Freezing of Gait: A Tribute to Nir Giladi.

Freezing of gait (FoG) is frequently triggered during gait initiation, a transition that depends on anticipatory postural adjustments (APAs). However, the neuroanatomical substrates linking brain morphometry to APA control during step initiation in FoG remain unclear. We investigated whether subcortical volumes and cortical thickness in motor-cognitive regions relate to APA features and clinical severity. Forty-four right-handed individuals with midstage PD (26 PD + FoG; 18 PD - FoG) performed step initiation. FreeSurfer-derived regional volumes and cortical thickness were extracted. Associations between morphometry and APA metrics were tested across all participants and within groups. Group differences were tested using the Mann-Whitney U tests, and partial Spearman correlations examined morphometry-clinical and morphometry-APA associations, controlling for UPDRS-III and daily levodopa dose. Compared with PD without FoG, the PD + FoG group showed higher UPDRS-III scores and levodopa doses, lower APA mediolateral amplitudes, and larger amygdala volumes. Across all participants, longer APA duration was associated with smaller putamen, thalamus, and dorsolateral prefrontal cortex volumes, whereas greater APA mediolateral amplitude was associated with lower frontopolar cortical thickness. In PD + FoG, freezing severity and APA features were associated with distinct morphometric patterns across the basal ganglia, thalamus, prefrontal, cingulate, SMA, and insular regions. These findings suggest that gait initiation impairment in PD reflects distributed morphometric alterations rather than a single regional substrate. APA measures may provide mechanistically relevant biomechanical markers for identifying neural systems involved in FoG.