Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results

Ralph J Koek; Josue Avecillas-Chasin; Scott E Krahl; James Wy Chen; David L Sultzer; Alexis D Kulick; Mark A Mandelkern; Maura Malpetti; Hailey L Gordon; Holly N Landry; Evan H Einstein; Jean-Philippe Langevin

doi:10.1016/j.jpsychires.2024.05.008

Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results

J Psychiatr Res. 2024 May 3:175:131-139. doi: 10.1016/j.jpsychires.2024.05.008. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, 760 Westwood Blvd., Room 58-229, Los Angeles, CA, USA, 90095-1759; Psychiatry Service, Mental Health and Behavioral Sciences, Sepulveda Ambulatory Care Center, VAGLAHS, 16111 Plummer St. (116A-11), North Hills, CA, USA, 91343. Electronic address: rkoek@ucla.edu.
² Department of Neurosurgery University of Nebraska Medical Center College of Medicine, 42nd and Emile, Omaha, Nebraska USA, 68198. Electronic address: josueavecillas@hotmail.com.
³ Department of Neurosurgery, University of California at Los Angeles (UCLA), 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA; Research Service, VAGLAHS (Clinical Neurophysiology), 16111 Plummer St., Building 1, North Hills, CA, USA, 91343. Electronic address: Scott.krahl@va.gov.
⁴ Department of Neurology, UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA; Neurology Service (Epilepsy Center of Excellence), VAGLAHS, 11301 Wilshire Blvd, Los Angeles, CA, USA, 90073. Electronic address: jwychen@g.ucla.edu.
⁵ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, 760 Westwood Blvd., Room 58-229, Los Angeles, CA, USA, 90095-1759; Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine Institute for Memory Impairments and Neurological Disorders, 3214 Biological Sciences III, Irvine, CA, USA, 92697-4545. Electronic address: dsultzer@hs.uci.edu.
⁶ Psychology Service (Neuropsychology), Mental Health and Behavioral Sciences, VAGLAHS, 16111 Plummer St. (116A-11) North Hills, CA, USA, 91343. Electronic address: alexis.kulick@va.gov.
⁷ Imaging Department, VAGLAHS, 11301 Wilshire Blvd, Los Angeles, CA, USA, 90073. Electronic address: mark.mandelkern@va.gov.
⁸ Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK. Electronic address: mm2243@cam.ac.uk.
⁹ STEM Pathways at Boston University, 610 Commonwealth Avenue, Room 402, Boston, MA, 02215, USA. Electronic address: hlgordon@bu.edu.
¹⁰ Private Practice at Happier Living, USA. Electronic address: Drlandry@happierliving.com.
¹¹ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, 760 Westwood Blvd., Room 58-229, Los Angeles, CA, USA, 90095-1759.
¹² Department of Neurosurgery, UCLA, 300 Stein Plaza Driveway Suite 420, Los Angeles, CA, 90095, USA; Southwest VA Epilepsy Center of Excellence, 11301 Wilshire Blvd, Bldg 500 (10H2), Los Angeles, CA, USA, 90073. Electronic address: jlangevin@mednet.ucla.edu.

PMID: 38733927
DOI: 10.1016/j.jpsychires.2024.05.008

Abstract

Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with ¹⁸FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.

Keywords: Amygdala; Case studies; Longitudinal study; Neuromodulation; Post-traumatic stress disorder; Treatment-resistance.

Published by Elsevier Ltd.