Subthalamic Nucleus Deep Brain Stimulation Enhanced Long-Latency Reflex II in Parkinson's Disease Through Rapid Subthalamic-Cortical Modulation.
TL;DR
LLR II was modulated by clinically effective STN-DBS parameters but was insensitive to dopaminergic medication, supporting its utility as a biomarker of DBS-related sensorimotor circuit modulation, potentially involving the hyperdirect pathway.
Abstract
Background
The long-latency reflex (LLR), particularly LLR II elicited by peripheral stimulation, is considered a transcortical reflex and may reflect cortical-subcortical excitability. Its relevance as a biomarker for subthalamic nucleus deep brain stimulation (STN-DBS) optimization in Parkinson's disease remains unclear.
Objective
To examine whether LLR II responses are modulated by STN-DBS stimulation parameters and dopaminergic medication, and to explore the potential mechanisms underlying STN-DBS-related motor improvement.
Methods
Thirteen Parkinson's disease patients with STN-DBS underwent median nerve stimulation to assess LLR II, quantified as the peak abductor pollicis brevis electromyography (EMG) response at 50-70 ms, normalized to prestimulus baseline EMG, across different stimulation intensities, contacts, and frequency conditions, including 60 Hz, 130 Hz, and an energy-matched condition. A single DBS pulse was also paired with the cortical N20 response at N20 - 2 ms (T1) or N20 + 10 ms (T2) to assess timing-dependent effects. Sixteen Parkinson's disease patients without DBS were tested in medication-on and -off states. Motor severity was assessed using tested-side Unified Parkinson's Rating Scale Part III (UPDRS III) subscores.
Results
LLR II ratio was higher at 70% and 100% of clinical stimulation intensity than during DBS-off (P = 0.0029 and P = 0.042, respectively). LLR II was higher at the most effective than at the least-effective contact (P = 0.042). The clinically most-effective frequency showed higher LLR II than DBS-off and the least-effective frequency (both P = 0.048). In the single-pulse DBS experiment, LLR II increased only at T2 compared to DBS-off (P = 0.047). No medication-state difference was observed.
Conclusions
LLR II was modulated by clinically effective STN-DBS parameters but was insensitive to dopaminergic medication, supporting its utility as a biomarker of DBS-related sensorimotor circuit modulation, potentially involving the hyperdirect pathway. © 2026 International Parkinson and Movement Disorder Society.