Patterns of Brain Activity in Autism and Williams Syndrome
Two neurodevelopmental disorders, Williams syndrome (WS) and autism, are both commonly described as having opposite social profiles: social avoidance in autism vs hypersociability in individuals with WS. The goal of this study was to contrast the brain activity associated with language processing in these two populations, in order to understand the very likely interplay between the use of language and the sociability dimension, on which these disorders diverge. Towards this aim, the N400 component of the event-related potentials was used to quantify the processing of semantic integration in these two populations. Results revealed that individuals with WS showed a significantly larger N400 effect, as compared to both typical controls and individuals with autism, while the latter group demonstrated the smallest N400 effect. The findings demonstrate quite opposite profiles of neural correlates of language processing in WS and autism, mirroring their contrasting social phenotypes.
Williams syndrome (WS) and autism (or, generally, autism spectrum disorders, ASD) are both neurodevelopmental disorders associated with atypical social and communication profiles. While individuals with WS are typically described as extremely sociable, friendly, empathic and possessing socially engaging language (Doyle et al., 2004; Järvinen-Pasley et al., 2008), those with ASD are characterized by impaired social interaction and communication skills. Although it is widely recognized that autism is a constellation of cognitive and behavioral deficits, impairments in social functioning and in verbal communication are consistently observed in all individuals with autism, regardless of intelligence quotient (IQ) level or severity of symptoms. On the other hand, despite the multifactorial nature of WS and its complex cognitive and behavioral profile, excessive sociability and a keen interest in interacting with people are the most robust behavioral characteristics of WS (cf. Järvinen-Pasley et al., 2008), a neurodevelopmental disorder caused by a hemizygous deletion of 25–30 genes on chromosome 7q11.23 (Korenberg et al., 2000).
In line with this polar social orientation of the two syndromes are their distinct language skills, which follow a remarkably similar divide. Although linguistic abilities can vary significantly across the autistic spectrum, from a complete absence of receptive and expressive speech to mild impairment in semantics (Tager-Flusberg, 2003, 2004), an overall deficit in the 'communicative use of language' is a defining feature of ASD and one of the triad of symptoms at the core of the ASD diagnosis [American Psychiatric Association (APA), 2000]. On the other hand, despite mild to moderate mental retardation, individuals with WS appear to have 'relative' proficiencies in linguistic skills (cf. Mervis et al., 1999), including elaborate and rich vocabularies and pictorial, affect-rich expressive language (Reilly et al., 2004; Brock et al., 2007; Gothelf et al., 2008), that make their speech engaging and facilitate—rather than impede, as in ASD—the likelihood of interaction and communication with others. It is this divide in language skills and use, which mirrors the opposite social profiles that led us to explore how individuals with WS and ASD process language.
One common factor that may underlie a wide range of language abnormalities in ASD can be conceptualized as a difficulty in using semantic context to understand and predict meaning (Tager-Flusberg, 2003, 2004; Harris et al., 2006; Walenski et al., 2006). Even individuals with high-functioning ASD have shown deficits in utilizing sentence context to determine the context-dependent pronunciation of words with several meanings (Firth and Snowling, 1983; Happe, 1997) and to comprehend idioms, an ability heavily relying on interpreting language in context (Kerbel and Grunwell, 1998). Furthermore, it has been demonstrated that a prototypical IQ profile for high-functioning autism is characterized by a relatively depressed score on tasks of comprehension, in the face of an otherwise preserved and even IQ profile (Siegel et al., 1996; Goldstein et al., 2002), underscoring that deficit in understanding language is one of the core features of ASD.
On the other hand, while much controversy has ensued in the field regarding which aspects of language—syntax, semantics, phonology or pragmatics—and how much of it is 'spared' in WS (see Karmiloff-Smith et al., 2003 for a review), there seems to be a general consensus that compared to the severe anomalies and deficiencies in non-verbal, visuospatial cognitive functioning, the expressive language of WS individuals is 'relatively' proficient (Mervis et al., 1999; Bellugi et al., 2000), even if distinct linguistic skills are not uniformly intact. When compared to their mental-age and, often, chronological-age peers, WS individuals as a group are unusually loquacious and highly expressive (Udwin and Yule, 1990), use a wide variety of affective and social engagement devices in their narratives, such as character speech, sound effects, intensifiers, etc. (Reilly et al., 2004), and give accurate and detailed verbal descriptions of objects (Bellugi et al., 1994) despite being unable to draw the same objects. On standardized vocabulary tests such as the Peabody Picture Vocabulary Test (PPVT), WS subjects perform well above their respective mental ages (Bellugi et al., 2000) and on fluency tasks they produce at least as many items as chronological-age controls, albeit generating more low-frequency words (Bellugi et al., 1994). Additionally, WS individuals produce associates related to the primary meaning of the homonym words as well as unimpaired controls do (Bellugi et al., 2000). Thus, notwithstanding the disagreements regarding the degree of impairment of the morphosyntactic aspects of language, which are beyond the scope of this project, it appears that the vocabulary and semantic organization are 'relative' strengths in WS, standing out in stark contrast to their overall intellectual disability and spatial deficits. Yet, it is important to note that the peculiarity of the choice of words generated on fluency tasks, coupled with experimental evidence indicating that individuals with WS (i) produce definitions compatible with both primary and secondary meanings of homonyms on definition tasks, and (ii) provide an equal number of primary and secondary associates to homonyms on a similarity judgment task (Bellugi et al., 2000), suggest an 'atypical' (rather than plainly impaired) semantic organization (cf. Karmiloff-Smith et al., 2003).
Thus, the goal of the current study was to contrast the semantic processing in WS and ASD, in order to understand the very likely interplay between the ability to derive meaning out of linguistic context and the sociability dimension, on which WS and ASD seem to represent two ends of the continuum (cf. Tager-Flusberg et al., 2006; Brock et al., 2008; Riby and Hancock, 2008). To quantify the contextual integration ability, we examined the degree to which an electrophysiological index of semantic processing, the N400 component of the event-related potentials (ERPs), distinguished individuals with WS from those with ASD. Considered a robust marker of contextual integration, N400 is sensitive to variations in the semantic content and is thought to reflect the extent to which an individual word is expected, or semantically plausible, given its current linguistic—sentential or discourse—context (Kutas and Hillyard, 1980, 1984).
In the general population, the occurrence of a semantically incongruent word at the end of a sentence is associated with a large N400, a negative-going potential occurring ~400 ms after the critical word onset (Kutas and Hillyard, 1980). The N400 magnitude is inversely related to the degree of semantic fit between a word and its context, such that a word more predictable from the preceding context generates a smaller N400 than a word that is less expected given the preceding words in the sentence (Kutas and Hillyard, 1980, 1984). Overall, it appears that the N400 indexes the ease of integration of stimuli into an ongoing context. When this integration is easier—that is, when a word fits with, or is predicted by the context—the amplitude of N400 is smaller (Kutas and Federmeier, 2000).
Given the behavioral evidence reviewed above, we have predicted that individuals with ASD will be impaired in their abilities to make use of context to establish a semantic expectation against which a target word is judged, manifested in smaller N400 amplitudes, as compared to typically developing (TD) controls. On the other hand, because individuals with WS show relatively preserved albeit atypical semantics, we expected them to exhibit N400 amplitudes comparable to those of TD controls. We have tested this 2-fold prediction using a sentence paradigm based on that described by Holcomb et al. (1992), in which auditory sentences are presented one word at a time, with the final word being either semantically congruent or incongruent with the meaning of the rest of the sentence. Using an auditory paradigm (which is used less commonly than visual/reading tasks in studying the N400 in adults) where participants are listening to 'spoken' language was critical given the primacy of this modality in both expressive language of individuals with WS and in impaired verbal communication in ASD. We also examined whether IQ differences affected their N400 responses or moderated the group differences on the N400.
Abstract and Introduction
Abstract
Two neurodevelopmental disorders, Williams syndrome (WS) and autism, are both commonly described as having opposite social profiles: social avoidance in autism vs hypersociability in individuals with WS. The goal of this study was to contrast the brain activity associated with language processing in these two populations, in order to understand the very likely interplay between the use of language and the sociability dimension, on which these disorders diverge. Towards this aim, the N400 component of the event-related potentials was used to quantify the processing of semantic integration in these two populations. Results revealed that individuals with WS showed a significantly larger N400 effect, as compared to both typical controls and individuals with autism, while the latter group demonstrated the smallest N400 effect. The findings demonstrate quite opposite profiles of neural correlates of language processing in WS and autism, mirroring their contrasting social phenotypes.
Introduction
Williams syndrome (WS) and autism (or, generally, autism spectrum disorders, ASD) are both neurodevelopmental disorders associated with atypical social and communication profiles. While individuals with WS are typically described as extremely sociable, friendly, empathic and possessing socially engaging language (Doyle et al., 2004; Järvinen-Pasley et al., 2008), those with ASD are characterized by impaired social interaction and communication skills. Although it is widely recognized that autism is a constellation of cognitive and behavioral deficits, impairments in social functioning and in verbal communication are consistently observed in all individuals with autism, regardless of intelligence quotient (IQ) level or severity of symptoms. On the other hand, despite the multifactorial nature of WS and its complex cognitive and behavioral profile, excessive sociability and a keen interest in interacting with people are the most robust behavioral characteristics of WS (cf. Järvinen-Pasley et al., 2008), a neurodevelopmental disorder caused by a hemizygous deletion of 25–30 genes on chromosome 7q11.23 (Korenberg et al., 2000).
In line with this polar social orientation of the two syndromes are their distinct language skills, which follow a remarkably similar divide. Although linguistic abilities can vary significantly across the autistic spectrum, from a complete absence of receptive and expressive speech to mild impairment in semantics (Tager-Flusberg, 2003, 2004), an overall deficit in the 'communicative use of language' is a defining feature of ASD and one of the triad of symptoms at the core of the ASD diagnosis [American Psychiatric Association (APA), 2000]. On the other hand, despite mild to moderate mental retardation, individuals with WS appear to have 'relative' proficiencies in linguistic skills (cf. Mervis et al., 1999), including elaborate and rich vocabularies and pictorial, affect-rich expressive language (Reilly et al., 2004; Brock et al., 2007; Gothelf et al., 2008), that make their speech engaging and facilitate—rather than impede, as in ASD—the likelihood of interaction and communication with others. It is this divide in language skills and use, which mirrors the opposite social profiles that led us to explore how individuals with WS and ASD process language.
One common factor that may underlie a wide range of language abnormalities in ASD can be conceptualized as a difficulty in using semantic context to understand and predict meaning (Tager-Flusberg, 2003, 2004; Harris et al., 2006; Walenski et al., 2006). Even individuals with high-functioning ASD have shown deficits in utilizing sentence context to determine the context-dependent pronunciation of words with several meanings (Firth and Snowling, 1983; Happe, 1997) and to comprehend idioms, an ability heavily relying on interpreting language in context (Kerbel and Grunwell, 1998). Furthermore, it has been demonstrated that a prototypical IQ profile for high-functioning autism is characterized by a relatively depressed score on tasks of comprehension, in the face of an otherwise preserved and even IQ profile (Siegel et al., 1996; Goldstein et al., 2002), underscoring that deficit in understanding language is one of the core features of ASD.
On the other hand, while much controversy has ensued in the field regarding which aspects of language—syntax, semantics, phonology or pragmatics—and how much of it is 'spared' in WS (see Karmiloff-Smith et al., 2003 for a review), there seems to be a general consensus that compared to the severe anomalies and deficiencies in non-verbal, visuospatial cognitive functioning, the expressive language of WS individuals is 'relatively' proficient (Mervis et al., 1999; Bellugi et al., 2000), even if distinct linguistic skills are not uniformly intact. When compared to their mental-age and, often, chronological-age peers, WS individuals as a group are unusually loquacious and highly expressive (Udwin and Yule, 1990), use a wide variety of affective and social engagement devices in their narratives, such as character speech, sound effects, intensifiers, etc. (Reilly et al., 2004), and give accurate and detailed verbal descriptions of objects (Bellugi et al., 1994) despite being unable to draw the same objects. On standardized vocabulary tests such as the Peabody Picture Vocabulary Test (PPVT), WS subjects perform well above their respective mental ages (Bellugi et al., 2000) and on fluency tasks they produce at least as many items as chronological-age controls, albeit generating more low-frequency words (Bellugi et al., 1994). Additionally, WS individuals produce associates related to the primary meaning of the homonym words as well as unimpaired controls do (Bellugi et al., 2000). Thus, notwithstanding the disagreements regarding the degree of impairment of the morphosyntactic aspects of language, which are beyond the scope of this project, it appears that the vocabulary and semantic organization are 'relative' strengths in WS, standing out in stark contrast to their overall intellectual disability and spatial deficits. Yet, it is important to note that the peculiarity of the choice of words generated on fluency tasks, coupled with experimental evidence indicating that individuals with WS (i) produce definitions compatible with both primary and secondary meanings of homonyms on definition tasks, and (ii) provide an equal number of primary and secondary associates to homonyms on a similarity judgment task (Bellugi et al., 2000), suggest an 'atypical' (rather than plainly impaired) semantic organization (cf. Karmiloff-Smith et al., 2003).
Thus, the goal of the current study was to contrast the semantic processing in WS and ASD, in order to understand the very likely interplay between the ability to derive meaning out of linguistic context and the sociability dimension, on which WS and ASD seem to represent two ends of the continuum (cf. Tager-Flusberg et al., 2006; Brock et al., 2008; Riby and Hancock, 2008). To quantify the contextual integration ability, we examined the degree to which an electrophysiological index of semantic processing, the N400 component of the event-related potentials (ERPs), distinguished individuals with WS from those with ASD. Considered a robust marker of contextual integration, N400 is sensitive to variations in the semantic content and is thought to reflect the extent to which an individual word is expected, or semantically plausible, given its current linguistic—sentential or discourse—context (Kutas and Hillyard, 1980, 1984).
In the general population, the occurrence of a semantically incongruent word at the end of a sentence is associated with a large N400, a negative-going potential occurring ~400 ms after the critical word onset (Kutas and Hillyard, 1980). The N400 magnitude is inversely related to the degree of semantic fit between a word and its context, such that a word more predictable from the preceding context generates a smaller N400 than a word that is less expected given the preceding words in the sentence (Kutas and Hillyard, 1980, 1984). Overall, it appears that the N400 indexes the ease of integration of stimuli into an ongoing context. When this integration is easier—that is, when a word fits with, or is predicted by the context—the amplitude of N400 is smaller (Kutas and Federmeier, 2000).
Given the behavioral evidence reviewed above, we have predicted that individuals with ASD will be impaired in their abilities to make use of context to establish a semantic expectation against which a target word is judged, manifested in smaller N400 amplitudes, as compared to typically developing (TD) controls. On the other hand, because individuals with WS show relatively preserved albeit atypical semantics, we expected them to exhibit N400 amplitudes comparable to those of TD controls. We have tested this 2-fold prediction using a sentence paradigm based on that described by Holcomb et al. (1992), in which auditory sentences are presented one word at a time, with the final word being either semantically congruent or incongruent with the meaning of the rest of the sentence. Using an auditory paradigm (which is used less commonly than visual/reading tasks in studying the N400 in adults) where participants are listening to 'spoken' language was critical given the primacy of this modality in both expressive language of individuals with WS and in impaired verbal communication in ASD. We also examined whether IQ differences affected their N400 responses or moderated the group differences on the N400.
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