Mind-wandering is characterised as the emergence of thought and emotions which shift attention away from a primary task. It is thought to consume up to 50 % of our waking lives and has several negative implications. Breath-counting is one task that has been utilised in conjunction with electroencephalography (EEG) to examine the brain states associated with mind-wandering. Research has consistently found reductions in alpha oscillations during periods of mind-wandering relative to breath-focus. It is possible that such fluctuations reflect an arousal mechanism warranting further investigation. Thirty-seven participants completed a 15 min breath-counting task, with simultaneous recording of EEG and skin conductance level (SCL). During this task participants were required to self-identify periods of mind-wandering via button-press. Event-related spectral perturbation (ERSP) analysis was used to quantify changes in global alpha power (8-13 Hz) relative to the button press. The -8 to -4 s period prior to button-press was assessed as mind-wandering, and the 4 to 8 s period following the button-press as breath-focus. Relative to breath-focus, mind-wandering was associated with a significant decrease in global alpha power and significant increase in SCL, consistent with perceptual decoupling theory. However, changes in global alpha power and SCL did not correlate. These results suggest arousal is not the primary mechanism underlying alpha changes observed during breath-counting, thus additional processes should be considered.

Much of our understanding of how the brain processes dynamic faces comes from research that compares static photographs to dynamic morphs, which exhibit simplified, computer-generated motion. By comparing static, video recorded, and dynamic morphed expressions, we aim to identify the neural correlates of naturalistic facial dynamism, using time-domain and time-frequency analysis. Dynamic morphs were made from the neutral and peak frames of video recorded transitions of happy and fearful expressions, which retained expression change and removed asynchronous and non-linear features of naturalistic facial motion. We found that dynamic morphs elicited increased N400 amplitudes and lower LPP amplitudes compared to other stimulus types. Video recordings elicited higher LPP amplitudes and greater frontal delta activity compared to other stimuli. Thematic analysis of participant interviews using a large language model revealed that participants found it difficult to assess the genuineness of morphed expressions, and easier to analyse the genuineness of happy compared to fearful expressions. Our findings suggest that animating real faces with artificial motion may violate expectations (N400) and reduce the social salience (LPP) of dynamic morphs. Results also suggest that delta oscillations in the frontal region may be involved with the perception of naturalistic facial motion in happy and fearful expressions. Overall, our findings highlight the sensitivity of neural mechanisms required for face perception to subtle changes in facial motion characteristics, which has important implications for neuroimaging research using faces with simplified motion.

T cell activation is governed through T cell receptors (TCRs), heterodimers of two sequence-variable chains (often an α and β chain) that synergistically recognize antigen fragments presented on cell surfaces. Despite this, there only exist repositories dedicated to collecting single-chain, not paired-chain, TCR sequence data. We addressed this gap by creating the Observed TCR Space (OTS) database, a source of consistently processed and annotated, full-length, paired-chain TCR sequences. Currently, OTS contains 5.35 million redundant (1.63 million non-redundant), predominantly human sequences from across 50 studies and at least 75 individuals. Using OTS, we identify pairing biases, public TCRs, and distinct chain coherence patterns relative to antibodies. We also release a paired-chain TCR language model, providing paired embedding representations and a method for residue in-filling conditional on the partner chain. OTS will be updated as a central community resource and is freely downloadable and available as a web application.

OBJECTIVE: Alpha and theta oscillations characterize the waking human electroencephalogram (EEG) and can be modulated by closed-loop auditory stimulation (CLAS). These oscillations also occur during rapid eye movement (REM) sleep, but their function here remains elusive. CLAS represents a promising tool to pinpoint how these brain oscillations contribute to brain function in humans. Here we investigate whether CLAS can modulate alpha and theta oscillations during REM sleep in a phase-dependent manner.
METHODS: We recorded high-density EEG during an extended overnight sleep period in 18 healthy young adults. Auditory stimulation was delivered during both phasic and tonic REM sleep in alternating 6 s ON and 6 s OFF windows. During the ON windows, stimuli were phase-locked to four orthogonal phases of ongoing alpha or theta oscillations detected in a frontal electrode.
RESULTS: The phases of ongoing alpha and theta oscillations were targeted with high accuracy during REM sleep. Alpha and theta CLAS induced phase-dependent changes in power and frequency at the target location. Frequency-specific effects were observed for alpha trough (speeding up) and rising (slowing down) and theta trough (speeding up) conditions. CLAS-induced phase-dependent changes were observed during both REM sleep substages, even though auditory evoked potentials were very much reduced in phasic compared to tonic REM sleep.
CONCLUSIONS: This study provides evidence that faster REM sleep rhythms can be modulated by CLAS in a phase-dependent manner. This offers a new approach to investigate how modulation of REM sleep oscillations affects the contribution of this vigilance state to brain function.

BACKGROUND: SARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs).
OBJECTIVE: This study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout.
METHODS: We used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs.
RESULTS: We included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups.
CONCLUSIONS: Our study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

Verbal working memory (vWM) is an essential limited-capacity cognitive system that spans the fronto-parietal network and utilizes the subprocesses of encoding, maintenance, and retrieval. With the recent widespread use of noninvasive brain stimulation techniques, multiple recent studies have examined whether such stimulation may enhance cognitive abilities such as vWM, but the findings to date remain unclear in terms of both behavior and critical brain regions. In the current study, we applied high-definition direct current stimulation to the left and right parietal cortices of 39 healthy adults in three separate sessions (left anodal, right anodal, and sham). Following stimulation, participants completed a vWM task during high-density magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer and whole-brain ANOVAs were used to identify the specific neuromodulatory effects of the stimulation conditions on neural responses serving distinct phases of vWM. We found that right stimulation had a faciliatory effect relative to left stimulation and sham on theta oscillations during encoding in the right inferior frontal, while the opposite pattern was observed for left supramarginal regions. Stimulation also had a faciliatory effect on theta in occipital regions and alpha in temporal regions regardless of the laterality of stimulation. In summary, our data suggest that parietal HD-tDCS both facilitates and interferes with neural responses underlying both the encoding and maintenance phases of vWM. Future studies are warranted to determine whether specific tDCS parameters can be tuned to accentuate the facilitation responses and attenuate the interfering aspects.

UNASSIGNED: In previous studies, there was an increase in mortality with secondary coinfections in all COVID-19 variants. However, no prior study has explored the association of coinfection with outcomes of hospitalized patients among the COVID-19 variants (Alpha, Delta, and Omicron).
UNASSIGNED: This observational cohort study involved 21,186 patients hospitalized with COVID-19 in 25 hospitals in Texas. Patients were divided into groups by surges of COVID-19: Alpha (November 1, 2020-February 10, 2021), Delta (July 10, 2021-October 14, 2021), and Omicron (December 21, 2021-March 3, 2022). Data were collected from electronic health records using methodology from the Viral Respiratory Illness Universal Study COVID-19 registry (NCT04323787) of COVID-19 hospitalizations. Multivariable Cox-proportional hazard regression model assessed the adjusted effect of different surge periods on mortality.
UNASSIGNED: Bacterial coinfections varied among hospitalization surges associated with Alpha (8.5%), Delta (11.7%), and Omicron (11.9%) variants. Adjusted analyses showed a higher 30-day and 90-day mortality in all variants when coinfections were present compared with isolated COVID-19 infection. In particular, 30-day and 90-day mortality were significantly worse with Delta compared to Alpha and Omicron.
UNASSIGNED: All variants were associated with a higher mortality when bacterial coinfections were present. Delta was associated with a higher risk-adjusted mortality at 30 days and thereafter.

While the shape of cortical oscillations is increasingly recognised to be physiologically and functionally informative, its relevance to the aging motor system has not been established. We therefore examined the shape of alpha and beta band oscillations recorded at rest, as well as during performance of simple and go/no-go reaction time tasks, in 33 young (23.3 ± 2.9 years, 27 females) and 27 older (60.0 ± 5.2 years, 23 females) adults. The shape of individual oscillatory cycles was characterised using a recently developed pipeline involving empirical mode decomposition, before being decomposed into waveform motifs using principal component analysis. This revealed four principal components that were uniquely influenced by task and/or age. These described specific dimensions of shape and tended to be modulated during the reaction phase of each task. Our results suggest that although oscillation shape is task-dependent, the nature of this effect is altered by advancing age, possibly reflecting alterations in cortical activity. These outcomes demonstrate the utility of this approach for understanding the neurophysiological effects of ageing.

BACKGROUND: People with psychosis and mood disorders experience disruptions in working memory; however, the underlying mechanism remains unknown. We focused on two potential mechanisms: first, poor attentional engagement should be associated with elevated levels of pre-stimulus alpha-band activity within the EEG, whereas impaired working memory encoding should be associated with reduced post-stimulus alpha suppression.
METHODS: We collected EEG data from 68 people with schizophrenia, 43 people with bipolar disorder with a history of psychosis, and 53 people with major depressive disorder, as well as 90 healthy comparison subjects (HCS), while they completed a spatial working memory task. We quantified attention lapsing, memory precision, and memory capacity from the behavioral responses, and we quantified alpha using both traditional wavelet analysis as well as a novel approach for isolating oscillatory alpha power from aperiodic elements of the EEG signal.
RESULTS: We found that (1) greater pre-stimulus alpha power estimated using traditional wavelet analysis predicted behavioral errors; (2) post-stimulus alpha suppression was reduced in the patient groups; and (3) reduced suppression was associated with lower likelihood of memory storage. However, we also observed that pre-stimulus alpha was larger among HCS compared to patients, and single-trial analyses showed that it was the aperiodic elements of the pre-stimulus EEG-not oscillatory alpha-that predicted behavioral errors.
CONCLUSIONS: These results suggest that working memory impairments in serious mental illness primarily reflect an impairment in the post-stimulus encoding processes rather than reduced attentional engagement prior to stimulus onset.

The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather, α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multiarticular muscles. We used a computational model of a Rhesus Macaque arm to simulate movements with feedforward α-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) coactivation or (ii) an alternative α-MN collateral projection to homonymous γ-MNs. We conclude that such α-MN collaterals are a physiologically tenable propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate with α-γ coactivation, and the few skeletofusimotor fibers (β-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar, and cortical mechanisms.