Novel and Conventional Interventions for Cognitive and Emotional Flexibility in Patient Trauma

Summary

This study is testing whether combining a rapid form of transcranial magnetic stimulation (TMS), an oral medication called d-cycloserine (DCS), and therapy can improve brain flexibility and emotional control in adults experiencing moderate-to-severe depression, anxiety, or trauma symptoms. TMS is a non-invasive treatment that uses gentle magnetic pulses to stimulate specific areas of the brain. In this phase of the study, all participants receive active accelerated TMS (delivering multiple brief sessions in a single day) along with DCS, a medication that helps enhance brain learning and plasticity. Participants will be randomly assigned to have TMS directed at one of two brain targets: a region called the precuneus (identified using personalized brain scans) or the dorsolateral prefrontal cortex (a standard area for mood treatment). Afterward, participants are randomly assigned to complete three weeks of either therapist-led talk therapy (a modified Unified Protocol) or self-guided educational videos and readings. The main goals are to determine which brain stimulation target works best and to see whether therapist-led therapy leads to more lasting symptom relief and brain changes compared to self-guided education.

Timeline

Start

2025-06-01

Primary completion

2026-12-01

Completion

2027-03-01

Publications

• Background Donald A. Vaughn, Brooke Marino, Alex Engelbertson, Aleksandra Dojnov, Lena Johnson, Madison Stine, Fidel Vila-Rodriguez, Nicholas Weiss, Georgine Nanos, Jonathan Downar, Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplasticity-Enhanced techniques in Depression (ONE-D): An open-label case series, Transcranial Magnetic Stimulation, Volume 5, 2025, 100200, ISSN 3050-5291, https://doi.org/10.1016/j.transm.2025.100200.
• Background Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

Drugs

Indications