Infants' ability to discriminate between auditory stimuli presented in rapid succession and differing in fundamental frequency (Rapid Auditory Processing [RAP] abilities) has been shown to be anomalous in infants at familial risk for Language Learning Impairment (LLI) and to predict later language outcomes. This study represents the first attempt to investigate RAP in Italian infants at risk for LLI (FH+), examining two critical acoustic features: frequency and duration, both embedded in a rapidly-presented acoustic environment. RAP skills of 24 FH+ and 32 control (FH-) Italian 6-month-old infants were characterized via EEG/ERP using a multi-feature oddball paradigm. Outcome measures of expressive vocabulary were collected at 20 months. Group differences favoring FH- infants were identified: in FH+ infants, the latency of the N2* peak was delayed and the mean amplitude of the positive mismatch response was reduced, primarily for frequency discrimination and within the right hemisphere. Moreover, both EEG measures were correlated with language scores at 20 months. Results indicate that RAP abilities are atypical in Italian infants with a first-degree relative affected by LLI and that this impacts later linguistic skills. These findings provide a compelling cross-linguistic comparison with previous research on American infants, supporting the biological unity hypothesis of LLI.
The ability to rapidly discriminate successive auditory stimuli within tens-of-milliseconds is crucial for speech and language development, particularly in the first year of life. This skill, called Rapid Auditory Processing (RAP), is altered in infants at familial risk for language and learning impairment (LLI) and is a robust predictor of later language outcomes. In the present study, we investigate the neural substrates of RAP, i.e., the underlying neural oscillatory patterns, in a group of Italian 6-month-old infants at risk for LLI (FH+, n = 24), compared to control infants with no known family history of LLI (FH−, n = 32). Brain responses to rapid changes in fundamental frequency and duration were recorded via high-density electroencephalogram during a non-speech double oddball paradigm. Sources of event-related potential generators were localized to right and left auditory regions in both FH+ and FH− groups. Time-frequency analyses showed variations in both theta (Ɵ) and gamma (ɣ) ranges across groups. Our results showed that overall RAP stimuli elicited a more left-lateralized pattern of oscillations in FH− infants, whereas FH+ infants demonstrated a more right-lateralized pattern, in both the theta and gamma frequency bands. Interestingly, FH+ infants showed reduced early left gamma power (starting at 50 ms after stimulus onset) during deviant discrimination. Perturbed oscillatory dynamics may well constitute a candidate neural mechanism to explain group differences in RAP. Additional group differences in source location suggest that anatomical variations may underlie differences in oscillatory activity. Regarding the predictive value of early oscillatory measures, we found that the amplitude of the source response and the magnitude of oscillatory power and phase synchrony were predictive of expressive vocabulary at 20 months of age. These results further our understanding of the interplay among neural mechanisms that support typical and atypical rapid auditory processing in infancy.
Early identification of autism spectrum disorder (ASD) is crucial for the formulation of effective intervention programs. Language deficits may be a hallmark feature of ASD and language delay observed in ASD shows striking similarities to that observed in children with language impairment (LI). Auditory processing deficits are seen in both LI and ASD, however, they have not previously been compared directly using Event-Related Potentials (ERPs) in the two at-risk populations. This study aims to characterize infants at-risk for ASD (HR-ASD) at the electrophysiological level and to compare them with infants at-risk for LI (HR-LI) and controls, to find specific markers with predictive value. At 12-month-old, auditory processing in HR-ASD, HR-LI and controls was characterized via ERP oddball paradigm. All infants were then evaluated at 20 months, to investigate the associations between auditory processing and language/ASD-related outcomes. In both HR-ASD and HR-LI, mismatch response latency was delayed compared to controls, whereas only HR-ASD showed overall larger P3 amplitude compared to controls. Interestingly, these ERP measures correlated with later expressive vocabulary and M-CHAT critical items in the whole sample. These results may support the use of objective measurement of auditory processing to delineate pathophysiological mechanisms in ASD, as compared to LI.
Substantial heritability has been reported for developmental dyslexia (DD), and KIAA0319 and ROBO1 appear as more than plausible candidate susceptibility genes for this developmental disorder. Converging evidence indicates that developmental difficulties in oral language and mathematics can predate or co-occur with DD, and substantial genetic correlations have been found between these abilities and reading traits. In this study, we explored the role of eight single-nucleotide polymorphisms spanning within KIAA0319 and ROBO1 genes, and DD as a dichotomic trait, related neuropsychological phenotypes and comorbid language and mathematical (dis)abilities in a large cohort of 493 Italian nuclear families ascertained through a proband with a diagnosis of DD. Marker-trait association was analyzed by implementing a general test of family-based association for quantitative traits (that is, the Quantitative Transmission Disequilibrium Test, version 2.5.1). By providing evidence for significant association with mathematics skills, our data add further result in support of ROBO1 contributing to the deficits in DD and its correlated phenotypes. Taken together, our findings shed further light into the etiologic basis and the phenotypic complexity of this developmental disorder.
Converging evidence indicates that developmental problems in oral language and mathematics can predate or co-occur with developmental dyslexia (DD). Substantial genetic correlations have been found between language, mathematics and reading traits, independent of the method of sampling. We tested for association of variants of two DD susceptibility genes, DCDC2 and DYX1C1, in nuclear families ascertained through a proband with DD using concurrent measurements of language and mathematics in both probands and siblings by the Quantitative Transmission Disequilibrium Test. Evidence for significant associations was found between DCDC2 and ‘Numerical Facts’ (p value = 0.02, with 85 informative families, genetic effect = 0.57) and between ‘Mental Calculation’ and DYX1C1 markers −3GA (p value = 0.05, with 40 informative families, genetic effect = −0.67) and 1249GT (p value = 0.02, with 49 informative families, genetic effect = −0.65). No statistically significant associations were found between DCDC2 or DYX1C1 and language phenotypes. Both DCDC2 and DYX1C1 DD susceptibility genes appear to have a pleiotropic role on mathematics but not language phenotypes.
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