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GABAergic interneurons are highly diverse and operate with a corresponding diversity of GABAA receptor subtypes in controlling behaviour. In this article, we review the significance of GABAA receptor heterogeneity for neural circuit development and central nervous system pharmacology. GABAA receptor subtypes were identified as selective targets for behavioural actions of benzodiazepines and of selected intravenous anesthetic agents using point mutations which render a specific receptor subtype insensitive to the action of the respective drugs and also by novel subtype-selective ligands. The pharmacological separation of anxiolysis and sedation guides the development of novel anxiolytics, while inverse agonism at extrasynaptic GABAA receptors involved in learning and memory is currently being evaluated as a novel therapeutic principle for symptomatic memory enhancement. [Copyright &y& Elsevier]

Evoked responses and oscillations represent two major electrophysiological phenomena in the human brain yet the link between them remains rather obscure. Here we show how most frequently studied EEG signals: the P300-evoked response and alpha oscillations (8-12 Hz) can be linked with the baseline-shift mechanism. This mechanism states that oscillations generate evoked responses if oscillations have a non-zero mean and their amplitude is modulated by the stimulus. Therefore, the following predictions should hold: (1) the temporal evolution of P300 and alpha amplitude is similar, (2) spatial localisations of the P300 and alpha amplitude modulation overlap, (3) oscillations are non-zero mean, (4) P300 and alpha amplitude correlate with cognitive scores in a similar fashion. To validate these predictions, we analysed the data set of elderly participants (N=2230, 60-82 years old), using (a) resting-state EEG recordings to quantify the mean of oscillations, (b) the event-related data, to extract parameters of P300 and alpha rhythm amplitude envelope. We showed that P300 is indeed linked to alpha rhythm, according to all four predictions. Our results provide an unifying view on the interdependency of evoked responses and neuronal oscillations and suggest that P300, at least partly, is generated by the modulation of alpha oscillations., Competing Interests: AS, CF, TH, CS, NM, UH, ML, AV, VN No competing interests declared, DE D.E. is a full-time employee of F. Hoffmann-La Roche Ltd, (© 2023, Studenova et al.)

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance., Competing Interests: Declaration of Competing Interest Authors declare no competing financial or non-financial interests in relation to the work., (Copyright © 2022. Published by Elsevier Inc.)

Background: The heartbeat-evoked potential (HEP) is a brain response to each heartbeat, which is thought to reflect cardiac signaling to central autonomic areas and suggested to be a marker of internal body awareness (eg, interoception)., Objectives: Because cardiac communication with central autonomic circuits has been shown to be impaired in patients with atrial fibrillation (AF), we hypothesized that HEPs are attenuated in these patients., Methods: By simultaneous electroencephalography and electrocardiography recordings, HEP was investigated in 56 individuals with persistent AF and 56 control subjects matched for age, sex, and body mass index., Results: HEP in control subjects was characterized by right frontotemporal negativity peaking around 300 to 550 ms after the R-peak, consistent with previous studies. In comparison with control subjects, HEP amplitudes were attenuated, and HEP amplitude differences remained significant when matching the samples for heart frequency, stroke volume (assessed by echocardiography), systolic blood pressure, and the amplitude of the T-wave. Effect sizes for the group differences were medium to large (Cohen's d between 0.6 and 0.9). EEG source analysis on HEP amplitude differences pointed to a neural representation within the right insular cortex, an area known as a hub for central autonomic control., Conclusions: The heartbeat-evoked potential is reduced in AF, particularly in the right insula. We speculate that the attenuated HEP in AF may be a marker of impaired heart-brain interactions. Attenuated interoception might furthermore underlie the frequent occurrence of silent AF., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Unemployed people could be at risk of developing inefficient sleep habits by spending excessive time in bed, as they lack a structuring activity. This could impact their mental health and reintegration into labour. This study aims to analyse possible associations between employment status and sleep parameters using actigraphy. Subjects (148 employed and 50 unemployed) were drawn from a German population-based cohort. Sleep parameters were measured with the SenseWear Bodymedia Pro 3 armband. Comparison of means concerning sleep duration, sleep efficiency, time of sleep and sleep fragmentation was performed separately for week days and weekends. Multiple linear regression analysis was performed to analyse group differences controlling for covariates. Finally, we defined cut-off scores for each sleep variable, and analysed the distribution of subjects above and below these values. Unemployed people did not sleep significantly longer than employed people. However, on week days, they displayed night sleep efficiency reduced by on average > 5% points, they lay down for 28 min longer, had later mid sleep time (38 min) and sleep offset (55 min), as well as more frequent awakenings after sleep onset accounting for being awake 28 min longer (all p ≤ 0.005). Sleep in unemployed subjects compared with employed subjects aged 41-64 years was less efficient, more fragmented and shifted to a later point of the night. Results support prior findings that unemployment has a negative influence on sleep quality. Unemployed individuals could benefit from intervention programmes aiming at the adoption of healthier sleep habits., (© 2021 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Aging is associated with increased white matter hyperintensities (WMHs) and with alterations of alpha oscillations (7-13 Hz). However, a crucial question remains, whether changes in alpha oscillations relate to aging per se or whether this relationship is mediated by age-related neuropathology like WMHs. Using a large cohort of cognitively healthy older adults (N = 907, 60-80 years), we assessed relative alpha power, alpha peak frequency, and long-range temporal correlations from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that a higher prevalence of WMHs in the superior and posterior corona radiata as well as in the thalamic radiation was related to elevated alpha power, with the strongest association in the bilateral occipital cortex. In contrast, we observed no significant relation of the WMHs probability with alpha peak frequency and long-range temporal correlations. Finally, higher age was associated with elevated alpha power via total WMH volume. We suggest that an elevated alpha power is a consequence of WMHs affecting a spatial organization of alpha sources., (Copyright © 2021. Published by Elsevier Inc.)