Matthew R. Johnson, Ph.D. - US grants

DESCRIPTION (provided by applicant): Both healthy and pathological aging entail some degree of cognitive and neural decline. Executive functions appear to be particularly affected by aging (Hasher &Zacks, 1988). Executive function has traditionally been associated most strongly with the prefrontal cortex (PFC), but recent research has shown that interactions between PFC and sensory association cortex also play an important role in executive processes. The broad objective of this proposal is to shed further light on how top-down executive processes affect activity in category-selective extrastriate (CSE) cortex, developing paradigms first in healthy young adults and then using them to study these processes'decline in older adults. Specific Aim #1: Examine mechanisms by which top-down processes suppress as well as enhance percepts and representations in young adults. Two functional magnetic resonance imaging (fMRI) studies will examine how perceptual and reflective attention processes act to suppress activity in CSE cortex related to non-attended stimuli. This aim has particular relevance to the mission of the NIA as recent studies have shown specific deficits in top-down suppression in older adults (Gazzaley et al., 2005), but relatively little is known about the specific mechanisms underlying such suppression, especially for reflective attention. Specific Aim #2: Analyze the information content of activity in CSE cortex caused by reflective processing. It is thought that activity in CSE cortex induced by reflective processes (e.g., working memory, mental imagery) represents information about the specific item in mind, but there is relatively little evidence for this in the literature. This fMRI experiment is aimed at decoding item information in CSE cortex during mental imagery. Future studies will then examine how information representation differs in young and older adults. This research is designed to further our knowledge of how the human brain performs high-level cognitive operations, collectively called "executive functions," which are known to be particularly susceptible to the cognitive decline that occurs in both healthy and pathological aging. The research plan includes three brain imaging experiments aimed at determining how several simple executive operations affect activity in areas of the brain involved in processing visual information. The ultimate goal is to compare the brain activity of younger adults to older adults while performing different types of executive functions in order to study how these processes deteriorate as people age.

PROJECT ABSTRACT Drug addiction is a significant problem in rural communities, yet rural drug users are understudied compared to urban populations. In addition, most studies of the human brain in drug abuse and addiction have focused on the direct effects of drug use or on systems involved with the reward, craving, and impulsivity associated with it. However, humans also rely on general cognitive mechanisms (such as attention and memory) to perform daily activities that affect their quality of life (e.g., performing their jobs or planning their health behaviors). Disturbances in the functions of these cognitive mechanisms can have widespread, significant consequences. Previous studies have shown that drug abusers do experience deficits in these core cognitive functions, but relatively little is known about the exact extent or nature of this dysfunction or its potential to predict life and health outcomes for drug users. This project seeks to collect neuroimaging and behavioral data from a sample of rural cocaine, methamphetamine, and/or opioid users (plus a sample of non-drug-using controls) to isolate specific breakdowns in core brain and cognitive functions (Aim 1) and develop models using those breakdowns to predict individual differences in quality of life and health (Aim 2). Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) will be used to measure brain function of drug users and control subjects as they perform a variety of tasks employing these core cognitive abilities in varying combinations and levels of complexity. The research team will also obtain measurements of brain structure and use surveys to assess a large number of variables relating to drug use patterns and other life/health outcomes (e.g., job success, quality of personal relationships, and physical health outside of drug use). Using these data, the project will isolate the specific neural and cognitive variables that best predict differences in quality of life and health at the time of data collection. This project will use state-of-the-art technological and statistical methods to characterize neural and cognitive dysfunction in drug abusers in more detail than previous studies, which will lead to greater predictive power. The project will also result in preliminary data on longitudinal follow-ups of life/health outcomes; future funding proposals will focus on using neurocognitive data to predict outcomes for months or years after primary data collection. The ability to predict life trajectories is particularly important for rural drug users, who receive less health care and social services than urban users and thus are more susceptible to becoming lost to the systems and services that could otherwise help them. This project will ultimately lead to better characterization of the impact of drug use on rural society, improved prediction of which rural drug users are most likely to respond to interventions, and better identification of users who are most in need of special attention in order to prevent tragic consequences. The broad, long-term objective is to aid the development of new interventions that are most likely to help rural drug users and produce new techniques that can also be applied to predicting and shaping outcomes for other disorders and conditions.