Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature

Abstract

<b><i>Introduction:</i></b> Up to 30% of patients with post-traumatic stress disorder (PTSD), especially combat veterans, remain refractory to conventional treatment. For them, deep brain stimulation (DBS) has been suggested. Here, we review the literature on animal models of PTSD in which DBS has been used to treat PTSD-type behavior, and we review and discuss patient reports of DBS for PTSD. <b><i>Methods:</i></b> A broad search was performed to find experimental animal articles and clinical reports on PubMed, Ovid MEDLINE, Cochrane Library, and PsycINFO, using combinations and variations of search words pertinent to DBS and PTSD. <b><i>Results:</i></b> The search yielded 30 articles, 24 on DBS in rat models of PTSD, and 6 publications between 2016 and 2020 reporting on a total of 3 patients. DBS in rat models targeted 4 brain areas: medial prefrontal cortex (mPFC), ventral striatum, amygdala, and hippocampus. Clinical publications reported on 2 male combat veterans who received DBS in basolateral amygdala, and 1 female with PTSD due to domestic abuse, who received DBS of mPFC. All 3 patients benefitted to various extents from DBS, at follow-ups of 4 years, 6 months, and 7 months, respectively. <b><i>Conclusions:</i></b> PTSD is the only potential clinical indication for DBS that shows extensive animal research <i>prior</i> to human applications. Nevertheless, DBS for PTSD remains highly investigational. Despite several years of government funding of DBS research in view of treating severe PTSD in combat veterans, ethical dilemmas, recruitment difficulties, and issues related to use of DBS in such a complex and heterogenous disorder remain prevalent.

Therapeutic potential of brain stimulation techniques in the treatment of mental, psychiatric, and cognitive disorders

“…A study with a war veteran suffering with PTSD showed that DBS‐mediated stimulation of the basolateral nucleus of the amygdala reduced more than 37% the symptoms 136 . Similar results were obtained in a follow‐up study of same patient and another PTSD patient 137 . Another case study showed that DBS in medial prefrontal cortex/uncinate fasciculate caused full recovery of patient from PTSD symptoms 138 .…”

“… 136 Similar results were obtained in a follow‐up study of same patient and another PTSD patient. 137 Another case study showed that DBS in medial prefrontal cortex/uncinate fasciculate caused full recovery of patient from PTSD symptoms. 138 Beside these, there is no other study available in the literature on DBS treatment in PTSD patients.…”

Serendipity and Observations in Functional Neurosurgery: From James Parkinson’s Stroke to Hamani’s & Lozano’s Flashbacks

“…None of these DBS targets, not even the first modern era DBS of Benabid et al [87], did result from animal experiment. Only three of the current human applications of DBS stemmed from prior work on animal: the lesioning of the STN in primate models of PD [88, 89] led to high-frequency DBS of the STN in human PD; the low-frequency stimulation of the pedunculopontine nucleus in monkey [90] led to attempts of low-frequency DBS in PD patients with freezing of gait; and the numerous works on DBS in rodent models of post-traumatic stress disorder (PTSD) led to a cautious trial of DBS of the basolateral amygdala in patients with PTSD [91, 92]. In fact, some of the serendipitous discoveries during human clinical DBS have led researchers in the opposite direction, that is, from bedside to bench.…”

Application of Deep Brain Stimulation in Refractory Post-Traumatic Stress Disorder

“…However, a substantial proportion of patients do not respond to treatment modalities, thus rendering them refractory. This incidence is markedly higher in defence personnel who have been through traumatic, life-altering experiences [ 2 ]. Out of all psychiatric disorders, PTSD shows the highest comorbidity rates.…”