# Structural constraints on large-scale brain activity in psychosis associated with chromosome 22q11.2 deletion syndrome

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2020 · $50,520

## Abstract

Project Summary
In the healthy brain, large-scale white matter architecture and local neuronal membrane properties
facilitate seamless transitions between cognitive states. Patients with schizophrenia display
significant white matter abnormalities with disorganized brain activity. However, the degree to which
dysfunctional brain activity in psychosis arises from structural or functional pathology remains
unknown. The identification of conclusive neuroimaging findings in this cohort has been challenged
by 1) inadequate methods to assess distributed multimodal pathological phenotypes, and 2) the
significant pathogenetic heterogeneity in schizophrenia. Practically, the latter challenge can be in part
addressed by the study of chromosome 22q11.2 deletion syndrome (22qDS), where the prevalence
of clinical schizophrenia is 25-fold higher than that of healthy individuals. The former challenge can be
addressed by recent advances in network science and machine learning, which have generated
insights about structure-function relationships in the healthy brain. Utilizing these methods to study
the spectrum of psychotic symptoms in a population with a defined genetic lesion is a promising
direction for investigating psychosis pathophysiology.
In this proposal, we describe the development of a novel time-point-based analysis of functional
neuroimaging data to study structure-function relationships in a sample of patients with 22qDS
currently being seen at the Hospital for the University of Pennsylvania. Using neuroimaging data from
a large sample of youths (n = 690) acquired through the Philadelphia Neurodevelopmental Cohort,
our preliminary analyses demonstrate previously uncharacterized relationships between brain
structure, brain activity, and working memory performance. In this proposal, we aim to 1) compare
brain state transition dynamics across the psychotic spectrum of 22qDS, 2) compare
structure-function coupling in 22qDS to healthy controls and relate structure-function
coupling to psychotic symptom severity, and 3) relate state transition dynamics to working
memory performance in 22qDS.
A better understanding of the underlying mechanism of psychosis-spectrum symptoms would lay the
groundwork for the development of targeted therapies for psychosis. Furthermore, utilizing a cohort
with a known genetic lesion provides a unique opportunity to bridge our understanding of molecular
mechanisms with neuroimaging biomarkers for psychosis-spectrum symptoms.

## Key facts

- **NIH application ID:** 9872025
- **Project number:** 5F30MH118871-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Eli Cornblath
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872025

## Citation

> US National Institutes of Health, RePORTER application 9872025, Structural constraints on large-scale brain activity in psychosis associated with chromosome 22q11.2 deletion syndrome (5F30MH118871-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872025. Licensed CC0.

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