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Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs) and influences performance in declarative and working memory (WM) tasks. These memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC-binding receptors are present. Previous studies revealed contradictory results regarding effects of acute stress on WM-related brain activity. We combined functional magnetic resonance imaging with a standardized psychosocial stress protocol to investigate the effects of acute mental stress on brain activity during encoding, maintenance, and retrieval of WM. Participants (41 healthy young men) underwent either a stress or a control procedure before performing a WM task. Stress increased salivary cortisol levels and tended to increase WM accuracy. Neurally, stress-induced increases in cortical activity were evident in PFC and posterior parietal cortex (PPC) during WM maintenance. Furthermore, hippocampal activity was modulated by stress during encoding and retrieval with increases in the right anterior hippocampus during WM encoding and decreases in the left posterior hippocampus during retrieval. Our study demonstrates that stress increases activity in PFC and PPC specifically during maintenance of items in WM, whereas effects on hippocampal activity are restricted to encoding and retrieval. The finding that psychosocial stress can increase and decrease activity in two different hippocampal areas may be relevant for understanding the often-reported phase-dependent opposing behavioral effects of stress on long-term memory.

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Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation. We used functional magnetic resonance imaging (fMRI) to identify neural correlates of visual and auditory alertness. A further aim was to investigate the modulatory effects of the cholinergic agonist nicotine. Nonsmoking participants were given either placebo or nicotine (NICORETTE gum, 2 mg) and performed a target-detection task with warned and unwarned trials in the visual and auditory modality. Our results provide evidence for modality-specific correlates of visual and auditory alertness in respective higher-level sensory cortices and in posterior parietal and frontal brain areas. The only region commonly involved in visual and auditory alertness was the right superior temporal gyrus. A connectivity analysis showed that this supramodal region exhibited modality-dependent coupling with respective higher sensory cortices. Nicotine was found to mainly decrease visual and auditory alertness-related activity in several brain regions, which was evident as a significant interaction of nicotine-induced decreases in BOLD signal in warned trials and increases in unwarned trials. The cholinergic drug also affected alerting-dependent activity in the supramodal right superior temporal gyrus; here the effect was the result of a significant increase of neural activity in unwarned trials. We conclude that the role of the right superior temporal gyrus is to induce an "alert" state in response to warning cues and thereby optimize stimulus processing and responding. We speculate that nicotine increases brain mechanisms of alertness specifically in conditions where no extrinsic warning is provided.

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