Conditioned Fear Extinction and Generalization in Post-Traumatic Stress Disorder
Posted September 16, 2010
Seth Norrholm, Ph.D., Emory University

Seth Norrholm, Ph.D. In fiscal year 2007 (FY07), Dr. Seth Norrholm was awarded a PTSD New Investigator Award to develop a new clinical assessment tool to aid in the treatment of post-traumatic stress disorder (PTSD) in war veterans. A hallmark feature of PTSD is the patient's inability to distinguish between dangerous and safe situations. The ability to inhibit fear can be tested in a simple laboratory experiment that uses the startle response as a way to measure fear. One paradigm Dr. Norrholm has examined is conditioned fear extinction in which fear learned through classical conditioning is subsequently extinguished. Specifically, combat-exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD, a psychiatric control group with major depression, and a healthy control group are presented with colored shapes with or without an aversive air blast, responses to concurrently presented acoustic startle are recorded, and extinction training is initiated 10 minutes after acquisition. Interestingly, Dr. Norrholm found that veterans with PTSD displayed greater fear-potentiated startle to the safety cue as well as delayed extinction of fear-potentiated startle compared to the healthy controls. Dr. Norrholm is also in the process of accessing stimulus generalization. This assessment will follow the presentation of the cues used in fear conditioning. In a pilot subject, rather than discriminating between stimuli, the subject showed a generalization gradient of fear-potentiated startle responses to tones within the test range. This suggests that stimulus generalization to acoustic startle responses may be a useful psychophysiological tool that may give insight into the generalization of fear in PTSD patients. Moreover, Dr. Norrholm suggests that use of the fear-potentiated startle paradigm will be an asset in determining extinction of learned fear. These exciting findings have been presented at both local and international conferences.


Public and Technical Abstracts: Conditioned Fear Extinction and Generalization in Post-Traumatic Stress Disorder

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Treatment of Active Duty Military with PTSD in Primary Care: PTSD-PC Program Early Findings
Posted June 14, 2010
Lt Col Jeffrey Cigrang, Ph.D., Wilford Hall Medical Center, San Antonio, Texas; Sheila Rauch, Ph.D., at VA Ann Arbor Healthcare System and University of Michigan Medical School, Ann Arbor Michigan; Laura Avila, Ph.D., at Brooke Army Medical Center, San Antonio, Texas

Lt Col Jeffrey Cigrang, Ph.D. The South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR), a multidisciplinary and multi-institutional research consortium focusing on post-traumatic stress disorder (PTSD), received a Department of Defense Fiscal Year 2007 PTSD Multidisciplinary Research Consortium Award. Under this award, Lt Col Jeffrey Cigrang and his partnering investigators, Drs. Sheila Rauch and Laura Avila, have been exploring a psychotherapy treatment for deployment-related PTSD. A substantial number of veterans of the wars in Iraq and Afghanistan are currently affected by PTSD, yet many report having received no professional help or inadequate help in the past year. Concern that one's military peers and leadership may negatively judge mental health help-seeking can be a significant barrier to accessing care in a specialty mental health clinic. The primary care (PC) clinic may be a more favorable environment for treatment of PTSD in terms of reduced stigma and increased reach to military members. PC is also an ideal setting for offering relatively brief, first-line help to service members with PTSD as part of a larger stepped model of care. These investigators are conducting an ongoing pilot study of a cognitive-behavioral treatment (CBT) designed for use by psychologists working in an integrated PC clinic that see active-duty military with deployment-related PTSD. The CBT protocol is comprised of four to six individual 30-minute appointments with a PC psychologist and practice assignments conducted over six to eight weeks. Treatment content is primarily based on an exposure model but includes elements of both prolonged exposure and cognitive processing therapies. Participants were recruited for the pilot study trial from the population of patients referred to the PC psychologist by their PC manager during routine clinical care. Participants are active-duty or activated reserve Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans seeking help for deployment-related PTSD symptoms with a PCL-M (scaled self-report PTSD questionnaire) score >32, and interest in treatment for PTSD in PC. Those with moderate to severe suicide risk, current alcohol dependence, psychotic disorder, or severe traumatic brain injury were not eligible to participate. To date, 10 participants have completed treatment and a one-month post-treatment evaluation. At one month post-treatment five participants (50%) no longer met criteria for PTSD. Psychological assessments given at follow-up indicated that the average PTSD symptom severity was significantly reduced from baseline as measured by both interviewer-administered and self-report inventories, the average depression symptom severity was also significantly reduced, and overall mental health functioning was increased. Six- and twelve-month follow-up evaluations are currently being conducted. These early findings are highly encouraging for the use of PTSD-PC as a viable first-step treatment protocol in the context of PC. Further, this intervention may help overcome barriers to care, such as stigma regarding mental health treatment, and meet the needs of many active-duty OIF/OEF veterans seeking help for PTSD.


Public and Technical Abstracts: The STRONG STAR Multidisciplinary PTSD Research Consortium

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High-Throughput Screening of Therapeutic Neural Stimulation Targets: Toward Principles of Preventing and Treating Post-Traumatic Stress Disorder
Posted June 2, 2010
Edward Boyden, Ph.D., Massachusetts Institute of Technology, Cambridge, Massachusetts

Post-traumatic stress disorder (PTSD) is characterized by extreme anxiety and fear, exacerbated by the cues and contexts associated with the initial trauma. Treatments such as psychotherapy are only partially effective, and while a few drugs have shown some efficacy, side effects are common. A treatment for PTSD that could directly correct the aberrant neural activity in the affected neural circuits, without altering the functions of unrelated neural circuits, would be of enormous value to persons suffering from PTSD. Dr. Edward Boyden, a researcher at the Massachusetts Institute of Technology, is currently investigating such an approach. If successful, these studies will identify neural circuit targets whose activation or silencing could be used to treat PTSD by a noninvasive means. By pinpointing these sites, Dr. Boyden believes that brain stimulation could be used to create circuit-specific interventions. Dr. Boyden received a PTSD Concept Award to pursue this innovative research.

In the first year of this study, Dr. Boyden found that the optical activation of infralimbic cortex neurons during exposure therapy in a mouse model of PTSD resulted in rapid and enduring remission of PTSD symptoms. To conduct these experiments, viruses expressing light-activated proteins in neurons were injected throughout the mouse brain. An array of optical fibers was then used to deliver light to specific areas of the brain, making it possible to turn on and off brain regions for precise lengths of time. The results of these studies have revealed a major new target for PTSD neuromodulation therapy and may advance translational efforts to use deep brain stimulation or transcranial magnetic stimulation to modulate neural circuits. Dr. Boyden is currently seeking collaborators to translate this technology into the clinic. These techniques appear to be safe and effective in non-human primates, and Dr. Boyden suggests that optical neural control might someday be suitable for use in human patients.

Image of Mouse Neuron Expressing Arch Gene


Boyden ES and Chow BY. 2010. "Defining an Algorithm for Inventing from Nature." Column, Technology Review. 1/19/2010.

Chan SY, Bernstein JG, and Boyden ES. 2009. Scalable fluidic injector arrays for viral targeting of intact 3-D brain circuits. Journal of Visualized Experiments 35, doi:10.3791/1489.

Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden E. 2010. High-performance genetically-targetable optical neural silencing via the class of light-driven proton pumps. Nature 463(7277):98-102.

Han X, Qian X, Bernstein JG, Zhou HH, Franzesi GT, Stern P, Bronson RT, Graybiel AM, Desimone R, Boyden ES. 2009. Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62(2):191-198.


Public and Technical Abstracts: High-Throughput Screening of Therapeutic Neural Stimulation Targets: Toward Principles of Preventing and Treating Post-Traumatic Stress Disorder

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