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Number processing abilities are important for academic and personal development. The course of initial specialization of ventral occipito-temporal cortex (vOTC) sensitivity to visual number processing is crucial for the acquisition of numeric and arithmetic skills. We examined the visual N1, the electrophysiological correlate of vOTC activation across five time points in kindergarten (T1, mean age 6.60 years), middle and end of first grade (T2, 7.38 years; T3, 7.68 years), second grade (T4, 8.28 years), and fifth grade (T5, 11.40 years). A combination of cross-sectional and longitudinal EEG data of a total of 62 children (35 female) at varying familial risk for dyslexia were available to form groups of 23, 22, 27, 27, and 42 participants for each of the five time points. The children performed a target detection task which included visual presentation of single digits (DIG), false fonts (FF), and letters (LET) to derive measures for coarse (DIG vs. FF) and fine (DIG vs. LET) digit sensitive processing across development. The N1 amplitude analyses indicated coarse and fine sensitivity characterized by a stronger N1 to digits than false fonts across all five time points, and stronger N1 to digits than letters at all but the second (T2) time point. In addition, lower arithmetic skills were associated with stronger coarse N1 digit sensitivity over the left hemisphere in second grade (T4), possibly reflecting allocation of more attentional resources or stronger reliance on the verbal system in children with poorer arithmetic skills. To summarize, our results show persistent visual N1 sensitivity to digits that is already present early on in pre-school and remains stable until fifth grade. This pattern of digit sensitivity development clearly differs from the relatively sharp rise and fall of the visual N1 sensitivity to words or letters between kindergarten and middle of elementary school and suggests unique developmental trajectories for visual processing of written characters that are relevant to numeracy and literacy., Competing Interests: SW has received in the last 5 years royalties from Thieme Hogrefe, Kohlhammer, Springer, Beltz. Her research work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, and Erika Schwarz Fonds. Outside professional activities and interests are declared under the link of the University of Zurich www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fraga-González, Di Pietro, Pleisch, Walitza, Brandeis, Karipidis and Brem.)

We performed an EEG graph analysis on data from 31 typical readers (22.27 ± 2.53 y/o) and 24 dyslexics (22.99 ± 2.29 y/o), recorded while they were engaged in an audiovisual task and during resting-state. The task simulates reading acquisition as participants learned new letter-sound mappings via feedback. EEG data was filtered for the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) bands. We computed the Phase Lag Index (PLI) to provide an estimate of the functional connectivity between all pairs of electrodes per band. Then, networks were constructed using a Minimum Spanning Tree (MST), a unique sub-graph connecting all nodes (electrodes) without loops, aimed at minimizing bias in between groups and conditions comparisons. Both groups showed a comparable accuracy increase during task blocks, indicating that they correctly learned the new associations. The EEG results revealed lower task-specific theta connectivity, and lower theta degree correlation over both rest and task recordings, indicating less network integration in dyslexics compared to typical readers. This pattern suggests a role of theta oscillations in dyslexia and may reflect differences in task engagement between the groups, although robust correlations between MST metrics and performance indices were lacking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fraga-González, Smit, Van der Molen, Tijms, Stam, de Geus and Van der Molen.)

Reading acquisition in alphabetic languages starts with learning the associations between speech sounds and letters. This learning process is related to crucial developmental changes of brain regions that serve visual, auditory, multisensory integration, and higher cognitive processes. Here, we studied the development of audiovisual processing and integration of letter-speech sound pairs with an audiovisual target detection functional MRI paradigm. Using a longitudinal approach, we tested children with varying reading outcomes before the start of reading acquisition (T1, 6.5 yo), in first grade (T2, 7.5 yo), and in second grade (T3, 8.5 yo). Early audiovisual integration effects were characterized by higher activation for incongruent than congruent letter-speech sound pairs in the inferior frontal gyrus and ventral occipitotemporal cortex. Audiovisual processing in the left superior temporal gyrus significantly increased from the prereading (T1) to early reading stages (T2, T3). Region of interest analyses revealed that activation in left superior temporal gyrus (STG), inferior frontal gyrus and ventral occipitotemporal cortex increased in children with typical reading fluency skills, while poor readers did not show the same development in these regions. The incongruency effect bilaterally in parts of the STG and insular cortex at T1 was significantly associated with reading fluency skills at T3. These findings provide new insights into the development of the brain circuitry involved in audiovisual processing of letters, the building blocks of words, and reveal early markers of audiovisual integration that may be predictive of reading outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Karipidis, Pleisch, Di Pietro, Fraga-González and Brem.)

Learning print-speech sound correspondences is a crucial step at the beginning of reading acquisition and often impaired in children with developmental dyslexia. Despite increasing insight into audiovisual language processing, it remains largely unclear how integration of print and speech develops at the neural level during initial learning in the first years of schooling. To investigate this development, 32 healthy, German-speaking children at varying risk for developmental dyslexia (17 typical readers and 15 poor readers) participated in a longitudinal study including behavioral and fMRI measurements in first (T1) and second (T2) grade. We used an implicit audiovisual (AV) non-word target detection task aimed at characterizing differential activation to congruent (AVc) and incongruent (AVi) audiovisual non-word pairs. While children's brain activation did not differ between AVc and AVi pairs in first grade, an incongruency effect (AVi > AVc) emerged in bilateral inferior temporal and superior frontal gyri in second grade. Of note, pseudoword reading performance improvements with time were associated with the development of the congruency effect (AVc > AVi) in the left posterior superior temporal gyrus (STG) from first to second grade. Finally, functional connectivity analyses indicated divergent development and reading expertise dependent coupling from the left occipito-temporal and superior temporal cortex to regions of the default mode (precuneus) and fronto-temporal language networks. Our results suggest that audiovisual integration areas as well as their functional coupling to other language areas and areas of the default mode network show a different development in poor vs. typical readers at varying familial risk for dyslexia., (Copyright © 2020 Wang, Karipidis, Pleisch, Fraga-González and Brem.)

Developmental dyslexia may involve deficits in functional connectivity across widespread brain networks that enable fluent reading. We investigated the large-scale organization of electroencephalography (EEG) functional networks at rest in 28 dyslexics and 36 typically reading adults. For each frequency band (delta, theta alpha and beta), we assessed functional connectivity strength with the phase lag index (PLI). Network topology was examined using minimum spanning tree (MST) graphs derived from the functional connectivity matrices. We found significant group differences in the alpha band (8-13 Hz). The graph analysis indicated more interconnected nodes, in dyslexics compared to typical readers. The graph metrics were significantly correlated with age in dyslexics but not in typical readers, which may indicate more heterogeneity in maturation of brain networks in dyslexics. The present findings support the involvement of alpha oscillations in higher cognition and the sensitivity of graph metrics to characterize functional networks in adult dyslexia. Finally, the current results extend our previous findings on children.

Atypical structural properties of the brain's white matter bundles have been associated with failing reading acquisition in developmental dyslexia. Because these white matter properties may show dynamic changes with age and orthographic depth, we examined fractional anisotropy (FA) along 16 white matter tracts in 8- to 11-year-old dyslexic (DR) and typically reading (TR) children learning to read in a fairly transparent orthography (Dutch). Our results showed higher FA values in the bilateral anterior thalamic radiations of DRs and FA values of the left thalamic radiation scaled with behavioral reading-related scores. Furthermore, DRs tended to have atypical FA values in the bilateral arcuate fasciculi. Children's age additionally predicted FA values along the tracts. Together, our findings suggest differential contributions of cortical and thalamo-cortical pathways to the developing reading network in dyslexic and typical readers, possibly indicating prolonged letter-by-letter reading or increased attentional and/or working memory demands in dyslexic children during reading.

A failure to build solid letter-speech sound associations may contribute to reading impairments in developmental dyslexia. Whether this reduced neural integration of letters and speech sounds changes over time within individual children and how this relates to behavioral gains in reading skills remains unknown. In this research, we examined changes in event-related potential (ERP) measures of letter-speech sound integration over a 6-month period during which 9-year-old dyslexic readers (n = 17) followed a training in letter-speech sound coupling next to their regular reading curriculum. We presented the Dutch spoken vowels /a/ and /o/ as standard and deviant stimuli in one auditory and two audiovisual oddball conditions. In one audiovisual condition (AV0), the letter "a" was presented simultaneously with the vowels, while in the other (AV200) it was preceding vowel onset for 200 ms. Prior to the training (T1), dyslexic readers showed the expected pattern of typical auditory mismatch responses, together with the absence of letter-speech sound effects in a late negativity (LN) window. After the training (T2), our results showed earlier (and enhanced) crossmodal effects in the LN window. Most interestingly, earlier LN latency at T2 was significantly related to higher behavioral accuracy in letter-speech sound coupling. On a more general level, the timing of the earlier mismatch negativity (MMN) in the simultaneous condition (AV0) measured at T1, significantly related to reading fluency at both T1 and T2 as well as with reading gains. Our findings suggest that the reduced neural integration of letters and speech sounds in dyslexic children may show moderate improvement with reading instruction and training and that behavioral improvements relate especially to individual differences in the timing of this neural integration.

The specialization of visual brain areas for fast processing of printed words plays an important role in the acquisition of reading skills. Dysregulation of these areas may be among the deficits underlying developmental dyslexia. The present study examines the specificity of word activation in dyslexic children in 3rd grade by comparing early components of brain potentials elicited by visually presented words vs. strings of meaningless letter-like symbols. Results showed a more pronounced N1 component for words compared to symbols for both groups. The dyslexic group revealed larger left-lateralized, word-specific N1 responses than the typically reading group. Furthermore, positive correlations between N1 amplitudes and reading fluency were found in the dyslexic group. Our results support the notion of N1 as a sensitive index of visual word processing involved in reading fluency.