# Dysfunctional State Representations in Psychosis: From Neurophysiology to Neuroplasticity-based Treatment

> **NIH NIH P50** · UNIVERSITY OF MINNESOTA · 2022 · $3,054,680

## Abstract

PROJECT SUMMARY: OVERALL
To respond adaptively to the environment, the brain must process information to develop accurate and stable
representations of the current state of the environment (“state representation”). This requires precise neural
activity timing synchrony between prefrontal and sensory systems and within prefrontal networks.
Our Center focuses on the unifying hypothesis that processes underlying state representation dysfunction are
relevant to psychosis, providing a window into pathophysiologic heterogeneity and precision treatment. Four
Projects span three species (nonhuman primates, mice, and humans) and eight methodologies (genetic
manipulations, slice physiology, ensemble recordings, LFP, behavior, EEG, fMRI, cognitive training). We use a
central computational perspective to translate and integrate across species and methodologies: Changes in
neural information processing affect parameters underlying attractor dynamics and influence state
representation processes. Such changes create observable effects in behavior and neurophysiology, which we
can study through the lens of attractor network models to inform our understanding of pathophysiologic
heterogeneity, clinical trajectories, and precision treatment.
Each Project: 1) Uses the same behavioral tasks to probe components of state representation across species
and experiments; 2) Accesses parallel neurophysiologic metrics, with a focus on neural system activity timing,
excitatory-inhibitory balance, and noise; 3) Uses advanced data-driven causal discovery analyses to facilitate
cross-paradigm integration and novel hypothesis generation. The Projects are supported by a Translational
Neurophysiology Core, a Computational Core, and an Administrative Core.
Aim 1 investigates behavior and neurophysiology of state representation dysfunctions characteristic of
psychosis in a nonhuman primate model of prefrontal network failure in psychosis mediated through NMDA-R
signaling (PROJECT 1); in mice with cell type-specific ablation of NMDA-R function and carrying psychosis-
associated genetic variants (PROJECT 2); and from an EEG-fMRI study of healthy controls and people with
early psychosis (PROJECT 3). Aim 2 develops attractor network models of state representation at multiple
levels of detail, incorporating behavioral, synaptic, and cellular microcircuit data from animal neurophysiology
studies (PROJECTS 1 & 2) to identify parameters that account for state representation dysfunctions
characteristic of psychosis and the behavioral and neurophysiological observations made in humans
(PROJECTS 3 & 4). Aims 3 and 4 focus on reliability and predictive significance of state representation
dysfunctions in early psychosis, and precision treatment approaches targeting specific dysfunctions.

## Key facts

- **NIH application ID:** 10377362
- **Project number:** 5P50MH119569-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** A DAVID REDISH
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $3,054,680
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377362

## Citation

> US National Institutes of Health, RePORTER application 10377362, Dysfunctional State Representations in Psychosis: From Neurophysiology to Neuroplasticity-based Treatment (5P50MH119569-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10377362. Licensed CC0.

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