Congratulations to the 2016-2017 DIBS Research Incubator Award Winners
Eight interdisciplinary research teams at Duke have been selected to receive the 2016-2017 Duke Institute for Brain Sciences Research Incubator Awards (five new awards and three continuation awards). The DIBS Research Incubator Awards program is designed to encourage innovative approaches to problems of brain function that transcend the boundaries of traditional disciplines. The award provides seed funding for collaborative research projects that will lead to a better understanding of brain function and translate into innovative solutions for health and society.
2016-2017 New Awards
- Repeated Transcranial Magnetic Stimulation (rTMS) Modulation of Insula-based Functional Connectivity
Investigators: Merideth Addicott (Psychiatry & Behavioral Sciences), Greg Appelbaum (Psychiatry & Behavioral Sciences), Timothy Strauman (Psychology & Neuroscience), Bruce Luber (Psychiatry & Behavioral Sciences)
Project Summary: This project will investigate the use of repetitive transcranial magnetic stimulation (rTMS) to change brain function and behaviors that could help support smoking cessation. rTMS is used to treat depression, and has shown promise in treating tobacco addiction. This study aims to develop a better understanding of how rTMS affects brain function in smokers and nonsmokers, and this information will support a larger study to investigate if rTMS improves smoking cessation in smokers who want to quit.
- Bioelectronic Medicine and Cholinergic Regulation of Postoperative Cognitive Dysfunction
Investigators: Niccolò Terrando (Anesthesiology), Warren Grill (Biomedical Engineering), Christina Williams (Psychology & Neuroscience), Chay Kuo (Cell Biology), Miles Berger (Anesthesiology)
Project Summary: Memory dysfunction is a common complication in patients after major surgery and may last for several months, even years, after an operation. We do not yet know why this decline in memory function occurs, and currently there is no effective medical treatment to prevent this complication. We developed a clinically-relevant model to study surgery-induced memory dysfunction in mice after a common type of orthopedic surgery. With this model we described how immune system activation impairs brain regions that are important for memory and learning (hippocampus). Using pharmacological strategies, we were able to prevent some of these changes, but also found these approaches are not appropriate for translation to human use. This project will identify cellular processes that may cause memory deficits after surgery. We will focus particularly on interactions between the nervous and immune systems. Since nerve stimulation is a safe and innovative treatment approach in humans, we will study its effects on these cellular processes and memory function after surgery in mice. Overall, this work is expected to have a major impact on global health by reducing the negative effects of surgery on memory and cognitive ability.
- Neurogenesis and Behavioral Recovery in Animal Models of Huntington’s Disease
Investigators: Richard Mooney (Neurobiology), Cagla Eroglu (Cell Biology), Debra Silver (Molecular Genetics & Microbiology)
Project Summary: Most neurons in the human brain are born early in development and must last the individual’s entire lifespan. Consequently, diseases or trauma that kill neurons can cause severe and irreparable damage to the brain and behavior. A major therapeutic challenge is to replace neurons that are killed by disease or trauma. A further challenge is that we do not understand how to insert new neurons into the adult brain and replace those that were previously lost. Huntington’s Disease (HD) is a severe neurological disorder that is characterized by massive neuron death in a part of the brain that controls complex sequences of movements, such as those that are necessary to having a conversation, playing the piano, or shooting a round of golf. Therapies that replace these lost cells do not exist. The PI’s group recently found that expressing a genetic mutation that causes HD in the brain of a songbird destabilizes their previously stereotyped songs and makes them sing much longer songs, reminiscent of the motor symptoms of HD. Notably, these behavioral changes are paralleled by massive loss of the same neurons that die in human HD. Moreover, a subset recovered stable songs after several months, and the adult songbird is able to replace neurons of the type that are killed by HD. This proposal seeks support for a collaborative effort to explore how replacing neurons in the adult brain can be harnessed to repair the brain and behavioral deficits that characterize HD.
- The Nature of Disgust: An Interdisciplinary Inquiry
Investigators: Kevin LaBar (Psychology & Neuroscience), Walter Sinnott-Armstrong (Philosophy), Nancy Zucker (Psychiatry & Behavioral Sciences)
Project Summary: Why is it that smelling something rotten can elicit the same feeling as squashing a bug, witnessing a hate crime, or hearing about a politician’s abuse of power? These various kinds of events elicit a shared experience of disgust, an emotion that is universal but poorly understood. We propose to form a research team involving scholars from philosophy, affective neuroscience, and psychiatry to understand how disgust is represented in the brain and how it contributes to psychiatric illness. We will determine whether a unique disgust signature exists in the nervous system and how the concept of disgust can be broken down into component parts to aid the diagnosis of medical conditions.
- Building a Fiber-integrated Microscope System for Two-color Optogenetic Probing of Ensemble Activity in Freely Behaving Animal
Investigators: Yiyang Gong (Biomedical Engineering), Fan Wang (Neurobiology)
Project Summary: Recording and manipulating neural activity are direct ways to study how the brain works. Because many neurons contribute to computations in the brain, modern neuroscience techniques have employed optogenetic strategies that isolate specific types of neurons for individual study. These strategies employ two components for optical probing of neural activity: a set of genes expressing light-sensitive proteins that report or manipulate neural activity; and a set of optical microscopy tools that deliver light to activate these proteins. Modern optical techniques have miniaturized optics so that rodent animal models can carry the optical equipment while performing freely-moving behavior. Thus far, these experiments have probed one neural population at a time. The next step in dissecting brain activity during complex behaviors requires examining how multiple neural populations interact together. We proposed to develop the optical and genetic technology that will enable observing or manipulating two types of neural populations simultaneously. First, we will develop a fluorescence microscope that simultaneously operates with two wavelengths, so that we can independently record or manipulate two neural populations. Second, we will develop and employ protein tools that are activated by the different wavelengths of light. Finally, we will target these protein tools to two different neural populations and study the two sets of neural activities during a rodent gap-crossing behavior. The combination of fundamental engineering and basic neuroscience developments in this proposal will better detail the interaction of neural populations during complex behaviors.
2016-2017 Continuation Awards
- Optimized Temporal Patterns of Spinal Cord Stimulation to Treat Chronic Pain
Investigators: Warren Grill (Biomedical Engineering), Ru-Rong Ji (Anesthesiology), Nandan Lad (Surgery)
Project Summary: Chronic pain is a prevalent and clinically challenging condition for which there are often not adequate treatments. For example, chronic low back pain is the most common cause of lost time due to disability, and imposes an annual economic burden of >$100 billion. Standard treatments for chronic pain, such as physical rehabilitation, pharmaceuticals, and surgery, work for some individuals, but for others who do not receive satisfactory pain relief from standard treatments, alternative approaches are required. Spinal cord stimulation (SCS) is an established surgical device therapy widely used for treating chronic pain, where an implanted battery-powered pulse generator (pacemaker) delivers electrical pulses to an electrode array placed in the spine. Although, SCS is FDA approved for treating chronic low back and limb pain, only ~ 60% of recipients experience a reduction of 50% or more in their pain. We propose to investigate a novel method of SCS that is expected to increase substantially the degree of pain reduction. The outcome of these collaborative studies will be an assessment of the feasibility of using a novel approach to treat chronic pain, and will provide the foundation for translational studies of this innovative approach in patients with chronic pain.
- The Power of Imagination
Investigators: Felipe De Brigard (Philosophy), Kevin LaBar (Psychology & Neuroscience), M. Zachary Rosenthal (Psychiatry & Behavioral Sciences)
Project Summary: Our tendency to entertain thoughts about alternative ways in which past events could have occurred but did not is ubiquitous. Usually, these episodic counterfactual thoughts are fleeting and infrequent. But not so for individuals suffering from anxiety. The constant presence of such thoughts in their lives and their incapacity to disengage from ruminating on regret-provoking counterfactual simulations is not only a hallmark of their condition, but also one of their most debilitating traits. Unfortunately, little is known about the cognitive and neural mechanisms underlying this maladaptive form of counterfactual rumination. The primary purpose of our proposed project is contribute to our understanding of the neural and cognitive basis of such abnormal counterfactual rumination in individuals with anxiety. In addition, we seek to test the hypothesis that, at the basis of their abnormal counterfactual rumination, lies a malfunction in the memory reconsolidation processes of individuals with anxiety. By uncovering the neural and cognitive mechanisms underlying abnormal counterfactual rumination in individuals with anxiety, as well as the precise ways in which counterfactual thinking and autobiographical memory interact in this population, we hope to unveil important clues that may help pursuing more effective clinical therapies for this condition.
- Pediatric Neurotrauma
Investigators: Cameron R. ‘Dale’ Bass (Biomedical Engineering), Mohamed Abou-Donia (Pharmacology & Cancer Biology), Carolyn Pizoli (Pediatrics), Carrie Muh (Surgery), Bruce Capehart (Psychiatry & Behavioral Sciences), Mustafa Bashir (Radiology)
Project Summary: Pediatric brain injury is common, but we know little about how impacts cause brain injuries, how to determine the injury severity, and how to treat brain injuries, especially for milder severities. Further, the long term consequences of repeated brain injuries are unknown. To address these pressing issues, we study adolescent elite female soccer players who are known to have a high incidence of on-field head injuries. Our collaborators have developed a novel way to determine the severity of the impacts using an ear based sensor (DASHR) that has been shown to be well-coupled to the human head, unlike any commercially-available system. Measuring on-field impacts with the DASHR system, we will investigate several novel techniques to sensitively determine the severity and time course of potential head injuries. These techniques include a blood test for markers of neurotrauma, a magnetic resonance imaging (MRI) technique to image changes in brain function, a noninvasive technique to measure the stiffness of the brain, a test for eye function, and a test for cognitive abilities and reaction times. All of these techniques have been found to potentially assess brain injuries by our collaborators, either in model systems or in adults. Using these techniques, we will characterize brain injury from impact through clinical/biological response, and will assess which technique or combination of techniques most effectively identifies brain injuries. Success of this project will provide new ways to understand and treat brain injuries in children.