Kavli Affiliate: Philip Starr
| Authors: Abhinav Sharma, Bahman Abdi Sargezeh, Amelia Hahn, Maria Shcherbakova, Wolf Julian Neumann, Simon Little, Philip Starr and Ashwini Oswal
| Summary:
Background: Bradykinesia in Parkinson′s disease (PD) may arise due to transient, network–wide neural dynamics that extend beyond beta–band oscillatory activity within the motor cortical-subthalamic nucleus (STN) circuit. Methods: We address this question by using Hidden Markov Models (HMMs) to identify neural states from chronic motor cortical and STN recordings in five PD patients (1,046 hours from 10 hemispheres), with concurrent measurements of bradykinesia using wearable sensors. Findings: We identified four neural states with distinct spectral and temporal features. Two states exhibited spectral signatures—particularly STN low and high gamma, STN delta/alpha, cortical beta, and cortico-STN beta coherence—that predicted worsening bradykinesia. However, STN beta power alone was not consistently predictive, challenging traditional beta-centric views. These states also displayed compensatory features associated with bradykinesia amelioration, including cortical delta/alpha activity, cortical high gamma, and cortico–STN high gamma coherence. Two additional states affected bradykinesia through temporal rather than spectral properties. Prolonged lifetimes of one of these state worsened symptoms, whereas increased occurrences of another, marked by local beta without cortico–STN beta coherence, improved motor function. Interpretation: Our findings highlight the multidimensional nature of bradykinesia and suggest that state-aware, adaptive interventions targeting state features—rather than single frequency bands—may offer new opportunities for improved deep brain stimulation in PD. Keywords: Hidden Markov Model (HMM), Neural states, Bradykinesia, Parkinson′s disease