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Biology subjects

Winkler, I.

Publications and source records attributed to Winkler, I..

14 recordsLinked to original sources

Human newborns form musical predictions based on rhythmic but not melodic structure

The ability to anticipate rhythmic and melodic structures in music is considered a fundamental human trait, present across all cultures and predating linguistic comprehension in human development. Yet, it remains unclear the extent to which this ability is already developed at birth. Here, we used temporal response functions to assess rhythmic and melodic neural encoding in newborns (N = 49) exposed to classical monophonic musical pieces (real condition) and control stimuli with shuffled tones and inter-onset intervals (shuffled condition). We computationally quantified context-based rhythmic and melodic expectations and dissociated these high-level processes from low-level acoustic tracking, such as local changes in timing and pitch. We observed encoding of probabilistic rhythmic expectations only in response to real but not shuffled music. This proves newborns ability to rely on rhythmic statistical regularities to generate musical expectations. We found no evidence for the tracking of melodic information demonstrating a downweighing of this dimension compared to the rhythmic one. This study provides neurophysiological evidence that the capacity to track statistical regularities in music is present at birth and driven by rhythm. Melodic tracking, in contrast, may receive more weight through development with exposure to signals relevant to communication, such as speech and music. SignificancePerception and appreciation of music stem from humans universal ability to track sequential pitch and timing variations, forming musical melodies and rhythms. To investigate the neurobiological origins of this capacity, we measured neural encoding of rhythm and melody in newborns listening to naturalistic music. We demonstrate a precocious ability to track high-level rhythmic statistical regularities beyond low-level acoustic features. Conversely, melodic tracking is virtually absent at birth, likely emerging with later exposure to pitch-varying signals such as speech and music. This reveals that newborns gradually rely on different sound dimensions to start making sense of the auditory environment. While rhythm and melody are both universal components of music, they do not emerge in parallel but instead develop along distinct timelines.

neuroscience↗

What are you talking about? Representation of the Topic of Speech in the Human Brain

A sentence outside context provides very restricted information to the listener. Real understanding requires one to be able to place it within the sequence of sentences forming a coherent "story" and just as importantly, within ones general knowledge of the "topic". Here we demonstrate the existence of functional brain networks robustly sensitive to the topic of ca. 6-minute-long coherent newspaper articles. Main network hubs are located in parietal and temporal brain regions. These networks changed very slowly during the course of the article, consistent with their involvement in representing the topic rather than the story aspect of the context. Because even the meaning of words can depend on the topic (see e.g., the word "shuttle" in transportation and weaving) the topic-sensitive network must also be intimately linked with the mental lexicon underlying language comprehension. Significance StatementWhen we listen to someone talking, our brain continuously integrates the speech stream with our general knowledge associated with the topic. While this is a central process of comprehension, it is still unclear how the brain maintains the relevant representations. Here we demonstrate the existence of a cortical network, which is sensitive to the topic of the speech just heard. This network may form the neural substrate for "topic representation" in the brain. Understanding how such representations are maintained and accessed would let us reveal the computations enabling rapid linguistic integration, a key process in human communication.

neuroscience↗

Temporal expectations modulate coupling between frontal and sensory brain areas

Temporal prediction enhances perceptual processing by aligning neural excitability with expected sensory events. While local oscillatory mechanisms are known to support timing, less is understood about how large-scale functional brain networks dynamically coordinate predictive processes. In particular, it remains unclear how functional connectivity (FC)--the integration of information into network hubs--differs during expectation formation (post-cue) versus outcome evaluation (post-target), and how this varies across levels of predictability. To investigate this, we recorded electroencephalogram (EEG) while participants performed a cued auditory target-detection task with varying temporal predictability (80% and 50%). Event-related potential (ERP) results revealed that implicit temporal predictability primarily modulated later evaluative processes (P3b, frontal negativity), rather than early sensory components, consistent with context updating under uncertainty. FC was analyzed using a data-driven approach based on Normalized Directed Transfer Entropy (NDTE) applied to EEG difference waveforms between high- and low-predictability conditions. Connectivity was examined separately for the post-cue and post-target periods to distinguish prediction and evaluation phases. Behaviorally, higher temporal predictability facilitated faster reaction times. Connectivity analyses revealed largely overlapping but somewhat distinct network dynamics for prediction and evaluation phases of the signal processing.

neuroscience↗

Interpersonal Synchronization in Mother-Child Dyads: Neural and Motor Coupling as a Mechanism for Motor Learning and Development in Preschoolers

Interpersonal movement synchrony (IMS) and brain-to-brain coupling play a crucial role in social behavior across species. In humans, IMS is often studied in structured tasks that require specific body movements, while spontaneous, unstructured movements have received less attention. In this study, we investigated both structured and spontaneous motor coordination in mother-child dyads. We recorded upper-body kinematics and dual-EEG from mothers and their preschool children during motor tasks and spontaneous face-to-face interactions. Our findings show that mother-child dyads synchronize their movements and neural activity, particularly in gamma band oscillations. This motor and neural synchrony evolves across task repetitions, with a strong correlation between motor and neural measures. Further, we observed that only motor synchronization was significantly related to the childs motor development stage, as assessed by the Movement Assessment Battery for Children. These results suggest that gamma band brain-to-brain coupling reflects joint motor coordination and mutual adaptation shaped by structured tasks and spontaneous interpersonal interactions.

neuroscience↗

Superovulation and aging perturb oocyte-granulosa cell communication

In vitro fertilization has been developed to overcome reduced fertility, which is increasingly due to a decline in reproductive cell quality during aging. Here, we quantitatively investigated the interplay between superovulation and aging in mouse oocytes and their paired granulosa cells using newly adapted isolation techniques. We tested the hypothesis that superovulation disrupts oocyte maturation, revealing the key intercellular communication pathways dysregulated by forced hormonal stimulation. We further demonstrated that granulosa cell transcriptional markers can prospectively predict an associated oocytes early developmental potential. By using naturally ovulated old mice as a non-stimulated reference, we showed that aging and superovulation dysregulate similar genes and interact with each other. By comparing mice and human transcriptional responses of granulosa cells, we found that age-related dysregulation of hormonal responses and cell cycle pathways was shared, though substantial divergence exists in other pathways. HighlightsO_LISuperovulation perturbs cumulus-oocyte communication C_LIO_LIGranulosa cell transcription predicts superovulated oocyte quality C_LIO_LISuperovulation and aging non-additively perturb similar sets of genes C_LI

developmental biology↗

Early maturation of sound duration processing in the infant brain

The ability to process sound duration is crucial already at a very early age for laying the foundation for the main functions of auditory perception, such as object perception and music and language acquisition. With the availability of age-appropriate structural anatomical templates, we can reconstruct EEG source activity with much-improved reliability. The current study capitalized on this possibility by reconstructing the sources of event-related potential (ERP) waveforms sensitive to sound duration in four- and nine-month-old infants. Infants were presented with short (200 ms) and long (300 ms) sounds equiprobably delivered in random order. Two temporally separate ERP waveforms were found to be modulated by sound duration. Generators of these waveforms were mainly located in primary and secondary auditory area and other language-related regions, such as the superior temporal and the inferior frontal gyri. The results show marked developmental changes between four and nine months, partly reflected by scalp-recorded ERPs, but appearing in the underlying generators in a far more nuanced way. The results also confirm the feasibility of the application of anatomical templates in developmental populations.

neuroscience↗

The effects of aging and hearing impairment on listening in noise

Listening in a noisy environment (e.g., speech in noise) relies on the fundamental ability to extract coherence from the variable sensory input. This allows the detection active sound sources and their segregation of them from the rest of the scene (figure-ground segregation). Peripheral and central causes of age-related decline of listening in noise were assessed by a tone-cloud-based figure detection task. In two conditions differing in the amount of noise, figure detection performance was equalized between young, normal-hearing, and hearing-impaired elderly listeners by adapting the stimulation separately to the abilities of each person. Based on behavioral measures and event-related brain potentials (ERP), in the absence of cognitive deficits, aging alone does not appear to significantly deteriorate the ability to detect sound sources in noise, although ERPs show delayed perceptual processes and some expected deterioration in attention and/or executive functions. However, even mild hearing impairment substantially reduces the ability to segregate individual sound sources within a complex auditory scene, and susceptibility to masking noise increases together with the severity of the hearing deficit. Significance StatementThis work provides new information about the contributions of central and peripheral causes to the typical age-related decline of listening in a noisy environment. Behavioral and neurophysiological data collected in a well-controlled model of listening in noise suggest that aging alone does not significantly reduce the ability to detect sound sources in a complex auditory scene. However, even mild hearing impairment significantly reduces this ability. The stimulus paradigm used appears to be quite sensitive to hearing loss, making it potentially useful for the early detection of hearing problems.

neuroscience↗

Neural phoneme discrimination in variable speech in newborns; associations with dyslexia risk and later language skills

A crucial skill in infant language acquisition is learning of the native language phonemes. This requires the ability to group complex sounds into distinct auditory categories based on their shared features. Problems in phonetic learning have been suggested to underlie language learning difficulties in dyslexia, a developmental reading-skill deficit. We investigated auditory abilities important for language acquisition in newborns with or without a familial risk for dyslexia with electrophysiological mismatch responses (MMRs). We presented vowel changes in a sequence of acoustically varying vowels, requiring grouping of the stimuli to two phoneme categories. The vowel changes elicited an MMR which was significantly diminished in infants whose parents had the most severe dyslexia in our sample. Phoneme-MMR amplitude and its hemispheric lateralization were associated with language test outcomes assessed at 28 months, an age at which it becomes possible to behaviourally test children and several standardized tests are available. In addition, statistically significant MMRs to violations of a complex sound-order rule were only found in infants without dyslexia risk, but these results are very preliminary due to small sample size. The results demonstrate the relevance of the newborn infants readiness for phonetic learning for their emerging language skills. Phoneme extraction difficulties in infants at familial risk may contribute to the phonological deficits observed in dyslexia. Research highlightsO_LIWe recorded mismatch responses (MMRs) to vowel changes in a variable speech stream C_LIO_LINewborns extracted relevant phonetic information from the stream, evidenced by MMRs C_LIO_LIHigh dyslexia risk infants had diminished MMRs to vowel changes C_LIO_LIMMR amplitudes and hemispheric lateralization correlated with later language skills C_LIO_LIPoor phoneme extraction may compromise phonological and language development C_LI

neuroscience↗

Beat processing in newborn infants cannot be explained by statistical learning based on transition probabilities

Newborn infants have been shown to extract temporal regularities from sound sequences, both in the form of learning regular sequential properties, and extracting periodicity in the input, commonly referred to as a beat. However, these two types of regularities are often indistinguishable in isochronous sequences, as both statistical learning and beat perception can be elicited by the regular alternation of accented and unaccented sounds. Here, we manipulated the isochrony of sound sequences in order to disentangle statistical learning from beat perception in sleeping newborn infants in an EEG experiment, as previously done in adults and macaque monkeys. We used a binary accented sequence that induces a beat when presented with isochronous timing, but not when presented with randomly jittered timing. We compared mismatch responses to infrequent deviants falling on either accented or unaccented (i.e., odd and even) positions. Results showed a clear difference between metrical positions in the isochronous sequence, but not in the equivalent jittered sequence. This suggests that beat processing is present in newborns. However, the current paradigm did not show effects of statistical learning, despite previous evidence for this ability in newborns. These results show that statistical learning does not explain beat processing in newborn infants. Research highlightsSleeping newborns process musical beat. Transition probabilities are not enough to explain beat perception in newborn infants. No evidence of statistical learning (based on transition probabilities) without isochronous stimulation in newborns. Results converge with previous evidence on beat perception of newborn infants.

neuroscience↗

The function and decline of the female reproductive tract at single-cell resolution

The female reproductive tract (FRT) undergoes extensive remodeling during each reproductive cycle, regulated by systemic changes in sex hormones. Whether this recurrent remodeling influences a specific organs aging trajectory is unknown. To address this, we systematically characterized at single-cell resolution the morphological and transcriptional changes that occur in ovary, oviduct, uterus, cervix, and vagina at each phase of the mouse estrus cycle, during decidualization, and into aging. Transcriptional and cell-to-cell communication networks in estrus cycle and aging are enriched for ECM reorganization and inflammation, two essential components of FRT remodeling. We directly link the organ-specific level of these two processes over reproductive lifespan with the gradual, age-related development of fibrosis and chronic inflammation. Our data represent a comprehensive atlas of the FRT lifespan, revealing pathological consequences of incomplete resolution of recurrent inflammation and tissue repair.

genomics↗

Speech prosody supports speaker selection and auditory stream segregation in a multi-talker situation

To process speech in a multi-talker environment, listeners need to segregate the mixture of incoming speech streams and focus their attention on one of them. Potentially, speech prosody could aid the segregation of different speakers, the selection of the desired speech stream, and detecting targets within the attended stream. For testing these issues, we recorded behavioral responses and extracted event-related potentials and functional brain networks from electroencephalographic signals recorded while participants listened to two concurrent speech streams, performing a lexical detection and a recognition memory task in parallel. Prosody manipulation was applied to the attended speech stream in one group of participants and to the ignored speech stream in another group. Naturally recorded speech stimuli were either intact, synthetically F0-flattened, or suppressed by the speaker. Results show that prosody - especially the parsing cues mediated by speech rate - facilitates stream selection, while playing a smaller role in auditory stream segmentation and target detection.

neuroscience↗

Do we parse the background into separate streams in the cocktail party?

AO_SCPLOWBSTRACTC_SCPLOWIn the cocktail party situation, people with normal hearing usually follow a single speaker among multiple concurrent ones. However, there is no agreement in the literature as to whether the background is segregated into multiple streams/speakers. The current study varied the number of concurrent speech streams and investigated target detection and memory for the contents of a target stream as well as the processing of distractors. A male-spoken target stream was either presented alone (single-speech), together with one male-spoken (one-distractor), or a male- and a female-spoken distractor (two-distractor). Behavioral measures of target detection and content tracking performance as well as target- and distractor detection related ERPs were assessed. We found that the detection sensitivity and the target N2b amplitude decreased whereas the P3b amplitude increased from the single-speech to the concurrent speech streams conditions. Importantly, the behavioral distractor effect differed between the conditions with one- vs. two-distractor (distraction by the female speaker was lower than that of the male speaker in either condition) and the target N2b elicited in the presence of two distractors was significantly smaller than that elicited in the presence of one distractor. Further, the voltage in the N2b time window significantly differed between the one- and two-distractor conditions for the same (M2) speaker. These results show that speech processing was different in the presence of one vs. two distractors, and thus, the current data suggest that the two background speech streams were segregated from each other.

neuroscience↗

de novo identification of maximally deregulated subnetworks based on multi-omics data with DeRegNet

BackgroundWith a growing amount of (multi-)omics data being available, the extraction of knowledge from these datasets is still a difficult problem. Classical enrichment-style analyses require predefined pathways or gene sets that are tested for significant deregulation to assess whether the pathway is functionally involved in the biological process under study. De novo identification of these pathways can reduce the bias inherent in predefined pathways or gene sets. At the same time, the definition and efficient identification of these pathways de novo from large biological networks is a challenging problem. ResultsWe present a novel algorithm, DeRegNet, for the identification of maximally deregulated subnetworks on directed graphs based on deregulation scores derived from (multi-)omics data. DeRegNet can be interpreted as maximum likelihood estimation given a certain probabilistic model for de-novo subgraph identification. We use fractional integer programming to solve the resulting combinatorial optimization problem. We can show that the approach outperforms related algorithms on simulated data with known ground truths. On a publicly available liver cancer dataset we can show that DeRegNet can identify biologically meaningful subgraphs suitable for patient stratification. DeRegNet is freely available as open-source software. ConclusionThe proposed algorithmic framework and its available implementation can serve as a valuable heuristic hypothesis generation tool contextualizing omics data within biomolecular networks.

systems biology↗

In vitro evaluation of the activity of terpenes and cannabidiol against Human Coronavirus E229

The activity of a new, terpene-based formulation, code-named NT-VRL-1, against Human Coronavirus (HCoV) strain 229E was evaluated in human lung fibroblasts (MRC-5 cells), with and without the addition of cannabidiol (CBD). The tested formulation exhibited an antiviral effect when it was pre-incubated with the host cells prior to virus infection. The combination of NT-VRL-1 with CBD potentiated the antiviral effect better than the positive controls pyrazofurin and glycyrrhizin. There was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect seen under the microscope after 72 h. To the best of our knowledge, this is the first report of activity of a combination of terpenes and CBD against a coronavirus.

microbiology↗