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Previous studies showed that functional connectivity (FC) within resting state (RS) networks is modulated by previous experience. In this study the effects of sustained cognitive performance on subsequent RS FC were investigated in healthy young (25-30 years; n = 15) and middle-aged (50-60 years; n = 14) male schoolteachers. Participants were scanned (functional magnetic resonance imaging [MRI]) after a cognitively demanding and a control intervention (randomized tester-blind within-subject design). Independent component analysis (ICA) was used to decompose the data into spatially independent networks. This study focused on the executive control (ExN), the left and right frontoparietal (FPN), and the default mode network (DMN). The effects of cognitive performance and age were calculated with a full-factorial analysis of variance (ANOVA). A main effect of age was found in the left inferior frontal gyrus for the ExN and in the middle frontal gyrus for the DMN with middle-aged teachers having reduced RS FC. Sustained cognitive performance increased subsequent RS FC between the ExN and a lingual/parahippocampal cluster, and between the left FPN and a right calcarine/precuneus cluster. In these clusters, FC strength correlated positively with the perceived amount of effort during the intervention. Further, sustained cognitive performance affected subsequent RS FC between the ExN and the right temporal superior gyrus differently in young and middle-aged men. The results suggest that effects of age on RS FC are already present at middle age. Sustained cognitive performance increased RS FC between task-positive networks and other brain regions, although a change in RS FC within the networks was not found.

Acute administration of the N-methyl-D-aspartate receptor antagonist ketamine induces schizophrenia-like symptoms in healthy volunteers; furthermore, a window on ketamine's chronic effects is provided by regular recreational users. The current study utilized both acute ketamine administration in healthy volunteers and chronic ketamine abusers to investigate semantic processing, one of the key cognitive deficits in schizophrenia. Semantic processing was examined using a semantic priming paradigm. In experiment 1, acute effects of low (75 ng/mL) and high (150 ng/mL) ketamine doses were compared in a placebo-controlled double-blind independent group design with 48 participants. In experiment 2, 19 regular recreational ketamine users were compared with 19 ketamine-naive polydrug controls and 26 non-drug-using controls. In both experiments, semantic priming parameters were manipulated to distinguish between ketamine's effects on (1) automatic and strategic processing and (2) the facilitation and inhibition components of semantic priming for strongly (directly) related primes and targets. Acute effects of ketamine on semantic priming for weakly (indirectly) related primes and targets were also assessed in experiment 1. Acutely, ketamine impaired the employment of strategic mechanisms but not automatic processing within both the direct and indirect semantic priming tasks. Acute ketamine administration also induced clear schizophrenia-like symptoms. Schizotypy traits in the cognitive and perceptual domains tended to correlate with increased semantic priming in long-term ketamine users. In summary, acute and chronic ketamine-induced changes partially mirrored the findings on semantic priming in schizophrenia.

Results indicate that chronic but not acute exposure to ketamine may increase the propensity to adopt superstitious conditioning. These findings are discussed in terms of acute and chronic ketamine models of delusion-like belief formation in schizophrenia.

a b s t r a c tWe investigated the relationship between individual differences in acute fatigue and endogenous cortisol changes elicited by the sustained performance of cognitively demanding tasks (fatigue condition). Healthy males provided salivary cortisol measurements and subjective fatigue ratings, and were scanned (functional magnetic resonance imaging) during memory encoding and recognition tasks in fatigue and control conditions. A group of 15 'responders' showed significantly higher cortisol levels in the fatigue condition than 12 'non-responders'. Responders showed higher subjective fatigue and reduced encoding and recognition activation than non-responders in the fatigue condition. An interaction in activation changes in the right hippocampus during encoding reflected decreased activation in responders, but somewhat increased activation in non-responders in the fatigue compared to control condition. Moreover, decreased hippocampal activation in responders was associated with increased subjective fatigue. Findings are consistent with a central role for the hippocampus in differences between responders and non-responders and also implicate the right hippocampus in individual differences in induced cognitive fatigue effects.

This investigation was inspired by growing evidence that middle-aged persons in a cognitively demanding profession might be characterized by subtle cognitive fatigue. We studied young and middle-aged male schoolteachers. They were compared in a study with functional magnetic resonance imaging to evaluate differences during successful memory encoding. The schoolteachers were additionally subjected to an induced fatigue condition involving the sustained performance of cognitively demanding tasks and to a control condition. Results showed age-related brain activation differences underlying behavioral performance including: (1) greater activation in middle-aged vs. young teachers in bilateral prefrontal cortex (PFC) areas; and (2) differential fatigue effects in the left anterior cingulate cortex (ACC) depending on age group. Middle-aged schoolteachers showed decreased ACC activation in the fatigue compared to the control condition, whereas no change in activation was found in young teachers. Findings demonstrate age effects in these middle-aged subjects that are typically found in older adults, specifically in PFC over-activation. Findings also indicate that already in middle age cognitive aging may be associated with greater resource depletion following sustained task performance. The findings underscore the notion that persons in a cognitively demanding profession can experience subtle age effects, which are evident on fMRI and which impact daily functioning. Possible practical implications for middle-aged schoolteachers are discussed.