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Adolescent striatal neurophysiological maturation underlying the transition to adult stabilization of behavior

Award Number: R37MH080243
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2008
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Adolescent striatal neurophysiological maturation underlying the transition to adult stabilization of behavior - Project Summary/Abstract This is the second renewal on a line of inquiry characterizing the neural basis of the maturation of reward and motivation through the adolescent period, a time of critical vulnerability to the emergence of major psychopathol- ogy (e.g., substance use disorder, schizophrenia, mood disorders), which are typically impacted by deficiencies in these systems. Building on the findings from the first two grants using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography, and reward learning assessments, indicating heightened influence of reward/motivation (i.e., dopaminergic) systems in adolescence, we now propose to study their wider effects on establishing adult trajectories by characterizing developmental changes in habit formation and relatedly, stabili- zation of neural activity. The neural mechanisms that underlie maturation to established neurocognitive behav- iors have not been studied in human development and can provide unique insights into how adult trajectories are formed. The central hypothesis is that neurobehavioral processes underlying stabilization of behavior from adolescence to adulthood are supported by frontolimbic specialization and stabilization of neural activity. We will study 192 typically developing 10-26 year-olds with habit tasks in fMRI and EEG, and 45 pediatric epilepsy patients with intracerebral EEG. In Aim 1, we will characterize the neurodevelopment of habit formation as a probe for how modes of stable behavior are acquired defining adulthood, which rodent models have found is limited in adolescence and has not been studied in humans. We will use a well-established habit task and determine developmental changes in behavior and BOLD fMRI activity. In Aim2, we will characterize how changes in frontostriatal systems including using non-invasive indirect measures of dopamine through brain tissue iron, which in the previous grant we found is closely associated with dopamine, and functional connectivity, which our previous grant found specializes through adolescence, underlie neurocognitive stabilization into adult- hood. Finally, in order to understand how neural systems are stabilizing through adolescence into adult- hood, in Aim 3, we will characterize developmental changes in oscillations and in the variability of neural activity in key regions involved in habit formation using electroencephalography (EEG) and intracerebral stereo-eletroenceph- alography (sEEG). sEEG will be performed in collaboration with our co-investigator, a pediatric neurosurgeon who implants electrodes in preparation for resection due to epilepsy, providing critical data for characterizing de- velopmental changes in neural activity directly. These studies have never been performed in human development and can provide novel evidence regarding the neural mechanisms underlying normative establishment of adult trajectories informing how these may lead to maladaptive trajectories such as in psychopathology, which emerges during the transition from adolescence to adulthood.


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: 2026 ( Subtotal = $702,237 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	15	1/28/2026	NON-COMPETING CONTINUATION	$702,237
														Subtotal = $702,237

Issue Date FY: 2025 ( Subtotal = $591,526 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	14	1/23/2025	NON-COMPETING CONTINUATION	$591,526
														Subtotal = $591,526

Issue Date FY: 2024 ( Subtotal = $702,604 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	13	8/14/2024	NON-COMPETING CONTINUATION	$70,260
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	13	1/22/2024	NON-COMPETING CONTINUATION	$632,344
														Subtotal = $702,604

Issue Date FY: 2023 ( Subtotal = $693,319 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	12	2/4/2023	NON-COMPETING CONTINUATION	$693,319
														Subtotal = $693,319

Issue Date FY: 2022 ( Subtotal = $667,432 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	11	4/8/2022	COMPETING CONTINUATION	$667,432
														Subtotal = $667,432

Grand Total All Awards = $3,357,118

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Adolescent striatal neurophysiological maturation underlying the transition to adult stabilization of behavior

Award Number: R37MH080243

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/12/2008

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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