Kaisa Lohvansuu

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.

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 childrens 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.

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.

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.

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.

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.

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 US. 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. The brain responses to the phoneme length contrast, however, 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.

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

ABSTRACT 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. HIGHLIGHTSAssociations of infant ERPs to speech and reading speed in 14 years were studied.ERPs of infants at‐risk for dyslexia predicted 44% of reading speed at 14 years.The prediction was mediated via preschool‐age rapid naming (RAN).This suggests that poor automatization of lexical access hinders reading and RAN.Atypical infant ERPs index a deficient development of representations on background.

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

The brains 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.

Epilepsy in neuropathologically verified Alzheimer’s disease

PURPOSE Subjects with Alzheimers 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 ± 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.