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Summary Systems-level organization in spontaneous infra-slow (<0.1Hz) brain activity, measured using blood oxygen signals in fMRI and optical imaging, has become a major theme in the study of neural function in both humans and animal models. Yet the neurophysiological basis of infra-slow activity (ISA) remains unresolved. In particular, is ISA a distinct physiological process, or is it a low-frequency analog of faster neural activity? Here, using whole-cortex calcium/hemoglobin imaging in mice, we show that ISA in each of these modalities travels through the cortex along stereotypical spatiotemporal trajectories that are state dependent (wake versus anesthesia) and distinct from trajectories in delta (1–4 Hz) activity. Moreover, mouse laminar electrophysiology reveals that ISA travels through specific cortical layers and is organized into unique cross-laminar temporal dynamics that are different from higher frequency local field potential activity. These findings suggest that ISA is a distinct neurophysiological process that is reflected in fMRI blood oxygen signals. [ABSTRACT FROM AUTHOR]

Neurovascular coupling (NVC) and neurometabolic coupling (NMC) provide the basis for functional magnetic resonance imaging and positron emission tomography to map brain neurophysiology. While increases in neuronal activity are often accompanied by increases in blood oxygen delivery and oxidative metabolism, these observations are not the rule. This decoupling is important when interpreting brain network organization (e.g., resting-state functional connectivity [RSFC]) because it is unclear whether changes in NMC/NVC affect RSFC measures. We leverage wide-field optical imaging in Thy1-jRGECO1a mice to map cortical calcium activity in pyramidal neurons, flavoprotein autofluorescence (representing oxidative metabolism), and hemodynamic activity during wake and ketamine/xylazine anesthesia. Spontaneous dynamics of all contrasts exhibit patterns consistent with RSFC. NMC/NVC relative to excitatory activity varies over the cortex. Ketamine/xylazine profoundly alters NVC but not NMC. Compared to awake RSFC, ketamine/xylazine affects metabolic-based connectomes moreso than hemodynamic-based measures of RSFC. Anesthesia-related differences in NMC/NVC timing do not appreciably alter RSFC structure., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)