A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism

Abstract

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend for abnormally lateralized temporal responses to language (i.e. greater activation on the right, rather than the expected left) in a small sample (n = 12) of sleeping 2-3 year olds with autism in contrast to typically developing children, a finding also reported in autistic adults and adolescents. It was unclear, however, if findings of atypical laterality would be observed in a larger sample, and at even earlier ages in autism, such as around the first birthday. Answers to these questions would provide the foundation for understanding how neurofunctional defects of autism unfold, and provide a foundation for studies using patterns of brain activation as a functional early biomarker of autism. To begin to examine these issues, a prospective, cross-sectional design was used in which brain activity was measured in a large sample of toddlers (n = 80) during the presentation of a bedtime story during natural sleep. Forty toddlers with autism spectrum disorder and 40 typically developing toddlers ranging in age between 12-48 months participated. Any toddler with autism who participated in the imaging experiment prior to final diagnosis was tracked and diagnoses confirmed at a later age. Results indicated that at-risk toddlers later diagnosed as autistic display deficient left hemisphere response to speech sounds and have abnormally right-lateralized temporal cortex response to language; this defect worsens with age, becoming most severe in autistic 3- and 4-year-olds. Typically developing children show opposite developmental trends with a tendency towards greater temporal cortex response with increasing age and maintenance of left-lateralized activation with age. We have now demonstrated lateralized abnormalities of temporal cortex processing of language in autism across two separate samples, including a large sample of young infants who later are diagnosed with autism, suggesting that this pattern may reflect a fundamental early neural developmental pathology in autism.

Figure 1

Clusters of significant response to all speech stimuli in the typically developing (n = 40) and autism spectrum disorder (n = 40) groups, and clusters of significant difference in brain response between groups. Colours indicate relative strength and direction of the effect size (η²) [for individual group maps, positive values (warm colours) indicate greater brain response to speech compared with non-stimulation; and negative values (cool colours) indicate lower brain response to speech compared with non-stimulation in individual group maps; for group comparison map, positive values (warm colours) indicate greater brain response in the typically developing compared with autism spectrum disorder group]. R = right; L = left.

Figure 2

Graphs of amplitude (mean fit coefficient) (A) and extent (volume in µl of active voxels with t > 2.0) (B) of brain response within the cluster of significant group difference in brain response to all speech in the left hemisphere superior temporal gyrus. Values are shown for all speech (used to identify the significant cluster) and separately for the component conditions. Mean values for the autism spectrum disorder (ASD) group are shown in red and those for the typically developing group are shown in blue. Error bars indicate the standard error of the mean.

Figure 3

Graph of extent (volume in µl of active voxels with t > 2.0) of brain response within each hemisphere of the entire superior temporal gyrus anatomical region of interest. Values are shown for all speech and separately for the component conditions. Mean values for the autism spectrum disorder (ASD) group are shown in red for left hemisphere and pink for right hemisphere, and those for the typically developing group are shown in blue for the left hemisphere and light blue for the right hemisphere. Error bars indicate the standard error of the mean.

Figure 4

(A and B) Voxel-based within-group laterality score maps during the forward speech condition (expressed as signed η² effect size values; warm colours = left greater than right; cool colours = right greater than left) for typically developing and autism spectrum disorder groups in the superior temporal gyrus (shown at 51 left/right). (C) Group difference map showing the cluster of significant difference in laterality between groups, with more left-lateralized values in the typically developing compared with autism spectrum disorder group [36 voxels (each with t = 1.66, P_one-tailed = 0.05), superior temporal gyrus-wide P < 0.05, with a peak at 50 left, 5 posterior and 4 superior].