Ten interdisciplinary research teams at Duke have been selected to receive the 2014-2015 Duke Institute for Brain Sciences Research Incubator Awards (four new awards and six 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.
Project Summary: Humanity now relies heavily on supervisory control professionals. Whether it be air traffic controllers, pilots of unmanned vehicles, nuclear power plant management, or even in medical applications like anesthesiology or radiology, it is essential that operators are able to monitor and react to complex inputs that fluctuate in priority and frequency. Because the control of such automated systems typically vary between short periods of heavy engagement that tax the operators cognitive faculties and longer periods of relative boredom, there is a great need for tools that effectively monitor the cognitive state of the operator and provide an alert in the event of likely performance failures.
Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive and durable approach for measuring neural function. This technique may be particularly suited to supervisory control settings since it has shown initial promise as a measure of cognitive workload, but there are very few studies examining practical applications of fNIRS with enough subjects to have confidence in the results. We propose to investigate whether increases in mental workload can be detected with fNIRS and if these results correlate with performance in terms of reaction time and errors in a representative human supervisor control task of one operator controlling multiple unmanned aerial vehicles.
Investigators: Geri Dawson (Psychiatry and Behavioral Sciences), Helen Egger (Psychiatry and Behavioral Sciences), Cynthia Kuhn (Pharmacology and Cancer Biology), Kevin LaBar (Psychology and Neuroscience), Patrick Seed (Pediatrics), Nancy Zucker (Psychiatry and Behavioral Sciences)
Project Summary: Most of us are familiar with gut sensations: the pangs of hunger, the butterflies of anxiety. It is part of our daily experience that our gut communicates with our brain and that this communication impacts our behavior (we eat when hungry). Researchers have begun to probe this bi-directional gut-brain communication. Studies in animal models have revealed that manipulation of the bacteria profile of the gut cannot only affect behavior, but may also impact brain development. “Bottom up” processes such as changing the composition of the gut bacteria influence anxiety. Evidence of “top-down modulation” has also been demonstrated. Stress has been found to impact the composition of the microbiome. Animal studies have led researchers to the intriguing speculation that altering the composition of gut-microbiome in humans may affect psychiatric conditions such as anxiety. The use of probiotics as a clinical tool has yielded mixed findings. Probiotics are micro-organisms that positively impact the host organism and alter the composition of the gut bacteria profile. The most robust effects have been seen in lowering abdominal discomfort in irritable bowel syndrome. There remain numerous questions about the efficacy and mechanism of gut-brain relationships. Conflicting results may be due to the fact that probiotics have largely been administered in human adults. In animal models, changes in stress reactivity were more sustained when interventions with probiotics occurred earlier in development. In this high-risk, high-impact study, we conduct the first trial of probiotics in 30 young children with anxiety and abdominal pain and examine changes in anxiety and pain.
Investigators: Murali Doraiswamy (Psychiatry and Behavioral Sciences), Tobias Egner (Psychology and Neuroscience), Scott Huettel (Psychology and Neuroscience), Walter Sinnott-Armstrong (Philosophy and the Kenan Institute for Ethics)
Project Summary: When a psychopath kills a stranger for money, does he have any sense that his act is immoral—as most of us would? Do people who say sincerely that nothing is wrong with homosexual sodomy actually have an implicit negative attitude that they need to overcome? Do people who lie have any inclination to think that lying is immoral? Are all of our moral judgments ultimately based on such implicit moral attitudes? To answer such questions, we need some way to determine who has an implicit moral attitude and, if so, how strong it is. Unfortunately, no such test exists yet. Our goal is to develop several measures of implicit attitudes, using reaction times, accuracy rates, subliminal primes, eye movements, and brain activity. We plan to develop, refine, and validate these varied tests by comparing their results to each other as well as to independent measures of moral judgment. These new tests will enable us to test popular theories in moral psychology, to study the effects of implicit moral attitudes on behaviors in a variety of contexts, and eventually to improve the diagnosis, treatment, and prediction of recidivism in psychopaths and other mental illnesses associated with deficits in moral judgment and behavior. These new tools could thereby aid both theory and practice.
Project Summary: We are all in part defined by the memories of our experiences, which not only record our past, but also inform how we react to present actions and predict future events. A remarkable feature of our memory is its longevity. Multiple lines of evidence spanning a half-century of research suggest it is the alteration and modification of specific connections (synapses) between neurons that enable for the long-term coding of experience into memory in a process termed synaptic plasticity. Moreover, abnormalities in this process are thought to underlie many of our most devastating neurodevelopmental disorders, including intellectual disability and autism spectrum disorders. One mechanism that has emerged to modify neuronal synapses is the specific translation (production) of proteins at sites of neuronal communication, enabling a long-term enhancement of their connectivity. Mutations in genes, such as FMR1 disrupt this process leading to Fragile X Syndrome in humans and related phenotypes in mice. Unfortunately, it has previously not been possible to decode the identity of proteins that are translated at the synapse, severely hampering our understanding of the mechanisms of synaptic plasticity and the basis for disorders related to its disruption.
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.
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: 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.
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