Date of Award

8-7-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Jessica Turner

Second Advisor

Anne Murphy

Third Advisor

Mukesh Dhamala

Fourth Advisor

Eddy Nahmias

Fifth Advisor

Judith Ford

Abstract

Schizophrenia (Sz) is a psychotic disorder characterized by multifaceted symptoms including hallucinations (e.g. vivid perceptions that occur in the absence of external stimuli). Auditory hallucinations are the most common type of hallucination in Sz; roughly 70 percent of Sz patients report hearing voices specifically (e.g. auditory verbal hallucinations). Prior functional magnetic resonance imaging (fMRI) studies have provided initial insights into the neural mechanisms underlying hallucinations, implicating an anatomically-distributed network of cortical (sensory, insular, and inferior frontal cortex) and subcortical (hippocampal, striatal) regions. Yet, it remains unclear how this distributed network gives rise to hallucinations impacting different sensory modalities.

The insular cortex is a central hub of a larger functional network called the salience network. By regulating default-mode network activity (associated with internally-directed thought), and fronto-parietal network activity (associated with externally-directed attention), the salience network is able to orient our attention to the most pressing matters (e.g. bodily pain, environmental threats, etc.). Abnormal salience monitoring is thought to underlie Sz symptoms; improper monitoring of salient internal events (e.g. auditory-verbal imagery, visual images) plausibly generates hallucinations, but no prior study has directly tested this hypothesis by exploring how sensory networks interact with the salience network in the context of hallucinations in Sz.

This dissertation project combined exploratory and hypothesis-driven approaches to delineate functional neural markers of Sz symptoms. The first analysis explored the relationship between Sz symptom expression and altered functional communication between salience and default-mode networks. The second analysis explored fMRI signal fluctuations associated with modality-dependent (e.g. auditory, visual) hallucinations. The final analysis tested the hypothesis that abnormal functional communication between salience and sensory (e.g. auditory, visual) networks underlies hallucinations in Sz. The results suggest that there are three key players in the generation of auditory hallucinations in Sz: auditory cortex, hippocampus, and salience network. A novel functional network model of auditory hallucinations is proposed to account for these findings.

DOI

https://doi.org/10.57709/12240898

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