👤 Bruno Nazarian

In this functional magnetic resonance imaging study, we investigated whether language production and understanding recruit similar phoneme-specific networks. We did so by comparing the brain's response to different phoneme categories in minimal pairs: Bilabial-initial words (eg "monkey") were contrasted to alveolar-initial words (eg "donkey") in 37 participants performing both language production and comprehension tasks. Individual-specific region-of-interest analyses showed that the same sensorimotor networks were activated across the language modalities. In motor regions, word production and comprehension elicited the same phoneme-specific topographical activity patterns, with stronger haemodynamic activations for alveolar-initial words in the tongue cortex and stronger activations for bilabial-initial words in the lip cortex. In the posterior and middle superior temporal cortex, production and comprehension likewise resulted in similar activity patterns, with enhanced activations to alveolar- compared to bilabial-initial words. These results disagree with the classical asymmetry between language production and understanding in neurobiological models of language, and instead advocate for a cortical organization where phonology is carried by similar topographical activations in motor cortex and distributed activations in temporal cortex across the language modalities. Show less

Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in this process. Through the automatization of the mapping ability, this area progressively becomes specialized in written word recognition. Yet, despite its key role in reading, the area also responds to speech. This observation raises questions about the actual nature of neural representations encoded in the VWFA and, therefore, the underlying mechanism of the cross-modal responses. Here, we addressed this issue by applying fine-grained analyses of within- and cross-modal repetition suppression effects (RSEs) and Multi-Voxel Pattern Analyses in fMRI and sEEG experiments. Convergent evidence across analysis methods and protocols showed significant RSEs and successful decoding in both within-modal visual and auditory conditions, suggesting that populations of neurons within the VWFA distinctively encode written and spoken language. This functional organization of neural populations enables the area to respond to both written and spoken inputs. The finding opens further discussions on how the human brain may be prepared and adapted for an acquisition of a complex ability such as reading. Show less

The "MEG-GLOUPS" dataset offers a curated collection of raw magnetoencephalography recordings from seventeen French participants engaged in a pseudoword learning task as well as resting-state activity before and after the task. A dataset called Gloups with the same participants and a similar learning task adapted to functional magnetic resonance imaging is already available. In the learning task, participants were instructed to pronounce monosyllabic pseudowords, which were presented both visually and auditorily. These pseudowords were either phonotactically legal or illegal in the participants' native language, French. We organized the dataset according to the Brain Imaging Data Structure (BIDS), pre-processed the data and performed a minimal analysis of Event-Related Fields (ERFs), to ensure data quality and integrity of the dataset. This data collection includes comprehensive descriptions of the theoretical background, methods, data recordings, and technical validation. Show less

Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found that CRISPR knockout of KDM5B in stem-cell-derived atrial cardiomyocytes led to a shortening of the action potential duration and widespread transcriptomic dysregulation of genes relevant to atrial homeostasis and conduction. Our results highlight the contribution of rare coding and structural variants to AF, including genetic links between AF and cardiomyopathies, and expand our understanding of the rare variant architecture for this common arrhythmia. Show less

The neuromuscular junction (NMJ) is a regionally specialized area of myofibers defined, in part, by specific gene expression from underlying myonuclei. We sought to obtain a more complete picture of the mRNA transcripts and proteins playing a role in NMJ formation and maintenance using laser capture microdissection (LCM) and to define expression profiles of the nuclear domain at the NMJ. NMJs (800) were isolated from normal mouse tibialis anterior muscle by LCM, with an equal amount of adjacent non-NMJ regions isolated. Many known components of the NMJ were found significantly differentially expressed. Three differentially expressed potential novel components of the NMJ were chosen for further study, and each was validated by immunostaining with and without blocking peptides (3/3), quantitative RT-PCR (3/3), and in situ hybridization (1/3). The three genes validated were dual-specificity phosphatase-6 (DUSP6), ribosomal receptor-binding protein-1 (RRBP1), and vacuolar protein sorting-26 (VPS26). Query of each of these novel components in a 27-time point in vivo muscle regeneration series showed expression commensurate with previously known NMJ markers (nestin, alpha-ACh receptor). Understanding and discovering elements responsible for the integrity and function of NMJs is relevant to understanding neuromuscular diseases such as spinal muscular atrophy. Our LCM-based mRNA expression profiling provided us with new means of identification of specific genes potentially responsible for NMJ stability and function and new candidates for involvement in disease pathogenesis. Show less