Multimodal mapping of neural activity and cerebral blood flow reveals long-lasting neurovascular dissociations after small-scale strokes

Abstract

Neurovascular coupling, the close spatial and temporal relationship between neural activity and hemodynamics, is disrupted in pathological brain states. To understand the altered neurovascular relationship in brain disorders, longitudinal, simultaneous mapping of neural activity and hemodynamics is critical yet challenging to achieve. Here, we use a multimodal neural platform in a mouse model of stroke and realize long-term, spatially resolved tracking of intracortical neural activity and cerebral blood flow in the same brain regions. We observe a pronounced neurovascular dissociation that occurs immediately after small-scale strokes, becomes the most severe a few days after, lasts into chronic periods, and varies with the level of ischemia. Neuronal deficits extend spatiotemporally, whereas restoration of cerebral blood flow occurs sooner and reaches a higher relative value. Our findings reveal the neurovascular impact of ministrokes and inform the limitation of neuroimaging techniques that infer neural activity from hemodynamic responses.

Rapid development of strong, persistent, spatiotemporally extensive cortical synchrony and underlying oscillations following acute MCA focal ischemia

“…Future recordings will be required to determine the cortical extent of post pMCAo synchrony and whether it is pervasive in other stroke models including awake stroke models. An awake model of mini strokes found that spatiotemporal neuronal deficits extend beyond cerebral blood flow restoration in the days and weeks after ischemic onset 36 . Future studies should examine whether spatiotemporal synchrony extend in the long-term after pMCAo and if these neuronal network dynamics are related to residual blood flow dynamics.…”

Plasticity after cortical stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits

“…Another reason is related to technical limitations of ISI, which probably lacks the resolution to detect the activity of small numbers of neurons (scattered over a large cortical area or multiple layers) that exhibit compensatory plasticity (i.e., their signals are not sufficient to generate an ISI map). Alternatively, changes in blood flow and oxygen context after stroke (i.e., impaired neurovascular coupling (He et al, 2020)) may affect our ability to detect new ISI maps after stroke. To address these concerns about ISI, we also recorded whisker-evoked responses in the spared D3 barrel with in vivo 2P calcium imaging, which provides single cell resolution and is, in principle, impervious to changes in blood flow ( Fig.…”

Longitudinal imaging of VIP interneurons reveals sup-population specific effects of stroke that can be rescued with chemogenetic therapy

“…A number of previous studies from our lab and others has shown that focal cortical stroke leads to a long lasting dampening of cortical excitability and responsiveness to sensory stimulation that correlates with deficits in sensorimotor function of the affected limb 7,8,[32][33][34] . Based on the rationale that VIP interneurons could act as a dis-inhibitory circuit and thus potentially restore cortical responsiveness after stroke, we first characterized the effects of excitatory hM3Dq stimulation on VIP neurons in somatosensory cortex.…”