Raut Ryan V, Rosenthal Zachary P, Wang Xiaodan, Miao Hanyang, Zhang Zhanqi, Lee Jin-Moo, Raichle Marcus E, Bauer Adam Q, Brunton Steven L, Brunton Bingni W, Kutz J Nathan
Allen Institute, Seattle, WA, USA.
Department of Physiology & Biophysics, University of Washington, Seattle, WA, USA.
Nature. 2025 Sep 24. doi: 10.1038/s41586-025-09544-4.
Neural activity in awake organisms shows widespread, spatiotemporally diverse correlations with behavioural and physiological measurements. 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 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 of pupil diameter. Extending this framework to behavioural and electrophysiological measurements from the Allen Brain Observatory, 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 that spontaneous, spatially structured fluctuations in brain-wide physiology on timescales of seconds-widely interpreted to reflect regionally specific neural communication-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.
清醒生物体中的神经活动与行为和生理测量结果呈现出广泛的、时空多样的相关性。我们提出，这种共变部分反映了一个潜在的与觉醒相关过程的结构化、非线性动力学，该过程在数秒的时间尺度上组织全脑和全身的生理活动。通过将这种解释置于动态系统理论的框架内，我们得出了一个惊人的预测：单一的、标量的觉醒测量值（例如瞳孔直径）应该足以重建大规模脑生理的多维、时空测量值的连续演变。在此，为了验证这一假设，我们在清醒小鼠中进行了全脑多模态光学成像和行为监测。我们证明，神经元钙、代谢和脑血氧的秒级时空动态可以从由瞳孔直径的时间延迟嵌入重建的低维非线性流形中准确而简约地建模。将这个框架扩展到艾伦脑科学研究所的行为和电生理测量中，我们展示了通过从共享的觉醒流形进行映射，将不同的实验数据整合到一个统一的生成模型中的能力。我们的结果支持了这样一个假设，即全脑生理在秒级时间尺度上的自发、空间结构化波动——广泛认为反映了区域特异性神经通信——在很大程度上是一个低维、全生物体动态系统的表现。反过来，将觉醒本身重新定义为一个潜在的动态系统，为跨模态、情境和尺度观察到的脑、身体和行为波动提供了一个新的视角。
