Translational Research Updates: Tools, toys, theories, and trying to get funded Greg Siegle University of Pittsburgh School of Medicine Supported by MH Greg Siegle is an unpaid consultant for Trial IQ and Neural Impact

Topics RDoC Ambulatory EEG One super-cool upcoming article Automating fMRI meta-analyses Getting translational research funded

The NIMH Research Domain Criteria (RDoC) mentalhealth.gov/research-funding/rdoc Please do: -Look at dimensions that span disorders – this means recruiting across traditional disorder boundaries -Consider psychopathology as extremes of normal dimensions -Integrate genetic, neurobiological, behavioral, environmental, and experiential components -Translate RDoC domains to interventions

RDoC example: Negative Valence Systems Responses to acute threat (Fear). Responses to potential harm (Anxiety) Responses to sustained threat Frustrative non-reward Loss funding/rdoc/negative-valence-systems- workshop-proceedings.shtml

Why care? Targeting brain Mechanisms Measuring Brain-Behavior Target Altering Brain-Behavior Target: Neurofeedback Ambulatory EEG is here! e.g., Alpha EEG (8- 13Hz) activity represents inactivity. Increased LEFT frontal alpha in depression  assymetry Davidson (2000) American Psychologist Bargain: $299! 1) Train on brain target directly. Several case series: reduced asymmetry & lasting reductions in depression and anxiety in treatment- refractory MDD and dysthymia patients (up to 5-year follow-up; e.g., Baehr, 1997) – Difficult to replicate – Training on failure feedback is difficult to tolerate Train on emotion template and maintain or avoid that Train on an emotion & situation, test without emotion

Must read article: Forgeard, M. J. C., Haigh, E. A. P., Beck, A. T., Davidson, R. J., Henn, F. A., Maier, S. F., Mayberg, H. S., Seligman, M. E. P. (in press). Beyond depression: Towards a process-based approach to research, diagnosis, and treatment. Clinical Psychology: Science & Practice, 18(4). – Learned Helplessness is not dead – it’s in the lateral habenula… – Biological taxonomies are essential – Convergence among psychological and neurobiological processes – Implications for diagnosis and treatment Neurobehavioral interventions Go to the “prefrontal doctor” or “cingulate doctor” – not a psychiatrist or psychologist

Finding your brain targets – automated meta-analyses at neurosynth.org

Interpreting your brain data: The fMRI Individual Differences Database!

Everything old is new again Hekmat H, Vanian D (1971): Behavior modification through covert semantic desensitization. J Consult Clin Psychol. 36: MePowerful Myselfstrong….

Funding: NIMH mechanisms Basic mechanistic research – RDoC: RFA-MH – Dimensional Approaches to Research Classification in Psychiatric Disorders (R01) – RFA-HL Mechanistic Pathways Linking Psychosocial Stress and Behavior (R01) Interventions – PAR Translational Research for the Development of Novel Interventions for Mental Disorders (R21/R33) applications to speed the translation of emerging findings on the neuroscience of mental disorders into novel intervention approaches A range of non-pharmacologic treatment approaches will be accepted, including those based on neurophysiological, cognitive, affective, and/or social neuroscience models, basic behavioral science, and neurodevelopmental models – PAR , Pilot Intervention and Services Research Grants (R34) Includes “rehabilitative efforts to reduce residual symptoms and/or enhance functioning.” – PA , Collaborative R34s for Pilot Studies of Innovative Treatments in Mental Disorders (Collaborative R34) This FOA should be used when at least two but no more than three sites are needed to complete the study. – PAR Innovative Pilot Studies of Novel Mechanism of Action Compounds for Treating Psychiatric Disorders (U01)

Funding: Outside NIMH There are mechanisms – PA , Cross-Disciplinary Translational Research at NIH (R01) Institutes: NIDA (Drug Abuse), NCI (Cancer) Extend basic or clinical research findings to yield a knowledge base for the development of novel, efficacious drug abuse prevention or treatment interventions. – PA , Translational Research to Help Older Adults Maintain their Health and Independence in the Community (R01) Institutes: NIA (Aging) – PA , Collaborative R34s for Pilot Studies of Innovative Treatments in Mental Disorders (Collaborative R34) Institutes: NIMH, NCCAM (Complementary)

Funding: Strategies for getting past review Tell your reviewers that your agency wants it – Quote the PA – Quote the Institute Strategic plan e.g., NIMH Opportunities to Develop New Psychosocial and Behavioral Therapies ■ Determine the basic mechanisms by which psychosocial interventions operate to produce therapeutic change to increase opportunities for innovative developments. – Quote the branch, e.g., NIMH Division of Adult Translational Research and Treatment Development (DATR) mission Define predictors and understand the mechanism of treatment response. Create and refine biomarkers, behavioral assessments, and phenotypic characterizations of disease. Evaluate existing therapeutics for new indications, and, in collaboration with academic, industry, and regulatory agencies, hasten the development of more effective new treatments for mental illness.

Funding: Strategies for getting past review Rumors: ITV doesn’t like mechanism. – Strategy: “If we don’t measure mechanism we could miss our effects” – Note: Program is speaking regularly to ITV reviewers

Funding: Strategies for getting past review Rumor: APDA doesn’t like intervention – Strategy: Discuss short-term interventions as a probe of causal relationships between brain and symptoms – Emphasize public health relevance of developing the intervention – Consider R21 mechanisms. They may indulge cheap over expensive. – Pilot data helps even if the app says you don’t need pilot data

Funding: Strategies for getting past review Rumor: NCCAM wants us…. – “studies focusing on CAM interventions used frequently by the American public, and on the conditions for which they are most frequently used are particularly encouraged.” If we can show we’re a viable mainstream (i.e., app-downloadable) but unconventional treatment source, we have a shot…. Talk to program! – Basic and Translational Research NCCAM's support of basic research emphasizes and encourages in vitro and in vivo studies of the biological effects and mechanisms of action underlying complementary and alternative medicine (CAM) approaches, as well as studies characterizing the active elements of an intervention,