# Generative Modeling of Excitation:Inhibition Balance Abnormalities in Schizophrenia

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY / ABSTRACT:
Cognitive deficits are, arguably, the most prevalent, the most disabling, and the most economically costly
symptom of schizophrenia (SZ). There are, however, no FDA-approved medications to improve cognitive
function in SZ. Computational models have proposed that cognitive deficits in SZ arise from disruptions to
cortical excitation:inhibition (E:I) balance, and these models have inspired new outcome measures for
randomized control trials (RCTs), as well as new model paradigms for SZ. Nevertheless, it is unclear whether
computational models of E:I balance in SZ will spur innovations in cognitive-enhancing therapeutics.
Conventional approaches to modeling of E:I balance in SZ are limited in several ways, which may negatively
impact their ability to improve the assessment and treatment of cognitive deficits among those with SZ. The
following F31 NRSA proposal seeks to translate a recently-validated modeling approach, which does not
exhibit these limitations, to the study of E:I balance in SZ. Mesoscale Individualized Neurodynamic (MINDy)
modeling, which was created by members of this NRSA proposal team, is an approach for inferring the
biophysical parameters of an individual’s brain using functional magnetic resonance imaging (fMRI) data.
MINDy models provide a proxy-measure for E:I balance that is, unlike conventional computational models of
E:I balance in SZ, both statistically reliable (Test-Retest R > 0.7) and quick to compute for every region of
interest in the brain (~1min compute time). The following NRSA proposal leverages these advantages to
investigate disruptions in brain-wide E:I associated dynamics among those with SZ using a wide range of
clinically-relevant study designs. For aim one of this NRSA, we will use MINDy to investigate brain wide
disruptions to E:I-associated dynamics among individuals with SZ by using resting-state fMRI data from the
Human Connectome Project – Early Psychosis (HCP-EP) study. While conventional approaches have
demonstrated that SZ is primarily associated with disruptions to E:I balance in association cortical areas such
as the prefrontal cortex, there is some evidence that E:I balance may also be disrupted in sensory cortical
areas. This has not been explored with computational models of E:I balance. We hypothesize that MINDy will
uncover disruptions to E:I-associated dynamics in both association and sensory cortical areas among those
with SZ. For aim two of this NRSA, we will use MINDy to investigate genetic contributions to individual
differences in brain-wide E:I balance among a sample of approximately 900 monozygotic and dizygotic twin
pairs from the Adolescent Brain and Cognitive Development Twin (ABCD-Twin) study. While existing work
suggests that general changes in gene expression across the neocortex are related to differences in E:I
balance between cortical areas, aim two of this NRSA proposal will be the first study to investigate whether the
distribution of E:I balance...

## Key facts

- **NIH application ID:** 11065856
- **Project number:** 1F31MH136686-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** jacob pine
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11065856

## Citation

> US National Institutes of Health, RePORTER application 11065856, Generative Modeling of Excitation:Inhibition Balance Abnormalities in Schizophrenia (1F31MH136686-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11065856. Licensed CC0.

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