Jaime Pineda - US grants

DESCRIPTION: (Applicant's Abstract) The goal of the proposal is to understand the nature of addictive behavior. Specifically, the cognitive, motivational, and neurobiological dimensions of that behavior that are dysfunctional. We propose to study human smokers and nonsmokers and non-human subjects to test the hypothesis that the control of conscious control over the decision to engage in a voluntary action is generally one of inhibition and not of initiation. That is, the planning and execution of an action are usually completed prior to the person becoming aware of it. However, it is hypothesized that an agent can still, at some point after the instant of awareness of a decision, "veto" (or inhibit) the decision and thereby cancel the motor command. We further hypothesize that drugs affect the timing between decision making (DM) and awareness (A) and thus the ability to "veto" the action. We will also examine the motivational regulation of the direction of attention and its effect on this temporal window of conscious awareness of a decision to act. Finally, we will examine the hypothesis that the objective, electrophysiological indices of DM-A timing occur in non-human primates and are modulated by motivationally-directed, arousal-related activity in the noradrenergic system. Studies will examine event-related potential (ERPs) components extracted from the ongoing EEG. ERPs are sensitive to the temporal dynamics of system-wide information processing, and analogs of the readiness potential (RP), N100 and P300 components will be sought. These components have been hypothesized to reflect aspects of decision making and attention (i.e., motor, sensory, cognitive, respectively) and can be used as time markers of when an event occurred with respect to awareness of the event. Paradigms based on Benjamin Libet's work (1985), specifically designed to examine DM-A timing will be used, as well as paradigms that induce high incentive and/or anxiety. Animal behavioral paradigms will incorporate systematic variations in stimulus and response contingencies similar to those used in the human studies. Animal ERPs will be analyzed to determine whether they exhibit analogous potentials systematically time-locked to aspects of the behavioral or sensory paradigms. Pharmacological agents will be administered systematically or infused locally at target sites in animals to activate or suppress neuronal noradrenergic activity to determine its necessary and sufficient role in the onset, duration, magnitude, spatial distribution, or functional properties of DM-A timing. The outcome of these studies will identify more "objective" indices of decision making, provide a better understanding of conscious control over actions, determine the sensitivity of this process to motivational stimuli, and clarify the role that the noradrenergic system plays in it. With such an understanding it will be easier to design rational cognitive or pharmacological therapies to ameliorate and prevent drug abuse.

DESCRIPTION (provided by applicant): The UCSD MARC U-STAR Fellows Program will annually prepare 16 ethnically underrepresented undergraduate students for biomedical research careers in academics or private industry. Due to the growing interrelatedness and interdisciplinary nature of contemporary research activity, a variety of research- associated departments and programs have collaborated to submit the proposal, i.e., Bioengineering, Biological Sciences, Chemistry-Biochemistry, Cognitive Science, Psychology, Center for Language Research, and the Temporal Dynamics of Learning Center. The MARC initiative is further provided direct institutional support through the enthusiastic participation of some 90 research faculty from across a wide range of UCSD graduate and undergraduate programs, the School of Medicine, and the School of Pharmacy and Pharmaceutical Sciences. MARC Fellows will participate in a 24-month research regimen under the personalized supervision/mentorship of research faculty, as well as take part in a variety of MARC-specific workshops, research-related writing activities leading to authorship/co-authorship of a paper to be submitted for publication to undergraduate science journals, career exploration activities featuring practicing professionals, travel for research presentations to regional or national professional meetings, and intensive summer research immersion programs, one at UCSD, one at another R-1 institution. A major UCSD MARC U-STAR goal will be establishment of a strong, underrepresented student research-based support community through which MARC Fellows can easily network and collaborate with peers involved in a wide variety of other undergraduate research programs housed under UCSD's Academic Enrichment Programs in which MARC U-STARS will be located. A second major element of UCSD MARC will involve highly focused academic support and research preparation for underrepresented freshman, sophomore and new community college transfer students through the Pre-MARC Activities. This initiative will annually provide 50-60 students with a wide variety of pre-research activities in order to fuel their growing interest to enter MARC and, subsequently, Ph.D. or MD/Ph.D. programs as a means of entering productive, exciting research careers. Relevance: MARC's primary mission is to attract, train and prepare highly qualified minority students for entry into health-related research in the biomedical sciences. Through such training, the nation's health/medical research workforce can become dramatically more diversified as ethnic populations previously underrepresented in such disciplines are provided expanded access and support from scientists and health research professionals at UCSD.