From peri-implant distance ranges to spatial niches: a resolution-aware analytical framework for the intracortical microelectrode–brain interface

Intracortical microelectrodes (IMEs) record local neural activity from within the cortex. Current studies of IME tissue responses provide whole-transcriptome multicellular spots, targeted transcript coordinates, regional ribonucleic acid (RNA) or protein profiles, registered morphology, and exploratory associations between tissue measurements and recording performance. Implant-centered distance locates these measurements relative to the device. This methodological framework review extends implant-centered analyses by defining spatial niches that characterize local cellular, molecular, and structural context at defined neighborhood scales. We organize niche-level analyses into niche identification, implant-referenced spatial organization, and niche-conditioned molecular relationships, with platform-specific guidance for Visium, Xenium, and GeoMx inputs. Finally, we propose candidate relationships between niche-derived features and recording outcomes at matched functional scales for testing in future IME studies.