# Auditory Cortex Connectivity in Emerging Psychosis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $630,319

## Abstract

Summary
Auditory verbal hallucinations (AVH) are a pervasive debilitating symptom of psychosis. Understanding the
pathology and pathophysiology underlying AVH would provide scientific knowledge about brain abnormalities in
psychosis, and reveal a target neurobiological system for novel interventions such as brain stimulation. Yet, it is
not known where in the brain disorders of structure or function lead to AVH, what role gray matter (local
information processing) and white matter (information flow between distributed gray matter areas) abnormalities
play, whether distinct patterns of pathophysiology underlie different types of AVH, when neurobiological
abnormalities emerge in the prepsychotic prodromal phase, and how pathology and pathophysiology progress in
the early disease course after psychosis and AVH emerge. This project aims to understand the neurobiology of
AVH by examining structure and function in a left-hemisphere dominant language circuit thought to be involved
in the genesis of AVH cross-diagnostically during initial stages of psychosis comprising the clinical high risk stage,
the first psychotic episode stage, and longitudinally into the early psychosis stage. Individuals will express a range
of severity of auditory perceptual aberrations, beginning with no symptoms, progressing through attenuated
psychotic auditory misperceptions and then AVH of increasing intensity and duration, culminating in severe
constant AVH. Our overarching hypothesis is that AVH are caused by a final common pathway of overactivity in
left Wernicke's area that leads to overstimulation of upstream auditory sensory cortices and downstream semantic
language stores. We will examine neurophysiology (simultaneous EEG and MEG) and hemodynamic measures
of brain activity (MRI-based arterial spin labeling) to assess resting level activation and network functional
connectivity in a distributed frontal (Broca's area), temporal (Wernicke's area and primary auditory cortex), and
limbic system (putamen) language-related circuit, gray matter volumes in these areas (structural MRI) and the
integrity of the white matter tracts connecting them (MRI-based Diffusion Spectrum Imaging), and EEG & MEG
during a verbal fluency task. Our pilot data indicate that worse AVH are associated with increased verbal fluency
at all disease stages. Further AVH of voices commenting appear to arise due to hypo-connected Broca's and
Wernicke's areas, whereas AVH of other (typically negative) voices are associated with hyper-connectivity with
the limbic putamen. We hypothesize that abnormalities in this language system will be detected in the prodromal
and at risk stage that will correlate with auditory perceptual aberrations, in the first episode stage that correlate
with AVH intensity, and that the pathology and pathophysiology will worsen during the first year post-psychotic
break, particularly in the white matter integrity and the network functional connectivity dynamics. Regarding
therapeutic...

## Key facts

- **NIH application ID:** 10216626
- **Project number:** 5R01MH113533-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Dean F Salisbury
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $630,319
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216626

## Citation

> US National Institutes of Health, RePORTER application 10216626, Auditory Cortex Connectivity in Emerging Psychosis (5R01MH113533-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10216626. Licensed CC0.

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