Objective: To characterize the subcortical grey matter adaptations related to Freezing of Gait in Parkinson’s Disease (PD).

Background: Owing to its connections with motor, cognitive and limbic areas, the basal ganglia circuitry may be at the heart of Freezing of Gait (FOG), as suggested by the most recent pathophysiological models[1]. Previous studies failed to capture the precise subcortical adaptations associated with FOG. Hence, we investigated whether the morphology of subcortical nuclei differentiated between freezers and non-freezers and predicted FOG conversion.

Methods: Vertex-based grey matter analysis was performed on high-resolution T1-weighted MR images of 57 PD patients (36 Non-Freezers, 21 Freezers) and 19 age-matched controls. Fifteen structures were segmented using FMRIB’s integrated registration and segmentation tool (FIRST)[2]. Local volumes were assessed by vertex analysis and nonparametric permutation. Participants underwent extensive motor and cognitive assessments and were classified with the New Freezing of Gait Questionnaire (NFOG-Q) when scanned and two years later.

Results: Freezers (12 Freezers at baseline, 9 Converters) showed local expansions at dorsomedial aspect of Right and Left Thalamus compared to Controls (Pmax: 0.009; Pmax: 0.04) and Non-Freezers (Pmax: 0.015; Pmax: 0.015) and local contractions in the head of the Right Caudate compared to Non-Freezers (Pmax: 0.05). At baseline, extent of Right Thalamus expansion and Right Caudate contraction predicted conversion to FOG with AUC of 85.8%. Thalamus expansions also correlated with better performance on the Frontal Assessment Battery (FAB) (r = 0.58, P=0.009), Trail Making Test (Part B: r = -0.63, P=0.003) and timed auditory Stroop while turning (r = -0.64, P=0.009). Within the PD subgroup, baseline Freezers also showed local expansions in the tail of the Right Caudate compared to Non-Freezers (P=0.013) and Converters (P=0.032). The extent of these expansions were associated with worse FAB (r = -0.46, P<0.001), MOCA (r = -0.39, P=0.011), MiniBEST scores (r = -0.47, P<0.001) and with longer freezing at gait initiation (NFOG-Q q6) (r = 0.71, P=0.021).

Conclusions: Local volume changes in Thalamic and Caudate nuclei discriminate between cohorts with and without FOG and predict the conversion to FOG in PD. The maladaptive changes seen in the Caudate further implicate its role in Freezing.

References: 1. Ehgoetz Martens KA, Hall JM, Georgiades MJ, Gilat M, Walton CC, Matar E, et al. The functional network signature of heterogeneity in freezing of gait. Brain [Internet]. 2018; Available from: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awy019/4850500. 2. Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage [Internet]. Elsevier Inc.; 2011;56:907–22. Available from: http://dx.doi.org/10.1016/j.neuroimage.2011.02.046.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alteration-to-basal-ganglia-morphology-in-freezing-of-gait-in-parkinsons-disease/