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bioRxiv · 10.1101/2024.11.10.622852

Spatially mismatched cerebral blood flow and neuronal activity by intracortical microstimulation

Yonza, A. K. I.·Tao, L.·Kucharz, K.·Lind, B. L.·zhang, X.·Kim, K.·Cai, C.
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Abstract

Intracortial microstimulation (ICMS) is widely used in brain-machine interface for neuroprosthetics, particularly with aims of restoring lost sensory and motor functions. However, it remains poorly understood whether neuronal and blood flow responses by ICMS are spatially and temporally matched, as well as their underlying mechanism. Neurovascular coupling (NVC) is the process by which neuronal activity regulates blood flow in the brain to meet local metabolic demands. A hypothetically suboptimal NVC by ICMS may exacerbate the neuronal survival near electrode, contributing to neurodegeneration. In this study, we used wide-field imaging, laser speckle imaging and two-photon imaging in transgenic mice expressing calcium fluorescent indicators in neurons or vascular mural cells to examine this hypothesis. Our results showed blood flow responses are delayed at peak time and prolonged in duration compared with neuronal responses. By varying the stimulation amplitudes, we found that low stimulation intensity lower than 50A preserved NVC. In contrast, high intensity stimulation caused spatially mismatched NVC, i.e. in the adjacent range within 200[~]400 m from electrode tip, elicited blood flow compromises but neuronal activities increase. Ca2+ is the key regulator of contractile tone of vascular mural cells. Our results showed that Ca2+ sensitivity at vascular mural cells, i.e. vessel diameter change per unit of Ca2+ change, was decreased in the adjacent region of electrode, which partially explained the compromised and mismatched NVC, and which likely further lead to ischemia and neurodegeneration. This study offers a new insight into ICMS-associated neuronal and vascular physiology, and provides an important implication towards optimal design of ICMS: low intensities is more neuroprotective than high intensities by preserving NVC and preventing ischemia. Our discoveries pave the way for new research consideration and contribute to the development of more advanced brain-machine interface.

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Yonza, A. K. I., Tao, L., Kucharz, K., Lind, B. L., zhang, X., Kim, K., Cai, C.. 2024-11-11. Spatially mismatched cerebral blood flow and neuronal activity by intracortical microstimulation. https://doi.org/10.1101/2024.11.10.622852

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