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Bertels, J.

Publications and source records attributed to Bertels, J..

12 recordsLinked to original sources

A single cell atlas defines perinatal factors that drive murine bone marrow development

Processes that direct initial colonization and maturation of the bone marrow remain elusive, despite lifelong importance to hematopoiesis. Bone marrow mesenchymal and stromal cell (BMSC) maturation establishes supportive niches prior to hematopoietic stem cell (HSC) recruitment. We define mouse BMSC progenitor identities and temporal emergence in a developmental single cell atlas spanning fetal life through 18 months of age. We clarify Cxcl12-abundant reticular (CAR) cell and osteoblast development, including temporal emergence of signaling modalities that direct HSC quiescence and regenerative capacity. CAR cells are absent until birth, with a developmental block during fetal maturation related to transcriptional changes during perinatal life. Temporal changes in Early B Cell Factor (Ebf) 1-3 expression and activity correlate with CAR formation and niche establishment, including Ebf2 repression and induction of Ebf3 activities that direct metabolic changes. Changes in systemic physiology underlie these transcriptional changes, including perinatal induction of lipid metabolism, inflammation, and hypoxic signaling. These systemic factors direct CAR cell emergence after birth, providing temporal and developmental resolution underlying the colonization and maturation of the bone marrow environment.

developmental biology↗

Signal space beamforming for gain- and geometry-independent interference suppression in wearable MEG

Optically pumped magnetometers (OPMs) for wearable magnetoencephalography (MEG) offer substantial flexibility compared to cryogenic MEG, but they also introduce new challenges related to environmental noise and movement artefacts. State-of-the-art denoising techniques such as signal space separation require not only dense OPM arrays but also the fine calibration of sensor gain and geometry. This may complicate their use in complex experimental situations involving uncooperative patients or subjects such as newborns or fetuses, where OPM positioning may be unstable or plain unknown. To address this limitation, we introduce signal space beamforming (SSB), a version of beamforming applied to sensor signals and designed to suppress interferences independently of sensor gain and geometry. We show that SSB operates via a trade-off between noise suppression and neural signal preservation that is controlled by a single soft-threshold parameter, which we calibrated using phantom measurements. We then validated the effectiveness of SSB across several datasets. Using interictal OPM-MEG recordings in epileptic patients, SSB successfully cleaned signals while preserving epileptiform discharges. Moving onto cutting-edge early neurodevelopmental OPM-MEG recordings, SSB allowed to recover auditory evoked responses in newborns and fetuses similar to previous findings but with more streamlined preprocessing and higher response amplitude in the case of the fetal data. We contend that SSB provides a pragmatic solution to exploit OPM-MEG data recorded in challenging conditions where geometry-dependent methods cannot be used, opening new frontiers for pioneering clinical and fundamental applications of the OPM technology.

neuroscience↗

Can you feel what I am saying? Speech-based vibrotactile stimulation enhances the cortical tracking of attended speech in a multi-talker background

In environments with multiple talkers, humans can tune in to a speaker of interest while ignoring competing voices. In such conditions, however, auditory cortices track the attended speech envelope rhythms (cortical tracking of speech, CTS) less accurately than in quiet, hindering intelligibility. Visual speech cues (e.g., lip movements) can enhance this CTS, but it remains unclear whether other non-auditory sensory cues, such as tactile input, provide comparable benefits through similar neural mechanisms. Here, using magnetoencephalography, we quantified syllabic (4-8 Hz) and phrasal (<1 Hz) CTS while participants attended to connected speech alone, together with synchronous or asynchronous speech-based vibrations, or with the corresponding speaker video, in both quiet and a multi-talker background noise. We hypothesized that, in noise, speech-based vibrotactile stimulation improves comprehension by enhancing CTS and modulating auditory-seeded functional brain connectivity with extra-auditory neocortical brain areas. Results revealed that synchronous vibrotactile stimulation improved comprehension in multi-talker noise and increased syllabic CTS at right auditory cortex, with this CTS increase magnitude correlating with comprehension performance. Audio-tactile CTS enhancement was accompanied by stronger beta-band auditory cortex connectivity with ipsilateral angular and ventral inferior temporal gyri, alongside reduced alpha-band coupling with the precuneus. These findings suggest that vibrotactile input can support speech-in-noise processing by impacting both local auditory cortical activity and auditory-seeded long-range functional connectivity.

neuroscience↗

Fetal magnetoencephalography based on optically pumped magnetometers

The fetus in the third trimester of gestation has already the remarkable capacity to process external sensory information in utero. So far, investigations of fetal brain responses to sensory information have mostly relied on cryogenic magnetoencephalography (MEG), which is suitable to record fetal brain activity and is not much affected by layers of maternal tissues. Nevertheless, this solution is extremely expensive and limited to a couple of laboratories worldwide. In this work, we took advantage of the next generation cryogenic-free MEG, that is MEG based on optically pumped magnetometers (OPM), to develop a system that could record both fetal and newborn brain responses to auditory stimulation in a longitudinal design. Twenty-one pregnant women in their late third trimester of gestation (35-40 weeks of gestational age) were exposed to sequences of 500 Hz tones. Fetal brain activity was recorded using a wearable belt equipped with OPM sensors arranged on the womens abdomen based on fetal head position. Results revealed that fetal OPM-MEG successfully recorded significant evoked brain responses to auditory stimuli that peaked ~300 ms post-stimulus at the group level. A similar auditory paradigm was performed with on-scalp OPM-MEG in 14 one-month-old infants, with 9 participants common to both timepoints. Infant responses showed a significant latency decrease compared to the fetal ones in terms of magnetometers; a decrease that did not reach significance level for virtual gradiometers. This work demonstrates the ability of OPM-MEG to non-invasively record fetal brain responses to external sensory stimuli. It paves the way for a wider use of fetal MEG to investigate fetal cognition and positions OPM-MEG as the most promising lifespan-compliant solution for monitoring early brain development.

neuroscience↗

The infant brain rapidly entrains to visual statistical regularities during stimulus exposure

Statistical learning (SL) has been studied quite extensively in infancy. Still, most evidence relies on post-exposure behavioural tasks whose directionality (familiarity vs. novel effects) may not be straightforward to predict nor to interpret. In addition, these tasks do not tell anything about the online learning dynamics and may be influenced by memory effects. In this work, we investigated online SL mechanisms by tracking neural entrainment to visual regularities in a group of 4- to 6-month-old infants exposed to a stream of shapes presented at 6 Hz. Shapes were either organized in doublets or presented randomly. Results revealed that entrainment at the doublet frequency of 3 Hz and harmonics varied across conditions and trials. Infants showed greater occipital entrainment to the doublet frequency in the deterministic condition than in the random one, especially over the first trials of exposure. This suggests that the brain can detect visual regularities from early infancy. Further, this sensitivity emerged early over the exposure period and did not show a learning curve when the evolution of the doublet-level SNR was assessed in relation with the base-level SNR over time. Hence, considering its time course and the brain regions involved, neural entrainment at the doublet frequency seems to reflect a bottom-up detection mechanism rather than a learning process. These findings are crucial to better understand how infants extract regularities during stimulus exposure and what neural entrainment can reveal in a visual SL task.

neuroscience↗

Extending the applicability of optically pumped magnetoencephalography toward early human life

Characterizing the early development of the human brain is critical from both fundamental and clinical perspectives. However, existing neuroimaging techniques are either not well suited to infants or have limited spatial or temporal resolution. The advent of optically pumped magnetometers (OPMs) has revolutionized magnetoencephalography (MEG) by enabling wearable and thus more naturalistic recordings while maintaining excellent sensitivity and spatiotemporal resolution. Nevertheless, its adaptation to studying neural activity in infancy poses several challenges. In this work, we present an original close-to-scalp OPM-MEG setup that successfully recorded brain responses to sounds in newborns. We exposed one-month-old infants to continuous streams of tones and observed significant evoked responses, which peaked [~]250 ms poststimulus at bilateral auditory cortices. When tones were presented at a steady fixed pace with an oddball tone every fourth tone, significant neural responses were found both at the frequency of the standard tones (3 Hz) and of the oddball tones (0.75 Hz). The latter reflects the ability of the newborn brain to detect auditory change and synchronize to regular auditory patterns. Additional analyses support the added value of triaxial OPMs to increase the number of channels on small heads. Finally, OPM-MEG responses were validated with those obtained from the same participants using an adult-sized cryogenic MEG. This study demonstrates the applicability of OPM-MEG to study early postnatal periods; a crucial step towards future OPM investigations of typical and pathological early brain development.

neuroscience↗

Cortical tracking of lexical speech units in a multi-talker background is immature in school-aged children

Children have more difficulty perceiving speech in noise than adults. Whether these difficulties relate to immature processing of prosodic or linguistic elements of the attended speech is still unclear. To address the impact of noise on linguistic processing per se, we assessed how acoustic noise impacts the cortical tracking of intelligible speech devoid of prosody in school-aged children and adults. Twenty adults and twenty children (7-9 years) listened to synthesized French monosyllabic words presented at 2.5 Hz, either randomly or in 4-word hierarchical structures wherein 2 words formed a phrase, and 2 phrases formed a sentence, with or without babble noise. Neuromagnetic responses to words, phrases and sentences were identified and source-localized. Children and adults displayed significant cortical tracking of words in all conditions, and of phrases and sentences only when words formed meaningful sentences. In children compared with adults, cortical tracking of linguistic units was lower for all units in conditions without noise, and similarly impacted by the addition of babble noise for phrase and sentence units. Critically, when there was noise, adults increased the cortical tracking of monosyllabic words in the inferior frontal gyri but children did not. This study demonstrates that the difficulties of school-aged children in understanding speech in a multi-talker background might be partly due to an immature identification of lexical but not supra-lexical linguistic units. HighlightsO_LIChildren track the hierarchical linguistic units of clear speech devoid of prosody C_LIO_LIThis cortical tracking is left-hemisphere dominant as the adult brain C_LIO_LIBabble noise reduces cortical tracking of sentences in children and adults C_LIO_LIUnlike adults, children are not able to enhance cortical tracking of words in noise C_LI

neuroscience↗

Neurodevelopmental oscillatory basis of speech processing in noise

Humans extraordinary ability to understand speech in noise relies on multiple processes that develop with age. Using magnetoencephalography (MEG), we characterize the underlying neuromaturational basis by quantifying how cortical oscillations in 144 participants (aged 5 to 27 years) track phrasal and syllabic structures in connected speech mixed with different types of noise. While the extraction of prosodic cues from clear speech was stable during development, its maintenance in a multi-talker background matured rapidly up to age 9 and was associated with speech comprehension. Furthermore, while the extraction of subtler information provided by syllables matured at age 9, its maintenance in noisy backgrounds progressively matured until adulthood. Altogether, these results highlight distinct behaviorally relevant maturational trajectories for the neuronal signatures of speech perception. In accordance with grain-size proposals, neuromaturational milestones are reached increasingly late for linguistic units of decreasing size, with further delays incurred by noise. TeaserThe neural signature of speech processing in silence and noise features multiple behaviorally relevant developmental milestones

neuroscience↗

The role of reading experience in atypical cortical tracking of speech and speech-in-noise in dyslexia

Dyslexia is a frequent developmental disorder in which reading acquisition is delayed and that is usually associated with difficulties understanding speech in noise. At the neuronal level, children with dyslexia were reported to display abnormal cortical tracking of speech (CTS) at phrasal rate. Here, we aimed to determine if abnormal tracking is a cause or a consequence of dyslexia and if it is modulated by the severity of dyslexia or the presence of acoustic noise. We included 26 school-age children with dyslexia, 26 age-matched controls and 26 reading-level matched controls. All were native French speakers. Childrens brain activity was recorded with magnetoencephalography while they listened to continuous speech in noiseless and multiple noise conditions. CTS values were compared between groups, conditions and hemispheres, and also within groups, between children with best and worse reading performance. Syllabic CTS was significantly reduced in the right superior temporal gyrus in children with dyslexia compared with controls matched for age but not for reading level. Among children with dyslexia, phrasal CTS tended to lateralize to the left hemisphere in severe dyslexia and lateralized to the right hemisphere in children with mild dyslexia and in all control groups. Finally, phrasal CTS was lower in children with dyslexia compared with age-matched controls, but only in informational noise conditions. No such effect was seen in comparison with reading-level matched controls. Overall, our results confirmed the finding of altered neuronal basis of speech perception in noiseless and babble noise conditions in dyslexia compared with age-matched peers. However, the absence of alteration in comparison with reading-level matched controls suggests that such alterations are a consequence of reduced reading experience rather than a cause of dyslexia. HighlightsO_LIThe cortical tracking of speech (CTS) was assessed in dyslexia and proper controls C_LIO_LIPhrasal CTS and its resistance to noise were altered in dyslexia C_LIO_LISuch alterations were not found in comparison with controls matched for reading level C_LIO_LIThe severity of dyslexia modulated the hemispheric lateralization of phrasal CTS C_LI

neuroscience↗

The transcriptomic landscape of the photoperiodic stress response in Arabidopsis thaliana resembles the response to pathogen infection.

Plants are exposed to regular diurnal rhythms of light and dark. Changes in the photoperiod by the prolongation of the light period cause photoperiod stress in short day-adapted Arabidopsis thaliana. Here we report on the transcriptional response to photoperiod stress of wild-type A. thaliana and photoperiod stress-sensitive cytokinin signalling and clock mutants. Transcriptomic changes induced by photoperiod stress included numerous changes in reactive oxygen (ROS)-related transcripts and showed a strong overlap with changes occurring in response to ozone stress and pathogen attack, which have in common the induction of an apoplastic oxidative burst. A core set of photoperiod stress-responsive genes has been identified, including salicylic acid (SA) biosynthesis and signalling genes. Genetic analysis revealed a central role for NPR1 in the photoperiod stress response as npr1-1 mutants were stress-insensitive. Photoperiod stress treatment led to a strong increase in camalexin levels which is consistent with shared photoperiod stress and pathogen response pathways. Photoperiod stress induced resistance of Arabidopsis plants to a subsequent infection by Pseudomonas syringae cv. tomato DC3000 indicating priming of the defence response. Together, photoperiod stress causes transcriptional reprogramming resembling plant pathogen defence responses and induces systemic acquired resistance in the absence of a pathogen. One sentence summaryPhotoperiod stress results in significant dynamic transcriptomic changes related to oxidative stress similar to those caused by pathogen attack and primes the defence response against a subsequent pathogen infection.

plant biology↗

Intrinsic/extrinsic duality of large-scale neural functional integration in the human brain

Human brain activity is not merely responsive to environmental context but includes intrinsic dynamics, as suggested by the discovery of functionally meaningful neural networks at rest, i.e., even without explicit engagement of the corresponding function. Yet, the neurophysiological coupling mechanisms distinguishing intrinsic (i.e., task-invariant) from extrinsic (i.e., task-dependent) brain networks remain indeterminate. Here, we investigated functional brain integration using magnetoencephalography throughout rest and various tasks recruiting different functional systems and modulating perceptual/cognitive loads. We demonstrated that two distinct modes of neural communication continually operate in parallel: extrinsic coupling supported by phase synchronization and intrinsic integration encoded in amplitude correlation. Intrinsic integration also contributes to phase synchronization, especially over short (second-long) timescales, through modulatory effects of amplitude correlation. Our study establishes the foundations of a novel conceptual framework for human brain function that fundamentally relies on electrophysiological features of functional integration. This framework blurs the boundary between resting-state and task-related neuroimaging.

neuroscience↗

Cortical tracking of speech in noise accounts for reading strategies in children

Humans propensity to acquire literacy relates to several factors, among which, the ability to understand speech in noise (SiN). Still, the nature of the relation between reading and SiN perception abilities remains poorly understood. Here, we dissect the interplay between (i) reading abilities, (ii) classical behavioral predictors of reading (phonological awareness, phonological memory and lexical access), and (iii) electrophysiological markers of SiN perception in 99 elementary school children (26 with dyslexia). We demonstrate that cortical representation of phrasal content of SiN relates to the development of the lexical (but not sublexical) reading strategy. In contrast, classical behavioral predictors of reading abilities and the ability to benefit from visual speech to represent the syllabic content of SiN account for global reading performance (i.e., speed and accuracy of lexical and sublexical reading). Finally, we found that individuals with dyslexia properly integrate visual speech information to optimize processing of syntactic information, but not to sustain acoustic/phonemic processing. These results clarify the nature of the relation between SiN perception and reading abilities in typical and dyslexic child readers, and identified novel electrophysiological markers of emergent literacy.

neuroscience↗