Bilateral Subthalamic Nucleus Theta-Frequency Stimulation Improves Hippocampal-Based Verbal Fluency in Patients with Parkinson's Disease A Double-Blinded Randomized Crossover Trial

• Published in: Neurosurgery Vol. 67; no. Supplement_1
• Main Authors: Lam, Jordan, Williams, Marcus, Mark, Catherine, Lee, Justin, Petkus, Andrew, Lee, Brian, Liu, Charles Y, Lee, Darrin J
• Format: Journal Article
• Language: English
• Published: Philadelphia Wolters Kluwer Health, Inc 01.12.2020
• Subjects: Cognition & reasoning; Neurosurgery; Parkinson's disease; Phonetics; Surgical techniques
• ISSN: 0148-396X; 1524-4040
• DOI: 10.1093/neuros/nyaa447_608

INTRODUCTION Cognitive outcomes following deep brain stimulation (DBS) in Parkinson's disease (PD) have gained much attention with particular concern for verbal fluency. Current stimulation paradigms utilize high (gamma) frequency stimulation for optimal motor benefits; however, little work has been done to optimize stimulation parameters for cognition. Recent evidence implicates a role of subthalamic nucleus (STN) low (theta) frequency oscillations in cognition and suggests that theta-frequency stimulation could improve cognition in PD. METHODS Twelve patients with bilateral STN DBS for PD underwent a double-blinded, randomized neuropsychological evaluation during stimulation at (1) 130–135Hz (gamma), (2) 10Hz (theta) and (3) off. Processing speed, verbal fluency, and executive functions were evaluated using the Delis-Kaplan Executive Function System Verbal Fluency, Color-Word Interference Test and random number generation task. Performance at each stimulation frequency was compared within subjects. Preoperative (mean 4.7 months) scores were compared to postoperative (mean 11 months) scores. RESULTS Hippocampal-based (autobiographical and spatial) verbal fluency differed significantly between stimulation frequencies (P = .04). Post-hoc testing revealed improved performance during 10Hz versus 130Hz stimulation (P = .02) and a trend towards worse performance during 130Hz stimulation versus off stimulation (P = .09). There were no significant differences between stimulation frequencies in phonetic or semantic verbal fluency, color-word interference or random number generation (P > .05). Comparing preoperative to postoperative scores, there was a trend towards improved color-word switching postoperatively (p = .08), but no differences in color-word reading/inhibition, phonetic verbal fluency, or category switching (P > .05). CONCLUSION Our study is the first to show improved hippocampal-based verbal fluency during theta versus gamma-frequency stimulation, corroborating a role of STN theta oscillations in cognition. Further work is needed to explore if theta-frequency stimulation can be interleaved with gamma-frequency stimulation to improve both motor and cognitive outcomes.