlation with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (r = -0.435, p = 0.006). Topological parameters, including characteristic path length (L p), global efficiency (E g), normalised shortest path length (λ) and nodal local efficiency (N le), correlated moderately with the MDS-UPDRS, HAMA, MoCA, PDQ-39, and FOG-Q, respectively. Conclusion: DTI is a valuable tool for detecting changes in water molecule dispersion and the topological structure of the brain in patients with PD. The thalamus may play a significant role in the gait abnormalities observed in PD.