A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback

During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence of neural fluctuations, across the brain, on closed-loop brain/body/environment interactions strongly supporting the idea that brain function cannot be fully understood through open-loop approaches alone.Author summary: Animals actively exploring or interacting with their surroundings must process a cyclical flow of information from the environment through sensory receptors, the central nervous system, the musculoskeletal system and back to the environment. This closed-loop sensorimotor system is essential for an animal's ability to adapt and survive in complex environments. Importantly, closed loop feedback signals also regulate brainwide neural circuits for behavior. Specifically, the activity of coherent populations of neurons inform motor behaviours and in turn are influenced by sensory feedback signals mediated by the environment. We develop a theory that suggests that this feedback can explain the marked changes in large-scale neural dynamics and sensory processing (together referred to as brain state) that coincide with the onset of active behaviours. This feedback may contribute to flexible context dependent neural computations in brain systems.