Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.

Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes.

Neural attentional filters and behavioural outcome follow independent individual trajectories over the adult lifespan.

Preserved communication abilities promote healthy ageing. To this end, the age-typical loss of sensory acuity might in part be compensated for by an individual's preserved attentional neural filtering. Is such a compensatory brain-behaviour link longitudinally stable? Can it predict individual change in listening behaviour? We here show that individual listening behaviour and neural filtering ability follow largely independent developmental trajectories modelling electroencephalographic and behavioural data of = 105 ageing individuals (39-82 y).

Trajectories and contributing factors of neural compensation in healthy and pathological aging.

Neural degeneration is a hallmark of healthy aging and can be associated with specific cognitive impairments. However, neural degeneration per se is not matched by unremitting declines in cognitive abilities. Instead, middle-aged and older adults typically maintain surprisingly high levels of cognitive functioning, suggesting that the human brain can adapt to structural degeneration by neural compensation.

Neural α Oscillations and Pupil Size Differentially Index Cognitive Demand under Competing Audiovisual Task Conditions.

Cognitive demand is thought to modulate two often used, but rarely combined, measures: pupil size and neural α (8-12 Hz) oscillatory power. However, it is unclear whether these two measures capture cognitive demand in a similar way under complex audiovisual-task conditions. Here we recorded pupil size and neural α power (using electroencephalography), while human participants of both sexes concurrently performed a visual multiple object-tracking task and an auditory gap detection task.

Predicting speech from a cortical hierarchy of event-based time scales.

How do predictions in the brain incorporate the temporal unfolding of context in our natural environment? We here provide evidence for a neural coding scheme that sparsely updates contextual representations at the boundary of events. This yields a hierarchical, multilayered organization of predictive language comprehension. Training artificial neural networks to predict the next word in a story at five stacked time scales and then using model-based functional magnetic resonance imaging, we observe an event-based “surprisal hierarchy” evolving along a temporoparietal pathway.

Neural tracking in infants - An analytical tool for multisensory social processing in development.

Humans are born into a social environment and from early on possess a range of abilities to detect and respond to social cues. In the past decade, there has been a rapidly increasing interest in investigating the neural responses underlying such early social processes under naturalistic conditions. However, the investigation of neural responses to continuous dynamic input poses the challenge of how to link neural responses back to continuous sensory input.

Dynamic large-scale connectivity of intrinsic cortical oscillations supports adaptive listening in challenging conditions.

In multi-talker situations, individuals adapt behaviorally to this listening challenge mostly with ease, but how do brain neural networks shape this adaptation? We here establish a long-sought link between large-scale neural communications in electrophysiology and behavioral success in the control of attention in difficult listening situations. In an age-varying sample of N = 154 individuals, we find that connectivity between intrinsic neural oscillations extracted from source-reconstructed electroencephalography is regulated according to the listener's goal during a challenging dual-talker task. These dynamics occur as spatially organized modulations in power-envelope correlations of alpha and low-beta neural oscillations during approximately 2-s intervals most critical for listening behavior relative to resting-state baseline.

Neural attentional-filter mechanisms of listening success in middle-aged and older individuals.

Successful listening crucially depends on intact attentional filters that separate relevant from irrelevant information. Research into their neurobiological implementation has focused on two potential auditory filter strategies: the lateralization of alpha power and selective neural speech tracking. However, the functional interplay of the two neural filter strategies and their potency to index listening success in an ageing population remains unclear.

Unilateral Acoustic Degradation Delays Attentional Separation of Competing Speech.

Hearing loss is often asymmetric such that hearing thresholds differ substantially between the two ears. The extreme case of such asymmetric hearing is single-sided deafness. A unilateral cochlear implant (CI) on the more severely impaired ear is an effective treatment to restore hearing.

Circadian fluctuations in glucocorticoid level predict perceptual discrimination sensitivity.

Slow neurobiological rhythms, such as the circadian secretion of glucocorticoid (GC) hormones, modulate a variety of body functions. Whether and how endocrine fluctuations also exert an influence on perceptual abilities is largely uncharted. Here, we show that phasic increases in GC availability prove beneficial to auditory discrimination.

Local cortical desynchronization and pupil-linked arousal differentially shape brain states for optimal sensory performance.

Instantaneous brain states have consequences for our sensation, perception, and behaviour. Fluctuations in arousal and neural desynchronization likely pose perceptually relevant states. However, their relationship and their relative impact on perception is unclear.

Working-memory disruption by task-irrelevant talkers depends on degree of talker familiarity.

When one is listening, familiarity with an attended talker's voice improves speech comprehension. Here, we instead investigated the effect of familiarity with a distracting talker. In an irrelevant-speech task, we assessed listeners' working memory for the serial order of spoken digits when a task-irrelevant, distracting sentence was produced by either a familiar or an unfamiliar talker (with rare omissions of the task-irrelevant sentence).

Modular reconfiguration of an auditory control brain network supports adaptive listening behavior.

Speech comprehension in noisy, multitalker situations poses a challenge. Successful behavioral adaptation to a listening challenge often requires stronger engagement of auditory spatial attention and context-dependent semantic predictions. Human listeners differ substantially in the degree to which they adapt behaviorally and can listen successfully under such circumstances.

Probing the limits of alpha power lateralisation as a neural marker of selective attention in middle-aged and older listeners.

In recent years, hemispheric lateralisation of alpha power has emerged as a neural mechanism thought to underpin spatial attention across sensory modalities. Yet, how healthy ageing, beginning in middle adulthood, impacts the modulation of lateralised alpha power supporting auditory attention remains poorly understood. In the current electroencephalography study, middle-aged and older adults (N = 29; ~40-70 years) performed a dichotic listening task that simulates a challenging, multitalker scenario.

Predicting "When" in Discourse Engages the Human Dorsal Auditory Stream: An fMRI Study Using Naturalistic Stories.

Unlabelled: The hierarchical organization of human cortical circuits integrates information across different timescales via temporal receptive windows, which increase in length from lower to higher levels of the cortical hierarchy (Hasson et al., 2015). A recent neurobiological model of higher-order language processing (Bornkessel-Schlesewsky et al.

Disruption of calcitonin gene-related peptide signaling accelerates muscle denervation and dampens cytotoxic neuroinflammation in SOD1 mutant mice.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal vacuolization and glial activation are pathologic hallmarks in the superoxide dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide calcitonin gene-related peptide (CGRP) associated with vacuolization and astrogliosis in the spinal cord of these mice.

Sentence understanding depends on contextual use of semantic and real world knowledge.

Human language allows us to express our thoughts and ideas by combining entities, concepts and actions into multi-event episodes. Yet, the functional neuroanatomy engaged in interpretation of such high-level linguistic input remains poorly understood. Here, we used easy to detect and more subtle "borderline" anomalies to investigate the brain regions and mechanistic principles involved in the use of real-world event knowledge in language comprehension.

Processing of false belief passages during natural story comprehension: An fMRI study.

The neural correlates of theory of mind (ToM) are typically studied using paradigms which require participants to draw explicit, task-related inferences (e.g., in the false belief task).

Cross-linguistic variation in the neurophysiological response to semantic processing: evidence from anomalies at the borderline of awareness.

The N400 event-related brain potential (ERP) has played a major role in the examination of how the human brain processes meaning. For current theories of the N400, classes of semantic inconsistencies which do not elicit N400 effects have proven particularly influential. Semantic anomalies that are difficult to detect are a case in point ("borderline anomalies", e.

Meaningful physical changes mediate lexical-semantic integration: top-down and form-based bottom-up information sources interact in the N400.

Models of how the human brain reconstructs an intended meaning from a linguistic input often draw upon the N400 event-related potential (ERP) component as evidence. Current accounts of the N400 emphasise either the role of contextually induced lexical preactivation of a critical word (Lau, Phillips, & Poeppel, 2008) or the ease of integration into the overall discourse context including a wide variety of influencing factors (Hagoort & van Berkum, 2007). The present ERP study challenges both types of accounts by demonstrating a contextually independent and purely form-based bottom-up influence on the N400: the N400 effect for implausible sentence-endings was attenuated when the critical sentence-final word was capitalised (following a lowercase sentence context).

Think globally: cross-linguistic variation in electrophysiological activity during sentence comprehension.

This paper demonstrates systematic cross-linguistic differences in the electrophysiological correlates of conflicts between form and meaning ("semantic reversal anomalies"). These engender P600 effects in English and Dutch (e.g.