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Determining and enhancing the cellular selectivity of transcranial magnetic stimulation using optical physiology and computational models

Award Number: K99MH144381
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 09/02/2026

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Determining and enhancing the cellular selectivity of transcranial magnetic stimulation using optical physiology and computational models - PROJECT SUMMARY Transcranial magnetic stimulation (TMS) is FDA-approved for the treatment of drug-resistant depression, obsessive-compulsive disorder, and migraine, and is under investigation for a range of other psychiatric and neurological disorders. TMS works by generating pulsed electric fields (E-fields) in the brain using an electromagnetic coil placed outside the head, enabling noninvasive modulation of brain activity. Unfortunately, the therapeutic effects of TMS are often modest and variable between individuals. Improving TMS efficacy has been challenging because we lack a mechanistic understanding of how the TMS-induced E-field (the treatment “dose”) alters activity within the diverse neuron subtypes and circuits of the cerebral cortex. Previously, I developed biophysical neuron models predicting that differences in axonal morphology between neuronal subtypes lead to differences in their sensitivities to specific E-field parameters. Here, I propose to directly test these predictions by recording from neurons experiencing E-field pulses. I will use genetically encoded optical indicators to monitor subcellular and cellular responses to E-field doses mimicking the local E-field induced by TMS in the cerebral cortex. In my early postdoctoral training, I deployed a subset of these tools in cultured neurons. With co-mentorship from two faculty with complementary expertise, I will learn the experimental approaches necessary to express and image optical calcium and voltage indicators in ex vivo cortical brain slices that retain the cellular composition and circuitry found in vivo. During the K99 phase, I will determine how E-field- driven subcellular voltage changes in cell bodies, axons, and dendrites depend on their morphological features and membrane properties (Aim 1). I will also determine how excitatory and inhibitory neuronal subtypes and specific excitatory cortical afferents are differentially activated by E-fields (Aim 2). With this training, I will then determine how ongoing activity (i.e., network state) and specific circuit elements (i.e., neuron subtypes and synaptic connections) contribute to E-field-driven short-latency circuit activity during the R00 phase (Aim 3). The data will be used to build neuron models that capture the relationship between E-field dose and neural response. This project will generate fundamental insights into the mechanisms of TMS and computational tools to guide the rational design of stimulation protocols. My laboratory training will be supplemented with coursework at the Marine Biological Laboratory, faculty skills training workshops at Dartmouth, and support from a multidisciplinary mentorship team. Overall, my training plan will provide critical professional development, new experimental approaches, and expertise in cortical physiology that, combined with my computational background, will equip me with a unique skillset bridging neurobiology and engineering to advance brain stimulation technologies. My future lab will use computational models and physiological recordings to design stimulation protocols that achieve more precise and selective modulation of brain circuits for research and therapeutic applications.


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 = $0 )
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research - Other Research	001	1	8/27/2026	NEW	-$114,152
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research - Other Research	000	1	8/13/2026	NEW	$114,152
														Subtotal = $0

Grand Total All Awards = $0

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Determining and enhancing the cellular selectivity of transcranial magnetic stimulation using optical physiology and computational models

Award Number: K99MH144381

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 09/02/2026

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