Work

Spatially and temporally mismatched blood flow and neuronal activity by high-intensity intracortical microstimulation

Year: 2025

Type: article

Abstract: Introduction Intracortial microstimulation (ICMS) is widely used in neuroprosthetic brain-machine interfacing, particularly in restoring lost sensory and motor functions. Spiking neuronal activity requires increased cerebral blood flow to meet local metabolic demands, a process conventionally denoted as neurovascular coupling (NVC). However, it is unknown precisely how and to what extent ICMS elicits NVC and how the neuronal and blood flow responses to ICMS correlate. Suboptimal NVC by ICMS may compromise oxygen and energy delivery to the activated neurons thus impair neuroprosthetic functionality. Material and method We used wide-field imaging (WFI), laser speckle imaging (LSI) and two-photon microscopy (TPM) to study living, transgenic mice expressing calcium (Ca 2+ ) fluorescent indicators in either neurons or vascular mural cells (VMC), as well as to measure vascular inner lumen diameters. Result By testing a range of stimulation amplitudes and examining cortical tissue responses at different distances from the stimulating electrode tip, we found that high stimulation intensities (≥50 μA) elicited a spatial and temporal neurovascular decoupling in regions most adjacent to electrode tip (<200 μm), with significantly delayed onset times of blood flow responses to ICMS and compromised maximum blood flow increases. We attribute these effects respectively to delayed Ca 2+ signalling and decreased Ca 2+ sensitivity in VMCs. Conclusion Our study offers new insights into ICMS-associated neuronal and vascular physiology with potentially critical implications towards the optimal design of ICMS in neuroprosthetic therapies: low intensities preserve NVC; high intensities disrupt NVC responses and potentially precipitate blood supply deficits.

Source: Brain stimulation

DOI: 10.1016/j.brs.2025.04.015