A computational framework for fitting biophysical basal-ganglia network models, applied to Parkinsonian beta...

Objective.Fitting biophysically detailed spiking-network models to data is constrained by computational cost: simulating thousands of coupled conductance-based neurons at sub-millisecond time steps makes large parameter searches impractical on conventional hardware, so circuit-level models have relied on manual tuning, reduced neuron formalisms, or modest network sizes. We present an integrated pipeline that makes automated, data-driven fitting of such models tractable on a single cloud graphics processing unit (GPU).Approach.The pipeline couples a just-in-time (JIT) compiled implementation of a biophysically detailed subthalamic-pallidal (STN, GPe, GPi) network in JAX with covariance-matrix-adaptation evolution strategy black-box optimization under Optuna, and a fixed-indegree connectivity scheme so that fitted configurations transfer across network sizes. Because fitting is inexpensive, each configuration is reported with its sensitivity to search bounds, loss weights, optimizer seeds, neuronal heterogeneity, and connectivity density.Main results.On an NVIDIA L4 GPU, JIT compilation and kernel fusion accelerate a 450-neuron simulation by approximately 736-fold over the same model run as an un-jitted Python loop, with a further twofold from GPU over an 8-core CPU. A 1000-trial optimization completes in roughly 17 min, and a fitted configuration transfers across a hundredfold range of network size for less than a twofold increase in wall time. Applied to firing-rate, coefficient-of-variation, and beta-band targets from the MPTP-primate parkinsonism literature, the pipeline recovers a parkinsonian configuration whose subthalamic beta power peaks near 29 Hz and is highly elevated relative to healthy. The probes separate a data-constrained increase in STN-to-GPe excitatory weight, robust under a symmetric-bounds control, from a prior-constrained reduction in GPe-to-STN inhibitory weight that reverses when bounds are made symmetric.Significance.The pipeline is an accessible, transparent tool for fitting biophysically detailed network models, turning parameter identifiability into a routine output; the basal ganglia result is a proof-of-concept rather than a mechanistic claim about pathological beta.