An in silico cortico-basal ganglia-thalamic testbed for comparing visual and deep brain stimulation in Parkinson’s disease
TL;DR
Findings show persistence across the tested dose, GPi→TC, and three-parameter local domains but do not establish evoked relay fidelity, global parameter robustness, biological mechanisms, or clinical efficacy.
Abstract
Deep brain stimulation (DBS) is an established intervention for Parkinson’s disease (PD), whereas the network-level effects of prescribed periodic visual input implemented with 10 Hz base pulses remain uncertain. We developed a conductance-based cortico-basal ganglia-thalamic (CBT) model comprising 11 Hodgkin-Huxley neuronal populations and a prescribed periodic visual-input unit (RET) to compare 130 Hz subthalamic nucleus (STN) DBS with the archived periodic visual-input condition on the same calibrated PD network. Primary conditions used N = 10 independent runs each. Additional analyses included an unpaired 0–5 mA/cm 2 DBS-amplitude series, a matched-seed internal-globus-pallidus-to-thalamocortical-relay (GPi→TC) sensitivity analysis at 0.8, 1.0, and 1.2 × nominal coupling ( N = 10 per scale), and a matched-seed three-parameter ±20% local sensitivity analysis ( N = 5 per parameter-condition cell). DBS reduced the model-internal STN synaptic-current beta measure from 0.0184 ± 0.0060 to 0.0018 ± 0.0004 a.u. (Holm-corrected p = 1.1 × 10 –5 ), whereas periodic visual input increased thalamocortical relay (TC) and reticular thalamic (RE) firing and enhanced cortical pyramidal (PY) gamma (30–80 Hz) and narrowband 38–42 Hz power. Cortical PY firing was 4.86 ± 0.84 Hz in PD, 5.28 ± 0.87 Hz with DBS ( p = 0.285 versus PD), and 10.33 ± 0.85 Hz with periodic visual input (Holm-corrected p = 1.18 × 10 –10 versus PD). The ampltude series showed a non-monotonic STN response at 1 mA/cm 2 ; from 2 to 5 mA/cm 2 , mean STN beta values occupied a narrow range of 0.00186–0.00212 a.u. In the GPi→TC analysis, TC spontaneous firing remained 0 Hz in 30/30 runs, and all 750,000 saved voltage samples were finite and subthreshold (–72.06 to –54.74 mV; no 0-mV crossings). Across the three-parameter analysis, DBS raw STN-beta suppression remained 88.9%–95.8%, and periodic visual input increased TC firing 3.70–4.29-fold relative to nominal PD. These findings show persistence across the tested dose, GPi→TC, and three-parameter local domains but do not establish evoked relay fidelity, global parameter robustness, biological mechanisms, or clinical efficacy.