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Multi-target repetitive Transcranial Magnetic Stimulation (rTMS) treatment for Major Depressive Disorder (MDD) and comorbid pain

Award Number: K01MH123887
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/04/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Multi-target repetitive Transcranial Magnetic Stimulation (rTMS) treatment for Major Depressive Disorder (MDD) and comorbid pain - PROJECT SUMMARY Major Depressive Disorder (MDD) and fibromyalgia (FM) are highly comorbid, disabling and resistant to treatment. More than half of MDD patients present with pain symptoms, and the comorbidity is associated with reduced quality of life, poor pharmacological treatment outcomes, and opioid use disorders. New approaches to help comorbid patients are urgently needed. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment may ameliorate both pain and mood symptoms, possibly through modulation of shared underlying pathophysiological brain networks. Preliminary data indicate rTMS applied to the left dorsolateral prefrontal cortex (lDLPFC) significantly improved both depressive and moderate pain symptoms but failed to improve more severe comorbid pain. In this application, we propose to test the efficacy of a multi-target rTMS protocol that may be more successful in treating both mood and pain symptoms in comorbid MDD/FM. This includes two complementary objectives: 1) to test the effects of a novel rTMS protocol for comorbid MDD and FM, and 2) to provide critical additional training to the candidate that will facilitate her transition into independence as a researcher specializing in the comorbidity of mood disorders with chronic pain and their treatment with rTMS. This will be achieved through a randomized, sham-controlled study with two experimental conditions: A) Active rTMS to lDLPFC (established target for MDD) and sham rTMS to the primary motor cortex (M1, established pain target); and B) Active rTMS to both, lDLPFC and M1. We anticipate that multi-site rTMS will be more efficacious to treat both MDD and FM symptoms than the single site rTMS protocol. Additionally, we will determine the differences and similarities of neural signatures of MDD and FM and how these interact in the comorbid condition using machine learning techniques. The K01 project will take place at UCLA with the mentoring support from the director of the Neuromodulation Division, two co-mentors and four other collaborators with expertise in rTMS, depression, chronic pain, multimodal imaging, and machine learning analysis. This approach will achieve the project’s specific aims to: 1. Evaluate the effect of multi-site vs. single site rTMS on clinical symptoms; 2. Determine the interaction of networks affected in MDD and chronic pain and how they are modulated by rTMS; and 3. Examine the interaction between analgesic and antidepressant effects of rTMS. If these aims are achieved, the short-term outcome of this project will help determine the efficacy of multi-site rTMS for comorbid MDD and FM, identify the overlap of the neural signature of MDD and FM and how it is modulated by rTMS, and characterize the relationship between rTMS-induced antidepressant and analgesic effects. In the long-term, current rTMS procedures may be significantly improved for the treatment of MDD with comorbid chronic pain.


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: 2027 ( Subtotal = $182,887 )
2027	2027	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research - Other Research	000	5	11/6/2026	NON-COMPETING CONTINUATION	$182,887
														Subtotal = $182,887

Issue Date FY: 2026 ( Subtotal = $182,887 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	4	12/22/2025	NON-COMPETING CONTINUATION	$182,887
														Subtotal = $182,887

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	3	6/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $182,887 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	3	5/9/2024	NON-COMPETING CONTINUATION	$182,887
														Subtotal = $182,887

Issue Date FY: 2023 ( Subtotal = $182,887 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	2	3/30/2023	NON-COMPETING CONTINUATION	$182,887
														Subtotal = $182,887

Issue Date FY: 2022 ( Subtotal = $182,887 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	1	4/4/2022	NEW	$182,887
														Subtotal = $182,887

Grand Total All Awards = $914,435

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Multi-target repetitive Transcranial Magnetic Stimulation (rTMS) treatment for Major Depressive Disorder (MDD) and comorbid pain

Award Number: K01MH123887

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/04/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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