The present application examines the involvement of the noradrenergic (NA)-locus coeruleus (LC) system in the selection, switching and maintenance of the attentional focus, as indexed by event-related potentials (ERPs). It is hypothesized that this neurotransmitter system plays a significantly greater role in the selection and switching of attention than in maintaining vigilance. NA-LC originates in the dorsal pontine brainstem and its unique pattern of cortical innervation, regional and laminar specificities, electrophysiological properties, and postsynaptic effects suggest that it is involved in cortical, state-dependent responsiveness to novel and relevant stimuli. These, and similar physiological processes, may underlie the psychological constructs of stimulus selectivity, switching, and the maintenance of attention. The proposed studies continue and extend the previous investigations with respect to the onset, duration, and magnitude of electrophysiological indices of orienting (switching), selectively attending to a channel (maintenance), and processing meaningful targets in an attended channel (selectivity). Both human and non-human primate subjects will be exposed to trains of auditory and visual stimulation and instructed or operantly trained to perform discrimination tasks which are designed to elicit the various aspects of attention that will be correlated with the electrophysiology. Human studies will be used to quantify and develop a database of the timing, duration, and magnitude of electrophysiological correlates that can serve as a basis for comparison with and as a guide for the development of the animal models. Second, localization studies using nonhuman primates will utilize epidural, transcortical, and subcortical recordings to map out the specific cortical sites where such processing takes place. Cortical activity will be initially recorded from anterior cingulate cortex, temporo-parietal junction, and hippocampus, areas hypothesized to be involved in attentional mechanisms and in the generation of endogenous ERP potentials. Third, the necessary and sufficient role that the NA-LC system plays in these psychological processes will be analyzed. Studies will include the manipulation of noradrenergic activity using systemically-(human and monkey) and locally-administered (monkey) pharmacological agents designed to activate or suppress neuronal activity. Successful completion of these aims will result in more specific hypotheses regarding the similarities and differences between primate species, the neural sources of attentional processing, and the role of NA-LC in controlling and regulating the attentional focus.
| Pineda, J A; Herrera, C; Kang, C et al. (1998) Effects of cigarette smoking and 12-h abstention on working memory during a serial-probe recognition task. Psychopharmacology (Berl) 139:311-21 |
