Infant brain responses associated with reading-related skills before school and at school age.

INTRODUCTION: In Jyväskylä Longitudinal Study of Dyslexia, we have investigated neurocognitive processes related to phonology and other risk factors of later reading problems. Here we review studies in which we have investigated whether dyslexic children with familial risk background would show atypical auditory/speech processing at birth, at six months and later before school and at school age as measured by brain event-related potentials (ERPs), and how infant ERPs are related to later pre-reading cognitive skills and literacy outcome. PATIENTS AND METHODS: One half of the children came from families with at least one dyslexic parent (the at-risk group), while the other half belonged to the control group without any familial background of dyslexia. RESULTS: Early ERPs were correlated to kindergarten age phonological processing and letter-naming skills as well as phoneme duration perception, reading and writing skills at school age. The correlations were, in general, more consistent among at-risk children. Those at-risk children who became poor readers also differed from typical readers in the infant ERP measures at the group level. ERPs measured before school and at the 3rd grade also differed between dyslexic and typical readers. Further, speech perception at behavioural level differed between dyslexic and typical readers, but not in all dyslexic readers. CONCLUSIONS: These findings suggest persisting developmental differences in the organization of the neural networks sub-serving auditory and speech perception, with cascading effects on later reading related skills, in children with familial background for dyslexia. However, atypical auditory/speech processing is not likely a sufficient reason by itself for dyslexia but rather one endophenotype or risk factor.

Activity of adenosine diphosphates and triphosphates on a P2Y(T) -type receptor in brain capillary endothelial cells.

1. A P2Y (nucleotide) receptor activity in a clonal population (B10) of rat brain capillary endothelial cells is coupled to inhibition of adenylyl cyclase and has functional similarities to the P2Y(T) (previously designated 'P2T') receptor for ADP of blood platelets. However, the only P2Y receptor which was detectable in a previous study of B10 cells by mRNA analysis was the P2Y(1) receptor, which elsewhere shows no transduction via cyclic nucleotides. We have sought here to clarify these issues. 2. The inhibition of forskolin-stimulated adenylyl cyclase induced by purified nucleotides was measured on B10 cells. The EC(50) value for 2-methylthioADP (2-MeSADP) was 2.2 nM and, surprisingly, 2-MeSATP was an almost equally strong agonist (EC(50)=3.5 nM). ATP and 2-ClATP were weak partial agonists (EC(50)=26 microM and 10 microM respectively) and under appropriate conditions could antagonise the activity on 2-MeSADP. 3. A known selective antagonist of the platelet P2Y(T) receptor, 2-propylthioadenosine-5'-(beta,gamma)-difluoromethylene) triphosphonate (AR-C 66096), was a competitive antagonist of this B10 cell receptor, with pK(B)=7.6. That ligand is inactive at the P2Y(1) receptor in the same cells. Conversely, the competitive P2Y(1) receptor antagonists, the 3', 5'- and 2', 5'-adenosine bis-monophosphates, are, instead, weak agonists at the adenylyl cyclase-inhibitory receptor. 4. The inhibition of adenylyl cyclase by 2-MeSADP was completely abolished by pertussis toxin. 5. In summary, these brain endothelial cells possess a P2Y(T)-type receptor in addition to the P2Y(1) receptor. The two have similarities in agonist profiles but are clearly distinguishable by antagonists and by their second messenger activations. The possible relationships between the B10 and platelet P2Y(T) receptors are discussed.

Cortical responses of infants with and without a genetic risk for dyslexia: I. Age effects.

We studied auditory event-related potentials (ERP) in newborns and 6-month-old infants, about half of whom had a familial risk for dyslexia. Syllables varying in vowel duration were presented in an oddball paradigm, in which ERPs to deviating stimuli are assumed to reflect automatic change detection in the brain. The ERPs of newborns had slow positive deflections typical of their age, but significant stimulus and group effects were found only by the age of 6 months. In both groups, the responses to the deviant /ka/ were more positive than those to the standard /kaa/ stimuli, contrary to the findings of adult ERPs to duration changes. The results also suggested differences in brain activation pattern between the groups.

Cortical responses of infants with and without a genetic risk for dyslexia: II. Group effects.

Infants born to families with a background of developmental dyslexia have an increased risk of becoming dyslexic. In our previous study no major group or stimulus effects in the event-related potentials (ERPs) of at-risk and control infants were found until the age of 6 months. However, in the current study, when we made the stimulus presentation rate slower, the ERPs to the short deviant /ka/ were different from those to the long standard /kaa/ stimulus already in newborns. In addition, clear group differences in the ERPs were found. The results demonstrate that infants born with a high familial risk for dyslexia process speech/auditory stimulus durations differently from control infants at birth.