Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression: a Home-Based Randomized Sham-Controlled Trial and Biomarkers of Response

Award Number: K23MH144148
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: 08/31/2031

Group Awards By:

View Award Description

Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression: a Home-Based Randomized Sham-Controlled Trial and Biomarkers of Response - PROJECT SUMMARY / ABSTRACT Up to 55% of patients with major depressive disorder (MDD) fail to respond to standard treatments and progress to treatment-resistant depression (TRD). The neuroplasticity deficit hypothesis of depression—centered on disrupted excitatory and inhibitory signaling and impaired synaptic remodeling—offers a compelling framework for developing novel interventions. Current interventional psychiatry approaches such as electroconvulsive therapy, ketamine, and repetitive transcranial magnetic stimulation target neuroplasticity but lack scalability. Transcranial direct current stimulation (tDCS) has emerged as a promising alternative that is safe, cost-effective, and suitable for remote, home-based delivery. However, clinical trials using conventional once-daily tDCS protocols in TRD have yielded mixed results, likely due to subtherapeutic dosing. Our group developed a novel “spaced” tDCS protocol, involving multiple daily sessions separated by short intervals to better engage late- phase neuroplasticity, which showed promising preliminary therapeutic effects. In addition to improving the effectiveness and scalability of tDCS, there is a critical need to elucidate its neurophysiological mechanisms. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) enables causal, real-time assessment of cortical excitability and inhibition through TMS-evoked potentials. Resting-state EEG (rsEEG) provides a complementary, scalable tool for assessing large-scale brain network dynamics and has shown promise in predicting treatment response. We propose a randomized, double-blind superiority trial comparing active versus sham home-based spaced tDCS in 74 adults with TRD. We will use TMS-EEG to assess changes in neuroplasticity, as indexed by cortical evoked activity (CEA), over the dorsolateral prefrontal cortex (Aim 1). rsEEG metrics, including spectral power and inter-site phase clustering, will be examined as complementary markers of large-scale network plasticity and as predictors of treatment response (Aim 2). The primary clinical outcome will be change in depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale, testing the hypothesis that active spaced tDCS is superior to sham in reducing depression severity (Aim 3). The applicant’s career development objectives include gaining expertise in neurophysiological biomarker acquisition and analysis (TMS-EEG, rsEEG), advanced training in clinical trial design and statistical methods, and launching an independent research program focused on biomarker-informed neuromodulation strategies for TRD. The applicant will be mentored by Dr. Zafiris Daskalakis (Chair, UCSD Psychiatry and TMS-EEG expert), with co-mentorship from Dr. André Brunoni (tDCS trialist) and Dr. Lawrence Appelbaum (rsEEG expert). Consultant Dr. Xin Tu will provide guidance in biostatistics and data modeling. The applicant will develop the skills and experience necessary to become an independent interventional psychiatry physician-scientist, and his work will advance our understanding of the mechanisms and clinical utility of spaced home-based tDCS for TRD.


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 = $199,271 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	8/31/2026	NEW	$199,271
														Subtotal = $199,271

Grand Total All Awards = $199,271

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression: a Home-Based Randomized Sham-Controlled Trial and Biomarkers of Response

Award Number: K23MH144148

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: 08/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer