Cindy A. Lustig, Ph.D. - US grants

In everyday life, we must frequently change our behavior in response to environmental cues and our own internal goals. For example, a stoplight turning green might automatically elicit the response of stepping on the gas pedal to move forward. However, you must change that response if we see a child entering the intersection, or if your goal is to make a left turn. Failures to control behavior in these ways can have important consequences. Research with humans and other primates shows that a network of brain regions including frontal and parietal cortex is important for the cognitive control of behavior. Research with rodents shows that the neurotransmitter acetylcholine is an important chemical messenger used by the brain in situations that require control. With support from the National Science Foundation, Dr. Lustig will use pharmacological fMRI to integrate these two lines of research and establish how acetylcholine influences cognitive control functions in the human brain. Participants will take one of three doses (placebo, low dose, high dose) of a drug that increases acetylcholine's action in the brain by slowing the rate at which it is broken down. They will then undergo functional brain imaging while performing tasks that make low or high demands for the cognitive control of behavior in response to changing environmental cues. The results will answer several important questions about how acetylcholine acts in the human brain to influence the control of behavior. First, they will show which parts of the human frontal-parietal control network are specifically influenced by acetylcholine. Second, they will show whether all aspects of performance are influenced by increased cholinergic function, or only those that make high demands for cognitive control. Third, they will clarify whether acetylcholine has its effects by increasing the engagement of control-related brain regions or by helping those brain regions to act more efficiently. The project also compares several different methods of analyzing pharmacological fMRI data to determine which may be best for future studies examining how different drugs influence brain function.

This work will help us better understand how the human brain allows us to control and change our behavior in order to accomplish our goals. This ability improves as children mature into adults, and is disrupted in many clinical disorders or when normal adults are stressed or fatigued. The project will help to integrate human and animal research, and to improve the technology by which scientists study the action of drugs on the brain. Dr. Lustig's research team actively involves both graduate and undergraduate students. The laboratory specifically targets the inclusion of students from under-represented groups, recruiting from synergistic NSF programs such as the Undergraduate Research Opportunities Program. As part of their experience in the lab, students receive training in experimental methods, brain anatomy, and the fundamentals of fMRI. Students independently present this work via posters and slide presentations at local or regional meetings, and are involved in presentation at national meetings and journal publication.

[unreadable] DESCRIPTION (provided by applicant): The long-term goal of this project is to improve memory training programs so that they better benefit older adults, particularly those of advanced age or lower initial ability. Memory problems are a major complaint for older adults. Improving training programs to benefit those at greatest disadvantage would address this public concern. These goals are especially relevant to the Behavioral and Social Research division of the National Institute on Aging. The NIA BSR Review Committee Report (May, 2004) specifically identified behavioral interventions to improve cognitive function as an important mission of this agency. It called for greater theoretical depth in this area, and better integration of individual differences and population level research overall. The present proposal integrates an established theoretical perspective and new individual- differences data collected by the PI to inform an experimental manipulation hypothesized to increase training effectiveness. This proposal builds on an extended (seven days) training program that has shown robust, long-lasting benefits to older adults' memory, including successful transfer to other memory tasks (Jennings & Jacoby, 2003; Jennings et al., 2005). This program specifically targets the controlled memory processes that decline most with age (Jennings & Jacoby, 1993; Hasher & Zacks, 1979). It consists of several short study- test cycles during which participants first study a list of words, and then complete a recognition test during which they must discriminate studied words from unstudied words. Unstudied words are repeated during the test period, so that controlled memory processing is required to discriminate between studied and repeated-unstudied words. When a participant reaches criterion at the current level of difficulty, the number of items between repetitions is increased. Participants are thus continuously challenged to increase their engagement of cognitive control. Data collected by the PI leads to the hypothesis that encoding strategy is a major mediator of age and individual differences in the amount of training benefits (Bissig & Lustig, in press; see also Craik & Byrd, 1982). This hypothesis will be tested by enforcing encoding strategies to observe their effects on training benefits, especially for the oldest-old. It is expected that deep, integrateive encoding will lead to substantial benefits in the training task, benefits that may also transfer to other memory tests. Memory problems are a major complaint for older adults. Improving memory programs to benefit those who are at greatest disadvantage would address this public concern. The National Advisory Council on Aging's review of NIA's Behavioral and Social Science Research division (May, 2004) specifically identified behavioral interventions to improve cognitive function as an important mission, called for greater theoretical depth in this area, and encouraged better integration of individual differences and population level research. [unreadable] [unreadable] [unreadable]