Closed-loop neuromodulation for studying spontaneous activity and causality

Having established that spontaneous brain activity follows meaningful coactivation patterns and correlates with behavior, researchers have turned their attention to understanding its function and behavioral significance. We suggest closed-loop neuromodulation as a neural perturbation tool uniquely well suited for this task. Closed-loop neuromodulation has primarily been viewed as an interventionist tool to teach subjects to directly control their own brain activity. We examine an alternative operant conditioning model of closed-loop neuromodulation which, through implicit feedback, can manipulate spontaneous activity at the network level, without violating the spontaneous or endogenous nature of the signal, thereby providing a direct test of network causality.