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Mechanisms of Information Seeking in the Primate Brain

Award Number: R01MH116937
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/10/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Mechanisms of Information Seeking in the Primate Brain - Project Summary. The brain systems that control our motivation, emotions, and decisions rely at their most fundamental level on predicting the future: learning what outcomes to expect, when they will arrive, and how valuable they will be. It is only natural that we are strongly motivated to seek information that will reduce our uncertainty. But despite its importance in everyday decision making and clinical settings, little is known about how information seeking behavior is controlled – how the brain anticipates information, endows it with value, and sends it to motivational circuits to drive behavior. We identified set of anatomically connected areas, including the anterior cingulate cortex and subregions of the basal ganglia, that encode the quantitative level of reward uncertainty to control information seeking to resolve that uncertainty. We also showed that the value of information is computed through a conserved algorithm in the brains of macaques and humans, and that this algorithm governs value-based decisions through the lateral habenula (LHb). Leveraging this insight, the Aims will answer several key questions. We will study a crucial but understudied pathway in primates: concentrating on whether and how the thalamus causally mediates prefrontal cortical computations that regulate information seeking. And we will assess how the anatomically defined cortical-basal ganglia-thalamus loop performs the computational steps of estimating and representing reward probability distributions, computing their uncertainties, and how it causally uses these representations to set the value of information and regulate information seeking decisions. Our key overarching hypothesis is that the thalamus transmits information about uncertainty to the cortex and causally regulates cortical uncertainty processing to control information seeking. Aim 1 will uncover whether and how the primate thalamus regulates the motivation to seek information to reduce uncertainty through online modulation of the neocortex. Based on preliminary data, we hypothesize that anterior medial thalamus is a key source of uncertainty signals, and that it causally regulates cortical computation to guide information seeking. Aim 2 will assess whether and how different subregions within the cortical basal ganglia thalamic loop represent probability distributions and their uncertainties and use them to motivate information seeking decisions. Our hypothesis is that the decision variables in the cortex are computed from distributional representations of value and uncertainty to guide deliberative information seeking decisions through LHb and moment-to-moment information seeking behavior through the basal ganglia, and that these processes are dependent on thalamic inputs. The Aims offer an unprecedented opportunity to understand the mechanisms of information seeking, and to study clinically relevant primate brain areas that have remained understudied. In the long term, research on information seeking will provide crucial insight about neural circuit function in health and disease in an age in which information seeking has become a critical component of adaptive behavior.


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 = $583,376 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Mental Health Research Grants	002	7	9/9/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$583,376
2025	2024	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	6	9/9/2025	COMPETING CONTINUATION	$0
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	5	2/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $583,376

Issue Date FY: 2024 ( Subtotal = $734,192 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	001	6	9/17/2024	COMPETING CONTINUATION	$734,192
2024	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	5	9/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $734,192

Issue Date FY: 2023 ( Subtotal = $393,750 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	5	1/30/2023	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2022 ( Subtotal = $393,750 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	001	4	5/16/2022	NON-COMPETING CONTINUATION	$39,375
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	4	1/31/2022	NON-COMPETING CONTINUATION	$354,375
														Subtotal = $393,750

Issue Date FY: 2021 ( Subtotal = $393,750 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	3	2/23/2021	NON-COMPETING CONTINUATION	$393,750
														Subtotal = $393,750

Issue Date FY: 2020 ( Subtotal = $393,438 )
2020	2020	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	2	1/24/2020	NON-COMPETING CONTINUATION	$393,438
														Subtotal = $393,438

Issue Date FY: 2019 ( Subtotal = $391,563 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Mental Health Research Grants	000	1	4/9/2019	NEW	$391,563
														Subtotal = $391,563

Grand Total All Awards = $3,283,819

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Mechanisms of Information Seeking in the Primate Brain

Award Number: R01MH116937

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/10/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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