Critically Assessing the Unanswered Questions of How, Where, and When to Induce Plasticity in the Posttraumatic...

Extinction of traumatic memory, a primary treatment approach (termed exposure therapy) in posttraumatic stress disorder (PTSD), occurs through relearning and may be subserved at the molecular level by long-term potentiation of relevant circuits. In parallel, repetitive transcranial magnetic stimulation (TMS) is thought to work through long-term potentiation-like mechanisms and may provide a novel, safe, and effective treatment for PTSD. In a recent failed randomized controlled trial we emphasized the necessity of correctly identifying cortical targets, the directionality of TMS protocols, and the role of memory activation. Here, we provide a systematic review of TMS for PTSD to further identify how, where, and when TMS treatment should be delivered to alleviate PTSD symptoms. We conducted a systematic review of the literature by searching for repetitive TMS clinical trials involving patients with PTSD and outcomes. We searched MEDLINE through October 25, 2023, for "TMS and PTSD" and "transcranial magnetic stimulation and posttraumatic stress disorder." Thirty-one publications met our inclusion criteria (k = 17 randomized controlled trials, k = 14 open label). Randomized controlled trial protocols were varied in terms of TMS protocols, cortical TMS targets, and memory activation protocols. There was no clear superiority of low-frequency (k = 5) versus high-frequency (k = 6) protocols or by stimulation location. Memory provocation or exposure protocols (k = 7) appear to enhance response. Overall, TMS appears to be effective in treating PTSD symptoms across a variety of TMS frequencies, hemispheric target differences, and exposure protocols. Disparate protocols may be conceptually harmonized when viewed as potentiating proposed anxiolytic networks or suppressing anxiogenic networks.