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Neural mechanisms underlying intracortical microstimulation for sensory restoration

Nature Biomedical Engineering (2026)Cite this article

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Abstract

Sensation plays a pivotal role in the orchestration of our daily lives. Intracortical microstimulation (ICMS) can elicit artificial sensations in persons who have lost sensation due to neurological injury or disease. Despite ongoing clinical studies to assess the safety and efficacy of ICMS, the mechanisms underlying neural activation by ICMS and their implications for perception are not well understood. This Review delves into the current understanding of ICMS mechanisms, drawing parallels with physiological sensory processing in the cortex. We explore emerging approaches and note challenges to current technologies, including resolution and the tissue response to electrode insertion. We conclude by highlighting the basic principles of ICMS, lingering questions and important focus areas for continued development.

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Fig. 1: Basic mechanisms of ICMS.
Fig. 2: Computational model of ICMS reveals current–distance relationships.
Fig. 3: Permanent and temporary depression of neural activity induced by ICMS.
Fig. 4: Cortical physiology and electrode insertions.
Fig. 5: Emerging approaches and technologies for ICMS.

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Acknowledgements

We dedicate this Review to the late Sliman Bensmaia, whose work on somatosensation and neuroprostheses in both non-human primates and humans helped lay the foundation for much of our current understanding of ICMS in sensory cortices and strongly motivated this work. We also thank F. Li and N. Suematsu for providing feedback on the manuscript. This Review was supported by NIH F32MH130022, T32NS086749, R01NS105691, R01NS115707, R01NS129632, NSF CAREER CBET 1943906, NIH U01 NS126052, R01 NS117405 and R37 NS040894.

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Authors and Affiliations

  1. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

    Christopher Hughes & Takashi D. Y. Kozai

  2. Center for the Neural Basis of Cognition, Pittsburgh, PA, USA

    Christopher Hughes & Takashi D. Y. Kozai

  3. Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA

    Xing Chen

  4. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    Warren Grill

  5. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    Takashi D. Y. Kozai

  6. McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Takashi D. Y. Kozai

  7. Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA, USA

    Takashi D. Y. Kozai

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  4. Takashi D. Y. Kozai
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Correspondence to Christopher Hughes or Takashi D. Y. Kozai.

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Competing interests

X.C. is the co-founder and shareholder of Phosphoenix BV. Since the preparation of this Review, C.H. has become employed by Blackrock Neurotech, which has developed technology discussed herein. This employment did not influence the content or conclusions of the Review. T.D.Y.K. and W.G. declare no competing interests.

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Hughes, C., Chen, X., Grill, W. et al. Neural mechanisms underlying intracortical microstimulation for sensory restoration. Nat. Biomed. Eng (2026). https://doi.org/10.1038/s41551-025-01583-6

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