Objective: To evaluate the feasibility and preliminary effects of theta-burst stimulation (TBS) on motor function and verbal fluency in Parkinson’s disease (PD) patients with subthalamic nucleus (STN) deep brain stimulation (DBS). We hypothesized that 1-2 hours of TBS would provide comparable motor symptom control with improved cognition, compared to conventional continuous DBS (cDBS), as measured by UPDRS-III and verbal fluency.

Background: Parkinson’s disease (PD) is marked by progressive motor and cognitive dysfunction. STN cDBS is an effective treatment for motor symptoms in PD but may result in executive dysfunction. TBS, a patterned DBS paradigm with bursts of high-frequency pulses at theta frequency intervals, has emerged as a potential cognition-sparing alternative. TBS may enhance cognition by modulating broad frontal cortical networks, however its effects on motor function and cognition in PD remain uncertain (1–4).

Method: This was a pilot, randomized, double-blinded, within-subject crossover study. Fifteen PD patients with previously optimized STN DBS underwent testing under three conditions: (1) baseline cDBS, (2) TBS (200Hz intraburst frequency, 5Hz cycling, adjusted for energy (TEED)), and (3) OFF stimulation. Primary outcomes were motor function assessed using the MDS-UPDRS III, and verbal fluency across autobiographical, spatial, semantic, and phonemic categories (5,6). The secondary outcome was average TEED across subjects. Statistical comparisons were made using repeated measures ANOVA and paired t-tests, with Benjamini-Hochberg correction for false discovery rate (FDR = 0.05).

Results: TBS provided motor symptom control comparable to cDBS, with no significant differences in MDS-UPDRS III scores between conditions (cDBS: 22.5 ± 10.8 vs. TBS: 22.7 ± 11.2, p = 0.87). Despite TBS requiring amplitude adjustments in some tremor-dominant patients, average TEED was lower for TBS compared to cDBS (TBS:cDBS ratio = 0.87, p < 0.0001). Overall cognitive outcomes were similar, although autobiographical fluency showed a significant improvement after prolonged TBS compared to baseline (9.4 vs. 18 words, p = 0.047).

Conclusion: TBS may offer comparable motor control to cDBS with lower TEED while enhancing autobiographical verbal fluency. Larger, long-term trials of TBS are justified to confirm its efficacy, safety, and role as a cognition-sparing cDBS alternative in PD management.

Figure 1.

References: 1. Horn MA, Gulberti A, Gülke E, Buhmann C, Gerloff C, Moll CKE, et al. A new stimulation mode for deep brain stimulation in Parkinson’s disease: Theta burst stimulation. Mov Disord. 2020 Aug;35(8):1471–5.
2. Lam J, Lee J, Williams M, Cohn M, Wilson M, Mark C, et al. Cognitive effects of theta frequency bilateral subthalamic nucleus stimulation in Parkinson’s disease: A pilot study. Brain Stimul. 2021 Mar;14(2):230–40.
3. Lee DJ, Drummond NM, Saha U, De Vloo P, Dallapiazza RF, Gramer R, et al. Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson’s disease. Brain Stimul. 2021 Jul;14(4):754–60.
4. Wong JK, Hu W, Barmore R, Lopes J, Moore K, Legacy J, et al. Safety and tolerability of burst-cycling deep brain stimulation for freezing of gait in Parkinson’s disease. Front Hum Neurosci. 2021 Apr 26;15:651168.
5. Ryan L, Cox C, Hayes SM, Nadel L. Hippocampal activation during episodic and semantic memory retrieval: comparing category production and category cued recall. Neuropsychologia. 2008 Mar 18;46(8):2109–21.
6. Sheldon S, McAndrews MP, Pruessner J, Moscovitch M. Dissociating patterns of anterior and posterior hippocampal activity and connectivity during distinct forms of category fluency. Neuropsychologia. 2016 Sep;90:148–58.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/theta-burst-subthalamic-deep-brain-stimulation-for-parkinsons-disease-a-pilot-study-of-motor-and-cognitive-effects/