This is a K23 Career Development Award application for Lisa M. McTeague, Ph.D., a clinical psychologist and Instructor in the Department of Psychiatry at Stanford University. Dr. McTeague's long-term career goal is to understand the neural basis of emotional reactivity impairments in severe affective illness in the service of identifying multimodal approaches to better remediate these deficits. This K23 award would enable Dr. McTeague to gain proficiency in 1) cutting-edge functional neuroimaging (fMRI), 2) transcranial magnetic stimulation (TMS) as a direct tool for investigating intact and disordered brain activation, 3) translating the principles of experimental medicine to psychosocial treatment toward ameliorating emotional dysfunction, and 4) leveraging these new techniques in conjunction with her established expertise in cognitive- behavioral treatment and psychophysiology for a series of grant submissions to help solidify her independence. This project focuses on posttraumatic stress disorder (PTSD) as a syndrome with well-characterized emotion deficits that may be susceptible to exogenous stimulation (i.e., TMS), which could, in turn, be utilized to enhance conventional psychotherapy outcomes. Trauma-focused exposure-based therapies are the first-line treatments for PTSD but half of patients meet diagnostic criteria upon completion. A fundamental component of exposure is the process of thorough emotional engagement-both subjectively and objectively-ensuring that the ultimate experience of habituation is optimally powerful. Dr. McTeague previously observed that chronic PTSD is marked by stark blunting of defensive mobilization, foremost in startle reflex responding during aversive imagery, suggestive of deficient limbic (and associated network) activation. To meaningfully advance these conclusions and point to intervention targets, Dr. McTeague proposes to assess brain activation and autonomic responding in 40 patients with PTSD and 20 trauma-exposed healthy participants during neutral and aversive as well as equally high arousing appetitive imagery. The inclusion of the latter will inform on whether PTSD is marked by core deficiencies in emotion networks as opposed to strategic avoidance-either outcome integral to intervention planning (Aim 1). To assess whether aberrant, state-dependent, interactions between limbic and prefrontal circuitry characterize PTSD, single pulses of TMS will be administered to two prefrontal regions during imagery (Aim 2). Finally, prefrontal-limbic circuits will be excited in patients with a single (non-therapeutic) session of rTMS to assess for (potentially normalizing) effects on emotional processing in an immediately subsequent imagery session (Aim 3). Successful completion would provide a more sophisticated neurobiological circuit understanding to Dr. McTeague's prior observation of blunted responding while furnishing essential guidance on the feasibility of using TMS to enhance emotional reactivity and regulation neurocircuitry as a preamble to imaginal exposure for PTSD (planned R01 application).

Public Health Relevance

Psychotherapy research for posttraumatic stress disorder (PTSD) has made substantial progress in ameliorating distress; especially treatments that help patients emotionally engage in their traumatic memories (i.e., imaginal exposure) so that their related fear and avoidance dissipates. Nonetheless, almost half of patients still meet criteria for PTSD upon completion and findings suggest difficulty emotionally engaging may contribute to poor response. The current application seeks to use a brain-based technique, transcranial magnetic stimulation, which has helped to treat depression, to try to stimulate those brain regions understood to be essential to emotional experience and impaired in PTSD. In summary, the aim is to enhance emotion engagement and regulation and possibly uncover new brain-based interventions that could help ready the brain so a patient can then fully engage and thus optimize emotion-focused psychotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH104849-02
Application #
8902272
Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Chavez, Mark
Project Start
2014-08-01
Project End
2018-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Psychiatry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
McTeague, Lisa M; Laplante, Marie-Claude; Bulls, Hailey W et al. (2018) Face Perception in Social Anxiety: Visuocortical Dynamics Reveal Propensities for Hypervigilance or Avoidance. Biol Psychiatry 83:618-628
Badran, Bashar W; Dowdle, Logan T; Mithoefer, Oliver J et al. (2018) Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Brain Stimul 11:492-500
Dryman, M Taylor; McTeague, Lisa M; Olino, Thomas M et al. (2017) Evaluation of an open-access CBT-based Internet program for social anxiety: Patterns of use, retention, and outcomes. J Consult Clin Psychol 85:988-999
Li, Xingbao; Sahlem, Gregory L; Badran, Bashar W et al. (2017) Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers. Am J Addict 26:788-794
McTeague, Lisa M; Huemer, Julia; Carreon, David M et al. (2017) Identification of Common Neural Circuit Disruptions in Cognitive Control Across Psychiatric Disorders. Am J Psychiatry 174:676-685
McTeague, Lisa M (2016) Reconciling RDoC and DSM approaches in clinical psychophysiology and neuroscience. Psychophysiology 53:323-7
McTeague, Lisa M; Goodkind, Madeleine S; Etkin, Amit (2016) Transdiagnostic impairment of cognitive control in mental illness. J Psychiatr Res 83:37-46
Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M (2016) RDoC, DSM, and the reflex physiology of fear: A biodimensional analysis of the anxiety disorders spectrum. Psychophysiology 53:336-47
Miller, Shefali; McTeague, Lisa M; Gyurak, Anett et al. (2015) COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL. Depress Anxiety 32:594-604
McTeague, Lisa M; Gruss, L Forest; Keil, Andreas (2015) Aversive learning shapes neuronal orientation tuning in human visual cortex. Nat Commun 6:7823