MEG detection of delayed auditory evoked responses in autism spectrum disorders: towards an imaging biomarker for autism.

Motivated by auditory and speech deficits in autism spectrum disorders (ASD), the frequency dependence of superior temporal gyrus (STG) 50 msec (M50) and 100 msec (M100) neuromagnetic auditory evoked field responses in children with ASD and typically developing controls were evaluated. Whole-cortex magnetoencephalography (MEG) was obtained from 17 typically developing children and 25 children with ASD. Subjects were presented tones with frequencies of 200, 300, 500, and 1,000 Hz, and left and right STG M50 and M100 STG activity was examined. No M50 latency or amplitude Group differences were observed. In the right hemisphere, a Group x Frequency ANOVA on M100 latency produced a main effect for Group (P=0.01), with an average M100 latency delay of 11 msec in children with ASD. In addition, only in the control group was the expected association of earlier M100 latencies in older than younger children observed. Group latency differences remained significant when hierarchical regression analyses partialed out M100 variance associated with age, IQ, and language ability (all P-values <0.05). Examining the right-hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, a specificity of 81%, and a positive predictive value (PPV) of 86% was obtained at a threshold of 116 msec. The M100 latency delay indicates disruption of encoding simple sensory information. Given similar findings in language impaired and non-language impaired ASD subjects, a right-hemisphere M100 latency delay appears to be an electrophysiological endophenotype for autism.

Incidental learning of abstract rules for non-dominant word orders.

One way in which adult second language learners may acquire a word order that differs from their native language word order is through exposure-based incidental learning, but little is known about that process and what constrains it. The current studies examine whether a non-dominant word order can be learned incidentally, and if so, whether the rule can be generalized to new words not previously seen in the non-dominant order. Two studies examined the incidental learning of rules underlying the order of nouns and verbs in three-word strings. The self-timed reading speeds of native English speakers decreased as a result of practice with a non-dominant rule (words ordered either as "verb noun noun" or "noun noun verb"). The same pattern of results was also found for new words ordered according to the previously encountered rule, suggesting learning generalized beyond the specific instances encountered. A second experiment showed such rule learning could also occur when the nouns were replaced with pronounceable pseudowords. Learning was therefore possible in the absence of any pre-existing relationships between the items. Theoretical and educational implications are discussed.

Impairments in phonological processing and nonverbal intellectual function in parents of children with autism.

Language difficulties have been implicated to be a part of the broad autism phenotype in first-degree relatives of individuals with autism. Phonological processing difficulties in particular have been reported by some, but not all groups studying parents or siblings of probands with autism. In the present study, we examined a broad battery of language tasks and general cognitive abilities in parents of children with autistic disorder. Parents of individuals with autism (n = 22) were compared to matched adult controls on a series of cognitive and language measures. Parents of children with autism exhibited lower performance on the matrix reasoning subtest and total performance IQ than did controls, but did not show differences in verbal IQ measures, when tested with the Wechsler Abbreviated Scale of Intelligence (WASI). In addition, parents of children with autism had lower performance on a nonword repetition task, but did not show differences on tests of figurative language, receptive language, expressive language, and verbal fluency and on a questionnaire assessing history of reading difficulties. Results from this study are generally consistent with the cognitive profiles reported for parents of children with autism. Our finding of nonword repetition difficulties, along with others' previous findings for nonword reading in autism families, suggests that problems in phonological processing might be characteristic of the broad autism phenotype.

Electrophysiological signatures: magnetoencephalographic studies of the neural correlates of language impairment in autism spectrum disorders.

While magnetoencephalography (MEG) is of increasing utility in the assessment of pediatric patients with seizure disorders, this reflects only a part of the clinical potential of the technology. Beyond epilepsy, a broad range of developmental psychiatric disorders require the spatial and temporal resolution of brain activity offered by MEG. This article reviews the application of MEG in the study of auditory processing as an aspect of language impairment in children. Specifically, the potential application of MEG is elaborated in autism spectrum disorders (ASD), a devastating disorder with prevalence of 1 in 150. Results demonstrate the sensitivity of MEG for detection of abnormalities of auditory processing in ASD ('electrophysiological signatures') and their clinical correlates. These findings offer promise for the comprehensive assessment of developmental neuropsychiatric disorders.

Right hemisphere metaphor processing? Characterizing the lateralization of semantic processes.

Previous laterality studies have implicated the right hemisphere in the processing of metaphors, however it is not clear if this result is due to metaphoricity per se or another aspect of semantic processing. Three divided visual field experiments varied metaphorical and literal sentence familiarity. We found a right hemisphere advantage for unfamiliar sentences containing distant semantic relationships, and a left hemisphere advantage for familiar sentences containing close semantic relationships, regardless of whether sentences were metaphorical or literal. This pattern of results is consistent with theories postulating predominantly left hemisphere processing of close semantic relationships and predominantly right hemisphere processing of distant semantic relationships.

A voxel-based morphometry study of gray matter in parents of children with autism.

Previous structural imaging studies of autistic individuals have identified gray matter abnormalities. It remains unclear, however, which abnormalities contribute to the etiology of autism and, among these abnormalities, which reflect genetic factors. Using voxel-based morphometry, we compared regional gray matter volume in 23 parents of autistic children to an age and sex-matched control sample. We identified relative local gray matter volume increases and decreases in the parent group that are consistent with previous research with autistic individuals. Further, differences were identified in regions that are functionally associated with social-cognitive and motor processes that are impaired in autism. This investigation constitutes the first whole-brain study of regional brain volume in the parents of autistic children, and suggests that a number of structural changes observed in autism may be familial.