Neurostimulation for treatment-resistant posttraumatic stress disorder: an update on neurocircuitry and therapeutic targets

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  • 1 Department of Neurosurgery and
  • 2 Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
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Posttraumatic stress disorder (PTSD) is a widespread and often devastating psychiatric condition. Core symptoms include intrusive and distressing thoughts, heightened reactivity, mood changes, cognitive impairments, and consequent avoidance of trauma-related stimuli. Symptoms of PTSD are often refractory to standard treatments, and neuromodulatory techniques have therefore drawn significant interest among the most treatment-resistant patients. Transcranial magnetic stimulation has demonstrated minimal efficacy, and deep brain stimulation trials are currently ongoing. PTSD is a disorder of neural circuitry; the current understanding includes involvement of the amygdala (basolateral and central nuclei), the prefrontal cortex (ventral medial and dorsolateral regions), and the hippocampus. Neuroimaging and optogenetic studies have improved the understanding of large-scale neural networks and the effects of microcircuitry manipulation, respectively. This review discusses the current PTSD literature and ongoing neurostimulation trials, and it highlights the current understanding of neuronal circuit dysfunction in PTSD. The authors emphasize the anatomical correlations of PTSD’s hallmark symptoms, offer another potential deep brain stimulation target for PTSD, and note the need for continued research to identify useful biomarkers for the development of closed-loop therapies. Although there is hope that neuromodulation will become a viable treatment modality for PTSD, this concept remains theoretical, and further research should involve institutional review board–approved controlled prospective clinical studies.

ABBREVIATIONS ACC = anterior cingulate cortex; BLA = basolateral amygdala; CE = central nuclei; DBS = deep brain stimulation; GABAergic = γ-aminobutyric acidergic; mPFC = medial PFC; OFC = orbitofrontal cortex; PAG = periaqueductal gray; PCL = PTSD checklist; PFC = prefrontal cortex; PTSD = posttraumatic stress disorder; RDoC = Research Domain Criteria; TMS = transcranial magnetic stimulation; TR-PTSD = treatment-resistant PTSD; vmPFC = ventral medial PFC.

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Contributor Notes

Correspondence M. Benjamin Larkin: Baylor College of Medicine, Houston, TX. michael.larkin@bcm.edu.

ACCOMPANYING EDITORIAL DOI: 10.3171/2020.5.JNS201127.

INCLUDE WHEN CITING Published online July 31, 2020; DOI: 10.3171/2020.4.JNS2061.

Disclosures Dr. Goodman received donated devices from Medtronic for an NIH research study. Dr. Sheth is a consultant for Abbott, Koh Young, and Neuropace. Dr. Storch is a consultant for Levo Therapeutics. He receives royalties from Wiley, Oxford, Elsevier, Lawrence Erlbaum, APA, and Springer. He receives honoraria from the International OCD Foundation. He received clinical or research support for the study described (includes equipment or material) from the NIH, the Texas Higher Education Coordinating Board, ReBuild Texas, the Red Cross, and the Greater Houston Community Foundation.

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