# Empirical validation of a cerebellar-cortical hallucination circuit

> **NIH NIH R01** · MCLEAN HOSPITAL · 2024 · $671,484

## Abstract

Project Summary / Abstract
 Projects like the BRAIN initiative hold the potential for a fundamentally new approach to therapeutics for
severe mental illness. Neuromodulation technologies promise to allow selective intervention in which
pathophysiology is specifically targeted for correction. These initiatives are critically dependent on the correct
identification of circuit dysfunction that causes psychiatric symptoms. NIMH has prioritized this as a strategic
objective: Identify and characterize the neural circuit mechanisms contributing to human behavior and their
disruption in mental illnesses.
 Neuroimaging studies have generated promising leads while almost never demonstrating that these
findings represent targets that can be engaged for therapeutic benefit. We thus lack a key perquisite for
translation into the clinic: For imaging biomarkers to make the leap to translational use, they would need to
accurately identify the circuits that give rise to symptoms.
 In this project we seek to understand how brain circuit dysfunction causes auditory hallucinations in
schizophrenia. Published, technically challenging imaging studies provide a critical clue: These “symptom
capture” experiments that collect MRI imaging during hallucinations have identified a disparate pattern of
activations across multiple subcortical and cortical brain regions. Our hypothesis is that these brain regions
are part of a single circuit than spans cerebellar, thalamic, and cortical brain regions. In our preliminary data we
are able to identify the cerebellar node of this circuit, and then, in an independent cohort of participants with
schizophrenia, we used neuromodulation to manipulate this circuit. We observe that non-invasive
neuromodulation can manipulate connectivity across this entire circuit. Restoration of connectivity in this circuit
is reflected in reduction of hallucination severity.
 In this proposal we seek to confirm and extend this result. We will use non-invasive neuromodulation to
specifically target this circuit and observe change induced on the hallucination circuit in a sham-controlled
study. If successful, this project will establish a circuit-level understanding of how pathophysiology is causally
linked to hallucinations. This kind of mechanistic understanding of schizophrenia symptoms would be
unprecedented and would identify biological target for engagement to reduce these symptoms.

## Key facts

- **NIH application ID:** 10735879
- **Project number:** 5R01MH126000-03
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Roscoe O. Brady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,484
- **Award type:** 5
- **Project period:** 2022-01-01 → 2026-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10735879

## Citation

> US National Institutes of Health, RePORTER application 10735879, Empirical validation of a cerebellar-cortical hallucination circuit (5R01MH126000-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10735879. Licensed CC0.

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