Biology subjects

Schiltz, C.

Publications and source records attributed to Schiltz, C..

10 recordsLinked to original sources

bioRxiv2025

Structural basis for fork reversal and RAD51 regulation by the SCF ubiquitin ligase complex of F-box helicase 1

Replication fork reversal helps maintain genomic stability during replication stress. F-box helicase 1 (FBH1) catalyzes fork reversal and is an SCF (SKP-CUL1-F-box) E3 ubiquitin ligase that limits RAD51 association with chromatin. Here, we show that preferential binding of SCFFBH1 to the lagging strand template at DNA fork structures stimulates helicase activity and is required for fork reversal. A cryo-EM structure of SCFFBH1 bound to DNA representing a stalled fork reveals an intimate interaction between FBH1 and the fork junction. Disruption of this interface severely curtails fork reversal in vitro and replication progression in cells, providing a model for how ssDNA translocation by FBH1 facilitates annealing of parental DNA by a fundamentally different mechanism than the fork remodelers SMARCAL, HLTF, and ZRANB3. The structure also provides a model for SCFFBH1 disassembly of RAD51 filaments through translocation and ubiquitination, and implies that RAD51 is associated with the lagging strand at stalled forks.

biochemistry↗

bioRxiv2025

Lexical brain responses in 10-year-old children are impaired in dyslexia: an FPVS-EEG study

The developmental origin of the left occipitotemporal cortex specialization for automatic lexical access from vision remains unclear. Here we investigated cortical specialization for print processing in children with or without dyslexia, focusing on two distinct tuning levels: coarse-grained tuning for letter/symbol discrimination, and fine-grained tuning for word/pseudoword discrimination. 10-year-old typical readers (n=24) and children with dyslexia (n=14) were tested with electroencephalography (EEG) and fast periodic visual stimulation (FPVS), viewing streams of stimuli at a relatively fast rate (6Hz) for 40 seconds with deviant categories every 5 items (at 6Hz/5=1.2Hz). Deviant words or pseudowords among pseudo-font strings elicited clear coarse ocicpito-temporal discrimination responses significantly larger over the left than the right hemisphere (LH), numerically larger in typical readers. Unlike in adults, these responses were unaffected by lexicality. Deviant regular or irregular words among matched pseudowords generated a finer-grained word-selective response only over the LH. While irregular words elicited similar brain responses in both groups, regular words were not discriminated from pseudowords in children with dyslexia. These results demonstrate the sensitivity of FPVS-EEG to implicitly detect lexical neural responses in 10 years old children within a few minutes, as well as atypical lexical processing in children with dyslexia.

neuroscience↗

bioRxiv2024

Word-selective EEG/MEG responses in the English language obtained with Fast Periodic Visual Stimulation (FPVS)

Fast periodic visual stimulation (FPVS) allows the recording of objective brain responses of human word discrimination (i.e., reproducible word-category-selective responses) with a high signal-to-noise ratio. This approach has been successfully employed over the last decade in a number of scalp electroencephalography (EEG) studies. Three important advances were achieved in this study: (1) robust measures of written word-selective responses with this approach have not been reported in English; (2) responses have only been reported in EEG but not with MEG, and (3) without source localization. Thus, we presented English words periodically (2 Hz) among different types of letter strings (10Hz; consonant strings, non-words, pseudowords) whilst recording simultaneous EEG and MEG in 25 participants who performed a simple non-linguistic color detection task. Data were analyzed in sensor and in source space (L2-minimum-norm estimation, MNE). With only 4 minutes of stimulation we observed a robust word discrimination response in each condition including, importantly, even when words were embedded in word-like pseudowords. This response was larger in nonwords and largest in consonant strings. We observed left-lateralized responses in all conditions in the majority of our participants. Cluster-based permutation tests revealed that these responses were left-lateralized in sensor as well as in source space, with peaks in left posterior regions. Our results demonstrate that the FPVS paradigm can elicit robust English word-discrimination responses in EEG and MEG within only a few minutes of recording time. Together with source estimation, this can provide novel insights into the neural basis of visual word recognition in healthy and clinical populations.

neuroscience↗

bioRxiv2024

Automatic extraction of meaning from visual number symbols detected by frequency-tagged EEG in children.

Symbolic number representation and manipulation is key for successful mathematical learning. However, the mechanism by which at some point in development number symbols (i.e., 1, 2, 3, etc.) begin to automatically elicit useful meaning remains unresolved. Previous evidence highlighted that it is not possible to ignore the numerical magnitude when looking at number symbols, at least for adults. However, the neural mechanism behind the progressive automatization of symbol processing remains largely unknown, namely because these kinds of cognitive processes are difficult to isolate due to the general cognitive skills involved in any explicit task design. We thus developed an experimental paradigm specifically targeting the neural correlates of implicit magnitude representations by frequency-tagging magnitude changes within a visual stream of digits. Automatic magnitude processing was assessed by presenting a stream of number symbols with a frequency-tagged change of magnitude allowing to identify automatic categorization of the symbols by their magnitude in (pre)school-aged children. Stimuli were displayed with a sinusoidal contrast modulation at the frequency of 10 Hz and Steady-State Visual Evoked Potentials were recorded. These electrophysiological measurements showed a neural synchronization at the harmonics of the frequency of the magnitude changes recorded on electrodes encompassing bilateral occipitoparietal regions. The current findings indicate that magnitude is a salient semantic feature of the number symbols, which is deeply associated to digits in long-term memory across development. Significance StatementAcquiring strong semantic representations of numbers is crucial for future math achievement. However, the learning stage where magnitude information becomes automatically elicited by number symbols (i.e., Arabic digits from 1 to 9) remains unknown, namely due to the difficulty to measure unintentional automatic processing of magnitudes. We used a new experimental paradigm especially targeting the neural mechanisms involved in the automatic processing of magnitude information conveyed by number symbols. Frequency-tagged electrophysiological responses have the advantage to provide large amounts of reliable data with a high signal-to-noise ratio in a minimal amount of time. The current study is the first to take advantage of this in developmental populations to understand early automatic magnitude representations in childrens numeracy development. The electrophysiological responses demonstrate that the magnitude information is already automatically accessed from number symbols in children at the end of preschool, highlighting the importance of the first years of life for building automatized magnitude processing skills.

neuroscience↗

bioRxiv2023

Identifying conceptual neural responses to symbolic numerals

Neural processing of numerical concepts may be measured in humans automatically, without a related numerical task. However, the extent to which neural responses to symbolic numbers are due to physical stimulus confounds independently of conceptual representations remains unknown. Here, we targeted conceptual responses to parity (even vs. odd), using an electroencephalographic (EEG) frequency-tagging approach with a symmetry/asymmetry paradigm. Fifty second sequences of Arabic numerals (2-9) were presented at 7.5 Hz; odd and even numbers were alternated, so that differential responses to parity would be captured at 3.75 Hz (7.5 Hz/2). Parity responses were probed with four different stimulus sets, increasing in intra-numeral stimulus variability. Moreover, two control conditions were tested for each stimulus set, comprised of non-conceptual numeral alternations (strong control, for small inter-group physical differences: 2,3,6,7 vs. 4,5,8 and 9; weak control, for large physical differences: 2,4,5,7 vs. 3,6,8,9). Significant asymmetrical responses at 3.75 Hz were found over the occipitotemporal cortex to all conditions, thus even for arbitrary numeral groups. The weak control condition elicited the largest response in the stimulus set with the lowest level of variability (1 font). Only in the stimulus set with the highest level of variability (20 hand-drawn, colored exemplars per numeral) did the response to parity surpass both control conditions. These findings show that physical differences across small sets of Arabic numerals can strongly influence, and even account for, automatic brain responses. However, carefully designed control conditions and highly variable stimulus sets may be used towards identifying truly conceptual neural responses.

neuroscience↗

bioRxiv2023

Linguistic and attentional factors -not statistical regularities- contribute to word-selective neural responses with FPVS-oddball paradigms

In recent years, a fast periodic oddball-like paradigm has proved to be highly sensitive to measure category-selective visual word representation and characterize its development and neural basis. In this approach, deviant words are inserted in rapid streams of base stimuli every nth occurrence (e.g., Lochy et al., 2015). To understand the nature of word-selective representation and improve its measurement, we tested 22 adults with EEG, assessing the impact of discrimination coarseness (deviant words among nonwords or pseudowords), the relative frequency of item repetition (set size or item repetition controlled for deviant vs. base stimuli), and the nature of the orthogonal attentional task (focused or deployed spatial attention). In all stimulation sequences, base stimuli were presented at 10 Hz, with words inserted every 5 stimuli generating word-selective responses in the EEG spectra at 2 Hz and harmonics. Word-selective occipito-temporal responses were robust at the individual level, left-lateralized and sensitive to wordlikeness of base stimuli, being stronger in the coarser categorical contrast (among nonwords). Amplitudes were not affected by item repetition, showing that implicit statistical learning about a relative token frequency difference for deviant stimuli does not contribute to the word-selective neural activity, at least with relatively large stimulus set sizes (n=30). Finally, the broad attentional deployment task produced stronger responses than a focused task, an important finding for future studies in the field. Taken together, these results confirm the linguistic nature of word-selective responses, strengthen the validity and increase the sensitivity of the FPVS-EEG oddball paradigm to measure visual word recognition. HighlightsO_LIWord-selective responses measured in fast periodic visual stimulation with EEG are linguistic in nature C_LIO_LIWord-selective responses reflect prelexical or lexical processes depending on the contrast (words in nonwords or pseudowords respectively) C_LIO_LIUsing sufficiently large sets (30 items) prevents the extraction of statistical regularities and hence, statistical learning C_LIO_LIUsing an orthogonal task involving broad, rather than focused, spatial attention increases amplitude of the neural responses C_LIO_LISensitivity of the paradigm to detect significant responses at the individual level is very good (95% for prelexical and about 80% for lexical word responses) C_LI

neuroscience↗

bioRxiv2021

A neural signature of automatic lexical access in bilinguals

Bilingualism is often associated with beneficial effects on cognitive control and top-down processes. The present study aimed at bypassing these processes to assess automatic visual word recognition in bilinguals. Using fast periodic visual stimulation, we recorded frequency-tagged word-selective EEG responses in French monolinguals and late bilinguals (German native, French as second language). Words were presented centrally within rapid (10 Hz) sequences of letter strings varying in word-likeness, i.e., consonant strings, non-words, pseudo-words, while participants performed an orthogonal task. Automatic word-selective brain responses in the occipito-temporal cortex arose almost exclusively for the languages mastered by participants: two in bilinguals vs. one in monolinguals. Importantly, the amplitude of bilinguals responses to words within consonant strings were unaffected by the native vs. late-learnt status of the language. Furthermore, for all and only known languages, word-selective responses were reduced by embedding them in pseudo-words relative to non-words, both derived from the same language as the words. This word-likeness effect highlights the lexical nature of the recorded brain visual responses. A cross-language word-likeness effect was observed only in bilinguals and only with pseudo-words derived from the native language, indicating an experience-based tuning to language. Taken together these findings indicate that the amount of exposure to a language determines the engagement of neural resources devoted to word processing in the occipito-temporal visual cortex. We conclude that automatic lexical coding occurs at early visual processing in bilinguals and monolinguals alike, and that language exposure determines the competition strength of a language. Significance StatementBilingualism and its possible impact on automatic processes have rarely attracted interest, contrary to bilingualism and its mutual relation with the executive functions. We assessed automatic visual word recognition in bi- and monolingual individuals while purposively bypassing executive functions. Visual brain potentials frequency tagged to words, that were flashed in rapid trains of strings with varying word-likeness degrees, exposed the automatic encoding of word-form as well as language identity at early stages of visual word processing within the occipito-temporal visual cortex. The mechanisms involved in both encoding processes reflect experience-based activity as the one characterizing tight-tuned neurons in the VWFA. Our findings provide a novel framework to understand the mechanisms behind the incredible efficiency of bilinguals in handling multiple languages.

neuroscience↗

bioRxiv2019

Spontaneous and automatic processing of magnitude and parity information of Arabic digits: A frequency-tagging EEG study.

Arabic digits (1-9) are everywhere in our daily lives. These symbols convey various semantic information, and numerate adults can easily extract from them several numerical features such as magnitude and parity. Nonetheless, since most studies used active processing tasks to assess these properties, it remains unclear whether and to what degree the access to magnitude and especially to parity is automatic. Here we investigated with EEG whether spontaneous processing of magnitude or parity can be recorded in a frequency-tagging approach, in which participants are passively stimulated by fast visual sequences of Arabic digits. We assessed automatic magnitude processing by presenting a stream of frequent small digit numbers mixed with deviant large digits (and the reverse) with a sinusoidal contrast modulation at the frequency of 10 Hz. We used the same paradigm to investigate numerical parity processing, contrasting odd digits to even digits. We found significant brain responses at the frequency of the fluctuating change and its harmonics, recorded on electrodes encompassing right occipitoparietal regions, in both conditions. Our findings indicate that both magnitude and parity are spontaneously and unintentionally extracted from Arabic digits, which supports that they are salient semantic features deeply associated to digit symbols in long-term memory.

neuroscience↗

bioRxiv2019

The neural signature of numerosity: Separating numerical and continuous magnitude extraction in early visual cortex with frequency-tagged EEG

The ability to handle approximate quantities, or number sense, has been recurrently linked to mathematical skills, though the nature of the mechanism allowing to extract numerical information (i.e., numerosity) from environmental stimuli is still debated. A set of objects is indeed not only characterized by its numerosity but also by other features, such as the summed area occupied by the elements, which often covary with numerosity. These intrinsic relations between numerosity and non-numerical magnitudes led some authors to argue that numerosity is not independently processed but extracted through a weighting of continuous magnitudes. This view cannot be properly tested through classic behavioral and neuroimaging approaches due to these intrinsic correlations. The current study used a frequency-tagging EEG approach to separately measure responses to numerosity as well as to continuous magnitudes. We recorded occipital responses to numerosity, total area, and convex hull changes but not to density and dot size. We additionally applied a model predicting primary visual cortex responses to the set of stimuli. The model output was closely aligned with our electrophysiological data, since it predicted discrimination only for numerosity, total area, and convex hull. Our findings thus demonstrate that numerosity can be independently processed at an early stage in the visual cortex, even when completely isolated from other magnitude changes. The similar implicit discrimination for numerosity as for some continuous magnitudes, which correspond to basic visual percepts, shows that both can be extracted independently, hence substantiating the nature of numerosity as a primary feature of the visual scene.

neuroscience↗

bioRxiv2018

Teaching methods shape neural tuning to visual words in beginning readers

The impact of global vs. phonics teaching methods for reading on the emergence of left hemisphere neural specialization for word recognition is unknown in children. We tested 42 first graders behaviorally and with electroencephalography with Fast Periodic Visual Stimulation to measure selective neural responses to letter strings. Letter strings were inserted periodically (1/5) in pseudofonts in 40sec sequences displayed at 6Hz and were either words globally taught at school, eliciting visual whole-word form recognition (global method), or control words/pseudowords eliciting grapheme-phoneme mappings (phonic method). Selective responses (F/5, 1.2Hz) were left lateralized for control stimuli but bilateral for globally taught words, especially in poor readers. These results show that global method instruction induces activation in the right hemisphere, involved in holistic processing and visual object recognition, rather than in the specialized left hemisphere for reading. Poor readers, given their difficulties in automatizing grapheme-phoneme mappings, mostly rely on this alternative inadequate strategy.

neuroscience↗