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CRCNS US-France Research Proposal: Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression

Award Number: R01MH129018
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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The overarching goal of this work is to improve treatments of medication-resistant neuropsychiatric diseases with repetitive transcranial stimulation (rTMS) by tailoring the target to an individual's brain networks. We are indeed in critical need of these individualized treatments for mental health disorders, which affect nearly 50% of Americans during our lifetimes, and brain stimulation treatments, including rTMS represent innovative approaches for these patients. To alleviate depression, rTMS attempts to target a region of the prefrontal cortex generally located within the central executive network (CEN), which drives decision making, cognitive control, and is critically impaired in depression. However, rTMS is delivered without targeting an individual's CEN, and as such may inadvertently deliver stimulation outside the CEN. This application is motivated by recent developments in the field, including a large-scale whole-brain connectivity database derived from invasive recordings and the demonstration that rTMS in depressed patients induces brain changes that predict clinical improvement. In this proposal, we combine non- invasive TMS studies in healthy subjects and depressed patients with invasive direct stimulation studies from surgical patients. We test the hypothesis that the CEN connectivity is weakened in depression and can be maximally modulated by individualizing localization. The project consists of three aims: (1) investigate the excitability, connectivity, and neuronal properties within the CEN using direct brain recordings in surgical patients with epilepsy; (2) derive accurate TMS tools to measure CEN connectivity non-invasively in healthy and depressed populations; and (3) in a depressed population characterize inter-individual variability within the CEN and prospectively test if localization with TMS at the individual level more effectively modulates this brain network. This approach, which can be generalized to any brain region and disorder, utilizes a large database of direct brain recordings to map a brain network at an unparalleled level of detail, develops a link to direct brain recordings in order to yield validated non-invasive brain measures, and applies these insights to individually localize the network and improve targeted brain stimulation. Scientific outcomes include: (1) the first causal, functional map of the human CEN from direct brain recordings; (2) novel non-invasive brain measures of connectivity grounded in electrophysiology; (3) causal brain signatures of depression in the CEN; (4) a methodology to target an individual's CEN in the clinic; and (5) improved modulation of the CEN using this methodology. In summary, a successful outcome of the proposed work would yield an algorithm and guidelines for personalized TMS targeting based on fully validated brain signatures in depression. RELEVANCE (See instructions): Brain stimulation for depression targets the central executive network (CEN), involved in decision making and cognitive control, core in depression, and difficult to target in the clinic. Here we propose to study the connectivity of the CEN using a combination of invasive and non-invasive brain recordings; we will 1) investigate CEN connectivity from direct brain recordings, 2) derive accurate and causal tools to measure CEN connectivity non- invasively in healthy and depressed populations, and 3) test if CEN localization at the individual level can more effectively modulate this network. A successful outcome of the proposed work would yield an algorithm and guidelines for personalized TMS targeting based on fully validated brain signatures in depression.


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: 2023 ( Subtotal = $231,549 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	000	3	5/31/2023	NON-COMPETING CONTINUATION	$231,549
														Subtotal = $231,549

Issue Date FY: 2022 ( Subtotal = $208,088 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	004	2	7/20/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$201,859
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Mental Health Research Grants	002	2	4/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$208,088
2022	2021	PALO ALTO VETERANS INSTITUTE FOR RESEARCH	3801 MIRANDA AVE BLDG 101 A2-210	PALO ALTO	CA	94304	SANTA CLARA	USA	Mental Health Research Grants	001	1	4/22/2022	NEW	$0
2022	2021	PALO ALTO VETERANS INSTITUTE FOR RESEARCH	3801 MIRANDA AVE BLDG 101 A2-210	PALO ALTO	CA	94304	SANTA CLARA	USA	Mental Health Research Grants	000	1	11/2/2021	NEW	$0
2022	2021	PALO ALTO VETERANS INSTITUTE FOR RESEARCH	3801 MIRANDA AVE BLDG 101 A2-210	PALO ALTO	CA	94304	SANTA CLARA	USA	Mental Health Research Grants	003	1	7/20/2022	NEW	-$201,859
														Subtotal = $208,088

Issue Date FY: 2021 ( Subtotal = $201,859 )
2021	2021	PALO ALTO VETERANS INSTITUTE FOR RESEARCH	3801 MIRANDA AVE BLDG 101 A2-210	PALO ALTO	CA	94304	SANTA CLARA	USA	Mental Health Research Grants	000	1	7/2/2021	NEW	$201,859
														Subtotal = $201,859

Grand Total All Awards = $641,496

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CRCNS US-France Research Proposal: Probing the Dorsolateral Prefrontal Cortex and Central Executive Network for Improving Neuromodulation in Depression

Award Number: R01MH129018

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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