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2/2 - Anomalous Motor System Physiology in ADHD: Biomarker Validation and Modeling Domains of Function

Award Number: R01MH078160
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2006
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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2/2 - Anomalous Motor System Physiology in ADHD: Biomarker Validation and Modeling Domains of Function - PROJECT SUMMARY Attention Deficit Hyperactivity Disorder (ADHD), the most common childhood behavioral diagnosis, is a heterogeneous disorder linked to poor adult outcomes including high rates of academic underachievement, mental illness, substance abuse, and criminal activity. A critical obstacle to improving long-term ADHD outcomes is the current lack of quantitative neurophysiologic markers that could be used to improve precision treatment (behavioral and pharmacologic). In research funded during two grant periods, we addressed this barrier: Leveraging observed associations of ADHD-associated impairments in motor control with core impairments in cognitive and emotional control to pursue motor physiologic biomarkers linked to ADHD diagnosis and symptom severity. Engaging expertise of two research teams in different cities, we developed, refined, and effectively implemented innovative methods for evaluating motor physiology in school-age children with ADHD. During the first grant period we initiated Transcranial Magnetic Stimulation (TMS) investigations of motor cortex, discovering that Short Interval Cortical Inhibition (SICI) is reduced in children with ADHD and that this reduced SICI correlates with parent-ratings of ADHD symptom severity, with consistent findings across the two sites. During the second grant period, we developed (TMS-compatible) child-friendly games as paradigms for evaluation of motor cortex physiology under conditions requiring cognitive and emotional control. We found that SICI is reduced in children with ADHD during action selection and inhibition (as well as rest). Further, we discovered that TMS-evoked increases in motor evoked potential (MEP) amplitude from rest to task engagement (which we have denoted as “Task Related Up Modulation” - TRUM) are significantly diminished in ADHD. Interestingly, while both TRUM and SICI robustly correlate with ADHD severity, they show limited correlation with each other. These published findings, in conjunction promising preliminary analyses of TMS- behavioral associations, suggest a model in which these two promising, distinct physiologic biomarkers reflect differential domains of dysfunction in ADHD, with SICI reflecting mechanisms linked to maintaining attention and filtering distractions, while TRUM reflects the capacity to modulate response control particularly under cognitively and emotionally demanding conditions. To pursue validation of SICI and TRUM as physiologic biomarkers, we now propose: AIM 1 To establish test-retest reliability of SICI and TRUM in children with ADHD and typically developing (TD) controls. AIM 2 To quantify stimulant treatment-induced changes in SICI and TRUM in children with ADHD as a validation of utility of these biomarkers for treatment focused studies. AIM 3 To explore the differential association of SICI and TRUM with ADHD-relevant RDoC constructs of Cognitive Control and Emotional Positive/Negative Valence. Achieving these aims will lay groundwork for future use of SICI and TRUM as a pragmatic and biologically meaningful quantitative measure that can be applied to investigations of precision ADHD treatment, genetics, and risk factors for serious long-term outcomes.


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 = $344,811 )
2024	2024	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	15	5/30/2024	NON-COMPETING CONTINUATION	$344,811
														Subtotal = $344,811

Issue Date FY: 2023 ( Subtotal = $345,271 )
2023	2023	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	14	5/25/2023	NON-COMPETING CONTINUATION	$345,271
														Subtotal = $345,271

Issue Date FY: 2022 ( Subtotal = $345,271 )
2022	2022	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	13	6/22/2022	NON-COMPETING CONTINUATION	$345,271
														Subtotal = $345,271

Issue Date FY: 2021 ( Subtotal = $345,273 )
2021	2021	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	12	6/18/2021	NON-COMPETING CONTINUATION	$345,273
														Subtotal = $345,273

Issue Date FY: 2020 ( Subtotal = $363,122 )
2020	2020	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	11	7/10/2020	COMPETING CONTINUATION	$363,122
														Subtotal = $363,122

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	10	9/10/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	10	12/31/2016	EXTENSION WITH OR WITHOUT FUNDS	$47,958
2017	2015	HUGO W. MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER, INC.	707 N BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	9	12/31/2016	NON-COMPETING CONTINUATION	-$47,958
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $496,155 )
2016	2016	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	10	5/5/2016	EXTENSION WITH OR WITHOUT FUNDS	$496,155
														Subtotal = $496,155

Issue Date FY: 2015 ( Subtotal = $508,514 )
2015	2015	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	9	5/7/2015	NON-COMPETING CONTINUATION	$508,514
														Subtotal = $508,514

Issue Date FY: 2014 ( Subtotal = $517,131 )
2014	2014	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	8	6/7/2014	NON-COMPETING CONTINUATION	$408,143
2014	2014	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	8	6/17/2014	SUPPLEMENT FOR EXPANSION	$108,988
														Subtotal = $517,131

Issue Date FY: 2013 ( Subtotal = $401,562 )
2013	2013	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	7	6/5/2013	NON-COMPETING CONTINUATION	$401,562
2013	2010	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	5	8/27/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $401,562

Issue Date FY: 2012 ( Subtotal = $468,529 )
2012	2012	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	6	6/4/2012	COMPETING CONTINUATION	$468,529
														Subtotal = $468,529

Issue Date FY: 2010 ( Subtotal = $326,412 )
2010	2010	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	5	5/13/2010	NON-COMPETING CONTINUATION	$326,412
														Subtotal = $326,412

Issue Date FY: 2009 ( Subtotal = $336,844 )
2009	2009	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	001	4	5/26/2009	NON-COMPETING CONTINUATION	$336,844
2009	2008	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	3	3/20/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $336,844

Issue Date FY: 2008 ( Subtotal = $309,087 )
2008	2008	HUGO W MOSER RESEARCH INSTITUTE AT KENNEDY KRIEGER INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	3	6/27/2008	NON-COMPETING CONTINUATION	$309,087
														Subtotal = $309,087

Issue Date FY: 2007 ( Subtotal = $317,148 )
2007	2007	KENNEDY RESEARCH INSTITUTE, INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	2	6/20/2007	NON-COMPETING CONTINUATION	$317,148
														Subtotal = $317,148

Issue Date FY: 2006 ( Subtotal = $363,010 )
2006	2006	KENNEDY RESEARCH INSTITUTE, INC	707 NORTH BROADWAY	BALTIMORE	MD	21205	BALTIMORE CITY	USA	Mental Health Research Grants	000	1	8/30/2006	NEW	$363,010
														Subtotal = $363,010

Grand Total All Awards = $5,788,140

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2/2 - Anomalous Motor System Physiology in ADHD: Biomarker Validation and Modeling Domains of Function

Award Number: R01MH078160

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2006

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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