Quantifying the influence of stimulation protocols on neural network connectivity inference to optimize rapid network measurements.

Connectivity is key to understanding neural circuit computations. However, estimating in vivo connectivity using recording of activity alone is challenging. Issues include common input and bias errors in inference, and limited temporal resolution due to large data requirements. Perturbations (e.g. stimulation) can improve inference accuracy and accelerate estimation. However, optimal stimulation protocols for rapid network estimation are not yet established. Here, we use neural network simulations to identify stimulation protocols that minimize connectivity inference errors when using generalized linear model inference. We find that stimulation parameters that balance excitatory and inhibitory activity minimize inference error. We also show that pairing optimized stimulation with adaptive protocols that choose neurons to stimulate via Bayesian inference may ultimately enable rapid network inference.