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Oscillatory theta activity in a fronto-parietal network has been associated with working memory (WM) processes and may be directly related to WM performance. In their seminal study, Polanía et al. (2012) (de-)coupled a fronto-parietal theta-network by applying transcranial alternating current stimulation (tACS), and showed that anti-phase tACS led to slower and in-phase tACS to faster response times in a verbal WM task compared to placebo stimulation. In the literature, this 'synchronization-desynchronization' effect has only been partly replicated, and electric field modelling suggests that it might not be the fronto-parietal network that is primarily stimulated during in-phase tACS with a shared return electrode. This provides one possible reason for inconsistency in the literature. In this study, we aimed to reproduce the findings reported by Polanía et al. (2012). We also aimed to investigate whether in-phase theta tACS with multiple close-by return electrodes for focal stimulation of the frontal and the parietal cortex will have at least as much of a facilitatory effect as the in-phase stimulation as indicated by Polania et al. (2012). In a single-trial distributional analysis, we explored whether mean, variation and right-skewness of the response time distribution are affected. Against our hypothesis, we found no 'synchronization-desynchronization' effect by fronto-parietal theta tACS on response times using the same delayed letter discrimination task and stimulation parameters in two experiments, both between-subjects and within-subjects. However, we could show that in a more demanding 3-back task, fronto-parietal in-phase and in-phase focal theta tACS substantially improved task performance compared to placebo stimulation.

Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.

grant Klinische Forschergruppe (KFO) from the Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [241]