Spatiotemporal relationships between neuronal, metabolic, and hemodynamic signals in the awake and anesthetized mouse brain

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. [Display omitted] •NVC and NMC vary over the mouse cortex•Ketamine/xylazine (K/X) anesthesia alters cortical NVC more than NMC•K/X impacts functional connectivity (FC) based on hemodynamics less than metabolic FC•K/X-related changes in NVC or NMC timing do not predict state-dependent FC changes Wang et al. use wide-field optical imaging to determine how neurovascular coupling (NVC) and neurometabolic coupling (NMC) relative to pyramidal neuron activity vary over the cortex and whether anesthesia affects these relationships. Ketamine/xylazine alters NVC more than NMC. Anesthesia-related changes in NVC/NMC timing do not appreciably alter functional connectivity structure.