Geoffrey Potts - US grants

In addiction a set of perceptual representation (drugs and related paraphernalia) is tagged as salient and repeatedly selected for conscious processing. Understanding the neural systems by which perceptual representations are tagged as salient might allow better understanding of how these systems are disrupted in addiction. This proposal employs dense array ERPs and statistical, topographic, and dipole analyses to study the neural systems that attach salience to perceptual representations. Detecting task-relevant stimuli may require interaction between an orbito-frontal salience evaluation system and perceptual representations in the posterior brain. There is a potential ERP index of this orbito-frontal/posterior interaction: an inferior prefrontal P2a and a coincident posterior N2b. If the P2a indexes salience evaluation it should be independent of the stimulus and response modalities. If the N2b indexes perceptual processing it should be dependent upon stimulus feature. We test this model by manipulating target-defining feature, response type, and target salience. The task manipulations present relevant and irrelevant stimuli in different tasks: Passive, Silent Count, Keypress, and Withhold Keypress. In the Passive task there is no target detection so there should be no P2a. In the Count and Withhold tasks there is detection but no motor response; in the Keypress task there is both detection and a motor response. Since the perceptual and salience processing demands are equivalent we predict an equal P2a and N2b across active tasks. In the stimulus manipulation experiments the target-defining feature is changed. In one task subjects respond to visual stimuli occurring at a specific location while in another they respond to specific objects regardless of location. In a third task subjects respond to tones. We predict equivalent P2a's across target modalities but different topographic distributions of the N2b depending upon the salient feature. The final experiments manipulate the salience value of the stimulus. One study presents objects with no, small, or large reward value. The P2a should be larger to the more valuable stimuli with a constant N2b. The other study presents stimuli in different locations in salient and non-salient blocks. Constricted attention in the salient blocks should produce a larger P2a and N2b to foveal stimuli.

[unreadable] DESCRIPTION (provided by applicant): Cigarette smokers exhibit impulsive decision-making, choosing immediate reward derived from smoking despite potential long-term negative consequences. Impulsive choices on experimental tasks are also made by substance abusers and by patients with medial frontal cortex damage. Smokers also obsess about smoking, particularly during craving, i.e. smoking-related items are selected by attention. Attention selection has also been linked to medial frontal cortex. Medial frontal cortex (MFC) is a principle target of the brain's dopamine reward system, and decision-making and attention selection and their disruption in addiction have been linked to the brain's reward system. We suggest that neural hypersensitivity to reward expressed in MFC leads to both impulsive choice, i.e. the decision to smoke, and to differential attention to smoking-related stimuli in smokers. In earlier work we have used human event related potential (ERP) indices of medial frontal activity to show that impulsive individuals are more sensitive to reward while evaluating the motivational value of items and while monitoring behavioral actions. We propose to use the same designs, a passive monetary reward expectation design modeled after animal studies, and a monetary reward and punishment motivated active response task, to test if the neural reward system is more responsive in smokers, as in impulsive individuals. We will also test if a MFC reward-related attention selection ERP index is more responsive to task-irrelevant smoking cues in smokers (cue reactivity), and if smokers score higher on self-reported impulsivity. [unreadable] [unreadable] [unreadable]

The executive cognitive functions are humans' most advanced component mental operations. Examples of executive functions include manipulating the contents of working memory, inhibiting automatic but inappropriate responses, and flexibly switching between strategies. These functions allow people to make effective decisions, regulate social behavior, and plan ahead. The executive functions are the last to mature in development and are often the first to deteriorate in normal aging as well as mental disorders and neurological injury and disease. Research has yet to fully describe the neural bases of these higher-order mental operations, and understanding the neural bases of the executive functions might provide insight into why some people are better at planning and decision-making than others and allow for more effective intervention and treatment of executive function impairment. The neural bases of the executive functions likely involve networks of neural structures distributed throughout the brain working together in specific temporal sequences, with individual nodes active for only tens of milliseconds. A large literature exists suggesting the prefrontal cortex as a core structure within this network. The research enabled by the dense-sensor array electroencephalography (EEG) system, with extended frontal coverage, investigates the coordinated neural activity underlying the executive functions.

Event-related potentials (ERPs) are scalp recorded neural electrical responses to stimuli and actions embedded in the ongoing EEG. ERPs are an excellent means of assessing the timecourse of functionally relevant neural activity during cognitive processing, and hence a powerful tool for investigating the neural network dynamics that make executive functioning possible. Dense-sensor array EEG, like the 128 channel system here, improves ERP's spatial resolution, allowing better estimation of the neural sources of the scalp-recorded signal. Dense sensor array ERPs allows researchers to examine the neural network activity related to specific cognitive operations. Researchers will use this system to study learning and memory, potentially improving learning strategies, individual differences in risky decision-making (why some individuals make riskier choices than others), attention selection (how the brain may use economic principles, like expected value, to allocate its limited capacity processing resources), and other executive functions, their variability across individuals, and their disruption in neurological injuries (e.g. mild traumatic brain injury) and disease (e.g. Huntington's disease).