Predictors of developmental dyslexia in European orthographies with varying complexity.

BACKGROUND: The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. METHODS: General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). RESULTS: Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. CONCLUSIONS: Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

Discriminatory Brain Processes of Native and Foreign Language in Children with and without Reading Difficulties.

The association between impaired speech perception and reading difficulty has been well established in native language processing, as can be observed from brain activity. However, there has been scarce investigation of whether this association extends to brain activity during foreign language processing. The relationship between reading skills and neuronal speech representation of foreign language remains unclear. In the present study, we used event-related potentials (ERPs) with high-density EEG to investigate this question. Eleven- to 13-year-old children typically developed (CTR) or with reading difficulties (RD) were tested via a passive auditory oddball paradigm containing native (Finnish) and foreign (English) speech items. The change-detection-related ERP responses, the mismatch response (MMR), and the late discriminative negativity (LDN) were studied. The cluster-based permutation tests within and between groups were performed. The results showed an apparent language effect. In the CTR group, we found an atypical MMR in the foreign language processing and a larger LDN response for speech items containing a diphthong in both languages. In the RD group, we found unstable MMR with lower amplitude and a nonsignificant LDN response. A deficit in the LDN response in both languages was found within the RD group analysis. Moreover, we observed larger brain responses in the RD group and a hemispheric polarity reversal compared to the CTR group responses. Our results provide new evidence that language processing differed between the CTR and RD groups in early and late discriminatory responses and that language processing is linked to reading skills in both native and foreign language contexts.

Deviance detection in sound frequency in simple and complex sounds in urethane-anesthetized rats.

Mismatch negativity (MMN), which is an electrophysiological response demonstrated in humans and animals, reflects memory-based deviance detection in a series of sounds. However, only a few studies on rodents have used control conditions that were sufficient in eliminating confounding factors that could also explain differential responses to deviant sounds. Furthermore, it is unclear if change detection occurs similarly for sinusoidal and complex sounds. In this study, we investigated frequency change detection in urethane-anesthetized rats by recording local-field potentials from the dura above the auditory cortex. We studied change detection in sinusoidal and complex sounds in a series of experiments, controlling for sound frequency, probability, and pattern in a series of sounds. For sinusoidal sounds, the MMN controlled for frequency, adaptation, and pattern, was elicited at approximately 200 ms onset latency. For complex sounds, the MMN controlled for frequency and adaptation, was elicited at 60 ms onset latency. Sound frequency affected the differential responses. MMN amplitude was larger for the sinusoidal sounds than for the complex sounds. These findings indicate the importance of controlling for sound frequency and stimulus probabilities, which have not been fully controlled for in most previous animal and human studies. Future studies should confirm the preference for sinusoidal sounds over complex sounds in rats.

Unveiling the Mysteries of Dyslexia-Lessons Learned from the Prospective Jyväskylä Longitudinal Study of Dyslexia.

This paper reviews the observations of the Jyväskylä Longitudinal Study of Dyslexia (JLD). The JLD is a prospective family risk study in which the development of children with familial risk for dyslexia (N = 108) due to parental dyslexia and controls without dyslexia risk (N = 92) were followed from birth to adulthood. The JLD revealed that the likelihood of at-risk children performing poorly in reading and spelling tasks was fourfold compared to the controls. Auditory insensitivity of newborns observed during the first week of life using brain event-related potentials (ERPs) was shown to be the first precursor of dyslexia. ERPs measured at six months of age related to phoneme length identification differentiated the family risk group from the control group and predicted reading speed until the age of 14 years. Early oral language skills, phonological processing skills, rapid automatized naming, and letter knowledge differentiated the groups from ages 2.5-3.5 years onwards and predicted dyslexia and reading development, including reading comprehension, until adolescence. The home environment, a child's interest in reading, and task avoidance were not different in the risk group but were found to be additional predictors of reading development. Based on the JLD findings, preventive and intervention methods utilizing the association learning approach have been developed.

Attentional Processes in Children With Attentional Problems or Reading Difficulties as Revealed Using Brain Event-Related Potentials and Their Source Localization.

Visual attention-related processes include three functional sub-processes: alerting, orienting, and inhibition. We examined these sub-processes using reaction times, event-related potentials (ERPs), and their neuronal source activations during the Attention Network Test (ANT) in control children, attentional problems (AP) children, and reading difficulties (RD) children. During the ANT, electroencephalography was measured using 128 electrodes on three groups of Finnish sixth-graders aged 12-13 years (control = 77; AP = 15; RD = 23). Participants were asked to detect the direction of a middle target fish within a group of five fish. The target stimulus was either preceded by a cue (center, double, or spatial), or without a cue, to manipulate the alerting and orienting sub-processes of attention. The direction of the target fish was either congruent or incongruent in relation to the flanker fish, thereby manipulating the inhibition sub-processes of attention. Reaction time performance showed no differences between groups in alerting, orienting, and inhibition effects. The group differences in ERPs were only found at the source level. Neuronal source analysis in the AP children revealed a larger alerting effect (double-cued vs. non-cued target stimuli) than control and RD children in the left occipital lobe. Control children showed a smaller orienting effect (spatially cued vs. center-cued target stimuli) in the left occipital lobe than AP and RD children. No group differences were found for the neuronal sources related to the inhibition effect. The neuronal activity differences related to sub-processes of attention in the AP and RD groups suggest different underlying mechanisms for attentional and reading problems.

Reproducibility of Brain Responses: High for Speech Perception, Low for Reading Difficulties.

Neuroscience findings have recently received critique on the lack of replications. To examine the reproducibility of brain indices of speech sound discrimination and their role in dyslexia, a specific reading difficulty, brain event-related potentials using EEG were measured using the same cross-linguistic passive oddball paradigm in about 200 dyslexics and 200 typically reading 8-12-year-old children from four countries with different native languages. Brain responses indexing speech and non-speech sound discrimination were extremely reproducible, supporting the validity and reliability of cognitive neuroscience methods. Significant differences between typical and dyslexic readers were found when examined separately in different country and language samples. However, reading group differences occurred at different time windows and for different stimulus types between the four countries. This finding draws attention to the limited generalizability of atypical brain response findings in children with dyslexia across language environments and raises questions about a common neurobiological factor for dyslexia. Our results thus show the robustness of neuroscience methods in general while highlighting the need for multi-sample studies in the brain research of language disorders.

Longitudinal interactions between brain and cognitive measures on reading development from 6 months to 14 years.

Dyslexia is a neurobiological disorder impairing learning to read. Brain responses of infants at genetic risk for dyslexia are abnormal already at birth, and associations from infant speech perception to preschool cognitive skills and reading in early school years have been documented, but there are no studies showing predicting power until adolescence. Here we show that in at-risk infants, brain activation to pseudowords at left hemisphere predicts 44% of reading speed at 14 years, and even improves the prediction after taking into account neurocognitive preschool measures of letter naming, phonology, and verbal short-term memory. The association between infant brain responses and reading speed is mediated by preschool rapid automatized naming ability. Therefore, we suggest that rapid naming and reading speed could share a similar cognitive process of automatized access to lexicon via phonological representations, and brain activation to speech sounds in infancy probably acts as an index of deficient development of the same process.

Epilepsy in neuropathologically verified Alzheimer's disease.

PURPOSE: Subjects with Alzheimer's disease (AD) have been shown to be at a higher risk for epilepsy. The vast majority of the previous studies have not included a full neuropathological examination. METHODS: The objective of this study was to assess the prevalence of epilepsy and clinicopathological characteristics in a well-defined study group of 64 subjects with AD. We evaluated the clinicopathological findings in 64 subjects (mean age at death 85 ±â€¯8.6 years) from a longitudi-nal study cohort of patients with dementia. RESULTS: Eleven out of the 64 subjects (17%) had a history of epilepsy, which is comparable to previous studies. The subjects with AD and epilepsy were significantly younger at the time of AD diagnosis and at the time of hospitalisation. In addition, their duration of AD was longer. Concomitant neuropathology in addition to AD was common in both groups and the ApoE genotypes did not differ significantly between the groups. CONCLUSION: The strength of this study is a thorough neuropathological examination of all study subjects. Our findings support the previous literature regarding the prevalence of epilepsy in subjects with AD. We have shown that the subjects with AD and epilepsy differ significantly from the subjects without epilepsy.

Brain event-related potentials to phoneme contrasts and their correlation to reading skills in school-age children.

Development of reading skills has been shown to be tightly linked to phonological processing skills and to some extent to speech perception abilities. Although speech perception is also known to play a role in reading development, it is not clear which processes underlie this connection. Using event-related potentials (ERPs) we investigated the speech processing mechanisms for common and uncommon sound contrasts (/ba/-/da/-/ga/ and /ata/-/at:a/) with respect to the native language of school-age children in Finland and the United States. In addition, a comprehensive behavioral test battery of reading and phonological processing was administered. ERPs revealed that the children could discriminate between the speech sound contrasts (place of articulation and phoneme length) regardless of their native language. No differences emerged between the Finnish and US children in their change detection responses. However, the brain responses to the phoneme length contrast correlated robustly with reading scores in the US children with larger responses being linked to poorer reading skills. Finnish children also showed correlations between the reading and phonological measures and ERP responses, but the pattern of results was not as clear as for the US children. The results indicate that speech perception is linked to reading skills and this link is more robust for uncommon speech sound contrasts.

Event-related potentials to tones show differences between children with multiple risk factors for dyslexia and control children before the onset of formal reading instruction.

Multiple risk factors can affect the development of specific reading problems or dyslexia. In addition to the most prevalent and studied risk factor, phonological processing, auditory discrimination problems have also been found in children and adults with reading difficulties. The present study examined 37 children between the ages of 5 and 6, 11 of which had multiple risk factors for developing reading problems. The children participated in a passive oddball EEG experiment with sinusoidal sounds with changes in sound frequency, duration, or intensity. The responses to the standard stimuli showed a negative voltage shift in children at risk for reading problems compared to control children at 107-215 ms in frontocentral areas corresponding to P1 offset and N250 onset. Source analyses showed that the difference originated from the left and right auditory cortices. Additionally, the children at risk for reading problems had a larger late discriminative negativity (LDN) response in amplitude for sound frequency change than the control children. The amplitudes at the P1-N250 time window showed correlations to letter knowledge and phonological identification whereas the amplitudes at the LDN time window correlated with verbal short-term memory and rapid naming. These results support the view that problems in basic auditory processing abilities precede the onset of reading instruction and can act as one of the risk factors for dyslexia.

Event-related brain potentials to change in the frequency and temporal structure of sounds in typically developing 5-6-year-old children.

The brain's ability to recognize different acoustic cues (e.g., frequency changes in rapid temporal succession) is important for speech perception and thus for successful language development. Here we report on distinct event-related potentials (ERPs) in 5-6-year-old children recorded in a passive oddball paradigm to repeated tone pair stimuli with a frequency change in the second tone in the pair, replicating earlier findings. An occasional insertion of a third tone within the tone pair generated a more merged pattern, which has not been reported previously in 5-6-year-old children. Both types of deviations elicited pre-attentive discriminative mismatch negativity (MMN) and late discriminative negativity (LDN) responses. Temporal principal component analysis (tPCA) showed a similar topographical pattern with fronto-central negativity for MMN and LDN. We also found a previously unreported discriminative response complex (P340-N440) at the temporal electrode sites at about 140 ms and 240 ms after the frequency deviance, which we suggest reflects a discriminative processing of frequency change. The P340 response was positive with a clear radial distribution preceding the fronto-central frequency MMN by about 30 ms. The results indicate that 5-6-year-old children can detect frequency change and the occasional insertion of an additional tone in sound pairs as reflected by MMN and LDN, even with quite short within-stimulus intervals (150 ms and 50 ms). Furthermore, MMN for these changes is preceded by another response to deviancy, temporal P340, which seems to reflect a parallel but earlier discriminatory process.

Enhancement of brain event-related potentials to speech sounds is associated with compensated reading skills in dyslexic children with familial risk for dyslexia.

Specific reading disability, dyslexia, is a prevalent and heritable disorder impairing reading acquisition characterized by a phonological deficit. However, the underlying mechanism of how the impaired phonological processing mediates resulting dyslexia or reading disabilities remains still unclear. Using ERPs we studied speech sound processing of 30 dyslexic children with familial risk for dyslexia, 51 typically reading children with familial risk for dyslexia, and 58 typically reading control children. We found enhanced brain responses to shortening of a phonemic length in pseudo-words (/at:a/ vs. /ata/) in dyslexic children with familial risk as compared to other groups. The enhanced brain responses were associated with better performance in behavioral phonemic length discrimination task, as well as with better reading and writing accuracy. Source analyses revealed that the brain responses of sub-group of dyslexic children with largest responses originated from a more posterior area of the right temporal cortex as compared to the responses of the other participants. This is the first electrophysiological evidence for a possible compensatory speech perception mechanism in dyslexia. The best readers within the dyslexic group have probably developed alternative strategies which employ compensatory mechanisms substituting their possible earlier deficit in phonological processing and might therefore be able to perform better in phonemic length discrimination and reading and writing accuracy tasks. However, we speculate that for reading fluency compensatory mechanisms are not that easily built and dyslexic children remain slow readers during their adult life.

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.

Separating mismatch negativity (MMN) response from auditory obligatory brain responses in school-aged children.

Mismatch negativity (MMN) overlaps with other auditory event-related potential (ERP) components. We examined the ERPs of 50 9- to 11-year-old children for vowels /i/, /y/ and equivalent complex tones. The goal was to separate MMN from obligatory ERP components using principal component analysis and equal probability control condition. In addition to the contrast of the deviant minus standard response, we employed the contrast of the deviant minus control response, to see whether the obligatory processing contributes to MMN in children. When looking for differences in speech deviant minus standard contrast, MMN starts around 112 ms. However, when both contrasts are examined, MMN emerges for speech at 160 ms whereas for nonspeech MMN is observed at 112 ms regardless of contrast. We argue that this discriminative response to speech stimuli at 112 ms is obligatory in nature rather than reflecting change detection processing.

Newborn brain event-related potentials revealing atypical processing of sound frequency and the subsequent association with later literacy skills in children with familial dyslexia.

The role played by an auditory-processing deficit in dyslexia has been debated for several decades. In a longitudinal study using brain event-related potentials (ERPs) we investigated 1) whether dyslexic children with familial risk background would show atypical pitch processing from birth and 2) how these newborn ERPs later relate to these same children's pre-reading cognitive skills and literacy outcomes. Auditory ERPs were measured at birth for tones varying in pitch and presented in an oddball paradigm (1100 Hz, 12%, and 1000 Hz, 88%). The brain responses of the typically reading control group children (TRC group, N=25) showed clear differentiation between the frequencies, while those of the group of reading disability with familial risk (RDFR, 8 children) and the group of typical readers with familial risk (TRFR, 14 children) did not differentiate between the tones. The ERPs of the latter two groups differed from those of the TRC group. However, the two risk groups also showed a differential hemispheric ERP pattern. Furthermore, newborn ERPs reflecting passive change detection were associated with phonological skills and letter knowledge prior to school age and with phoneme duration perception, reading speed (RS) and spelling accuracy in the 2nd grade of school. The early obligatory response was associated with more general pre-school language skills, as well as with RS and reading accuracy (RA). Results suggest that a proportion of dyslexic readers with familial risk background are affected by atypical auditory processing. This is already present at birth and also relates to pre-reading phonological processing and speech perception. These early differences in auditory processing could later affect phonological representations and reading development. However, atypical auditory processing is unlikely to suffice as a sole explanation for dyslexia but rather as one risk factor, dependent on the genetic profile of the child.