Cortical Structure in Pre-Readers at Cognitive Risk for Dyslexia: Baseline Differences and Response to Intervention.

Early childhood is a critical period for structural brain development as well as an important window for the identification and remediation of reading difficulties. Recent research supports the implementation of interventions in at-risk populations as early as kindergarten or first grade, yet the neurocognitive mechanisms following such interventions remain understudied. To address this, we investigated cortical structure by means of anatomical MRI before and after a 12-week tablet-based intervention in: (1) at-risk children receiving phonics-based training (n = 29; n = 16 complete pre-post datasets), (2) at-risk children engaging with AC training (n = 24; n = 15 complete pre-post datasets) and (3) typically developing children (n = 25; n = 14 complete pre-post datasets) receiving no intervention. At baseline, we found higher surface area of the right supramarginal gyrus in at-risk children compared to typically developing peers, extending previous evidence that early anatomical differences exist in children who may later develop dyslexia. Our longitudinal analysis revealed significant post-intervention thickening of the left supramarginal gyrus, present exclusively in the intervention group but not the active control or typical control groups. Altogether, this study contributes new knowledge to our understanding of the brain morphology associated with cognitive risk for dyslexia and response to early intervention, which in turn raises new questions on how early anatomy and plasticity may shape the trajectories of long-term literacy development.

Myelin plasticity during early literacy training in at-risk pre-readers.

A growing body of neuroimaging evidence shows that white matter can change as a result of experience and structured learning. Although the majority of previous work has used diffusion MRI to characterize such changes in white matter, diffusion metrics offer limited biological specificity about which microstructural features may be driving white matter plasticity. Recent advances in myelin-specific MRI techniques offer a promising opportunity to assess the specific contribution of myelin in learning-related plasticity. Here we describe the application of such an approach to examine structural plasticity during an early intervention in preliterate children at risk for dyslexia. To this end, myelin water imaging data were collected before and after a 12-week period in (1) at-risk children following early literacy training (n = 13-24), (2) at-risk children engaging with other non-literacy games (n = 10-17) and (3) children without a risk receiving no training (n = 11-22). Before the training, regional risk-related differences were identified, showing higher myelin water fraction (MWF) in right dorsal white matter in at-risk children compared to the typical control group. Concerning intervention-specific effects, our results revealed an increase across left-hemispheric and right ventral MWF over the course of training in the at-risk children receiving early literacy training, but not in the at-risk active control group or the no-risk typical control group. Overall, our results provide support for the use of myelin water imaging as a sensitive tool to investigate white matter and offer a first indication of myelin plasticity in young children at the onset of literacy acquisition.

Pulsatile modulation greatly enhances neural synchronization at syllable rate in children.

Neural processing of the speech envelope is of crucial importance for speech perception and comprehension. This envelope processing is often investigated by measuring neural synchronization to sinusoidal amplitude-modulated stimuli at different modulation frequencies. However, it has been argued that these stimuli lack ecological validity. Pulsatile amplitude-modulated stimuli, on the other hand, are suggested to be more ecologically valid and efficient, and have increased potential to uncover the neural mechanisms behind some developmental disorders such a dyslexia. Nonetheless, pulsatile stimuli have not yet been investigated in pre-reading and beginning reading children, which is a crucial age for developmental reading research. We performed a longitudinal study to examine the potential of pulsatile stimuli in this age range. Fifty-two typically reading children were tested at three time points from the middle of their last year of kindergarten (5 years old) to the end of first grade (7 years old). Using electroencephalography, we measured neural synchronization to syllable rate and phoneme rate sinusoidal and pulsatile amplitude-modulated stimuli. Our results revealed that the pulsatile stimuli significantly enhance neural synchronization at syllable rate, compared to the sinusoidal stimuli. Additionally, the pulsatile stimuli at syllable rate elicited a different hemispheric specialization, more closely resembling natural speech envelope tracking. We postulate that using the pulsatile stimuli greatly increases EEG data acquisition efficiency compared to the common sinusoidal amplitude-modulated stimuli in research in younger children and in developmental reading research.

Neural synchronization and intervention in pre-readers who later on develop dyslexia.

A growing number of studies has investigated temporal processing deficits in dyslexia. These studies largely focus on neural synchronization to speech. However, the importance of rise times for neural synchronization is often overlooked. Furthermore, targeted interventions, phonics-based and auditory, are being developed, but little is known about their impact. The current study investigated the impact of a 12-week tablet-based intervention. Children at risk for dyslexia received phonics-based training, either with (n = 31) or without (n = 31) auditory training, or engaged in active control training (n = 29). Additionally, neural synchronization and processing of rise times was longitudinally investigated in children with dyslexia (n = 26) and typical readers (n = 52) from pre-reading (5 years) to beginning reading age (7 years). The three time points in the longitudinal study correspond to intervention pre-test, post-test and consolidation, approximately 1 year after completing the intervention. At each time point neural synchronization was measured to sinusoidal stimuli and pulsatile stimuli with shortened rise times at syllable (4 Hz) and phoneme rates (20 Hz). Our results revealed no impact on neural synchronization at syllable and phoneme rate of the phonics-based and auditory training. However, we did reveal atypical hemispheric specialization at both syllable and phoneme rates in children with dyslexia. This was detected even before the onset of reading acquisition, pointing towards a possible causal rather than consequential mechanism in dyslexia. This study contributes to our understanding of the temporal processing deficits underlying the development of dyslexia, but also shows that the development of targeted interventions is still a work in progress.

Speech perception deficits and the effect of envelope-enhanced story listening combined with phonics intervention in pre-readers at risk for dyslexia.

Developmental dyslexia is considered to be most effectively addressed with preventive phonics-based interventions, including grapheme-phoneme coupling and blending exercises. These intervention types require intact speech perception abilities, given their large focus on exercises with auditorily presented phonemes. Yet some children with (a risk for) dyslexia experience problems in this domain due to a poorer sensitivity to rise times, i.e., rhythmic acoustic cues present in the speech envelope. As a result, the often subtle speech perception problems could potentially constrain an optimal response to phonics-based interventions in at-risk children. The current study therefore aimed (1) to extend existing research by examining the presence of potential speech perception deficits in pre-readers at cognitive risk for dyslexia when compared to typically developing peers and (2) to explore the added value of a preventive auditory intervention for at-risk pre-readers, targeting rise time sensitivity, on speech perception and other reading-related skills. To obtain the first research objective, we longitudinally compared speech-in-noise perception between 28 5-year-old pre-readers with and 30 peers without a cognitive risk for dyslexia during the second half of the third year of kindergarten. The second research objective was addressed by exploring growth in speech perception and other reading-related skills in an independent sample of 62 at-risk 5-year-old pre-readers who all combined a 12-week preventive phonics-based intervention (GraphoGame-Flemish) with an auditory story listening intervention. In half of the sample, story recordings contained artificially enhanced rise times (GG-FL_EE group, n = 31), while in the other half, stories remained unprocessed (GG-FL_NE group, n = 31; Clinical Trial Number S60962-https://www.uzleuven.be/nl/clinical-trial-center). Results revealed a slower speech-in-noise perception growth in the at-risk compared to the non-at-risk group, due to an emerged deficit at the end of kindergarten. Concerning the auditory intervention effects, both intervention groups showed equal growth in speech-in-noise perception and other reading-related skills, suggesting no boost of envelope-enhanced story listening on top of the effect of combining GraphoGame-Flemish with listening to unprocessed stories. These findings thus provide evidence for a link between speech perception problems and dyslexia, yet do not support the potential of the auditory intervention in its current form.

Myelin water fraction in relation to fractional anisotropy and reading in 10-year-old children.

Diffusion-weighted imaging studies have repeatedly shown that white matter correlates with reading throughout development. However, the neurobiological interpretation of this relationship is constrained by the limited microstructural specificity of diffusion imaging. A critical component of white matter microstructure is myelin, which can be investigated noninvasively using MRI. Here, we examined the link between myelin water fraction (MWF) and reading ability in 10-year-old children (n = 69). To better understand this relationship, we additionally investigated how these two variables relate to fractional anisotropy (FA; a common index of diffusion-weighted imaging). Our analysis revealed that lower MWF coheres with better reading scores in left-hemispheric tracts relevant for reading. While we replicated previous reports on a positive relationship between FA and MWF, we did not find any evidence for an association between reading and FA. Together, these findings contrast previous research suggesting that poor reading abilities might be rooted in lower myelination and emphasize the need for further longitudinal research to understand how this relationship evolves throughout reading development. Altogether, this study contributes important insights into the role of myelin-related processes in the relationship between reading and white matter structure.

Feasibility, Enjoyment, and Language Comprehension Impact of a Tablet- and GameFlow-Based Story-Listening Game for Kindergarteners: Methodological and Mixed Methods Study.

BACKGROUND: Enjoyment plays a key role in the success and feasibility of serious gaming interventions. Unenjoyable games will not be played, and in the case of serious gaming, learning will not occur. Therefore, a so-called GameFlow model has been developed, which intends to guide (serious) game developers in the process of creating and evaluating enjoyment in digital (serious) games. Regarding language learning, a variety of serious games targeting specific language components exist in the market, albeit often without available assessments of enjoyment or feasibility. OBJECTIVE: This study evaluates the enjoyment and feasibility of a tablet-based, serious story-listening game for kindergarteners, developed based on the principles of the GameFlow model. This study also preliminarily explores the possibility of using the game to foster language comprehension. METHODS: Within the framework of a broader preventive reading intervention, 91 kindergarteners aged 5 years with a cognitive risk for dyslexia were asked to play the story game for 12 weeks, 6 days per week, either combined with a tablet-based phonics intervention or control games. The story game involved listening to and rating stories and responding to content-related questions. Game enjoyment was assessed through postintervention questionnaires, a GameFlow-based evaluation, and in-game story rating data. Feasibility was determined based on in-game general question response accuracy (QRA), reflecting the difficulty level, attrition rate, and final game exposure and training duration. Moreover, to investigate whether game enjoyment and difficulty influenced feasibility, final game exposure and training duration were predicted based on the in-game initial story ratings and initial QRA. Possible growth in language comprehension was explored by analyzing in-game QRA as a function of the game phase and baseline language skills. RESULTS: Eventually, data from 82 participants were analyzed. The questionnaire and in-game data suggested an overall enjoyable game experience. However, the GameFlow-based evaluation implied room for game design improvement. The general QRA confirmed a well-adapted level of difficulty for the target sample. Moreover, despite the overall attrition rate of 39% (32/82), 90% (74/82) of the participants still completed 80% of the game, albeit with a large variation in training days. Higher initial QRA significantly increased game exposure (ß=.35; P<.001), and lower initial story ratings significantly slackened the training duration (ß=-0.16; P=.003). In-game QRA was positively predicted by game phase (ß=1.44; P=.004), baseline listening comprehension (ß=1.56; P=.002), and vocabulary (ß=.16; P=.01), with larger QRA growth over game phases in children with lower baseline listening comprehension skills (ß=-0.08; P=.04). CONCLUSIONS: Generally, the story game seemed enjoyable and feasible. However, the GameFlow model evaluation and predictive relationships imply room for further game design improvements. Furthermore, our results cautiously suggest the potential of the game to foster language comprehension; however, future randomized controlled trials should further elucidate the impact on language comprehension.

Investigating the impact of early literacy training on white matter structure in prereaders at risk for dyslexia.

Recent prereading evidence demonstrates that white matter alterations are associated with dyslexia even before the onset of reading instruction. At the same time, remediation of reading difficulties is suggested to be most effective when provided as early as kindergarten, yet evidence is currently lacking on the early neuroanatomical changes associated with such preventive interventions. To address this open question, we investigated white matter changes following early literacy intervention in Dutch-speaking prereaders (aged 5-6 years) with an increased cognitive risk for developing dyslexia. Diffusion-weighted images were acquired before and after a 12-week digital intervention in three groups: (i) at-risk children receiving phonics-based training (n = 31); (ii) at-risk children engaging with active control training (n = 25); and (iii) typically developing children (n = 27) receiving no intervention. Following automated quantification of white matter tracts relevant for reading, we first examined baseline differences between at-risk and typically developing children, revealing bilateral dorsal and ventral differences. Longitudinal analyses showed that white matter properties changed within the course of the training; however, the absence of intervention-specific results suggests that these changes rather reflect developmental effects. This study contributes important first insights on the neurocognitive mechanisms of intervention that precedes formal reading onset.

Ahead of maturation: Enhanced speech envelope training boosts rise time discrimination in pre-readers at cognitive risk for dyslexia.

Dyslexia has frequently been related to atypical auditory temporal processing and speech perception. Results of studies emphasizing speech onset cues and reinforcing the temporal structure of the speech envelope, that is, envelope enhancement (EE), demonstrated reduced speech perception deficits in individuals with dyslexia. The use of this strategy as auditory intervention might thus reduce some of the deficits related to dyslexia. Importantly, reading-skill interventions are most effective when they are provided during kindergarten and first grade. Hence, we provided a tablet-based 12-week auditory and phonics-based intervention to pre-readers at cognitive risk for dyslexia and investigated the effect on auditory temporal processing with a rise time discrimination (RTD) task. Ninety-one pre-readers at cognitive risk for dyslexia (aged 5-6) were assigned to two groups receiving a phonics-based intervention and playing a story listening game either with (n = 31) or without (n = 31) EE or a third group playing control games and listening to non-enhanced stories (n = 29). RTD was measured directly before, directly after and 1 year after the intervention. While the groups listening to non-enhanced stories mainly improved after the intervention during first grade, the group listening to enhanced stories improved during the intervention in kindergarten and subsequently remained stable during first grade. Hence, an EE intervention improves auditory processing skills important for the development of phonological skills. This occurred before the onset of reading instruction, preceding the maturational improvement of these skills, hence potentially giving at risk children a head start when learning to read. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=e0BfT4dGXNA.

Digital Game-Based Phonics Instruction Promotes Print Knowledge in Pre-Readers at Cognitive Risk for Dyslexia.

Dyslexia is targeted most effectively when (1) interventions are provided preventively, before the onset of reading instruction, and (2) remediation programs combine letter-sound training with phoneme blending. Given the growing potential of technology in educational contexts, there has been a considerable increase of letter-sound trainings embedded in digital serious games. One such intervention is GraphoGame. Yet, current evidence on the preventive impact of GraphoGame is limited by the lack of adaptation of the original learning content to the skills of pre-readers, short training duration, and a restricted focus on explicitly trained skills. Therefore, the current study aims at investigating the impact of a preventive, and pre-reading adapted GraphoGame training (i.e., GraphoGame-Flemish, GG-FL) on explicitly trained skills and non-specifically trained phonological and language abilities. Following a large-scale screening (N = 1225), the current study included 88 pre-reading kindergarteners at cognitive risk for dyslexia who were assigned to three groups training either with GG-FL (n = 31), an active control game (n = 29), or no game (n = 28). Before and after the 12-week intervention, a variety of reading-related skills were assessed. Moreover, receptive letter knowledge and phonological awareness were measured every three weeks during the intervention period. Results revealed significantly larger improvements in the GG-FL group on explicitly trained skills, i.e., letter knowledge and word decoding, without finding transfer-effects to untrained phonological and language abilities. Our findings imply a GG-FL-driven head start on early literacy skills in at-risk children. A follow-up study should uncover the long-term impact and the ability of GG-FL to prevent actual reading failure.

Pre-literacy heterogeneity in Dutch-speaking kindergartners: latent profile analysis.

Research demonstrated that a dyslexia diagnosis is mainly given after the most effective time for intervention has passed, referred to as the dyslexia paradox. Although some pre-reading cognitive measures have been found to be strong predictors of early literacy acquisition, i.e., phonological awareness (PA), letter knowledge (LK), and rapid automatized naming (RAN), more insight in the variability of pre-reading profiles might be of great importance for early identification of children who have an elevated risk for developing dyslexia and to provide tailor-made interventions. To address this issue, this study used a latent profile analysis (LPA) to disentangle different pre-reading profiles in a sample of 1091 Dutch-speaking kindergartners. Four profiles emerged: high performers (16.50%), average performers (40.24%), below-average performers with average IQ (25.57%), and below-average performers with below-average IQ (17.69%). These results suggested two at-risk profiles diverging in IQ, which are presumably more likely to develop dyslexia later on. Although below-average profiles differed significantly in rapid naming and IQ, no clear evidence for the double-deficit theory was found in Dutch-speaking kindergartners. Educational level and reading history of the parents appeared to be predictive for children's classification membership. Our results point towards the heterogeneity that is already present in kindergartners and the possibility to identify at-risk profiles prior to reading instruction, which may be the foundation for earlier targeted interventions. However, more extended research is needed to determine the stability of these profiles across time and across different languages.

Sevoflurane impairs post-operative olfactory memory but preserves olfactory function.

BACKGROUND AND OBJECTIVE: The effect of anaesthesia on olfaction has not been systematically studied. Our aim is to compare the effects of general and regional anaesthesia on olfactory acuity and memory in the immediate post-operative period. METHODS: Sixty adult patients with the American Society of Anesthesiologists I and II status scheduled for elective minor surgery were included. Exclusion criteria were smoking, alcoholism, psychiatric disease and recent or past airway infection with resulting hyposmia. Patients were randomly allocated to one of three groups (in the analysis, n = 16 in each group): epidural anaesthesia (group E), general anaesthesia with propofol (group P) and general anaesthesia with sevoflurane (group S) of 40-120 min duration. The evening before surgery, at 0.5 and at 3 h post-operatively olfactory acuity and memory were tested, along with blood sampling to measure plasma melatonin and oxytocin levels. Olfactory acuity was tested with successive dilutions of n-butyl-alcohol, and olfactory memory (interpretation of odours) with the University of Pennsylvania Smell Identification Test. RESULTS: Patient characteristics did not differ between groups. Olfactory acuity was intact in all patients, before and after anaesthesia. Olfactory memory deteriorated in group S compared to groups P and E at both post-operative time-points. This was accompanied by a significant post-operative reduction of plasma melatonin levels in group S. Oxytocin levels remained constant in all groups. CONCLUSION: Our results manifest a specific effect of sevoflurane on olfactory memory, not observed with neuraxial or total intravenous anaesthesia. The misinterpretation of odours in the immediate post-operative period by sevoflurane could be mediated by the decreased levels of melatonin.

Benefits of salmon eating on traditional and novel vascular risk factors in young, non-obese healthy subjects.

AIM: The present clinical study tested the hypothesis that oil-rich fish consumption improves CHD risk factors. METHODS: Forty-eight (16 men) non-obese, healthy adults aged 20-55, consumed 125 g/day of salmon for a 4-week period followed by a 4-week period with no-fish (41 completers). Subjects were instructed to maintain dietary and physical activity patterns during the period of study. Blood pressure, anthropometric, body composition and dietary information with fasting blood samples to determine traditional and novel CHD risk markers and plasma fatty acids were obtained before and after each period. RESULTS: Compared to no-fish, eating salmon significantly decreased systolic, diastolic and mean arterial blood pressure by 4%, triglycerides by 15%, and LDL-cholesterol by 7%, and significantly increased HDL-cholesterol by 5% (P<0.05). The changes in blood pressure and lipids alone with salmon intake predict around a 25% reduction in CHD risk based on the PROCAM risk calculator. Plasma adiponectin demonstrated a trend towards improvement (8.39 micromol/L with salmon and 7.52 with no-fish; P=0.086) but no significant changes were found either in plasma leptin, glucose or insulin after salmon consumption. CONCLUSIONS: Daily consumption of salmon improves traditional risk predictors of CHD in non-obese subjects. Adiponectin may be involved but the impact on novel risk factors needs study in high-risk subjects.

Extracranial internal carotid artery Salmonella mycotic aneurysm complicated by occlusion of the internal carotid artery: depiction by color Doppler sonography, CT and DSA.

Mycotic aneurysms of the extracranial carotid artery are rare. Seventy-four cases have been described in the medical literature and only eight secondary to Salmonella infection. To our knowledge, color Doppler sonography, computed tomography (CT), and digital subtraction angiography (DSA) findings relating to the diagnosis and follow-up of extracranial internal carotid artery mycotic aneurysm complicated by occlusion have not previously been described in the literature. We present a report of color Doppler sonography, CT, and DSA findings of a mycotic aneurysm of the right extracranial internal carotid artery due to Salmonella associated with occlusion of the internal carotid artery, promptly diagnosed and followed up using these imaging modalities.