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Rationale: Working memory performance may be improved or decreased by amphetamine, depending on baseline working memory capacity and amphetamine dosage. This variable effect suggests an optimal range of monaminergic activity for working memory, either below or above which it is compromised. We directly tested this possibility with human participants by varying amphetamine dosage and measuring the efficiency of cortical processing in brain regions associated with working memory., Objectives: The modulation of cortical processing in a verbal working memory network by dextroamphetamine (D-amph) was examined using BOLD functional magnetic resonance imaging (fMRI) with healthy participants. The goal of the study was to test the hypothesis of an inverted U-shaped relationship between D-amph dose and processing efficiency of a verbal working memory system., Methods: D-amph dosage was increased cumulatively every 2 h across four scanning sessions collected in a single day. The primary measure used for analyses in this study was the extent of activation in brain regions empirically defined as a working memory network., Results: An inverted U-shaped relationship was observed between the amount of D-amph administered and working memory processing efficiency. This relationship was specific to brain areas functionally defined as working memory regions and to the encoding/maintenance phase (as opposed to the response phase) of the task., Conclusion: The results are consistent with the hypothesis that the neurochemical effects of amphetamine modulate the efficiency of a verbal working memory system. The effect of amphetamine on working memory in healthy individuals may provide insight regarding the working memory deficits seen in schizophrenia, given the overlap between neurochemical systems affected by amphetamine, and those disordered in schizophrenia.

This study examines whether orienting attention to biologically based social cues engages neural mechanisms distinct from those engaged by orienting to nonbiologically based nonsocial cues. Participants viewed a perceptually ambiguous stimulus presented centrally while performing a target detection task. By having participants alternate between viewing this stimulus as an eye in profile or an arrowhead, we were able to directly compare the neural mechanisms of attentional orienting to social and nonsocial cues while holding the physical stimulus constant. The functional magnetic resonance imaging results indicated that attentional orienting to both eye gaze and arrow cues engaged extensive dorsal and ventral frontoparietal networks. Eye gaze cues, however, more vigorously engaged two regions in the ventral frontal cortex associated with attentional reorienting to salient or meaningful stimuli, as well as lateral occipital regions. An event-related potential study demonstrated that this enhanced occipital response was attributable to a higher-amplitude sensory gain effect for targets appearing at locations cued by eye gaze than for those cued by an arrowhead. These results endorse the hypothesis that differences in attention to social and nonsocial cues are quantitative rather than qualitative, running counter to current models that assume enhanced processing for social stimuli reflects the involvement of a unique network of brain regions. An intriguing implication of the present study is the possibility that our ability to orient volitionally and reflexively to socially irrelevant stimuli, including arrowheads, may have arisen as a useful by-product of a system that developed first, and foremost, to promote social orienting to stimuli that are biologically relevant. [ABSTRACT FROM AUTHOR]