Spectral characteristics of subthalamic nucleus local field potentials in Parkinson's disease: Phenotype and movement matter.

Parkinson's disease (PD) is clinically heterogeneous across patients and may be classified in three motor phenotypes: tremor dominant (TD), postural instability and gait disorder (PIGD), and undetermined. Despite the significant clinical characterization of motor phenotypes, little is known about how electrophysiological data, particularly subthalamic nucleus local field potentials (STN-LFP), differ between TD and PIGD patients. This is relevant since increased STN-LFP bandpower at α-ß range (8-35 Hz) is considered a potential PD biomarker and, therefore, a critical setpoint to drive adaptive deep brain stimulation. Acknowledging STN-LFP differences between phenotypes, mainly in rest and movement states, would better fit DBS to clinical and motor demands. We studied this issue through spectral analyses on 35 STN-LFP in TD and PIGD patients during rest and movement. We demonstrated that higher ß2 activity (22-35 Hz) was observed in PIGD only during rest. Additionally, bandpower differences between rest and movement occurred at the α-ß range, but with different patterns as per phenotypes: movement-induced desynchronization concerned lower frequencies in TD (10-20 Hz) and higher frequencies in PIGD patients (21-28 Hz). Finally, when supervised learning algorithms were employed aiming to discriminate PD phenotypes based on STN-LFP bandpower features, movement information had improved the classification accuracy, achieving peak performances when TD and PIGD movement-induced desynchronization ranges were considered. These results suggest that STN-LFP ß-band encodes phenotype-movement dependent information in PD patients.

Subthalamic low beta bursts differ in Parkinson's disease phenotypes.

OBJECTIVE: Parkinson's disease (PD) patients may be categorized into tremor-dominant (TD) and postural-instability and gait disorder (PIGD) motor phenotypes, but the dynamical aspects of subthalamic nucleus local field potentials (STN-LFP) and the neural correlates of this phenotypical classification remain unclear. METHODS: 35 STN-LFP (20 PIGD and 15 TD) were investigated through continuous wavelet transform and machine-learning-based methods. The beta oscillation - the main band associated with motor impairment in PD - dynamics was characterized through beta burst parameters across phenotypes and burst intervals under specific proposed criteria for optimal burst threshold definition. RESULTS: Low-frequency (13-22 Hz) beta burst probability was the best predictor for PD phenotypes (75% accuracy). PIGD patients presented higher average burst duration (p = 0.018), while TD patients exhibited higher burst probability (p = 0.014). Categorization into shorter and longer than 400 ms bursts led to significant interaction between burst length categories and the phenotypes (p < 0.050) as revealed by mixed-effects models. Long burst durations and short bursts probability positively correlated, respectively, with rigidity-bradykinesia (p = 0.029) and tremor (p = 0.038) scores. CONCLUSIONS: Subthalamic low-frequency beta bursts differed between TD and PIGD phenotypes and correlated with motor symptoms. SIGNIFICANCE: These findings improve the PD phenotypes' electrophysiological characterization and may define new criteria for adaptive deep brain stimulation.