Dual Oscillatory Signatures in Pallidal Circuits Underlie Symptom Complexity in Huntington's Disease Patients

BACKGROUND: Huntington's disease (HD) presents a unique clinical challenge with coexisting hyperkinetic and hypokinetic symptoms, yet the underlying neural oscillatory mechanisms remain poorly understood. OBJECTIVE: The aim of this study was to characterize pathological pallidal neural activity in HD and identify biomarkers for therapeutic optimization. METHODS: We investigated pallidal oscillatory patterns in 15 patients with HD undergoing deep brain stimulation, recording video-synchronized local field potentials during symptom fluctuations and comparing findings with patients with Parkinson's disease and dystonia. RESULTS: HD exhibited distinct pallidal oscillatory signatures that differed from PD and dystonia. Theta power (2-8 Hz) increased during hyperkinetic states, whereas high beta power (20-30 Hz) elevated during hypokinetic states, both correlating significantly with clinical symptom severity. These patterns were not modulated by voluntary movement. Electrophysiological connectivity analysis integrated with neuroimaging analysis showed that globus pallidum externus-globus pallidus internus theta coherence correlated with indirect pathway structural connectivity, whereas pallidal high beta power associated with direct pathway functional connectivity, reflecting HD's dual circuit pathology. Spatial mapping localized theta oscillations to the posterior globus pallidus, with fibers projecting to motor cortical areas. CONCLUSIONS: We establish an electrophysiological framework explaining HD's complex symptomatology through dual oscillatory signatures. These findings provide circuit-specific biomarkers for disease monitoring and anatomical targets for optimizing deep brain stimulation in patients with HD. © 2026 International Parkinson and Movement Disorder Society.