Kimberly Kirkpatrick - US grants

Although it is well-established that schedule-induced drinking occurs on intermittent schedules of food reinforcement, the mechanism by which drinking arises is still a mystery. The proposed experiments will test four major hypotheses. First drinking is a conditioned response that is controlled by the same basic laws as other conditioned responses. Second, drinking arises in anticipation of upcoming food delivery rather than occurring as a reaction to the previous pellet. Third, competition occurs between drinking and the operant, which can result in the displacement of drinking to the early portion of the interpellent interval. Finally, drinking may be controlled by timing mechanisms in much the same way as operant responses. The experimental results will be interpreted with three major theories of timing to determine whether the temporal locus and duration of bouts of drinking may be theoretically modeled in the same manner as operant responses such as lever pressing. If necessary, modifications in the theories will be made to accommodate the results of the proposed experiments.

DESCRIPTION (applicant?s abstract): There is a lengthy literature showing the association between Type 1 Diabetes and eating disorders (ED) in both adult and adolescent populations (for review see Daneman & Rodin, 1999; Rodin & Daneman, 1992). The co morbidity of EDs in Type 1 patients can disrupt adherence to the Diabetes daily treatment regimen, result in poor glycemic control, and increase the risk of diabetes-related complications (e.g., nephropathy, neuropathy, retinopathy, cardiovascular disease) (e.g. Cantwell & Steel, 1996; Fairburn, Peveler, Daview, Mann & Mayou, 1991). There is a very small literature documenting EDs in Type 2 patients as well (Herpertz, et al., 2000; Kenardy, Bowen, Mensch, & Pearson, 1994; Wing, Marcus, Epstein, Blair, Burton, 1989). However, this literature addresses comorbidity in adults only, as Type 2 Diabetes is usually diagnosed in late adulthood. Comparisons in the adult literature have suggested that while the prevalence of EDs is similar in Type 1 and Type 2 diabetes patients, the distribution of the type of ED is different (Herpertz et al., 1998). This study, in adolescents with Type 1 or Type 2 diabetes, aims to: 1) assess the association between disordered eating attitudes/behaviors and glycemic control, 2) assess the association between eating attitudes/behaviors and adherence to physician recommended diabetes management, 3) compare scores on the Drive for Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorder Inventory and the distribution of clinically diagnosed eating disorders using the Eating Disorder Examination structured interview.

? DESCRIPTION (provided by applicant): Individual differences in impulsive behavior have received growing attention, particularly because impulsive choice is a primary endophenotype that predicts a wide range of problem behaviors. Impulsive choice occurs when choosing between a smaller reward that is available after a shorter delay (SS) and a larger reward after a longer delay (LL). Impulsive individuals tend to choose the SS reward even when the LL is more advantageous. Impulsive choice is a trait in humans, and in rats, and trait impulsive choice has been indicated as a primary endophenotype for attention deficit hyperactivity disorder (ADHD). High levels of impulsive choice are also associated with substance abuse, pathological gambling, and obesity as well as several other diseases and disorders. While impulsive choice is clearly related to a number of human health problems, identifying whether an individual is impulsive is not sufficient. Growing evidence suggests that there are two distinct pathways to impulsivity: one through deficits in time processing and one through deficits in reward processing. In addition to developing assays for identifying the contribution of timing and reward processes to impulsive choice in our previous NIMH award, upon which this renewal is based, we implemented several different time-based neurocognitive interventions that successfully promoted self-control. We found that the interventions operated to improve core timing processes by increasing temporal discrimination abilities. The present proposal therefore seeks to gain a deeper understanding of the two pathways to impulsivity, and to expand on our previously developed time-based interventions to moderate individual differences in impulsive choice. Aim 1 will determine the durability and generalizability of the time-based neurocognitive interventions, which is important for determining their efficacy for future translational applications. Aim 2 will isolate the mechanisms of action of the time-based interventions. We propose two separate time-based mechanisms that improve self-control: (1) improving delay tolerance, which leads to an increased ability to wait for longer delays, and (2) increasing temporal discrimination, which promotes the ability to make well-informed choices. Aim 2 will determine the nature and degree of contribution of these two components to the effectiveness of the time- based interventions. Aim 3 will employ either time-based or reward-based interventions to override deficits in timing and/or reward processing, providing different pathways to improving self-control. The combined set of studies will significantly advance our understanding of the functioning of the two pathways to impulsivity and will deepen our understanding of the neuro-cognitive interventions to increase their translational potential.

PROJECT SUMMARY The administrative core will provide oversight of all Cognitive and Neurobiological Approaches to Plasticity (C- NAP) center components and functions. The administrative core consists of the PI/PD, Associate Director (AD), Internal Advisory Committee (IAC), External Advisory Committee (EAC), Project Mentors, and Research Core Facility Directors. Collectively, the administrative core have research interests connected to the C-NAP core theme as well as extensive grant management, general administrative, center management, and faculty mentoring experience. We will recruit EAC members that are similarly impressive in their qualifications and whose research interests strongly align with C-NAP. C-NAP core facilities are each managed by a core director with relevant expertise; the research cores directly support the primary projects and programs. The faculty mentoring program and three C-NAP programs will be directed by the administrative core. The faculty mentoring program is tailored for each of the primary projects, with an external mentor that has strong expertise relevant to the project, and an internal mentor with general expertise in that area. The mentoring team will provide guidance on project development and implementation, supply feedback on manuscripts and grant applications, and give formative feedback on a semi-annual basis. The faculty mentoring program will provide critical support to facilitate primary project leaders in gaining significant extramural funding and graduating from the overall COBRE program. 1. The post-doctoral training program will deliver research mentoring to two post-doctoral fellows who will work on cross-cutting themes that bind together individual research programs and core facilities. This program will promote strong synergy across C-NAP and will increase the usage of core facilities. The program will provide a pathway to independence by providing a route for procuring extramural funding and eventual faculty positions. 2. The scientific exchange network (SEN) connects C-NAP with other centers and research units that complement C-NAP research mission. We have established connections with multiple partners and will aim to expand our network during COBRE Phase I. The SEN will supply collaborative research skills training, provide access to research core facilities, and promote collaborative research. 3. The pilot grant program will expand the scope of the research supported by C-NAP by funding 3 grants ($50K/year) annually, including mentoring to promote successful transition toward extramural funding. Additional components include plans to fund up to 5 small seed grants (@$5K each) annually to researchers across the State of Kansas, recruit three new faculty members at KSU and WSU, host two mini-conferences with our SEN partners, hold an annual colloquium series, organize training workshops on topics such as grant writing, career development, responsible conduct of research, specific research techniques, use of specialized equipment, and data analytics. The collection of projects, cores, and programs will ensure the formation of a thriving COBRE research center.  

OVERALL PROJECT SUMMARY This COBRE application will form a unique, thematic research center on Cognitive and Neurobiological Approaches to Plasticity (C-NAP). Four primary research projects bridge areas of excellence in the Cognitive and Behavioral Neuroscience programs at Kansas State University (KSU) and the Human Factors program at Wichita State University (WSU). The projects examine cognitive/neural plasticity across the lifespan, utilizing basic and translational/applied approaches in humans and animal models. The ultimate goal is to determine the mechanisms involved in cognitive and neural plasticity to improve functioning. This goal is highly relevant to the NIH core mission ?to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.? Three research core facilities will support the research projects and programs, a Behavioral Neuroscience Core (KSU), a Neuroinformatics Core (KSU), and a Driving Simulator Core (WSU), supplying unique research infrastructure resources within the State of Kansas. The success and growth of C-NAP will be enabled through: (1) a faculty mentoring program that will provide high-quality research mentoring by nationally-recognized researchers. The mentoring team will support all aspects of research program and grant application development to promote success in securing R01-level funding by each of the project leaders; (2) new faculty recruitment at KSU and WSU to ensure growth and longevity of C-NAP and vibrant usage of the core facilities; (3) a pilot grant program that will stimulate center growth by funding projects at universities in the region; (4) a post- doctoral training program that will provide multi-disciplinary training along cross-cutting themes that bridge core facilities and projects, coupled with creating pathways to independence; (5) a scientific exchange network (SEN) that will provide training opportunities and access to additional core facilities with the goal of promoting the research productivity and success of the COBRE core projects, pilot projects, post-doctoral and graduate student trainees, and associated C-NAP faculty. Initial partners include the Hoglund Brain Imaging and K-INBRE centers at the University of Kansas Medical School, COBRE centers at North Dakota State University and the University of Nevada-Reno, the small-animal imaging core at KSU, and the Envision Research Institute in Wichita. The SEN will grow and expand to other nearby universities and research centers (e.g., University of Kansas-Lawrence, University of Missouri-Kansas City, University of Missouri-Columbia, University of Nebraska- Lincoln, the University of Oklahoma, and the Traumatic Brain Injury Unit at Ft. Riley) providing rich opportunities for promoting the growth of research programs. The C-NAP center will host mini-conferences in Years 3 and 5 that will include participants from C-NAP projects, programs, and SEN members to showcase and share research with investigators from outside of the network, promoting the national reputation of C-NAP.