Posttraumatic Stress Disorder: Perspectives for the Use of Deep Brain Stimulation

Abstract

Objectives: Deep Brain Stimulation (DBS) has been either approved or is currently under investigation for a number of psychiatric disorders.

Materials and methods: We review clinical and preclinical concepts as well as the neurocircuitry that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD).

Results: PTSD is a chronic and debilitating illness associated with dysfunction in well-established neural circuits, including the amygdala and prefrontal cortex. Although most patients often improve with medications and/or psychotherapy, approximately 20-30% are considered to be refractory to conventional treatments. In other psychiatric disorders, DBS has been investigated in treatment-refractory patients. To date, preclinical work suggests that stimulation at high frequency delivered at particular timeframes to different targets, including the amygdala, ventral striatum, hippocampus, and prefrontal cortex may improve fear extinction and anxiety-like behavior in rodents. In the only clinical report published so far, a patient implanted with electrodes in the amygdala has shown striking improvements in PTSD symptoms.

Conclusions: Neuroimaging, preclinical, and preliminary clinical data suggest that the use of DBS for the treatment of PTSD may be practical but the field requires further investigation.

Keywords: Amygdala; anxiety; deep brain stimulation; fear extinction; posttraumatic stress disorder; prefrontal cortex.

Figure. 1

Schematic representation of coronal sections showing the nuclear subdividion of the amygdala in humans (left) and rodents (right). Although nomenclature varies, many regions are thought to have cross-species homology. Anterior commissure (ac); Basomedial nucleus (BM; BMA); Basolateral nucleus (BL; BLA); Basolateral nucleus paralaminar part (BLPL); Central nucleus (Ce, CEA); Central nucleus lateral part (CeL; CEAl); Central nucleus medial part (CeM; CEAm); Central nucleus capsular part (CEAc); Internal capsule (int); Lateral nucleus (La; LA); Medial nucleus (Me; MEA); Optic tract (opt); Substantia innominata (SI). Figure modified and reprinted from references ( and 106) with permission from Elsevier and reference (105) by permission from Macmillan Publishers Ltd.

Figure. 2

Prefrontal cortex in rodents and humans. In rodents the medial surface of the frontal cortex may be divided in frontal, anterior cingulate (AC), prelimbic (PL), and infralimbic cortices (IL) (A sagittal plane; B coronal plane). In C, cytoarchitectonic subdivision of the medial surface of the prefrontal cortex in humans. Numbers in C represent Brodmann areas. Aca, anterior commissure; Acb, nucleus accumbens; AgM, agranular cortex medial; AgL, agranular cortex lateral; CC, corpus callosum; Cl, claustrum; CP, caudate putamen; DPC, dorsal peduncular cortex; Ins, insula; MO, medial orbital cortex; Pir, piriform cortex; SI, primary somatosensory cortex; SII, somatosensory cortex; V, ventricle; tt, tenia tecta. Reprinted from references (18, 107) with permission from Elsevier.

Figure. 3

Basic schematic diagram illustrating important interactions between structures involved in fear conditioning and extinction. Black and dark gray thick lines indicate circuitry active in fear expression and extinction, respectively. Interrupted lines indicate competing memory traces that result in opposing behavioral responses. PFC; Prefrontal Cortex. PL; Prelimbic Cortex. IL; Infralimbic cortex. AMYG; Amygdala. BLA; Basolateral amygdala. ITC; Intercalated cell clusters. CEM; Central nucleus of Amygdala. Hipp; Hippocampus. Reprinted from reference (108) with permission from Elsevier.

Figure. 4

Postoperative CT fused to the preoperative MRI in a coronal plane across the electrode trajectories. Individual contact can be seen at the distal tip of the electrodes. Central nucleus (CE); Basolateral nucleus (BLA); Hippocampus (HPC); Lateral nucleus (LA). Reprinted from reference (101) with permission from Elsevier.