# Developmental Variations in Corticostriatal Thalamocortical Circuits and their Relationship to Psychopathology

> **NIH NIH R21** · CHILD MIND INSTITUTE, INC. · 2020 · $198,621

## Abstract

ABSTRACT
Detailed characterizations of brain development are essential to understanding factors underlying the
emergence of psychopathology and its progression. Corticostriatal thalamocortical (CSTC) circuits are central
to current models of both externalizing and internalizing psychopathologies. However, our understanding of
their development and the impact of pathologic processes on these circuits is primarily limited to regional
structural properties and specific disorders (e.g., Attention Deficit Hyperactivity Disorder). As such, there is a
need for a more comprehensive examination of CSTC circuit development and its relations to psychopathology.
The overarching goals of the proposed work are to characterize the development of CSTC circuits using
structural MRI and resting state functional MRI, and to link variations in their trajectories to the emergence of
psychopathology. We will model developmental trajectories of structural morphology and functional interactions
within seven CSTC networks defined based on their connectivity with large-scale cortical networks and relate
deviations to externalizing and internalizing behaviors. Consistent with recent calls for secondary analysis of
existing datasets to accelerate the identification of brain-behavior relationships that may serve as modifiable
clinical targets, the proposed work will make use of openly shared pediatric imaging datasets (ages: 5.0-24.0;
high resolution T1 anatomical and resting state functional scans for each participant). Specifically, we will
generate a large-scale aggregate cross-sectional sample (n = 3918) for the purposes of delineating trajectories
for the seven CSTC networks. We train age-prediction models for each of the networks and pool their
predictions to generate multivariate CSTC maturity profiles for each individual. These profiles will be used to
subtype individuals into neurobiologically homogenous subgroups, which are expected to differ with respect to
dimensional measures of psychopathology calculated using the bifactor model framework (i.e. general
psychopathology [p-factor], internalizing, externalizing). An aggregate longitudinal sample (n = 250; 3 time-
points per participant, each 12-15 months apart) will be generated to evaluate the ability of changes in CSTC
maturity profiles over time to predict longitudinal changes in psychopathology. Specific aims of the proposed
work are to: 1) Estimate the developmental trajectories of seven CSTC networks; 2) Determine associations
between CSTC network maturity profile subtypes and dimensions of psychopathology; and 3) Evaluate
predictive relationships between longitudinal changes in maturity profiles and those in dimensions of
psychopathology. Given the scale of the datasets employed, cloud-based computing, and optimized analytic
frameworks will be leveraged to ensure the feasibility of achieving the proposed work within the project period.
All codes developed will be openly shared.

## Key facts

- **NIH application ID:** 9840942
- **Project number:** 5R21MH118556-02
- **Recipient organization:** CHILD MIND INSTITUTE, INC.
- **Principal Investigator:** Aki Nikolaidis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,621
- **Award type:** 5
- **Project period:** 2018-12-19 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840942

## Citation

> US National Institutes of Health, RePORTER application 9840942, Developmental Variations in Corticostriatal Thalamocortical Circuits and their Relationship to Psychopathology (5R21MH118556-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840942. Licensed CC0.

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