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Dysfunctional State Representations in Psychosis: From Neurophysiology to Neuroplasticity-based Treatment

Award Number: P50MH119569
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Dysfunctional State Representations in Psychosis: From Neurophysiology to Neuroplasticity-based Treatment - OVERALL - PROJECT SUMMARY The purpose of our P50 Conte Center is to develop, test, and apply computational models of disrupted state representation processes to behavioral and neural measures relevant to psychosis spectrum illness across mouse, macaque, and human experiments. Our premise is that, in order to respond adaptively to the environment, the brain must process information to develop accurate and stable representations of the current state of the world; this requires neural processes that: 1) estimate the current state of the world; 2) use reward-based feedback to learn to recognize new states; and 3) maintain state representation across time gaps. State representation processes rely on precise neural activity including timing synchrony between prefrontal and sensory systems and across prefrontal and subcortical networks, including striatal systems. Our overarching hypothesis is that a range of computationally identifiable microcognitive processes contribute to state representation disruptions in psychosis, that these vary dimensionally across individuals (potentially manifesting as computational subprofiles), and that their underlying neural contributors, once understood, could serve as targets for precision treatments. Informed by our Center’s recent findings from NMDAR-antagonism in macaques, from NMDAR ablation and dopamine (ant)agonism in mice, and from EEG+fMRI studies in humans with and without psychosis, we will examine variable patterns of behavior and neurophysiology during task performance, examining the interplay between state estimation, state maintenance, and state learning computations. Aim 1: Computational science. Informed by biologically-grounded theoretical models and successes in the previous cycle, we will continue to develop methods to measure computational parameters of state representation processes, integrating across two tasks. Each task probes distinct neurocognitive and neural system operations– cognitive control and reward-based decision-making– highly relevant to psychosis. Aim 2: Non-human animal experimental science. Applying these computational methods, and drawing on findings from our human studies, we will analyze the behavior and neurophysiology of state representation processes relevant to psychosis, in mice and in macaques, under normal conditions and after manipulations of NMDAR and dopaminergic systems. Aim 3: Clinical science. Applying these computational methods, and drawing on findings from our non-human animal studies, we will identify the computational dimensions relevant to psychosis and their neural system correlates in humans (via EEG studies and innovative within-subject Precision Functional Mapping) with a focus on interactions among CEN, SN, and DMN network dynamics; we will identify how computational subprofiles in humans can be altered in response to manipulations of NMDAR and dopaminergic systems.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Mental Health Research Grants	000	6	11/20/2025	COMPETING CONTINUATION	$0
2026	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Mental Health Research Grants	001	5	11/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $3,095,644 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Mental Health Research Grants	002	6	6/2/2025	COMPETING CONTINUATION	$3,095,644
2025	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	000	5	2/13/2025	NON-COMPETING CONTINUATION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Mental Health Research Grants	001	5	6/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,095,644

Issue Date FY: 2024 ( Subtotal = $3,058,798 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	001	5	3/5/2024	NON-COMPETING CONTINUATION	$2,752,919
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	002	5	3/11/2024	NON-COMPETING CONTINUATION	$0
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	003	5	5/3/2024	NON-COMPETING CONTINUATION	$305,879
2024	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	000	4	2/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,058,798

Issue Date FY: 2023 ( Subtotal = $3,061,014 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	001	4	3/16/2023	NON-COMPETING CONTINUATION	$3,061,014
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	002	4	4/19/2023	NON-COMPETING CONTINUATION	$0
2023	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	000	3	11/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,061,014

Issue Date FY: 2022 ( Subtotal = $3,054,680 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	001	3	3/25/2022	NON-COMPETING CONTINUATION	$3,054,680
2022	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	000	2	12/17/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,054,680

Issue Date FY: 2021 ( Subtotal = $3,062,620 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	001	2	3/24/2021	NON-COMPETING CONTINUATION	$3,062,620
2021	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	000	1	10/16/2020	NEW	$0
														Subtotal = $3,062,620

Issue Date FY: 2020 ( Subtotal = $3,009,915 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Mental Health Research Grants	000	1	3/6/2020	NEW	$3,009,915
														Subtotal = $3,009,915

Grand Total All Awards = $18,342,671

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Dysfunctional State Representations in Psychosis: From Neurophysiology to Neuroplasticity-based Treatment

Award Number: P50MH119569

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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