Combining neurobiology and new learning:
Ketamine and Prolonged exposure: A potential rapid treatment for PTSD
In collaboration with Dr. Ilan Harpaz-Rotem's Stress and PTSD lab, we are examining the effect of a one-time ketamine infusion as a facilitator to a 7-day prolonged exposure psychotherapy in PTSD patients. In this study, lab members participate both as clinicians, administering the prolonged exposure therapies, and as analysts exploring the brain mechanisms involved in the observed changes.
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In Collaboration With:
Ilan Harpaz-Rotem, PhD ABPP at Yale University
Decision making across the lifespan
Older adults must make complex financial and healthcare decisions in a highly uncertain and rapidly changing environment, prompting age-related changes in attitudes towards uncertainty throughout development. There is substantial evidence that choices older adults make lead to poorer outcomes compared to those made by their midlife counterparts. Little is known about the cognitive and motivational features underlying individual differences in decision making under uncertainty in these populations. This project aims to identify basic mechanisms that underlie individual differences and age-related changes in decision making under uncertainty. This research is crucial to fully understanding the neural mechanisms of individual decision traits, accurately predicting choice behavior under the many varying circumstances of real life, and designing effective decision aids for older adults.
Related Publications
Tymula, A., Belmaker, L. A. R., Roy, A. K., Ruderman, L., Manson, K., Glimcher, P. W., & Levy, I. (2012). Adolescents’ risk-taking behavior is driven by tolerance to ambiguity. Proceedings of the National Academy of Sciences, 109(42), 17135-17140.
Tymula, A., Belmaker, L. A. R., Ruderman, L., Glimcher, P. W., & Levy, I. (2013). Like cognitive function, decision making across the life span shows profound age-related changes. Proceedings of the National Academy of Sciences, 110(42), 17143-17148.
Grubb, M. A., Tymula, A., Gilaie-Dotan, S., Glimcher, P. W., & Levy, I. (2016). Neuroanatomy accounts for age-related changes in risk preferences. Nature communications, 7(1), 1-5.
In Collaboration With:
Michael Grubb, PhD at Trinity College
Reconsolidation of Fear Memories
When a memory becomes activated, it enters a malleable stage in which it can be altered—the “reconsolidation window.” During this time, it is suggested that the initial memory can be updated or even deleted (extinction) instead of creating a “competing” memory. Whether this process can be utilized to better treat people diagnosed with Post Traumatic Stress Disorder (PTSD), a disorder characterized by a dysfunctional fear learning process, is still unknown. In this project, we set out to explore this hypothesis using fMRI along with a novel fear conditioning paradigm. Results of this study could open the door to new reconsolidation-directed pharmacotherapies and psychotherapies.
Related Publications
Schiller, D., Kanen, J. W., LeDoux, J. E., Monfils, M. H., & Phelps, E. A. (2013). Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement. Proceedings of the National Academy of Sciences, 110(50), 20040-20045
In Collaboration With:
Ilan Harpaz-Rotem, PhD ABPP at Yale University
Daniela Schiller, PhD at Mount Sinai
The Role of the Cannabinoid System in Fear Conditioning
Post Traumatic Stress Disorder (PTSD) is associated with alteration in endocannabinoid tone. While higher Cannabinoid receptor 1 (CB1r) availability has been previously shown in people with PTSD, a direct correlation between symptom severity, brain activation, and CB1r availability was never established. In this project, we set out to investigate the effects of CB1r availability in the striatum on the ‘fear circuit’ during fear updating and compare it to PTSD severity in U.S. veterans.
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In Collaboration With:
Ilan Harpaz-Rotem, PhD ABPP at Yale University
Kelly Cosgrove, PhD at Yale University
Dynamics, Rise and Decline of Goal-Directed Behavior across the Life Span
Goal-directed behavior results from the interaction of bottom-up sensory processing and top-down executive control. At short timescales, neural activity underlying this interaction is regulated by learning and homeostatic mechanisms, which are mediated through synaptic plasticity and neuromodulation. At a much longer timescale, arching from cognitive development to aging, neural activity is strongly influenced by changes in brain anatomy and functional connectivity. Studies that analyze behavioral flexibility throughout this hierarchy of timescales are rare. This line of research utilizes a rule-based decision task and combines experimental procedures (psychophysics and neuroimaging) with computational approaches (reinforcement learning and neural circuit modeling) to encompass the dynamics, rise and decline of goal-directed behavior in humans.
Related Publications
Tymula A, Rosenberg Belmaker LA, Ruderman L, Glimcher PW, and Levy I (2013) Like cognitive function, decision making across the life span shows profound age-related changes. Proceedings of the National Academy of Sciences of the USA 110: 17143-17148.
Ardid S, and Wang XJ (2013) A tweaking principle for executive control: neuronal circuit mechanism for rule-based task switching and conflict resolution. Journal of Neuroscience 33(50): 19504-19517.
In Collaboration With:
Salva Ardid, PhD at Universitat Politècnica de València
Using connectome-based predictive modeling to predict PTSD symptoms from decision-making attitudes
The neural networks involved in decision-making processes are large and span multiple regions within the brain. While regions such as the ventromedial PFC, anterior cingulate cortex, posterior cingulate cortex, and dorsal lateral PFC, ventral striatum, amygdala, and thalamus are all implicated in playing a dynamic role in decision-making processes, the functional connectivity underlying decision-making processes have yet to be examined. This project seeks to understand how neural networks involved in decision-making processes differ between those with PTSD and controls and whether predictive models would be able to characterize symptoms based on observed differences in neural signatures.
Related Publications
In Collaboration With:
Dustin Scheinost, PhD at Yale University