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Hippocampal-orbitofrontal interactions and reward learning

Award Number: R01MH121448
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/03/2019
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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Hippocampal-orbitofrontal interactions and reward learning - Project summary (<30 lines) Dysfunction of both the hippocampus and the orbitofrontal cortex have been implicated in a wide variety of neuropsychiatric disorders, including obsessive-compulsive disorder, mood disorders and addiction. However, their exact contribution remains unclear. A major problem is that most research on hippocampal mechanisms is derived from rodent work. However, the structure of the hippocampus has undergone dramatic changes across the course of evolution, particularly in those parts associated with psychopathologies. This necessitates the use of primate models, but there have been few studies of hippocampus in the primate. The current grant will investigate the neuronal properties of hippocampus in the primate and determine how it interacts with orbitofrontal cortex. The theoretical framework that we will employ is derived from computational psychiatry, with a particular focus on how the computational processes underlying reinforcement learning might contribute to neuropsychiatric disease. Our hypothesis is that both hippocampus and orbitofrontal cortex make critical contributions to model-based reinforcement learning, whereby hippocampus is responsible for constructing the cognitive map that instantiates the neural representation of the task model, and orbitofrontal cortex is responsible for using the cognitive map to generate reward predictions that can be used to guide decision-making. To test this hypothesis, we will use a combination of high-channel count neuronal recordings and electrical microstimulation. We will record from single neurons in the hippocampus during performance of a reward-based learning task and examine whether hippocampal neurons show value place tuning. We will then examine how hippocampus might communicate this information to orbitofrontal cortex by recording from both structures simultaneously. Our prediction is that this communication will be mediated via synchronization of theta rhythms. However, such measures are correlative. Establishing a causal role for neural rhythms has proven challenging, since it is difficult to manipulate a specific neuronal rhythm without affecting other neuronal rhythms and/or neuronal firing rates. We have recently developed a closed-loop approach, which involves recording rhythms in real-time and using those signals to control the application of electrical microstimulation. This allows us to disrupt a neuronal rhythm of a specific frequency. We will use this method to examine whether there is a causal role for the theta oscillation in reward-based learning. Taken together, the results of this proposal will provide convergent correlative and causal evidence for the role of hippocampus and orbitofrontal cortex in reward-based learning and the mechanism by which they communicate. This will help lay the groundwork for future potential therapeutic approaches for frontolimbic dysfunction based on closed-loop microstimulation.


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 = $411,763 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	000	5	10/20/2023	NON-COMPETING CONTINUATION	$370,587
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	001	5	8/14/2024	NON-COMPETING CONTINUATION	$41,176
														Subtotal = $411,763

Issue Date FY: 2023 ( Subtotal = $496,557 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	000	4	11/15/2022	NON-COMPETING CONTINUATION	$375,956
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	002	4	2/17/2023	NON-COMPETING CONTINUATION	$41,773
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	001	4	11/17/2022	SUPPLEMENT FOR EXPANSION	$78,828
														Subtotal = $496,557

Issue Date FY: 2022 ( Subtotal = $511,472 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	000	3	10/27/2021	NON-COMPETING CONTINUATION	$389,379
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	002	3	6/13/2022	NON-COMPETING CONTINUATION	$43,265
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	001	3	2/7/2022	SUPPLEMENT FOR EXPANSION	$78,828
														Subtotal = $511,472

Issue Date FY: 2021 ( Subtotal = $455,016 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	001	2	4/20/2021	NON-COMPETING CONTINUATION	$45,502
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	000	2	11/5/2020	NON-COMPETING CONTINUATION	$409,514
														Subtotal = $455,016

Issue Date FY: 2020 ( Subtotal = $444,883 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	001	1	3/11/2020	NEW	$44,488
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Mental Health Research Grants	000	1	12/3/2019	NEW	$400,395
														Subtotal = $444,883

Grand Total All Awards = $2,319,691

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Hippocampal-orbitofrontal interactions and reward learning

Award Number: R01MH121448

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/03/2019

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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