Noradrenergic modulation of the alerting system: Cue -related bold signal changes in a double-blind, placebo controlled, guanfacine challenge.
Item
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Title
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Noradrenergic modulation of the alerting system: Cue -related bold signal changes in a double-blind, placebo controlled, guanfacine challenge.
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Identifier
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AAI3330127
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identifier
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3330127
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Creator
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Clerkin, Suzanne M.
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Contributor
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Adviser: Jeffrey M. Halperin
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Psychobiology
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Abstract
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Background. Bottom-up regulation of alerting, or the capacity to phasically increase readiness to detect and respond to an impending stimulus, is thought to be mediated by the locus coeruleus noradrenergic (NA) system. Prior research has focused on the role of presynaptic alpha 2a autoreceptor inhibition of locus coeruleus (LC) firing and resultant downregulation of NA release in alerting. However, alpha2a adrenoceptors also act as heteroceptors to regulate neuronal excitability in select terminal regions, including prefrontal cortex (PFC). PFC regions provide top-down control of LC phasic activity. We tested bottom-up and top-down NA modulation of the alerting network by utilizing a 1.0mg oral dose of guanfacine in a double-blind, placebo-controlled challenge. Method. Sixteen healthy young adult volunteers performed a simple cued reaction time task while being scanned with functional magnetic resonance imaging (fMRI). Repeated Measures analysis of variance was used to test the effect of guanfacine treatment versus placebo on reaction time (RT) to cued and uncued targets. Results. There was a strong alerting effect for both treatment conditions, with decreased RT to cued targets versus uncued targets. However, there was no main effect of Treatment, nor was there a significant Treatment X Cue interaction for RT. Fairly similar patterns of cue-related BOLD signal changes were observed for both guanfacine and placebo in regions of the alerting network, including dorsolateral PFC (DLPFC), cingulate and frontal motor areas, temporoparietal junction (TPJ), thalamus, and striatum. However, comparison of treatment effects on cue-related BOLD signal changes revealed significantly greater extent and/or magnitude of cue-related activation following guanfacine in bilateral DLPFC (BA 46), left ventromedial PFC (BA 9), right orbitofrontal cortex (BA 47), and posterior rostral cingulate zone. Conclusions: Guanfacine might increase signal to noise ratio and delay-related firing in response to relevant cues, thereby priming appropriate regions to respond to stimuli. The lack of behavioral effects suggests that cue-related BOLD signal increases were induced by guanfacine, rather than by a change in behavior.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
