The Laureate Institute for Brain Research (LIBR) has recruited junior investigators with an impressive track record of scientific productivity to lead the four NeuroMAP projects with innovative neuroscience-based research to use individual differences on several biological levels together with sophisticated statistical approaches to generate clinically meaningful predictions of risk and outcomes for mood, anxiety, and eating disorders.
PROJECT 1:
Cerebellar Neuromodulation to Enhance Fear Extinction
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The goal of exposure-based therapies for anxiety is to present a fear inducing stimulus to the patient in a safe setting in order to extinguish (fear extinction) the previously conditioned (fear conditioned) association. Abnormalities in the fear extinction process characterize many anxiety disorders such as social phobias, panic disorder, and post-traumatic stress disorder. We hypothesize that an acute intervention such as transcranial direct current stimulation (tDCS) may be able to probe the plasticity of a neural network relevant to exposure therapy outcome and help aid early decision points regarding who is most likely to benefit from exposure therapy. Both animal and human investigations have supported an important role for the cerebellum in fear conditioning and fear extinction. Our investigative model uses fear of public speaking, a prevalent social phobia that is amenable to exposure based therapy. Public speaking phobia is typically less complicated by comorbidities than other anxiety disorders.
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Clarifying role of the cerebellum in fear extinction is important because 1] it enables one to modulate a brain structure that is accessible using tDCS and other neuromodulation tools, and 2] it may provide a severity indicator to help identify subsets of individuals with severe difficulties with fear extinction. The results from this study may lead to a program of research aimed at synergizing neuromodulation with behavioral therapy to increase treatment efficacy.
Dr. Cha is a board certified neurologist who investigates brain stimulation therapies guided by neuroimaging. She completed her medical degree at Mayo Medical School, internship at the Brigham and Women’s Hospital, neurology residency at UCSF, and subspecialty training in neurotology at UCLA. She is currently an Assistant Professor at the University of Tulsa and Principal Investigator at the Laureate Institute for Brain Research where she runs a non-invasive brain stimulation laboratory. |
PROJECT 2:
Predicting Response to Exposure Therapy Using a Carbon Dioxide Challenge in Patients with High Levels of Anxiety Sensitivity
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Anxiety disorders are the sixth leading cause of worldwide disability and the most common mental illness, with a lifetime prevalence affecting over a quarter of the population. Exposure therapy, an important component of cognitive behavioral therapy (CBT), is one of the most effective anxiety treatments, and has been shown to improve symptoms across a number of different anxiety disorders. Meta-analyses reveal an approximately 50% treatment response rate, with the remaining half of patients showing either no response (~25%) or dropping out of treatment early (~25%). Unfortunately, there are currently no tests for predicting which patients would benefit the most from exposure therapy. The current proposal will test whether brief inhalations of an air mixture containing 35% carbon dioxide (CO2) — a safe and noninvasive physiological test which alters breathing patterns — provides a window into whether an individual with anxiety can successfully adapt and learn in response to exposure therapy.
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The findings will reveal whether CO2 is a useful tool for predicting which patients would be the best candidates for exposure therapy.
Dr. Feinstein is a Clinical Neuropsychologist at the Laureate Institute for Brain Research and an Assistant Professor at the Oxley College of Health Sciences at the University of Tulsa. He received his PhD in Clinical Neuropsychology from the University of Iowa and completed his postdoctoral training at the California Institute of Technology and his clinical internship at the University of California, San Diego. |
PROJECT 3:
Response to Inflammatory Challenge in Major Depressive Disorder
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Depression is a very heterogeneous disorder that affects how one processes events - ‘what makes you feel good’ (positive valence), ‘what makes you feel bad’ (negative valence), and how the brain processes body-relevant information (interoception). Some have proposed that inflammation causes depression in a subset of people. However, very little is known about the biological differences between depressed individuals with and without inflammation. This project will study how an inflammatory stimulus is converted into biological changes that predispose to depression. To do this, we will experimentally perturb the immune system with a sugar molecule found on the cell wall of certain bacteria (lipopolysaccharide or LPS) that induces a transient immune response. Specifically, we will test whether depressed people with low inflammation differ from depressed people with high inflammation in the way that they respond emotionally,
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immunologically, and neurally to the LPS. Further, we will test whether individual differences in response to LPS can predict who will respond to treatment with cognitive behavioral therapy. This research will help us to understand the mechanisms through which inflammation leads to depression in vulnerable individuals, thus facilitating the development of new pharmacological or behavioral therapies, and identifying predictive biomarkers.
Dr. Savitz graduated with a Ph.D in Human Genetics from the University of Cape Town in 2006 and subsequently completed post-doctoral training in neuroimaging under Wayne Drevets at the NIMH. Jonathan is currently an assistant professor at the Laureate Institute of Brain Research and the Faculty of Community Medicine at the University of Tulsa, OK. |
PROJECT 4:
Neural Basis of Interoceptive Dysfunction and Anxiety in Anorexia Nervosa
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Anorexia nervosa (AN) is a serious mental illness with one of the highest mortality rates of all psychiatric disorders. It is characterized by fears of weight gain, pre-meal anxiety, reduced caloric intake, and food avoidance; features that often persist after weight restoration. How the experience of eating provokes such fear in anorexia nervosa is unknown. Altered anxiety expression has been suggested as one explanation, on the basis that anxiety disorders are well known antecedents to AN, are frequently comorbid, and show an increased aggregation among first degree family members of affected individuals. This project will examine whether the altered neural processing of interoceptive signals exacerbates the expression of meal associated anxiety and dysfunctional eating behaviors in AN. Specifically, the project will investigate how individuals with AN experience anxiety-related cardiorespiratory sensations during meal
anticipation relative to two groups: healthy |
comparison women, and women with generalized anxiety disorder (GAD). We will assess cardiorespiratory interoception and anticipatory meal anxiety within the functional neuroimaging environment using intravenous infusions of a sympathomimetic drug (isoproterenol) and saline. Physiological and neural responses will be compared across the groups, and they will be used to predict illness outcomes at one year for each patient group. This research will lay the groundwork for the development of targeted treatment approaches for anxiety in AN.
Dr. Khalsa graduated from the Medical Scientist Training Program at the University of Iowa, receiving M.D. and Ph.D. (neuroscience) degrees in 2009. He completed his residency training in Psychiatry at UCLA. Sahib is currently the Director of Clinical Studies at LIBR and an assistant professor at the Faculty of Community Medicine at the University of Tulsa, OK. |