(provided by candidate): This is an application for a K23-Mentored Patient-Oriented Career Development Award entitled """"""""Emotional Stimulus Processing in Normal Aging and Mild Alzheimer's Disease."""""""" Psychiatric symptoms are frequent and distressing complications of Alzheimer's disease (AD), but our understanding of the causes of these disturbances is limited. The primary goal of the proposed research is to probe the integrity of brain systems known to mediate emotional responses, using neurocognitive paradigms displaying emotionally-valenced stimuli, and functional magnetic resonance imaging (fMRI), in the healthy young and aged, and patients with mild AD. Regions of medial temporal lobe (i.e. the amygdala) and anterior cingulate cortex (ACC) are involved in generating and regulating emotional responses, respectively. These areas also demonstrate neuropathological changes in aging and AD. The overarching hypothesis of this proposal is that intrinsic amygdala hyperactivity, or lack of amygdala inhibition due to dysfunction of the ACC, may lead to the propensity for behavioral disinhibition, manifest as anxiety, irritability and agitation, as found in AD. An integrated series of fMRI studies is planned to address the following questions: (1) What are the patterns and extents of regional brain activation during viewing of emotional vs. neutral human facial expressions in the young, elderly, and patients with mild AD? (3) Is regional brain habituation and response to novelty during viewing of emotionally valenced stimuli different in the young, elderly, and subjects with mild AD? (4) Are regions involved in regulating emotional responses, such as the ACC, hypofunctional in mild AD compared to control subjects? (5) Do measures of psychiatric symptoms in mild AD correlate directly with amygdala activation and inversely with activation of the ACC? This functional dissection of emotional processing will provide new and important insights about the psychiatric alterations that occur in AD. In addition to the proposed research, the candidate seeks training in: 1) cognitive neuroscienee of emotion, age-related cognitive change, and the neurobiology of aging; 2) MRI physics and statistical aspects of neuroimaging; and 3) clinical research methods and ethics. The proposed research plan, didactic courses, and tutorial instruction from mentors and advisors will serve to foster the candidate's development into an independent clinical researcher in functional neuroimaging of neuropsychiatric disease.
| Wright, Christopher I; Negreira, Alyson; Gold, Andrea L et al. (2008) Neural correlates of novelty and face-age effects in young and elderly adults. Neuroimage 42:956-68 |
| Evans, Karleyton C; Wright, Christopher I; Wedig, Michelle M et al. (2008) A functional MRI study of amygdala responses to angry schematic faces in social anxiety disorder. Depress Anxiety 25:496-505 |
| Britton, Jennifer C; Gold, Andrea L; Feczko, Eric J et al. (2007) D-cycloserine inhibits amygdala responses during repeated presentations of faces. CNS Spectr 12:600-5 |
| Rauch, Scott L; Wedig, Michelle M; Wright, Christopher I et al. (2007) Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder. Biol Psychiatry 61:330-6 |
| Barrett, Lisa Feldman; Bliss-Moreau, Eliza; Duncan, Seth L et al. (2007) The amygdala and the experience of affect. Soc Cogn Affect Neurosci 2:73-83 |
| Rauch, Scott L; Wright, Christopher I; Savage, Cary R et al. (2007) Brain activation during implicit sequence learning in individuals with trichotillomania. Psychiatry Res 154:233-40 |
| Wright, Christopher I; Dickerson, Bradford C; Feczko, Eric et al. (2007) A functional magnetic resonance imaging study of amygdala responses to human faces in aging and mild Alzheimer's disease. Biol Psychiatry 62:1388-95 |
| Shin, Lisa M; Bush, George; Whalen, Paul J et al. (2007) Dorsal anterior cingulate function in posttraumatic stress disorder. J Trauma Stress 20:701-12 |
| Wright, Christopher I; Feczko, Eric; Dickerson, Bradford et al. (2007) Neuroanatomical correlates of personality in the elderly. Neuroimage 35:263-72 |
| Wright, Christopher I; Keuthen, Nancy J; Savage, Cary R et al. (2006) Brain correlates of negative and positive visuospatial priming in adults. Neuroimage 30:983-91 |
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