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The effect of right dlPFC cTBS on acute measures of anxiety, functional connectivity, and TMS-evoked BOLD responses

Award Number: R01MH138375
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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The effect of right dlPFC cTBS on acute measures of anxiety, functional connectivity, and TMS-evoked BOLD responses - The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression in anxiety disorders, depression, and posttraumatic stress disorder (PTSD). There seems to be clear mechanistic evidence that right dlPFC downregulation of amygdala activity should reduce fear and anxiety. Despite this mechanistic evidence, the primary approaches to treat anxiety with neuromodulation involve right dlPFC inhibition. Accordingly, there is a critical need to understand the mechanisms of action underlying neuromodulatory right dlPFC TMS protocols, yet there is not a standardized protocol to yield such evidence. Concurrent TMS/fMRI offers a unique translational perspective for understanding psychopathology. By experimentally stimulating a region of the brain and then directly measuring the activity evoked by this stimulation, it is possible to causally determine the downstream targets of this region, facilitating the development of novel TMS treatments for disorders like PTSD and anxiety. The objective of the current project is to develop a protocol using interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. As a proof of concept, we will determine the effect of continuous theta burst stimulation (cTBS) to the right dlPFC on TMS-evoked fMRI responses in anxious subjects. Our central hypothesis is that cTBS of the right dlPFC will drive down activity throughout its downstream targets, resulting in reduced anxiety and greater TMS-evoked deactivations in these downstream circuits. Accordingly, our approach will be to measure anxious arousal and TMS-evoked BOLD responses before and immediately after 1800 pulses of cTBS, or sham stimulation in 140 high anxious individuals using a within-subjects crossover design. Our primary outcome will be TMS-evoked BOLD responses in a network of downstream targets involved in emotion expression (i.e. amygdala, BNST, sgACC). Aim 1 will be to examine the effects of right dlPFC cTBS vs. sham on anxious arousal. Aim 2 will be to examine the effects of right dlPFC cTBS vs. sham on TMS-evoked BOLD responses. Our exploratory aim will be to determine the links between anxiety phenotype, anxious arousal, and TMS-evoked BOLD responses. Our study team features Dr. Desmond Oathes, who is a pioneer in the field of TMS/fMRI, Dr. Lily Brown, who is the head of the Center for the Treatment and Study of Anxiety, and is led by Dr. Nicholas Balderston, who is (to our knowledge) the only researcher who has successfully combined threat of shock with interleaved TMS/fMRI. This study is innovative because it is the first to combine these technologies to study the effect of neuromodulatory TMS on threat-related TMS-evoked BOLD responses. This project is significant because it will provide future researchers with a systematic approach for evaluating the effectiveness of neuromodulatory TMS protocols on several neural and behavioral indices of anxiety expression. It will also yield direct evidence that cTBS can modulate brain activity associated with anxiety.


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 = $762,440 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	3/25/2026	NEW	$762,440
														Subtotal = $762,440

Grand Total All Awards = $762,440

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The effect of right dlPFC cTBS on acute measures of anxiety, functional connectivity, and TMS-evoked BOLD responses

Award Number: R01MH138375

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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