Deep Brain Stimulation for Post-Traumatic Stress Disorder

Deep Brain Stimulation for Post-Traumatic Stress Disorder

In 2018 the application of DBS for PTSD was still strictly investigational and animal models suggest that stimulation of the amygdalaventral striatumhippocampus, and prefrontal cortex may be effective in fear extinction and anxiety-like behavior 1).


Neuroimaging, preclinical, and preliminary clinical data suggested that the use of DBS for the treatment of PTSD may be practical 2).


PTSD is the only potential clinical indication for DBS that shows extensive animal research prior 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 3).


Hamani et al. treated four posttraumatic stress disorder (PTSD) patients with DBS delivered to the subgenual cingulum and the uncinate fasciculus. In addition to validated clinical scales, patients underwent neuroimaging studies and psychophysiological assessments of fear conditioning, extinction, and recall. They show that the procedure is safe and potentially effective (55% reduction in Clinical Administered PTSD Scale scores). Posttreatment imaging data revealed metabolic activity changes in PTSD neurocircuits. During psychophysiological assessments, patients with PTSD had higher skin conductance responses when tested for recall compared to healthy controls. After DBS, this objectively measured variable was significantly reduced. Last, they found that a ratio between recall of extinguished and nonextinguished conditioned responses had a strong correlation with clinical outcomes. As this variable was recorded at baseline, it may comprise a potential biomarker of treatment response 4).


Amygdala Deep Brain Stimulation for Post-Traumatic Stress Disorder

Functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague-Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy 5)


1)

Lavano A, Guzzi G, Della Torre A, Lavano SM, Tiriolo R, Volpentesta G. DBS in Treatment of Post-Traumatic Stress Disorder. Brain Sci. 2018 Jan 20;8(1):18. doi: 10.3390/brainsci8010018. PMID: 29361705; PMCID: PMC5789349.
2)

Reznikov R, Hamani C. Posttraumatic Stress Disorder: Perspectives for the Use of Deep Brain Stimulation. Neuromodulation. 2016 Dec 19. doi: 10.1111/ner.12551. [Epub ahead of print] Review. PubMed PMID: 27992092.
3)

Meeres J, Hariz M. Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. Stereotact Funct Neurosurg. 2022 Jan 3:1-13. doi: 10.1159/000521130. Epub ahead of print. PMID: 34979516.
4)

Hamani C, Davidson B, Corchs F, Abrahao A, Nestor SM, Rabin JS, Nyman AJ, Phung L, Goubran M, Levitt A, Talakoub O, Giacobbe P, Lipsman N. Deep brain stimulation of the subgenual cingulum and uncinate fasciculus for the treatment of posttraumatic stress disorder. Sci Adv. 2022 Dec 2;8(48):eadc9970. doi: 10.1126/sciadv.adc9970. Epub 2022 Dec 2. PMID: 36459550.
5)

Langevin JP, De Salles AA, Kosoyan HP, Krahl SE. Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. J Psychiatr Res. 2010 Dec;44(16):1241-5. doi: 10.1016/j.jpsychires.2010.04.022. Epub 2010 May 26. PMID: 20537659.

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