Nine interdisciplinary research teams at Duke have been selected to receive the 2013-2014 Duke Institute for Brain Sciences (DIBS) Research Incubator Awards (five new awards and four continuation awards). The 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.
Investigators: Greg Appelbaum (Psychiatry and Behavioral Sciences); Scott Huettel (Psychology and Neuroscience); Jordynn Jack (English and Comparative Literature, UNC-Chapel Hill); James Moody (Sociology); Alex Rosenberg (Philosophy); and Angela Zoss (Duke University Libraries)
Project Summary: Over the recent decades, the field of neuroscience has increased massively in scope and scale. While once seen simply as an extension of biology, neuroscience has matured into an interdisciplinary venture that collaborates with numerous other fields (e.g., computer science, linguistics, psychology and economics). Given this growth, there is a profound need for new approaches that synthesize across the larger literature by identifying common relationships across thousands of studies. In the present application, we expand on a recently developed semantic network approach that maps the relationships between terms and concepts that appear in the larger neuroscience literature. By implementing network text analyses in representative corpora of published neuroscience papers, we will map the historical and current state of knowledge. This approach holds promise for revealing key principles that may not be evident in individual studies. Changes in conceptual maps will be examined over many years to create quantitative models of how the discipline changes over time, which in turn can generate predictions for future research. These semantic maps will be compared with functional brain data derived from meta-analyses using the large-scale fMRI synthesis tool NeuroSynth and resting-state fMRI data available through the Duke-UNC Brain Imaging and Analysis Center. Given the novelty of this approach for neuroscience, this proposal will also seek to build a unique community at Duke that combines expertise in neuroscience, humanistic inquiry and network analysis – thereby positioning Duke as a leader in this emerging field.
Project Summary: In the United States legal system, rules of procedure and rules of evidence work to limit the harmful effects of biases in human decision making. But these rules are based on centuries of common law tradition and have not always been linked to research on decision making, bias and the strategies decision makers use when weighing evidence. Our research group brings together legal experts and neuroscientists to answer these questions by conducting large-scale web-based studies to measure the decision strategies used by jurors, judges and prosecutors when weighing evidence. We will then use neuroimaging to investigate the brain processes that give rise to these strategies, including unconscious biases. Our ultimate goal is to establish a scientific body of knowledge on biases and heuristics in legal decision making that will contribute to the goal of a more informed, rational and humane justice system.
Investigators: James Burke (Neurology); Scott Cousins (Ophthalmology); Sina Farsiu (Biomedical Engineering and Ophthalmology); Eleonora Lad (Ophthalmology); Guy Potter (Psychiatry and Behavioral Sciences); and Heather Whitson (Medicine, Geriatrics)
Project Summary: Imaging of the retina, an extension of the brain, is becoming increasingly used for the diagnosis of neurodegenerative disorders such as multiple sclerosis. Recent studies have shown that retinal changes occur in Alzheimer’s disease (AD). We believe that retinal changes can be utilized for early diagnosis of AD and have the great advantages of being more sensitive, cheaper and significantly less invasive than other diagnostic techniques. We believe that both retina and the brain in AD undergo inflammation, which results in specific retinal changes that can be quantified using automated software developed by our group. The goal of this study is to compare retinal images between normal subjects and subjects with different stages of AD and to confirm that specific retinal changes occur in subjects with early AD. Novel imaging systems to quantify these retinal abnormalities will facilitate early diagnosis as well as fast and convenient monitoring of dementia progression in AD patients. In addition, quantification of these specific retinal changes can be employed to monitor efficacy of future therapies for AD.
Project Summary: Currently, there is no effective treatment for autism spectrum disorders (ASD) that targets the underlying biological mechanism because little is known about the pathophysiology. The apparent technical challenge in human studies renders mutant mice with targeted mutations equivalent to humans a unique opportunity because it allows manipulation at molecular and circuit levels. However, the current analytic paradigm of analyzing synaptic development and function in ASD mouse models has not offered little insight into the behavioral impairments in these mice. Human genetic studies have supported SHANK3 synaptic protein as one of the best causative genes for ASD. Shank3 mutant mice recapitulate the core behavioral impairments in ASD and then provide an exciting opportunity to develop a novel analytic approach of dissecting circuit dysfunction. The long term goal of this project is to define dysfunctional circuit underlying ASD behaviors. The central hypothesis is that the ASD-like behaviors in Shank3 deficient mice originate from aberrant neurophysiological activities of multiple neural circuits. The broad objective of this proposal is to establish a novel paradigm of dissecting and repairing the neural-circuit mechanisms underlying ASD-like behaviors. The specific objective is to identify and repair the dysfunctional neural circuits underlying social deficits and repetitive behaviors in Shank3 deficient mice by utilizing multi-circuit neurophysiological recording, optogenetic tools, and behavioral testing concurrently. The use of this approach in Shank3 mutant mice will be first to examine the circuit dysfunction in valid ASD mouse models. The knowledge about circuit dysfunctions in Shank3 models will provide insight to develop the effective intervention.
Project Summary: A revolutionary advance in studying the brain has come from a technique called “optogenetics.” Scientists program nerve cells within the brain to become light-sensitive, just like the nerve cells within the eye. The activity of such modified nerve cells can then be controlled with exquisite spatial and temporal precision using safe, low-energy lasers and other discrete light sources. Applying this method to nerve cells near the surface of the brain is easy: one can simply shine a laser at the brain area of interest. But many important brain areas are nestled in the wrinkles of the brain, or hidden below the gray matter in the middle of the head. Hence, to study deeper areas, scientists need to use fiber optics, the same as used in telecommunication cables. These fiber optics cause damage and are impractical for many potentially important experiments. We propose a replacement to fiber optics that will permit the expansion of optogenetics methods. Instead of providing light from external sources, we create the light within the brain. Using genes from fireflies or marine organisms, we can introduce one protein into a nerve cell (called a luciferase) that normally is inactive, but when exposed to a certain chemical (for example, one called luciferin) produces safe, low-energy light. The light-triggering chemical can be introduced with a simple IV injection (it crosses the blood-brain barrier). Our project will advance the fundamentals of this new method for non-fiber optic, non-brain-invasive optogenetics and demonstrate its efficacy in behaving mice and monkeys.
Investigators: David Beratan (Chemistry); Wolfgang Liedtke (Neurology); Thomas McIntosh (Cell Biology); Scott Moore (Psychiatry and Behavioral Sciences); and Angel Peterchev (Psychiatry and Behavioral Sciences)
Project Summary: Recent scientific studies have shown that the field generated by simple permanent magnets (like fridge magnets but stronger) can alter brain activity when such a magnet is placed on a person’s head for a few minutes. This is an exciting discovery that can lead to various new applications of magnetic fields in science and medicine. Strong magnetic fields are also encountered is some environments like medical MRI scanners. However, it is not understood why this type of magnetic field affects the brain and exactly how the brain cells respond to fields of various strengths, directions, and length of application. This project will explore in detail how the magnetic field affects brain tissue. Specifically, we will combine experimental measurements of how brain cells respond to various magnetic field characteristics, with theoretical and computational models of potential mechanisms underlying these effects. The outcome of this effort will provide a foundation to develop static magnetic field stimulation as a tool for neural research and as a potential safe and cost-effective treatment for brain disorders.
Project Summary: The aging brain does not endure anatomical and physiological decline passively; it actively attempts to counteract this decline by reorganizing its functions. In one example of this we have studied using MRI brain imaging, young adults will activate their right frontal lobes when performing a memory task, while older adults (OAs) will also use the left frontal lobes as well, and how much they do this is related to how well they do. The ability of OAs to use both hemispheres may be related to how strongly they are connected. One new way of testing this connection is by using transcranial magnetic stimulation (TMS), which produces a magnetic field in a coil placed outside the head to stimulate the brain directly below it. If used while MRIs are being recorded, the activation throughout the brain caused by the TMS can be measured, including the opposite brain hemisphere. This provides a direct measure of connectivity, which can be compared to how well OAs perform a memory task. Certain forms of TMS can enhance ability to perform a memory task. We will apply this form of TMS to the opposite hemisphere in OAs to test whether it helps their performance in a memory task, and compare that with their measures of brain connectivity. We will then give OAs TMS for two weeks, to test whether that would help make the memory enhancements last at least three months. We hope the results will lay the groundwork for further study leading to therapies for memory deficits in the elderly using TMS.
Investigators: Blanche Capel (Cell Biology); Debra Silver (Molecular Genetics and Microbiology); and Gregory Wray (Biology)
Project Summary: The human brain performs a variety of remarkable feats that underlie our unique mental abilities. In particular, the cerebral cortex is essential for many complex brain functions including cognitive function, sensory perception and consciousness. In terms of evolution, the cerebral cortex is the most recently acquired structure of the mammalian forebrain. Moreover, relative to other structures of the brain, the neocortex is dramatically expanded in humans and this expansion is thought to be responsible for our higher cognitive functions. Many psychiatric disorders, such as autism, bipolar disorder, and schizophrenia are thought to result from dysfunction in the neocortex. In addition, disruption of neocortical development results in broad classes of developmental disorders including microcephaly (reduced brain size). Despite the importance of the neocortex in our evolution, behavior, and mental disease, we know little of the human-specific genetic changes that distinguish the human neocortex from all other mammals. Our project seeks to address this gap in knowledge by identifying genes that are common to all mammals, but whose function has been uniquely coopted for human brain development. We will focus on those changes acquired in the human lineage that influence gene expression rather than encode a specific protein. We will dissect how these regulatory changes control gene expression in the stem cells that build the neocortex and control the process of brain development. Our long-term goal is to discover the broad repertoire of human-specific genetic changes that impact neocortical development. Significantly, this project will help to understand the genetic mechanisms underlying brain size, cognition, and psychiatric and neurodevelopmental disorders.
Project Summary: The trigeminal sensory-motor system detects tactile and painful sensory stimuli experienced by the head and face, and also regulates diverse voluntary orofacial motor behaviors such as chewing, swallowing and vocalization. In this project, we will focus on understanding mouse trigeminal sensorimotor circuits underlying two key functions of this system: active touch sensation and mastication-related behaviors. Furthermore, we will examine the functional neuronal connectivity in both normal mice and in a mouse model of orofacial pain to determine whether chronic pain conditions alter the wiring of the sensorimotor circuits. We will employ mono-synaptic rabies assisted trans-synaptic tracing, electrophysiology, calcium imaging, and behavioral analysis to dissect these neural circuits. These studies should not only provide insights into the neural basis of voluntary movement control and sensorimotor integration, but also establish the foundations for uncovering abnormally altered circuits in various neurological disorders.
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