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Detection of the Cortical Network Underlying Executive Control of Auditory Attention in Early Psychosis with Multimodal Imaging

Curtis, Mark T (2022) Detection of the Cortical Network Underlying Executive Control of Auditory Attention in Early Psychosis with Multimodal Imaging. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Selective attention is impaired at the first episode of psychosis (FEP). EEG and MEG can measure selective attention during an auditory oddball task, as the amplitude of the event-related potential ~100ms post-stimulus (EEG-measured N100/MEG-measured M100) increases with attention. N100/M100 enhancement is reduced in FEP. This project aimed to examine functional and structural abnormalities of the selective attention network underlying this impairment at the first episode of psychosis (FEP). Understanding the brain circuit underlying impaired selective attention in the early disease course can identify potential therapeutic targets. First, state-of-the-art infrastructure, which included the Human Connectome Project’s (HCP) processing pipelines and multi-modal parcellation, was implemented. Two experiments validated the use of these pipelines and parcellation and provided a novel understanding of structural deficits and structure-function relationships in early psychosis. This infrastructure was used to investigate the auditory attention network, a candidate model system susceptible to deficits in early psychosis. MEG source activity of the M100 revealed sensory and attention modulation deficits in auditory cortex regions in FEP. The cortical network underlying the attention modulation and deficits within this network in FEP was examined. A whole-brain analysis of the M100 source activity identified strong activation within several prefrontal and parietal regions, with additional strong modulatory activity within the bilateral precuneus. The next experiments examined functional connectivity between regions. It was determined that theta frequency (5-7Hz) was the frequency range for inter-regional connectivity. Changes in connectivity patterns with attention, using precuneus functional subregions as seed regions, revealed left and right hemisphere networks that increased activity with attention. Increased theta-band connectivity within these networks was impaired in early psychosis. Further, gray matter thickness was reduced within the left hemisphere network in FEP. The novel use of the HCP pipelines and parcellation to investigate auditory attention network deficits in FEP revealed functional deficits in auditory cortex and in a distributed network, with the precuneus as a hub, and structural deficits in the left hemisphere network. This circuitopathy provides a precise target system for novel interventions, such as non-invasive brain stimulation, which could ultimately improve functional outcome if targeted early in the disorder.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Curtis, Mark Tmac443@pitt.edumac4430000-0002-0467-7321
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAizenstein,
Committee MemberFiez,
Committee MemberLadouceur,
Committee MemberErickson,
Committee MemberFoxe,
Thesis AdvisorSalisbury,
Date: 25 April 2022
Date Type: Publication
Defense Date: 20 January 2022
Approval Date: 25 April 2022
Submission Date: 28 January 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 155
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Psychosis, Schizophrenia, Attention,
Date Deposited: 26 Apr 2022 03:20
Last Modified: 26 Apr 2022 03:20


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