Objective: To investigate the cognitive effects of low- (LFS) and very-low-frequency (VLFS) subthalamic deep brain stimulation (STN-DBS) in patients with Parkinson’s disease (PD).

Background: High-frequency (HFS) STN-DBS is an established therapy for motor symptoms in PD. However, axial symptoms often respond suboptimally, and the cognitive effects of DBS remain incompletely understood. Lower stimulation frequencies have recently gained attention due to their potential differential effects on motor and non-motor circuits.

Method: A systematic review and meta-analysis were conducted following a protocol registered in PROSPERO. Three databases (PubMed, Web of Science and EMBASE) were searched to identify studies assessing the cognitive impact of low-frequency STN-DBS. Eight cognitive domains were examined: verbal fluency, cognitive flexibility, executive control, working memory, attention, processing speed, episodic memory, and timing processing. Frequency conditions were categorized as VLFS (4-10 Hz), LFS (60-80 Hz), HFS (≥130 Hz), and stimulation OFF. Multilevel random-effects meta-analyses were performed to account for multiple outcomes within studies. Effect sizes were expressed as standardized mean differences (Hedges’ g).

Results: Twenty-one studies involving 355 patients (251 males) were included in the meta-analysis (mean sample size 16.9±4.7 patients, mean age 62.2±2.9 years, mean time after surgery 23.9±20.9 months). Compared with HFS, LFS and VLFS showed modest but significant improvements in verbal fluency and cognitive flexibility (Hedges’ g: 0.23 to 0.38). Comparisons with OFF stimulation showed that HFS was associated with worse verbal fluency (Hedges’ g: 0.16), whereas LFS and VLFS showed significantly better performance in this domain compared with OFF condition (Hedges’ g: 0.20). Executive control performance was better in the LFS and VLFS condition compared with OFF stimulation (Hedges’ g: 0.37). Differences in other cognitive domains were non-significant.

Conclusion: As a key multifunctional node, the STN contributes to both motor and non-motor processes. Lower frequency STN-DBS appears to better preserve cognitive function and possibly cognitive-motor interactions in PD, supporting that besides stimulation topography, frequency modulation can be a potential strategy to optimize DBS outcomes beyond motor control.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-effects-of-low-frequency-stn-dbs-in-parkinsons-disease-a-systematic-review-and-meta-analysis/