Neural Correlates of Syntax and Proto-Syntax: Evolutionary Dimension

Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity. Although studies of twins consistently indicate that a significant genetic component is involved, most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait. Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval. Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language.

Until recently, our understanding of how language is organized in the brain depended on analysis of behavioral deficits in patients with fortuitously placed lesions. The availability of functional magnetic resonance imaging (fMRI) for in vivo analysis of the normal brain has revolutionized the study of language. This review discusses three lines of fMRI research into how the semantic system is organized in the adult brain. These are (a) the role of the left inferior frontal lobe in semantic processing and dissociations from other frontal lobe language functions, (b) the organization of categories of objects and concepts in the temporal lobe, and (c) the role of the right hemisphere in comprehending contextual and figurative meaning. Together, these lines of research broaden our understanding of how the brain stores, retrieves, and makes sense of semantic information, and they challenge some commonly held notions of functional modularity in the language system.

Linguistic analyses suggest that sentences are not mere strings of words but possess a hierarchical structure with constituents nested inside each other. We used functional magnetic resonance imaging (fMRI) to search for the cerebral mechanisms of this theoretical construct. We hypothesized that the neural assembly that encodes a constituent grows with its size, which can be approximately indexed by the number of words it encompasses. We therefore searched for brain regions where activation increased parametrically with the size of linguistic constituents, in response to a visual stream always comprising 12 written words or pseudowords. The results isolated a network of left-hemispheric regions that could be dissociated into two major subsets. Inferior frontal and posterior temporal regions showed constituent size effects regardless of whether actual content words were present or were replaced by pseudowords (jabberwocky stimuli). This observation suggests that these areas operate autonomously of other language areas and can extract abstract syntactic frames based on function words and morphological information alone. On the other hand, regions in the temporal pole, anterior superior temporal sulcus and temporo-parietal junction showed constituent size effect only in the presence of lexico-semantic information, suggesting that they may encode semantic constituents. In several inferior frontal and superior temporal regions, activation was delayed in response to the largest constituent structures, suggesting that nested linguistic structures take increasingly longer time to be computed and that these delays can be measured with fMRI.