Lauren H. Hammer, Stephanie Cernera, Carina R. Oehrn, Jiaang Yao, Maria Shcherbakova, Amelia G. Hahn, Simon Little, Philip Starr
BACKGROUND: Adaptive deep brain stimulation (aDBS) using subthalamic nucleus (STN) beta-band oscillations as a biomarker for the akinetic-rigid symptoms of Parkinson's disease has been proposed to improve the efficacy of stimulation and decrease adverse effects. However, most studies validating STN beta oscillations as a biomarker used perioperative, off medication, and OFF stimulation conditions, limiting their potential relevance to real-world aDBS deployment. OBJECTIVE: We evaluated how stimulation and dopaminergic medication affect beta-range STN oscillatory activity and its ability to predict the hypokinetic parkinsonian state. METHODS: In six patients with Parkinson's disease who experienced residual levodopa-related motor fluctuations despite standard-of-care DBS, we studied medication cycle-induced fluctuations of peak STN beta oscillation power during active DBS. We evaluated the magnitude of beta oscillation fluctuations, the frequency of peak beta activity, and the ability to predict the off medication state. Neural signals were collected in the clinic during a medication challenge and at home during naturalistic medication cycles. RESULTS: Medication-induced beta oscillation fluctuations were smaller in the presence of therapeutic DBS compared with when the stimulator was off (P = 0.008). Therapeutic stimulation also decreased the frequency of peak beta activity (P < 0.001). As a result, the beta frequencies with the highest power in the OFF stimulation/off medication state were less accurate than other beta-range bands at predicting the patient's off medication state during active stimulation (P = 0.02). CONCLUSIONS: The spectral characteristics of STN beta oscillations and their performance as a biomarker in aDBS for Parkinson's disease are influenced by the stimulation and medication conditions in which it is implemented. © 2026 International Parkinson and Movement Disorder Society.