Solving the problem of inception: a cross-species perspective on strategies for a mechanistic refinement of intracortical microstimulation

J Neural Eng. 2026 Apr 23;23(2). doi: 10.1088/1741-2552/ae54cf.

Abstract

Objective.Microstimulation delivers electrical pulses directly into the brain, with one of its promises being to restore lost senses to millions of people. Yet a fundamental challenge remains: how do intracortical microstimulation (ICMS) patterns engage neural circuits to achieve the inception of specific experiences, such as vivid sensory percepts of touch and vision? Here, we define 'inception' as the initiation of percepts evoked by microstimulation through the mapping of stimulation to circuit-level activity that results in sensory experiences.Approach.This perspective proposes an integrated research framework that combines Reverse Translation, Forward Translation, and computational neuroscience to bridge insights between clinical observations and high-resolution animal studies.Framework.Our framework envisions the development and evaluation of ICMS strategies within a cross-species system that narrows the range of plausible underlying neural mechanisms and the set of evoked perceptual outcomes. Reverse Translation uses human perceptual reports about phosphenes, tones, and touch to guide investigations in rodents and non-human primates, mapping the cell types and circuits underlying each percept. Forward Translation leverages these biological insights to design refined ICMS protocols for selective circuit engagement. Bidirectional Translation weaves these approaches together through computational neuroscience, ensuring that experimental observations iteratively and continuously refine one another across species and experimental modalities.Significance.This integrated strategy aims to transform microstimulation research into a dynamic dialogue between fundamental science and human experience. Harnessing the Bidirectional Translation Framework can accelerate therapies that enhance quality of life for people with sensory or motor impairments, and contribute more broadly to systems neuroscience by uncovering the mechanisms by which causal manipulation changes activity in neurons and networks.

Keywords: cross-disciplinary research; cross-translational research; electrical stimulation; integrated team science; neural engineering; neurocomputation; translational neuroscience.

Publication types

  • Review

MeSH terms

  • Animals
  • Electric Stimulation* / methods
  • Humans
  • Species Specificity