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Investigating hierarchical critical periods in human neurodevelopment

Neuropsychopharmacology volume 51, pages 67–85 (2026)Cite this article

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Abstract

Identifying when periods of enhanced neurobiological plasticity occur throughout the human cortex is foundational to understanding when different neural circuits and the psychological processes that they support will be most impacted by adverse and enriching environments. Animal research has identified “critical periods” of plasticity that occur in primary cortices and enable profound environment-dependent sculpting of sensory function early in life. Recent evidence suggests that critical periods may additionally occur in the human brain during childhood and adolescence, where they are hypothesized to unfold hierarchically across sensorimotor and association cortical regions. In this article, we consider neural, environmental, and behavioral evidence for hierarchical critical periods in human development. We review neuroimaging studies that have characterized the development of in vivo correlates of critical period plasticity and synthesize research that has explored when lower-order and higher-order cortical regions exhibit differential environmental sensitivity. We outline how the field is well-positioned to further investigate the precise nature, timing, and consequences of putative critical periods and summarize approaches to making progress in this area. We end by describing the relevance of critical periods for understanding youth psychiatric risk and for informing age-specific environmental enrichment interventions capable of supporting healthy development by fostering resiliency.

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Fig. 1: An adolescent critical period of plasticity in murine association cortex.
Fig. 2: Human neuroimaging uncovers a hierarchical axis of child and adolescent cortical plasticity.
Fig. 3: Hierarchically-organized periods of heightened environmental sensitivity.
Fig. 4: Differentiating lifespan and critical period plasticity.

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Funding

Funding for some authors was provided by the Staunton Farm Foundation.

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Authors and Affiliations

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

    Valerie J. Sydnor, Amar Ojha, Angela Martinez, Finnegan J. Calabro & Beatriz Luna

  2. Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, PA, USA

    Valerie J. Sydnor, Amar Ojha & Beatriz Luna

  3. Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    Amar Ojha

  4. Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA

    Bart Larsen

  5. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Bart Larsen

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

    Finnegan J. Calabro & Beatriz Luna

  7. Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA

    Beatriz Luna

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  1. Valerie J. Sydnor
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  2. Amar Ojha
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  4. Angela Martinez
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Contributions

Valerie J. Sydnor, Amar Ojha, and Angela Martinez performed literature reviews for material presented in the article. Valerie J. Sydnor, Bart Larsen, and Beatriz Luna conceived of the topic; Finnegan J. Calabro provided expert input. Valerie J. Sydnor wrote the original article and created the figures. All authors critically revised the article.

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Sydnor, V.J., Ojha, A., Larsen, B. et al. Investigating hierarchical critical periods in human neurodevelopment. Neuropsychopharmacol. 51, 67–85 (2026). https://doi.org/10.1038/s41386-025-02246-5

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