Cognitive and Emotional Determinants of Subthalamic Oscillations During Freezing While Turning in Parkinson's Disease.

Freezing of gait (FoG) in Parkinson's disease (PD) is a disabling phenomenon that, beyond motor impairment, involves cognitive and emotional processes. However, their unique mechanisms and contributions to FoG remain unclear. In this study, we examined whether the severity of cognitive and emotional symptoms was associated with subthalamic nucleus (STN) oscillatory activity during freezing while turning. Local field potentials (LFPs) were recorded from the STN of 13 individuals with PD during both effective turning and freezing while turning. Given that the modulation of STN-LFPs during cognitive processing predominantly occurs within low-frequency bands, we applied linear mixed-effects models to assess associations between band-specific power during FoG and cognitive performance, measured by the Montreal Cognitive Assessment, as well as anxiety and depressive symptoms, assessed using the Hospital Anxiety and Depression scale. The specificity of these associations was evaluated through additional control analyses that used effective turning instead of freezing while turning. Subthalamic theta power during FoG while turning was positively associated with anxiety severity and negatively associated with MoCA scores, indicating higher theta power in more anxious and cognitively impaired individuals during turn-induced FoG. These findings were specific to FoG while turning, since there was no association between theta and other symptom domains such as depressive symptoms or any of the symptom domains during effective turning. No significant associations were detected with alpha or beta band activity. These findings demonstrate a selective association between anxiety, cognitive impairment, and subthalamic theta activity during FoG while turning, supporting a role for theta band oscillations in cognitive-affective contributions in PD FoG. Further, they add to prior evidence implicating long-range cortico-subthalamic theta synchronization in cognitive control and highlight the negative effects of anxiety on executive function in PD patients with FoG. Therefore, future research should examine whether interventions targeting cognitive control or anxiety may have an influence on theta oscillations and related FoG severity.