An in silico cortico-basal ganglia-thalamic testbed for comparing visual and deep brain stimulation in Parkinson's...

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/cm² 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/cm²; from 2 to 5 mA/cm², 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.