Semantic and pragmatic language development in typical acquisition, autism spectrum disorders, and Williams syndrome with reference to developmental neurogenetics of the latter

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references.The elucidation of the biological bases of a complex trait like human language proceeds from identification of precise behavioral phenotypes to investigation of the underlying genes. The human behavioral parts of this dissertation focus on understanding the reasons for children's overuse of definite article 'the', to refer to one of several objects in a context set, as opposed to the unique established referent. Competing theories argue the deficit is either in children's semantic computational knowledge (of uniqueness/maximality), or in their pragmatic/social awareness/theory-of-mind development. Experiments in this dissertation focused on children's comprehension and interpretation of the indefinite and definite determiners, as well as 'that', anaphors 'another' and 'same', and free relative clauses. The results in this thesis suggest that in typically developing (TD) children the late acquisition of determiner 'the' is due to the late maturation of the semantic principle of maximality. Children with autism spectrum disorders (ASD) and with Williams syndrome (WS) either manifested an adult-like competence, an absence of manifestation of knowledge, or a pattern found in TD younger children (where 'that' is understood better than 'the' as referring to the salient unique referent) -- indicating delay of development of the language faculty, but no deviance. This suggests that the observed deficits in ASD and WS pattern with those in TD, and hence are also semantic in nature. The mouse neurogenetic part of this dissertation investigates whether the GTF2I family of genes, causal to WS behavioral phenotype, also contributes to WS cortical development.(cont.) By overexpression of Gtf2i and Gtf2ird1 in the mouse neocortex via in utero electroporation, their effects on laminar patterning and cell morphogenesis during brain development are characterized. The present results suggest that these genes can synergistically contribute to the abnormal neocortical development in WS, and thereby could contribute to language deficits in WS. Beyond posing an explanatory challenge to linguistic theories, the research comparing typical and atypical development sheds light on the mechanisms of language development and impairment, and provides endophenotypic descriptions of ASD and WS, which are crucial for elucidating not only genetics of neurodevelopmental disorders, but also the genetic basis of the human language faculty.by Nadezhda N. Modyanova.Ph.D

Comparison of Grammar in Neurodevelopmental Disorders: The Case of Binding in Williams Syndrome and Autism With and Without Language Impairment

This study investigates whether distinct neurodevelopmental disorders show distinct patterns of impairments in particular grammatical abilities and the relation of those grammatical patterns to general language delays and intellectual disabilities. We studied two disorders (autism and Williams syndrome [WS]) and two distinct properties (Principle A that governs reflexives and Principle B that, together with its associated pragmatic rule, governs pronouns) of the binding module of grammar. These properties are known to have markedly different courses of acquisition in typical development. We compare the knowledge of binding in children with autism with language impairment (ALI) and those with normal language (ALN) to that of children with WS, matched on age to the ALN group, and on age and nonverbal mental age (MA) to the ALI group, as well as to two groups of typically developing (TD) controls, matched on nonverbal MA to ALI and ALN groups. Our results reveal a remarkably different pattern of comprehension of personal pronouns and reflexives in ALI as opposed to ALN, WS, and two groups of TD controls. All five groups demonstrated an equal delay in their comprehension of personal pronouns, in line with widely reported delays in TD literature, argued to be due to delayed pragmatic abilities. However, and most strikingly, the ALI group also showed a pronounced difficulty in comprehension of reflexive pronouns, and particularly of the knowledge that the antecedent of a reflexive must c-command it. The revealed pattern confirms the existence of a particular impairment concerning Principle A in this module of grammar, unrelated to general language delays or cognitive deficits generally present in a large portion of individuals with autism as well as WS, or to general pragmatic deficits, known to be particularly prevalent in the population with autism