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Multiscale computational frameworks for integrating large-scale cortical dynamics, connectivity, and behavior

Award Number: RF1DA055666
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/12/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Multiscale computational frameworks for integrating large-scale cortical dynamics, connectivity, and behavior - Project Summary/Abstract A central problem in neuroscience is to understand how activity arises from neural circuits to drive animal behaviors. Solving this problem requires integrating information from multiple experimental modalities and organization levels of the nervous system. While modern neurotechnologies are generating high-resolution maps of the brain-wide neural activity and anatomical connectivity, novel theoretical frameworks are urgently needed to realize the full potential of these datasets. Most state-of-the-art methods for analyzing high-dimensional data are based on detecting correlations in neural activity and do not provide links to the underlying anatomical connectivity and circuit mechanisms. As a result, conclusions derived with these methods rarely generalize across different behaviors and are hard to validate in perturbation experiments. In contrast, mechanistic theories, which combine connectivity, activity, and function, have been highly successful in understanding function of small neural circuits. Conditions under which insights from small circuits scale to large distributed circuits have not been explored. Mechanistic theories informed by multiple data modalities are critically missing to guide experiments probing global neural dynamics on the brain-wide scale. The main goal of this proposal is to develop computational frameworks for modeling global neural dynamics, which utilize anatomical connectivity and predict rich behavioral outputs on single trials. Our project will address two complementary aims. First, we will take advantage of recently available datasets of high-resolution brain- wide neural activity and anatomical connectivity to construct a multiscale model of functional dynamics across the mouse cortex. Integrating measurements across multiple scales, from mesoscopic to near-cellular resolution, we aim to reveal the effective degrees of freedom at each scale, which constrain global neural dynamics and drive rich patterns of behavior. Second, we will leverage techniques from dynamical systems theory and artificial recurrent neural networks to develop circuit reduction methods that infer interpretable low-dimensional circuit mechanisms of cognitive computations from high-dimensional neural activity data. Rather than merely detecting correlations, our method infers the structural connectivity of an equivalent low-dimensional circuit that fits projections of high-dimensional neural activity data and implements the behavioral task. We will apply this method to multi-area neural activity recordings from behaving animals to reveal distributed circuit mechanisms of context-dependent decision making. The computational frameworks developed in this proposal can be validated in perturbation experiments and extended to other nervous systems and behaviors.


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 = -$337 )
2025	2021	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Drug Use and Addiction Research Programs	001	2	1/7/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$337
2025	2021	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	1	10/8/2024	NEW	$0
														Subtotal = -$337

Issue Date FY: 2023 ( Subtotal = -$127,157 )
2023	2021	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	1	7/18/2023	NEW	-$818,559
2023	2021	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Drug Use and Addiction Research Programs	001	2	7/18/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$691,402
														Subtotal = -$127,157

Issue Date FY: 2021 ( Subtotal = $1,440,000 )
2021	2021	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	1	8/11/2021	NEW	$1,440,000
														Subtotal = $1,440,000

Grand Total All Awards = $1,312,506

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Multiscale computational frameworks for integrating large-scale cortical dynamics, connectivity, and behavior

Award Number: RF1DA055666

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/12/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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