# Cerebro-cerebellar circuitry in the pathophysiology of auditory hallucinations: dysmetria of auditory perceptual processing?

> **NIH NIH R21** · MCLEAN HOSPITAL · 2020 · $198,389

## Abstract

PROJECT SUMMARY/ABSTRACT
 This R21 proposal aims to provide detailed understanding of how finely parcellated subareas of the
auditory cortex (AC) are functionally connected with one another and with cerebellar regions in schizophrenia
(SZ) patients with auditory hallucinations (AH). AH can be disabling, and do not always respond to existing
treatments. A clear understanding of AH pathophysiology is needed to guide the development of more effective
treatments for AH, but such knowledge is currently lacking. Previous research suggests that the AC is abnormal
in AH, suggesting a possible perceptual basis for AH. The AC, however, is one of many brain regions implicated
in AH pathogenesis, and a better understanding of how AC interacts with other critical brain areas is needed.
 The cerebellum coordinates a host of cerebral cortical functions—including higher-level cognitive,
affective, and perceptual processes—rather than just motor functions, as traditionally believed. Consistent with
this framework, the myriad symptoms of psychosis have been proposed to reflect “dysmetria,” or incoordination,
of mental activity due to disruptions in cerebro-cerebellar circuits (Andreasen, et al., 1996; Schmahmann, 1998).
Given evidence that the cerebellum is reciprocally connected to AC and coordinates auditory processing, there
is motivation to understand how abnormal AC-cerebellar circuitry might lead to `auditory dysmetria', and AH.
 We propose to examine features of local AC circuitry and AC-cerebellar circuitry underlying AH by utilizing
an innovative and highly reliable AC parcellation strategy based on resting state functional magnetic resonance
imaging (rsfMRI). This parcellation method, which computes functional connectivity (FC) between voxels in AC
and the rest of the brain, will be used to segment AC into multiple subareas. Subdividing the AC at this fine-
grained a level could only be achieved before with postmortem (e.g., cytoarchitectonic) methods. Here, these
individual-specific and functionally defined AC subareas will serve as the seeds for FC between AC subareas
and between AC and cerebellum. Our aims are to identify features of AC inter-subarea FC (Aim 1) and features
of AC-cerebellar FC (Aim 2) that track with AH severity in SZ. We also aim to validate how these markers change
with intra-subject variations in AH (Aim 3), using data from an independent interventional longitudinal study.
 Our hypotheses are two-fold: (1) The AC is comprised of a complex local network of both primary sensory
and association subareas, and FC between AC subareas is meaningfully associated with AH. (2) The cerebellum
plays a key role in coordinating activity in AC subareas, and this process is `dysmetric' in AH. This project is
significant because it is the first step in a continuum of research that is expected to lead to the development of
more targeted and personalized treatments for AH. Repetitive transcranial magnetic stimulation (rTMS) is a
promising non-pharmac...

## Key facts

- **NIH application ID:** 10015346
- **Project number:** 5R21MH121831-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Hesheng Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,389
- **Award type:** 5
- **Project period:** 2019-09-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015346

## Citation

> US National Institutes of Health, RePORTER application 10015346, Cerebro-cerebellar circuitry in the pathophysiology of auditory hallucinations: dysmetria of auditory perceptual processing? (5R21MH121831-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10015346. Licensed CC0.

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