Arousal as a universal embedding for spatiotemporal brain dynamics
Neural activity in awake organisms shows widespread, spatiotemporally diverse correlations with behavioural and physiological measurements<sup>1-4</sup>. 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 imaging<sup>5</sup> 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<sup>6,7</sup> of pupil diameter. Extending this framework to behavioural and electrophysiological measurements from the Allen Brain Observatory<sup>8</sup>, 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 hypothesis<sup>9</sup> that spontaneous, spatially structured fluctuations in brain-wide physiology on timescales of seconds-widely interpreted to reflect regionally specific neural communication<sup>10,11</sup>-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.
Authors
- Jin‐Moo Lee (ORCID: https://orcid.org/0000-0002-3979-0906)
- Ryan V. Raut (ORCID: https://orcid.org/0000-0002-8761-1431)
- Bingni W. Brunton (ORCID: https://orcid.org/0000-0002-4831-3466)
- Marcus E. Raichle (ORCID: https://orcid.org/0000-0002-1847-9588)
- Zhanqi Zhang (ORCID: https://orcid.org/0000-0003-0594-6375)
- Steven L. Brunton (ORCID: https://orcid.org/0000-0002-6565-5118)
- Zachary P. Rosenthal (ORCID: https://orcid.org/0000-0001-8787-0858)
- Hanyang Miao (ORCID: https://orcid.org/0000-0001-5757-859X)
- J. Nathan Kutz (ORCID: https://orcid.org/0000-0002-6004-2275)
- Xiaodan Wang (ORCID: https://orcid.org/0000-0003-1675-3552)
- Adam Q. Bauer (ORCID: https://orcid.org/0000-0002-8364-3209)
Institutions
- University of Washington (US)
- Washington University in St. Louis (US)
- University of California San Diego (US)
- Mallinckrodt (United States) (US)
- University of Washington Applied Physics Laboratory (US)
- Allen Institute (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1038/s41586-025-09544-4
- Citations
- 17
- Primary Topic
- Neural dynamics and brain function
- Type
- article
- Field-Weighted Citation Impact
- 24.33