Modulation of inhibitory synaptic plasticity for restoration of basal ganglia dynamics in Parkinson’s disease
Bibliographic record
Abstract
Abstract Introduction Parkinson’s disease is characterized, in part, by hypoactivity of both direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN), giving rise to disrupted basal ganglia circuit activity. In this study, we explored the use of intracranial stimulation for eliciting long-term potentiation (LTP) of each of these pathologically underactive inhibitory projections for the restoration of basal ganglia circuit dynamics and amelioration of motor symptoms. Methods Data were collected from a total of 31 people with Parkinson’s disease (42 hemispheres). During deep brain stimulation (DBS) surgery, we assessed microelectrode stimulation-induced changes to inhibitory evoked field potentials (fEP) and hand kinematics before versus after a 40-second train of high-frequency stimulation (HFS) in the GPi (n = 7, 11 sites at 100 Hz) and STN (n = 10, 14 sites at 100 Hz; n = 4, 7 sites at 180 Hz). Additionally, we assessed changes to beta oscillations and hand kinematics in people with chronic DBS implants in the GPi (n = 6 at 125 Hz) and STN (n = 4 at 180 Hz). Results Intraoperatively, increases in fEP amplitude (p = 0.002) and improved motor performance (p = 0.003) were observed after 100 Hz HFS in the GPi; while in STN, HFS did not potentiate fEPs (p = 0.589) or improve motor performance (p = 0.460) (similar results yielded for 180 Hz in STN). Similarly, extraoperative GPi-DBS produced suppression of beta power (p=0.096) and motor improvement (p = 0.077) before versus after HFS at 125 Hz; while STN-DBS at 180 Hz did not significantly affect beta power (p = 0.267) or motor performance (p=0.850). Interpretation Our findings support that LTP-like effects in GPi may produce motor improvements that extend beyond stimulation cessation, aligning with optogenetic studies showing long-lasting motor recovery through periodic D1-striatal activation in rodents. The lack of effects in STN suggests that stimulation paradigms may require optimization for effective LTP induction. These findings nevertheless highlight the potential of LTP-based strategies for sustained therapeutic benefits in Parkinson’s disease, warranting further investigation into periodic stimulation paradigms for optimizing DBS efficacy and side effect profiles.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".