# Network Mediation of Experiential and Expressive Deficits in Psychotic Disorders

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $635,126

## Abstract

Project Summary / Abstract
 Psychotic disorders are readily identified by the so-called `positive symptoms' of hallucinations,
delusions, and thought disorder. However, the severity of `negative symptoms' (e.g. amotivation, anhedonia,
and facial expression deficits) are the best predictors of functional outcomes such as employment and
independent housing. Antipsychotic medications are modestly effective in ameliorating these symptoms. We
lack a consensus understanding of how these symptoms are mediated at the level of neural circuits. Without a
biological `target' such as circuit pathophysiology, our ability to develop new interventions is critically
hampered.
 Previous work from our laboratory and others have used task-free or `resting state' functional Magnetic
Resonance Imaging (rsfMRI) to examine the neural correlates of negative symptom severity. Our preliminary
data determined that negative symptom severity is correlated with dysconnectivity between the cerebellum and
Dorso-Lateral Pre-Frontal Cortex (DLPFC). We empirically tested this network-symptom relationship using
repetitive transcranial magnetic stimulation (rTMS) to manipulate network connectivity. We observed that rTMS
induced increases in functional connectivity were strongly associated with improvement in negative symptom
severity, consistent with the hypothesis that network connectivity mediates negative symptomology.
 We propose to test the hypothesis that cerebellar-DLPFC network dysconnectivity causes negative
symptoms in schizophrenia. Using a within-subject, longitudinal experimental design, we will measure network
connectivity and symptom severity before and after rTMS manipulation of cerebellar-DLPFC connectivity. We
will quantify symptom severity via reporter based methods as well as rater-independent; objective measures
that test amotivation, anhedonia, and facial expression. Our hypothesis is that reversal of network
dysconnectivity will give rise to reduced negative symptom severity and the magnitude of network engagement
will explain individual variance in symptomatic improvement.
 If successful, this project will establish a biological target for engagement by a variety of experimental
methods towards the amelioration of these disabling, medication-resistant symptoms of psychotic disorders.

## Key facts

- **NIH application ID:** 9846248
- **Project number:** 5R01MH116170-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Roscoe O. Brady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $635,126
- **Award type:** 5
- **Project period:** 2019-01-07 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846248

## Citation

> US National Institutes of Health, RePORTER application 9846248, Network Mediation of Experiential and Expressive Deficits in Psychotic Disorders (5R01MH116170-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9846248. Licensed CC0.

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