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Computational, Neural, and Behavioral Studies of Competition-Dependent Learning

Award Number: R01MH069456
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2004
PERIOD OF PERFORMANCE END DATE: 02/28/2030

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Computational, Neural, and Behavioral Studies of Competition-Dependent Learning - The overarching goal of this renewal application is to understand how stored memories change as a function of experience, and how these changes support our ability to discriminate similar stimuli. The inability to make such distinctions can lead to mundane errors and memory interference, but also devastating cognitive, semantic, communication, and developmental deficits. We focus on the challenging scenario when the differences between stimuli are subtle and the stimuli appear at different times, requiring memory. The specific goal of this proposal is to understand the interacting roles of the hippocampus and cortex in this scenario. Recent studies have found that the key to behavioral discrimination is differentiation of hippocampal representations — a phenomenon whereby the representations of similar stimuli are pushed apart beyond the orthogonality of pattern separation, to the point of anti-correlation. Crucially, existing computational models of the hippocampus do not exhibit differ- entiation and thus cannot provide a satisfactory account of memory-based discrimination learning. The major significance of this proposal is to remedy this critical gap, by formulating and testing a new neurocomputational theory that explains the causes of hippocampal differentiation and its consequences for discrimination behavior. Aim 1 breaks new theoretical ground by incorporating our theory of how unsupervised learning gives rise to differentiation (developed in the prior funding period) into a biologically grounded neural network model of hip- pocampus and its interactions with cortex, which will be used to explain existing results and to generate novel neural and behavioral predictions about discrimination learning. Aim 2 tests these predictions with fMRI. A key prediction is that the hippocampus has a time-limited role in discrimination learning, supporting activation of unique features of similar stimuli in visual cortex after (but not before) differentiation, then relinquishing this role after consolidation. This prediction and others are tested using new fMRI decoding methods based on deep learning to quantify how strongly visual cortex represents unique features of paired stimuli, and how this relates to hippocampal activity. Aim 3 combines innovative experimental approaches with greater causal leverage to further test model predictions: real-time closed-loop fMRI to manipulate cortical inputs to the hippocampus; in- tracranial EEG (iEEG) to measure the temporal precedence of hippocampal signals driving representation of unique features in visual cortex; and responsive neurostimulation (RNS) to transiently disrupt hippocampal pro- cessing in patients with chronic implants. In summary: This proposal tightly couples theoretical neural network modeling with experimental tests of model predictions using advanced correlational (fine-grained fMRI decoding, consolidation-related EEG signals) and causal (real-time fMRI, iEEG, RNS) human neuroscience methods. This work provides pivotal basic science insights into how the hippocampus supports learning. These insights may facilitate the development of evidence-based learning paradigms that improve discrimination behavior, with po- tential application to new treatments for psychiatric and neurological disorders.


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: 2025 ( Subtotal = $830,767 )
2025	2025	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	16	5/1/2025	COMPETING CONTINUATION	$830,767
														Subtotal = $830,767

Issue Date FY: 2024 ( Subtotal = -$78,387 )
2024	2020	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	001	14	2/16/2024	SUPPLEMENT FOR EXPANSION	-$4,413
2024	2020	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	15	2/16/2024	NON-COMPETING CONTINUATION	-$73,974
														Subtotal = -$78,387

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	15	6/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $563,223 )
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	001	15	7/29/2020	NON-COMPETING CONTINUATION	$531,516
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	14	6/11/2020	SUPPLEMENT FOR EXPANSION	$31,707
														Subtotal = $563,223

Issue Date FY: 2019 ( Subtotal = $455,418 )
2019	2019	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	14	7/13/2019	NON-COMPETING CONTINUATION	$455,418
														Subtotal = $455,418

Issue Date FY: 2018 ( Subtotal = $455,418 )
2018	2018	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	13	7/7/2018	NON-COMPETING CONTINUATION	$455,418
														Subtotal = $455,418

Issue Date FY: 2017 ( Subtotal = $455,418 )
2017	2017	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	12	6/14/2017	NON-COMPETING CONTINUATION	$455,418
														Subtotal = $455,418

Issue Date FY: 2016 ( Subtotal = $521,520 )
2016	2016	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	11	9/19/2016	COMPETING CONTINUATION	$521,520
														Subtotal = $521,520

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2013	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	10	5/19/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $370,385 )
2013	2013	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	10	5/9/2013	NON-COMPETING CONTINUATION	$370,385
														Subtotal = $370,385

Issue Date FY: 2012 ( Subtotal = $386,246 )
2012	2012	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	9	5/10/2012	NON-COMPETING CONTINUATION	$386,246
														Subtotal = $386,246

Issue Date FY: 2011 ( Subtotal = $386,548 )
2011	2011	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	8	6/24/2011	NON-COMPETING CONTINUATION	$386,548
														Subtotal = $386,548

Issue Date FY: 2010 ( Subtotal = $390,910 )
2010	2010	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	7	9/14/2010	NON-COMPETING CONTINUATION	$390,910
														Subtotal = $390,910

Issue Date FY: 2009 ( Subtotal = $385,268 )
2009	2009	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	6	8/5/2009	COMPETING CONTINUATION	$385,268
														Subtotal = $385,268

Issue Date FY: 2008 ( Subtotal = $240,425 )
2008	2008	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	5	3/25/2008	NON-COMPETING CONTINUATION	$240,425
														Subtotal = $240,425

Issue Date FY: 2007 ( Subtotal = $238,394 )
2007	2007	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	4	2/2/2007	NON-COMPETING CONTINUATION	$238,394
														Subtotal = $238,394

Issue Date FY: 2006 ( Subtotal = $243,482 )
2006	2006	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	3	1/31/2006	NON-COMPETING CONTINUATION	$243,482
														Subtotal = $243,482

Issue Date FY: 2005 ( Subtotal = $247,322 )
2005	2005	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	2	1/24/2005	NON-COMPETING CONTINUATION	$247,322
														Subtotal = $247,322

Issue Date FY: 2004 ( Subtotal = $258,411 )
2004	2004	PRINCETON UNIVERSITY	POST OFFICE BOX 5292	PRINCETON	NJ	08544	MERCER	USA	Mental Health Research Grants	000	1	1/26/2004	NEW	$258,411
														Subtotal = $258,411

Grand Total All Awards = $6,350,768

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Computational, Neural, and Behavioral Studies of Competition-Dependent Learning

Award Number: R01MH069456

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2004

PERIOD OF PERFORMANCE END DATE: 02/28/2030

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