For this pilot feasibility study, combat veterans whose PTSD has been associated with severe symptomatic suffering and functional impairment, despite treatment with all currently available pharmacological and psychotherapeutic treatments, will be recruited from clinics at a large, academically affiliated VA facility. An extensive screening over an extended baseline by the study psychiatrist and neurosurgeon will be conducted using standard interviews and clinical rating scales. Eligible subjects are required to have a cohabiting significant other willing to participate in safety and function monitoring throughout the study.

After successful completion of baseline eligibility requirements, comprehensive neuropsychological testing will be performed, as will structural MRI and FDG PET/CT of the amygdala, insula and medial Prefrontal cortex. PET/CT will be performed and analyzed by a nuclear medicine specialist collaborator familiar with this type of imaging research. Six consenting subjects meeting all eligibility criteria will then receive bilateral basolateral nucleus of the amygdala (BlnA) implantation of Medtronic Activa Primary Cell (PC) implantable deep brain stimulator systems (purchased through the VA Merit Review Grant) by functional neurosurgeons specialized in the procedure. This will be done during a 3-4 day inpatient stay on the VA Greater Los Angeles Neurosurgical Service. After a month of weekly safety monitoring with stimulators off, subjects will be will be hospitalized for 1 day on the Neurology Service's electroencephalography (EEG) telemetry unit, under the care and supervision of an epilepsy specialist neurologist who is a co-investigator in the study, for stimulator initiation. Stimulator settings will be adjusted by the study clinical neurophysiologist while patients are monitored by the study neurologist and psychiatrist. Only stimulator settings that do not cause epileptiform discharges, or potentially significant adverse psychiatric or medical (e.g., blood pressure, heart rate) changes will be used over the subsequent long-term follow-up.

After the EEG telemetry safety check, subjects will be randomized (3/3) to either have their stimulators turned on then (Week 0), or 3 months later (week 12). This staggered onset double-blind design has been used in other DBS trials in psychiatry. After week 0, for the next 2 years, subjects will be followed at regular intervals (weekly for 5 months, then monthly for 7 months, then quarterly for 12 months) by a psychiatrist, neurosurgeon, neurologist and neurophysiologist who will conduct an extensive battery of psychiatric and neurological testing (including periodic EEG recordings), as well as significant other interviews, while stimulator settings are adjusted based on standardized rating scale outcomes and adverse effects so as to optimize treatment outcome. The principal study hypothesis is that the symptomatic and functional benefits of chronic stimulation will outweigh the risks and adverse-effects, and that symptomatic improvement will be greater, without unacceptable adverse effects, in subjects with week 0, compared to week 12 stimulator initiation. Neuropsychological testing will be repeated after 6 months of stimulation to assess changes in cognitive function. Functional neuroimaging with PET/CT will be repeated after a year of stimulation to assess changes in the activity of brain regions known to function abnormally in PTSD.