Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism

Abstract

Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others.

Figure 1

Hyperactivation in temporal and frontal regions in adolescents with autism and their siblings, relative to control subjects. Activation map indicates areas where EFT-related activation (EFT versus control task) is significantly greater in autism and sibling groups versus control subjects. Map thresholded at uncorrected P = 0.001 on whole brain level and rendered onto 3D MNI template brain image in MRIcron. The table within this figure indicates the significant result after correction for multiple comparisons on FWE-corrected whole brain level. Graph indicates means (SE) for average contrast estimate (EFT—control task) from 4-mm-radius sphere around the FWE-corrected peak result (−60, −4, −18).

Figure 2

Between-group differences in EFT-related activation in adolescents with autism, their unaffected siblings and control subjects. Red indicates greater activation in autism versus control subjects. Blue indicates greater activation in control subjects versus autism. Green indicates greater activation in siblings versus control subjects. Brown indicates overlap between greater activation in autism (red) and siblings (green) relative to control subjects. Group difference maps thresholded at uncorrected P = 0.001 on whole brain level, k_E ≥ 10, and rendered as solid colours onto coronal sections of MNI template brain image in MRIcron. Number indicates y co-ordinate of coronal section. Sagittal section illustrates locations of coronal sections indicated.

Figure 3

(A–C) Correlations between impairments in reciprocal social interaction (subdomain B on the ADOS) and autism group mean contrast estimate (EFT—control task) in A, left fusiform gyrus, B, left supramarginal gyrus, and C, left V3 associative visual cortex. P-values indicate partial correlation after controlling for age and sex. CT = control task.