This proposal is designed to further our understandingof thecontribution of prefrontal cortex (PFCx) to human cognition. Neuropsychological and electrophysiological techniques will be employed to examine the role of subregions of PFCx in executive control of visual processing, novelty detection and response monitoring. 1) Experiments will be conducted to delineate the temporal (100-600 rnsec) and spatial dynamics of lateral PFCx-extrastriate interactions during visual attention using event-related potentials (ERPs) and EEG spectral techniques. 2) We will employ EEG spectral techniques to examine the temporal parameters of lateral PFCx-extrastriate interactions during the switching of attention to subregions of the visual field. 3) There is disagreement as to how object andspatial information is integrated in lateral PFCx. Behavioral andelectrophysiological experiments will be performed to assess the contribution of lateral PFCx to the integration of visual features. 4) The contribution of lateral PFCx andorbital PFCx to object, spatial and emotional working memory will be explored. 5)A distributed cortico-limbic network involving PFCx, anterior cingulate, temporal-parietal junction and posterior hippocampal formation is activated during novelty detection (200-500 msec). This network provides a neural measure of phasic attention to perturbations in the environment essential for mental flexibility andnew learning. Behavioral end electrophysiological experiments will examine how lateral and orbital PFCx contribute to different aspects of novelty processing. Experiments will examine the contribution of emotional valence as well as context to novelty processing. 6) Finally, behavioral performance is constantly monitored and detection of mistakes leads to reliable alterations in current andfuture action. In humans, detection of an error is accompanied by an error related potential (ERN) generated in anterior cingulate cortex within 100 msec after detection the erroneous response. We have shown that this cingulate measure of response monitoring is regulated by lateral PFCx. Two theories including response competition and the emotional valence of a detected error have been proposed to explain the role of prefrontal-cingulate circuits in response monitoring. Experiments will be conducted in patients with lateral or orbital PFCx damage to test these hypothesis. This proposal derives from ongoing research in our laboratory designed to elucidate the temporal dynamics and network properties of PFCx contributions to cognitive processes frequently impaired in neurological and psychiatric disease.
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