Large-scale, closed-loop interrogation of neural circuits underlying cognition

Cognitive functions are increasingly understood to involve coordinated activity patterns between multiple brain regions, and their disruption by neuropsychiatric disorders is similarly complex. Closed-loop neurostimulation can directly modulate neural signals with temporal and spatial precision. How to leverage such an approach to effectively identify and target distributed neural networks implicated in mediating cognition remains unclear. We review current conceptual and technical advances in this area, proposing that devices that enable large-scale acquisition, integrated processing, and multiregion, arbitrary waveform stimulation will be critical for mechanistically driven manipulation of cognitive processes in physiological and pathological brain networks.