David Beversdorf - US grants

DESCRIPTION: (provided by applicant) Withdrawal from opiates and cocaine causes upregulation of the noradrenergic system. My research has demonstrated a central nervous system noradrenergic modulation of cognitive flexibility in anagram problem solving. As a result, impaired cognitive flexibility due to upregulation of the noradrenergic system during opiate and cocaine withdrawal may increase maladaptive behaviors seen in withdrawal by impairing cognitive flexibility. With this proposal, we wish to explore noradrenergic modulation of cognitive flexibility in cocaine withdrawal. The long-term goal of this line of research is to guide future research into treatment of drug withdrawal based on this cognitive neuropharmacological model. Our hypothesis is that cognitive flexibility in problem solving in conditions of noradrenergic activation during cocaine withdrawal can be modified pharmacologically. Our primary specific aim is to test noradrenergic modulation of cognitive flexibility in patients withdrawing from cocaine. Initially, we will undertake a dose-response study in nonaddicted normal subjects in order to determine the optimal dose of the noradrenergic antagonist propranolol needed to modulate cognitive flexibility. We will also compare noradrenergic modulation of performance on various cognitive flexibility dependent (including anagram problem solving) and cognitive flexibility independent tasks in nonaddicted normal subjects. We will then test noradrenergic modulation of cognitive flexibility in patients withdrawing from cocaine. In normal individuals, cognitive flexibility is better after noradrenergic antagonists than after noradrenergic agonists, but no difference existed between noradrenergic antagonists and placebo. However, cocaine withdrawal upregulates the noradrenergic system sufficiently that withdrawal patients may function similarly to normal individuals receiving noradrenergic agonists. Therefore, we predict that the noradrenergic upregulation during cocaine withdrawal is sufficient that administration of noradrenergic antagonists will result in a significantly better performance on cognitive flexibility than placebo, whereas this is not observed in normal subjects. We will also compare withdrawal patients and nonaddicted normal control subjects on performance on various cognitive flexibility dependent (including anagram problem solving) and cognitive flexibility independent tasks. Future possibilities include assessment the anatomical substrate of problem solving using event-related fMRI. With better understanding of modulation of cognitive flexibility, future studies can test cocaine and opiate addicts, deriving rational pharmacotherapy for optimal treatment of drug addiction. Long-term goals include further development this model of noradrenergic modulation of cognitive flexibility and looking for potential benefits in cognitively impaired and drug-addicted patients. OSU is well equipped for these goals, including potential fMRI using the most powerful human MRI in the world, strong neuroscience and psychology programs, and an established drug addiction clinic.

[unreadable] DESCRIPTION (provided by applicant): I am a new faculty member in Neurology with fellowship training in Cognitive Neurology. I have put forth great effort to do research during my clinical training, but am seeking funding to release me from my current heavy burden of clinical responsibilities in order to develop as an independent investigator. My career development plan includes courses in neuroscience, cognitive neuroscience, behavioral pharmacology, statistics, and ethics, and regular guidance meetings with my mentor (Dr. Robert Bornstein, a neuropsychologist experienced in frontal lobe research) and collaborators. My previous research has shown that individuals with high-functioning adults with autism spectrum disorder (ASD) have impaired flexibility of the semantic network. This may relate to other problems with context utilization, problem solving, and social functioning in ASD. My previous research has also demonstrated a noradrenergic modulation of cognitive flexibility in normal individuals. I wish to further explore the modulation of cognitive flexibility. My hypothesis is that noradrenergic modulation of cognitive flexibility is specific to the noradrenergic system among catecholamines, that noradrenergic modulation of cognitive flexibility can occur with long-term treatment, and that noradrenergie antagonism can influence cognitive flexibility in ASD. My first Specific Aim is to further study the influence of catecholamines on cognitive flexibility. I will first test modulation of cognitive flexibility with varying doses of noradrenergic agents, and will test whether long-term propranolol can have the same effect as single-dose propranolol. I will then test whether dopaminergic agents can yield the same finding with cognitive flexibility. My second Aim is to study the effects of stress and propranolol on cognitive flexibility. I will test whether propranolol can reverse the impairment in cognitive flexibility that results from situational stressors. My third Aim is to learn the effects of noradrenergic antagonism on cognitive flexibility in individuals with ASD. I will test whether propranolol has a greater effect on cognitive flexibility in individuals with ASD than in matched controls. With better understanding of modulation of cognitive flexibility, future studies can further test noradrenergic modulation of cognitive flexibility in ASD. My long-term goal is to study neuropharmacology and cognitive neuroscience and look for benefits in cognitively impaired patients, with a particular focus on high-functioning adults with ASD. OSU and my outside consultants are well equipped for my current and future research goals, with ongoing autism research, possible potential for future high-field fMRI, and strong neuroscience training. [unreadable] [unreadable]

The neuroscience of creativity is a new and burgeoning area of research. The newness of the field presents a window of opportunity to make the newly founded Society for the Neuroscience of Creativity (this research area's first academic society) a mechanism that coalesces scientists around research priorities with educational relevance. Likewise, there is an opportunity to bring educators and education researchers into the dialogue at a critical early phase so that the growth of creativity neuroscience can be guided by and applied to real-world challenges and aspirations of educating a more creative workforce. From the perspective of the researcher, this meeting will streamline and catalyze progress in the neuroscience of creativity by supporting collaboration, cross-pollination, and reciprocal learning between researchers with related interests. The Society for the Neuroscience of Creativity is founded with a charter of outreach and inclusiveness. Among our major goals is the involvement of women and members of underrepresented minority groups in our meetings and online community, and direct educational outreach. Examples of planned activities to support these goals are the establishment of special travel funds for underrepresented minority students and for teachers of underserved minority students, and special outreach to high schools that serve low-income and minority students in the area where the meeting is held.

The proposed meeting of the Society for the Neuroscience of Creativity will be held on March 24th, 2017 in San Francisco, CA as a satellite to the Cognitive Neuroscience Society meeting. The primary objective of the proposed meeting is to establish an inclusive community of scholars and educators seeking to understand and actively leverage the mechanisms of the brain that support creative thinking, teaching, and learning. The Society for the Neuroscience of Creativity is founded in order to build a bridge across a conspicuous gap between creativity researchers and educators working to foster creativity, especially in Science, Technology, Engineering, and Math (STEM) fields where creative innovation is a key driver of advancements. The proposed conference is critical to establishing the newly founded society. In addition to this over-arching goal, we have identified a set of specific scientific priorities as critical for the productive development of the neuroscience of creativity. The meeting will highlight work that advances these priorities and actively encourage collaboration on these priorities among society members: 1) development of reliability for brain-based measures of creativity; 2) mapping the shared vs. distinct neural networks underlying different forms of creativity; 3) operationalizing key targets in education (especially in STEM fields) for which there is insufficient research about neural bases of relevant creative thinking; 4) identifying neural plasticity that mediates education-based improvements in creativity; 5) developing iterative, reciprocally-adaptive paradigms whereby neuroscience can inform improvements and individualization of educational approaches to fostering creativity; and 6) leveraging brain imaging to guide targeted, hypothesis-driven explorations of neural interventions that have potential to bolster creativity.

Creativity in STEM is the difference between basic competency and innovative advancement. To foster continued innovation, it is essential that we develop new methods to foster students' creative thinking skills in STEM. However, many issues regarding creativity remain unresolved. For example, we know little about how creativity develops, how the brain gives rise to creativity, and what sorts of educational experiences can make a student more creative over time. Indeed, even determining how to accurately measure creativity is a source of debate. This conference of the recently founded Society for the Neuroscience of Creativity (SfNC) establishes an inclusive community of scholars and educators seeking to understand and actively leverage the neural mechanisms that support creative thinking, teaching, and learning. Its specific goals are to 1) establish a reciprocally informative platform to keep researchers updated on the priorities of educators, and keep educators updated on relevant advances in creativity research, and 2) lay out a roadmap for creativity research. This project exemplifies the Education and Human Resources Core Research program's commitment to fundamental research on learning in STEM that combines theory, techniques, and perspectives from a wide range of disciplines and contexts.

By supporting collaboration and reciprocal learning between researchers with related interests, this meeting will streamline and catalyze progress in the neuroscience of creativity. Specific scientific priorities identified as critical for the productive development of the neuroscience of creativity include the development of measurement tools and the fostering of creativity through educational experiences. This meeting will also highlight work that advances these priorities and will actively encourage collaboration on these priorities. To foster a meaningful dialogue among researchers and educators, the meeting is targeted at an accessible size of 100-200 attendees. Further, the meeting is scheduled to immediately precede the larger Cognitive Neuroscience Society annual meeting so that attendees of that meeting can participate in the event as a preconference experience. A major goal of the SfNC is the involvement of women and members of underrepresented minority groups. This goal is reflected in the establishment of travel funds that support the participation of underrepresented minority students and teachers of underserved minority students. To further increase the meeting's broader impacts, the participation of local community partners including teachers, administrators, and program developers focused on STEM and music education is also a priority.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.