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Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation
Background
Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS.
Methods/Design
We describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic (EEG) telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale (CAPS) total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked
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FDG PET metabolic changes in limbic circuitry will also be evaluated.
Discussion
While the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD.
Trial registration
PCC121657
, 19 March 2014.
Journal Article
Unmanned combat aerial vehicles : current types, ordnance and operations
The field of unmanned combat aerial vehicles (UCAVs) is rapidly diversifying as an array of light, midsized, and heavy UCAVs and munitions enter the global marketplace. This has the potential to dramatically expand access to armed unmanned platforms and change the way unmanned aerial vehicles are used in combat. The influence of UCAVs on the conduct of war has already been felt in conflicts in the Caucasus, the Middle East and North Africa, where state and non-state actors have fielded a dizzying number of UCAVs from around the world. At the same time, advanced militaries are beginning to equip UCAVs with increasingly sophisticated munitions, some of which are heavier and can fly farther than the types of weapons used by UCAVs in the past.
Book
AN INVESTIGATION OF OUTCOME EXPECTANCIES AS A PREDICTOR OF TREATMENT RESPONSE FOR COMBAT VETERANS WITH PTSD: COMPARISON OF CLINICIAN, SELF-REPORT, AND BIOLOGICAL MEASURES
Background Outcome expectancy, or the degree to which a client believes that therapy will result in improvement, is related to improved treatment outcomes for multiple disorders. There is a paucity of research investigating this relation in regards to posttraumatic stress disorder (PTSD). Additionally, the bulk of the research on outcome expectancy and treatment outcomes has relied mostly on self‐report outcome measures. Methods The relation between outcome expectancy on self‐report measures, clinician‐rated measures, and two biological indices (fear‐potentiated startle and cortisol reactivity) of PTSD symptoms was explored. The sample included combat veterans (N = 116) treated with virtual reality exposure therapy for PTSD. Results Results supported a negative association between outcome expectancy and both self‐report and clinician‐rated symptoms at the conclusion of treatment, but outcome expectancy was related to the magnitude of change during treatment for self‐report measures only. Outcome expectancy was unrelated to biological measures of treatment response. Conclusions These findings suggest that outcome expectancy may be related to patient and clinician perceptions of outcomes, but not biological indices of outcome for PTSD.
Journal Article
Battle zone : the inspiring truth behind popular combat video games
Bravely storming the beaches of Normandy. Holding down the front lines while under attack from the enemy. Battling enemy fighters through the streets of a wartorn city. Fans of combat video games enjoy these scenarios and many more.
Book
Engineering principles of combat modeling and distributed simulation
Explore the military and combat applications of modeling and simulation Engineering Principles of Combat Modeling and Distributed Simulation is the first book of its kind to address the three perspectives that simulation engineers must master for successful military and defense related modeling: the operational view (what needs to be modeled);.
eBook
Selective prevention of combat-related post-traumatic stress disorder using attention bias modification training: a randomized controlled trial
Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat.
We conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments.
PTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight-session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01-9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches.
Four sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215.
Journal Article
Ethics and autonomous weapons
Autonomous weapons are capable, once programmed, of searching for and engaging a target without direct intervention by a human operator. Critics of these weapons claim that 'taking the human' out-of-the-loop' represents a further step towards the de-humanisation of warfare, while advocates of this type of technology contend that the power of machine autonomy can potentially be harnessed in order to prevent war crimes. This book provides a thorough and critical assessment of these two positions.
Book
Trauma, treatment and Tetris: video gaming increases hippocampal volume in male patients with combat-related posttraumatic stress disorder
Tetris has been proposed as a preventive intervention to reduce intrusive memories of a traumatic event. However, no neuroimaging study has assessed Tetris in patients with existing posttraumatic stress disorder (PTSD) or explored how playing Tetris may affect brain structure.
We recruited patients with combat-related PTSD before psychotherapy and randomly assigned them to an experimental Tetris and therapy group (n = 20) or to a therapy-only control group (n = 20). In the control group, participants completed therapy as usual: eye movement desensitization and reprocessing (EMDR) psychotherapy. In the Tetris group, in addition to EMDR, participants also played 60 minutes of Tetris every day from onset to completion of therapy, approximately 6 weeks later. Participants completed structural MRI and psychological questionnaires before and after therapy, and we collected psychological questionnaire data at follow-up, approximately 6 months later. We hypothesized that the Tetris group would show increases in hippocampal volume and reductions in symptoms, both directly after completion of therapy and at follow-up.
Following therapy, hippocampal volume increased in the Tetris group, but not the control group. As well, hippocampal increases were correlated with reductions in symptoms of PTSD, depression and anxiety between completion of therapy and follow-up in the Tetris group, but not the control group.
Playing Tetris may act as a cognitive interference task and as a brain-training intervention, but it was not possible to distinguish between these 2 potential mechanisms.
Tetris may be useful as an adjunct therapeutic intervention for PTSD. Tetris-related increases in hippocampal volume may ensure that therapeutic gains are maintained after completion of therapy.
Journal Article