This proposal for a Mentored Clinical Scientist Development Award describes a plan to apply neurobehavioral probes and CBF activation to clinical schizophrenia research. The sponsor, Dr. Rajiv Tandon, will supervise the development of the candidate, Dr. Stephan Taylor. Dr. Tandon will directly train the candidate in clinical schizophrenia research and facilitate his training with Dr. Robert Koeppe, in PET techniques to measure CBF, and with Dr. Sylvan Kornblum, in the cognitive psychology of attention. The training will occur through regular laboratory interactions, during formal coursework through participation in the scientific meetings and during scheduled visits to the laboratories of Drs. Weinberger and Cohen. Knowledge of the mechanism of attentional impairment in schizophrenia may provide important information about the pathophysiology of schizophrenia, since attentional dysfunction may mark vulnerability or trait characteristics of the illness. Attentional dysfunction may occur because of localized abnormalities in central regions or systems which allocate selective attention, e.g., prefrontal cortex, or because of more widespread abnormalities, e.g., from a failure or cortical ontogenesis, which could affect the earliest levels of sensory processing. Preliminary functional neuroimaging data indicate an abnormally hyperactive response of the striate and extra-striate cortex to visual stimuli. Experiments analyzing the response to simple visual stimuli in the striate and extra-striate cortex, with and without attentional modulation, will follow-up preliminary results. This experimental design will aim to determine if attentional impairment in schizophrenia is associated with dysfunction at the level of the sensory cortex or with dysfunction in heteromodal association cortex (e.g., prefrontal cortex), or with abnormal activation in both types of cortex. The successful conclusion of the research plan will provide important clues about pathophysiological mechanisms of this severe and debilitating mental illness. As a result of the proposed training plan, Dr. Taylor should be able to independently pursue further questions that require cognitive psychological frameworks to interpret functional neuroimaging results in psychiatric populations.
| Taylor, Stephan F; Phan, K Luan; Britton, Jennifer C et al. (2005) Neural response to emotional salience in schizophrenia. Neuropsychopharmacology 30:984-95 |
| Taylor, Stephan F; Welsh, Robert C; Wager, Tor D et al. (2004) A functional neuroimaging study of motivation and executive function. Neuroimage 21:1045-54 |
| Liberzon, Israel; Phan, K Luan; Decker, Laura R et al. (2003) Extended amygdala and emotional salience: a PET activation study of positive and negative affect. Neuropsychopharmacology 28:726-33 |
| Phan, K Luan; Taylor, Stephan F; Welsh, Robert C et al. (2003) Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a fMRI study. Biol Psychiatry 53:211-5 |
| Taylor, Stephan F; Phan, K Luan; Decker, Laura R et al. (2003) Subjective rating of emotionally salient stimuli modulates neural activity. Neuroimage 18:650-9 |
| Phan, K Luan; Liberzon, Israel; Welsh, Robert C et al. (2003) Habituation of rostral anterior cingulate cortex to repeated emotionally salient pictures. Neuropsychopharmacology 28:1344-50 |
| Taylor, Stephan F; Liberzon, Israel; Decker, Laura R et al. (2002) A functional anatomic study of emotion in schizophrenia. Schizophr Res 58:159-72 |
| Dantzer, R; Konsman, J P; Bluthe, R M et al. (2000) Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci 85:60-5 |
| Taylor, S F; Koeppe, R A; Tandon, R et al. (2000) In vivo measurement of the vesicular monoamine transporter in schizophrenia. Neuropsychopharmacology 23:667-75 |
| Taylor, S F; Liberzon, I; Koeppe, R A (2000) The effect of graded aversive stimuli on limbic and visual activation. Neuropsychologia 38:1415-25 |
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