Local and long-range input balance: A framework for investigating frontal cognitive circuit maturation in health and disease | Science Advances

Frontal cortical circuits undergo prolonged maturation across childhood and adolescence; however, it remains unknown what specific changes are occurring at the circuit level to establish adult cognitive function. With the recent advent of circuit dissection techniques, it is now feasible to examine circuit-specific changes in connectivity, activity, and function in animal models. Here, we propose that the balance of local and long-range inputs onto frontal cognitive circuits is an understudied metric of circuit maturation. This review highlights research on a frontal-sensory attention circuit that undergoes refinement of local/long-range connectivity, regulated by circuit activity and neuromodulatory signaling, and evaluates how this process may occur generally in the frontal cortex to support adult cognitive behavior. Notably, this balance can be bidirectionally disrupted through various mechanisms relevant to psychiatric disorders. Pharmacological or environmental interventions to normalize or reset the local and long-range balance could hold great therapeutic promise to prevent or rescue cognitive deficits.