# Linking the Development of Association Cortex Plasticity to Trans-Diagnostic Psychopathology in Youth

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $791,421

## Abstract

PROJECT SUMMARY
 Association cortex undergoes protracted development throughout childhood and adolescence. This
extended window of association cortex plasticity is understood to enhance executive and socioemotional
functioning, whereas experiences that diminish plasticity—such as environmental adversity—confer risk for
psychopathology. At present, the biological origins of prolonged association cortex plasticity in humans remain
under characterized, precluding a mechanistic understanding of how neurodevelopmental malleability interacts
with the environment to foster either resilience or psychiatric vulnerability. Animal studies of cortical plasticity
have identified maturational increases in inhibitory neurotransmission and cortical myelination as two key
biological regulators of plasticity. As inhibition and myelination increase and the murine cortex transitions from
plastic to mature, intrinsic cortical activity transitions from widespread and synchronized (producing high
amplitude neural recordings) to suppressed and sparse — producing low amplitude recordings. This
development-linked shift in intrinsic activity amplitude thus provides an animal model-informed, functional
readout of local circuit plasticity. We recently leveraged this functional marker in humans and found that
declines in the amplitude of intrinsic fMRI fluctuations (termed fluctuation amplitude) were coupled to the
maturation of cortical myelin and temporally unfolded along a hierarchical, sensorimotor-association cortical
axis (Sydnor et al., Nature Neuroscience 2023). Here we will map the normative progression of developmental
plasticity from sensory to association cortex and link precocious reductions in association cortex plasticity to
transdiagnostic overall psychopathology. Building upon our initial work examining plasticity measures in one
cross-sectional dataset, we propose to generalize our findings to two additional cross-sectional datasets (the
HCP-Development and the Healthy Brain Network; total n=6,530) and map within-participant change using the
ABCD study (n=11,563). These datasets will allow us to comprehensively map the development of our
functional measure of plasticity (Aim 1) and link it to both the development of a major plasticity restricting factor
(intracortical myelin; Aim 2). Next, we will determine whether lower socioeconomic status (SES) is associated
with accelerated closure of plasticity in association cortex (Aim 3), and finally delineate links to trans-diagnostic
overall psychopathology (Aim 4). This research program capitalizes upon a highly successful first project
period (>60 publications) and robust preliminary data and a highly cohesive team of UPenn investigators with
expertise in neurodevelopmental psychopathology and neuroinformatics (Satterthwaite), network science and
machine learning (Bassett), imaging statistics (Shinohara), psychometrics (Moore), and developmental
psychology (Mackey). Together, this innovative proposal will provide...

## Key facts

- **NIH application ID:** 10932287
- **Project number:** 5R01MH113550-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Danielle Smith Bassett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $791,421
- **Award type:** 5
- **Project period:** 2018-06-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932287

## Citation

> US National Institutes of Health, RePORTER application 10932287, Linking the Development of Association Cortex Plasticity to Trans-Diagnostic Psychopathology in Youth (5R01MH113550-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10932287. Licensed CC0.

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