# Cerebellar Modulation of Cognition in Psychosis

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $822,401

## Abstract

PROJECT SUMMARY/ABSTRACT
Psychotic disorders including schizophrenia, bipolar disorder, and related illnesses are severe, debilitating, and
often fatal. Cognitive impairments in psychosis are among the leading predictors of disability and poor quality
of life; despite this, there are no first line interventions to target these symptoms. Neuroimaging correlates of
cognitive impairment in psychosis have been identified using fMRI techniques; however, these studies are
mostly correlational in nature, limiting application of these findings to intervention. In order to develop targeted
cognitive interventions, there is an urgent need to 1) identify neural circuits that are causally linked to cognitive
function, and 2) demonstrate that circuits are modifiable and that circuit-level change is associated with
cognitive change. This project is a renewal of a R01 funded multi-year, multi-PI plan to identify the circuit basis
of medication refractory symptoms of psychotic disorders. With NIMH support we found that cerebellar-cortical
functional connectivity is linked to both psychotic symptoms (hallucinations) and negative symptoms of
schizophrenia. Functional connectivity can be engaged and manipulated non-invasively using neuromodulation
techniques such as transcranial magnetic stimulation (TMS). The combination of TMS and longitudinal imaging
can help establish causal links between circuits and cognition. In the current project we have identified distinct
cortical-cerebellar circuits linked to cognitive deficits in psychosis and its prodrome. We replicated this finding
and have pilot data that this circuit can be successfully engaged using rTMS. Thus, the goals of this project are
1) to test whether neural circuit dysfunction is dynamically and causally associated with cognitive impairments
in people with psychotic disorders, and 2) to test whether TMS drives dynamic change in both neural circuitry
and cognitive performance. We hypothesize that the relationship between circuit connectivity and cognition
reflects dynamic states intra-individually and over time. Additionally, we hypothesize that the connectivity state
of this circuit is modifiable by TMS and that circuit manipulation will result in cognitive change. The PIs have
expertise in cognition and imaging in psychosis and the fMRI-guided TMS protocols proposed here, including
successful engagement of cerebellar-cortical targets, as well as access to the equipment and resources
necessary to carry out the study. If our hypotheses are supported, we will have identified an actionable target
that can be immediately deployed in intervention trials to test the potential for fMRI-guided TMS to drive
enduring change in cognitive circuitry and performance in psychosis.

## Key facts

- **NIH application ID:** 10803405
- **Project number:** 2R01MH116170-06
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Roscoe O. Brady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $822,401
- **Award type:** 2
- **Project period:** 2019-01-07 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803405

## Citation

> US National Institutes of Health, RePORTER application 10803405, Cerebellar Modulation of Cognition in Psychosis (2R01MH116170-06). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10803405. Licensed CC0.

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