Arousal as a universal embedding for spatiotemporal brain dynamics

Abstract

Neural activity in awake organisms shows widespread, spatiotemporally diverse correlations with behavioural and physiological measurements^1-4. We propose that this covariation reflects in part the structured, nonlinear dynamics of an underlying arousal-related process that organizes brain-wide and body-wide physiology on the timescale of seconds. By framing this interpretation within dynamical systems theory, we arrive at a surprising prediction: a single, scalar measurement of arousal (for example, pupil diameter) should suffice to reconstruct the continuous evolution of multidimensional, spatiotemporal measurements of large-scale brain physiology. Here, to test this hypothesis, we perform multimodal cortex-wide optical imaging⁵ and behavioural monitoring in awake mice. We demonstrate that the seconds-scale spatiotemporal dynamics of neuronal calcium, metabolism and brain blood oxygen can be accurately and parsimoniously modelled from a low-dimensional, nonlinear manifold reconstructed from a time delay embedding^6,7 of pupil diameter. Extending this framework to behavioural and electrophysiological measurements from the Allen Brain Observatory⁸, we demonstrate the ability to integrate diverse experimental data into a unified generative model via mappings from a shared arousal manifold. Our results support the hypothesis⁹ that spontaneous, spatially structured fluctuations in brain-wide physiology on timescales of seconds-widely interpreted to reflect regionally specific neural communication^10,11-are in large part expressions of a low-dimensional, organism-wide dynamical system. In turn, reframing arousal itself as a latent dynamical system offers a new perspective on fluctuations in brain, body and behaviour observed across modalities, contexts and scales.