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Ameen, M.

Publications and source records attributed to Ameen, M..

4 recordsLinked to original sources

Neural speech tracking in newborns: prenatal learning and contributing factors

IntroductionEarly language development in infants is being increasingly studied, though only recently with direct measurements of brain activity rather than with behavioral or physiological measurements. In the current study, we use electroencephalographic (EEG) recordings of 2-week-old infants to look for signs of prenatal learning and to investigate newborns abilities to process language. We also look at the influence of prenatal stress factors and at the predictive value of the newborns language processing abilities for later language development. MethodsSixty pregnant women played a rhyme to their abdomen twice a day from the 34th week of pregnancy until birth, to familiarize the fetus with the rhyme. At around 2 weeks after delivery (mean age 16 days), the newborns were exposed to the familiar rhyme as well as to an unfamiliar one while their EEG was recorded. Additionally, three manipulations of the familiar rhyme were played: (1) low-pass filtered, (2) with changed rhythm, and (3) inverted and played backwards. The data was analyzed to see how well the infant brain signal followed the speech envelope in each condition. Accounting for the heterogenous approach used for neural speech tracking in the literature, we used four methods, namely: (1) coherence, (2) Hilbert coherence, (3) temporal response functions (TRF), and (4) mutual information (MI). The maternal prenatal depression was evaluated with Edinburgh Prenatal Depression Score and the chronic fetal stress was measured from the hair cortisol levels of the 2 week-olds. The language development at 6 months of age was evaluated with the Bayley Scales. Results and discussionOverall, the results indicate the presence of prenatal learning, with the unfamiliar rhyme eliciting stronger cortical tracking (higher coherence and MI) than the familiar rhyme, which suggests stronger brain-to-speech coupling for the unfamiliar rhyme, perhaps deriving from more effort to process the unexpected stimulus. However, the original version of the familiar rhyme proved to be the easiest to track compared to the language- and rhythm-manipulations, (higher MI for the original rhyme than the language manipulation and higher coherence and mTRF correlation coefficients for the original rhyme than the rhythm manipulation). This indicates language discrimination and a prosodic-based learning of the familiar rhyme. Furthermore, there is an indication of phonotactic sensitivity at this young age, with less tracking (lower Hilbert coherence and lower mTRF correlation coefficients) of the low-pass filtered rhyme than the original version, indicating that the phonological cues erased by the filtering were important for the newborns ability to follow the rhyme. Furthermore, the mothers depression scores positively correlated with the infants tracking ability for the familiar rhyme. This suggests that a slightly lower mood was more stimulative for the fetal language development. The chronic fetal stress levels, however, were negatively correlated with the cortical tracking abilities. Importantly, the newborns cortical tracking was positively correlated with the infants language development at 6 months of age, underlining the predictive value of the early assessment of language processing. ConclusionPrenatal learning is well established, but evidence including (healthy) brain data in the first weeks of life is scarce. The current study shows that newborns can discriminate between a familiar and unfamiliar rhyme, while also highlighting the role of prosody in early language processing, and bringing new evidence of their sensitivity to phonotactic cues in auditory stimuli. Furthermore, the newborns ability to track a rhyme is correlated with their language development at 6 months. The newborns cortical tracking of the familiar rhyme is further increased by moderately low maternal mood, but decreased by fetal stress. Future studies with similar fine-grained linguistic designs but of older infants should teach us the timeline of what exactly is learned prenatally and at very early age in respect to language.

developmental biology↗

Transcription factor stoichiometry, motif affinity and syntax regulate single-cell chromatin dynamics during fibroblast reprogramming to pluripotency

The concentration and stoichiometry of transcription factors (TFs) determine cellular identity and can be manipulated to drive cell state transitions. Understanding how changes in TF concentration regulate chromatin state and expression across cell state transitions remains a challenge. We investigated this relationship by profiling chromatin accessibility and gene expression at single-cell resolution across a densely sampled time course of reprogramming human fibroblasts to induced pluripotent stem cells via ectopic expression of OCT4, SOX2, KLF4, and MYC (OSKM). Using deep learning sequence models of base-resolution chromatin accessibility profiles across cell states, we deciphered predictive transcription factor (TF) motif syntax in regulatory elements, inferred affinity- and concentration-dependent dynamics of TF footprints, linked peaks to putative target genes, and elucidated rewiring of cis-regulatory networks. Our models reveal that early in reprogramming, OSK, at supraphysiological concentrations, rapidly open transient regulatory elements by occupying non-canonical low-affinity binding sites. As OSK concentration falls, the accessibility of these transient elements decays as a function of motif affinity. We find that these OSK-dependent transient elements sequester the somatic TF AP-1. This redistribution is strongly associated with the silencing of fibroblast-specific genes within individual nuclei. Together, our integrated single-cell resource and models reveal insights into the cis-regulatory code of reprogramming at unprecedented resolution. We establish a quantitative, predictive framework that links TF stoichiometry, motif syntax, and somatic silencing to provide new perspectives on the control of cell identity by TFs during fate transitions.

genetics↗

Integrative single-cell analysis of cardiogenesis identifies developmental trajectories and non-coding mutations in congenital heart disease

Congenital heart defects, the most common birth disorders, are the clinical manifestation of anomalies in fetal heart development - a complex process involving dynamic spatiotemporal coordination among various precursor cell lineages. This complexity underlies the incomplete understanding of the genetic architecture of congenital heart diseases (CHDs). To define the multi-cellular epigenomic and transcriptional landscape of cardiac cellular development, we generated single-cell chromatin accessibility maps of human fetal heart tissues. We identified eight major differentiation trajectories involving primary cardiac cell types, each associated with dynamic transcription factor (TF) activity signatures. We identified similarities and differences of regulatory landscapes of iPSC-derived cardiac cell types and their in vivo counterparts. We interpreted deep learning models that predict cell-type resolved, base-resolution chromatin accessibility profiles from DNA sequence to decipher underlying TF motif lexicons and infer the regulatory impact of non-coding variants. De novo mutations predicted to affect chromatin accessibility in arterial endothelium were enriched in CHD cases versus controls. We used CRISPR-based perturbations to validate an enhancer harboring a nominated regulatory CHD mutation, linking it to effects on the expression of a known CHD gene JARID2. Together, this work defines the cell-type resolved cis-regulatory sequence determinants of heart development and identifies disruption of cell type-specific regulatory elements as a component of the genetic etiology of CHD.

genomics↗

The brain tunes to unfamiliar voices during sleeping

The brain continues to respond selectively to environmental stimuli even during sleep. However, the functional role of such responses, and whether they reflect information processing or rather sensory inhibition is not fully understood. Here, we presented 17 human sleepers (14 females) with their own name and two unfamiliar first names, spoken by either a familiar voice (FV) or an unfamiliar voice (UFV), while recording polysomnography during a full nights sleep. We detected K-complexes, sleep spindles, and micro-arousals, and then assessed event-related potentials, oscillatory power as well as intertrial phase synchronization in response to the different stimuli presented during non-rapid eye movement (NREM) sleep. We show that UFVs evoke more K-complexes and micro-arousals than FVs. When both stimuli evoke a K-complex, we observed larger evoked potentials, higher oscillatory power in the high beta (>16Hz) frequency range, and stronger time-locking in the delta band (1-4 Hz) in response to UFVs relative to FVs. Crucially, these differences in brain responses disappear when no K-complexes are evoked by the auditory stimuli. Our findings highlight discrepancies in brain responses to auditory stimuli based on their relevance to the sleeper and propose a key role for K-complexes in the modulation of sensory processing during sleep. We argue that such content-specific, dynamic reactivity to external sensory information enables the brain to enter a sentinel processing mode in which it engages in the many important processes that are ongoing during sleep while still maintaining the ability to process vital information in the surrounding. Significance statementPrevious research has shown that sensory processing continues during sleep. Here, we studied the capacity of the sleeping brain to extract and process relevant sensory information. We presented sleepers with their own names and unfamiliar names spoken by either a familiar (FV) or an unfamiliar voice (UFV). During non-rapid eye movement (NREM) sleep, UFVs elicited more K-complexes and micro-arousals than FVs. By contrasting stimuli which evoked K-complexes, we demonstrate that UFVs triggered larger evoked potentials, stronger time-locking in the delta (1-4Hz) band, and higher oscillatory power (>16Hz) relative to FVs. These differences in brain responses disappeared when no K-complexes were evoked. Our results suggest a pivotal role for K-complexes in the selective processing of relevant information during NREM sleep.

neuroscience↗