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Predictive Coding as a Framework for Understanding Psychosis

Award Number: R01MH112887
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2017
PERIOD OF PERFORMANCE END DATE: 10/31/2023

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Predictive Coding as a Framework for Understanding Psychosis - 7. Project Summary This application responds to the NIMH PAR-16-136, “Using the NIMH Research Domain Criteria (RDoC) Approach to Understand Psychosis.” Psychotic symptoms, such as delusions and hallucinations, are treatment-resistant in many patients and are associated with high levels of distress and impairment. Treatment advances have been slowed by the lack of a model of how these symptoms arise and persist. Adopting the RDoC approach, we suggest that these symptoms may result from abnormalities in the neural and cognitive processes that underlie perception, action, and belief formation. Hierarchical predictive coding represents an explanatory framework that unites function and dysfunction in perception action and belief formation. We perceive, act, and believe based on our prior experiences, and we update those priors in light of new data and the prediction errors they elicit. We suggest that hallucinations and delusions form, and are maintained, via aberrant predictive coding mechanisms that vitiate perception, action and belief. We will test these hypotheses with a suite of predictive coding measures in a large sample, capturing variability in symptom severity and duration. We will use functional magnetic resonance imaging (fMRI) during tasks of perception, action, and belief, electroencephalography to measure mismatch negativity (MMN) to unexpected perceptual stimuli, and magnetic resonance spectroscopy (MRS) to measure glutamate concentrations, which may underlie the perturbed MMN and fMRI signals in people with psychosis. We will bring together behavioral and brain data with formal computational modeling that will allow us to estimate, from each individual subject's data, the strength of their priors and prediction errors across a hierarchy of representational richness from simple stimuli through more complex percepts, action choices, and beliefs. We propose four specific aims: (1) testing whether inappropriately strong top-down perceptual priors cause hallucinations; (2) testing if delusions are caused by aberrant prediction error signaling; (3) examining whether psychotic symptoms result from a failure to attribute outcomes to one's own actions appropriately; (4) and assessing whether glutamate levels are related to predictive coding phenomena assayed in Aims 1-3. In a fifth exploratory aim, we will examine whether predictive coding abnormalities change over course of illness. Our overall goal is to provide a computationally rigorous test of the predictive coding account of delusions and hallucinations. Depending on the outcome, we will either discard the theory, or use it to design and test treatment approaches more tailored to the specific, and this far unmet, needs of individuals with psychosis.


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: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	5	4/4/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $670,370 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	001	5	5/12/2022	NON-COMPETING CONTINUATION	$67,037
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	5	11/1/2021	NON-COMPETING CONTINUATION	$603,333
														Subtotal = $670,370

Issue Date FY: 2021 ( Subtotal = $686,134 )
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	001	4	10/28/2020	NON-COMPETING CONTINUATION	$0
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	002	4	4/7/2021	NON-COMPETING CONTINUATION	$68,613
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	4	10/27/2020	NON-COMPETING CONTINUATION	$617,521
														Subtotal = $686,134

Issue Date FY: 2020 ( Subtotal = $701,897 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	001	3	2/3/2020	NON-COMPETING CONTINUATION	$70,189
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	3	12/3/2019	NON-COMPETING CONTINUATION	$631,708
														Subtotal = $701,897

Issue Date FY: 2019 ( Subtotal = $712,532 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	11/19/2018	NON-COMPETING CONTINUATION	$712,532
														Subtotal = $712,532

Issue Date FY: 2018 ( Subtotal = $783,334 )
2018	2018	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	11/28/2017	NEW	$783,334
														Subtotal = $783,334

Grand Total All Awards = $3,554,267

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Predictive Coding as a Framework for Understanding Psychosis

Award Number: R01MH112887

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2017

PERIOD OF PERFORMANCE END DATE: 10/31/2023

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