Neural processing of intentional biological motion in unaffected siblings of children with autism spectrum disorder: an fMRI study

Abstract

Despite often showing behaviorally typical levels of social cognitive ability, unaffected siblings of children with autism spectrum disorder have been found to show similar functional and morphological deficits within brain regions associated with social processing. They have also been reported to show increased activation to biological motion in these same regions, such as the posterior superior temporal sulcus (pSTS), relative to both children with autism and control children. It has been suggested that this increased activation may represent a compensatory reorganization of these regions as a result of the highly heritable genetic influence of autism. However, the response patterns of unaffected siblings in the domain of action perception are unstudied, and the phenomenon of compensatory activation has not yet been replicated. The present study used functional magnetic resonance imaging to determine the neural responses to intentional biological actions in 22 siblings of children with autism and 22 matched controls. The presented actions were either congruent or incongruent with the actor's emotional cue. Prior studies reported that typically developing children and adults, but not children with autism, show increased activation to incongruent actions (relative to congruent), within the pSTS and dorsolateral prefrontal cortex. We report that unaffected siblings did not show a compensatory response, or a preference for incongruent over congruent trials, in any brain region. Moreover, interaction analyses revealed a sub-region of the pSTS in which control children showed an incongruency preference to a significantly greater degree than siblings, which suggests a localized deficit in siblings. A sample of children with autism also did not show differential activation in the pSTS, providing further evidence that it is an area of selective disruption in children with autism and siblings. While reduced activation to both conditions was unique to the autism sample, lack of differentiation to incongruent and congruent intentional actions was common to both children with ASD and unaffected siblings.

Keywords: ASD; Action perception; Autism; BOLD; CC; Endophenotype; ROI; Superior temporal sulcus; US; autism spectrum disorder; blood oxygen level-dependent; control children; dlPFC; dorsolateral prefrontal cortex; fMRI; pSTS; posterior superior temporal sulcus; region-of-interest; unaffected siblings.

Figure 1

Diagram depicting the paradigm used in the present study. The actor orients towards a cup and displays a positive or negative emotion, then a reach in either direction while maintaining a neutral expression. Four outcomes are possible, two of which are congruent with intention and two are not.

Figure 2

(A): Peak activations (relative rise from onset to timepoint 5) in compensatory pSTS for both groups and separated by group. Also shown are the differential (B) and aggregate (C) group-averaged waveforms for control children (red line) and unaffected siblings (blue line).

Figure 3

(A): Peak activations (relative rise from onset to timepoint 5) in the trait-defined dlPFC for both groups and separated by group. Also shown are the differential (B) and aggregate (C) group-averaged waveforms for control children (red line) and unaffected siblings (blue line).

Figure 4

Surface representations for ROIs used or created in the current study. (A): Representation of the “compensatory” right hemisphere pSTS ROI (right) and “trait” left hemisphere dlPFC (left). (B): Regions defined by a whole-brain analysis. The purple region represents the area where control children showed an incongruent > congruent effect most strongly. The green region represents the area where control children showed an incongruency preference to a significantly greater degree than unaffected siblings did. No brain regions existed where unaffected siblings responded significantly more strongly to incongruent relative to congruent trials. The green region includes areas that are occluded by the purple region. (C): Visual depiction of the pSTS region defined using activation-likelihood estimation meta-analysis.

Figure 5

Peak activations (relative rise from onset to timepoint 5) in the pSTS region in which control children showed a preference in activation to incongruent over congruent trials to a significantly greater degree than unaffected siblings.

Figure 6

Aggregate and differential waveforms for the ASD group in the pSTS region in which control children showed a preference in activation to incongruent over congruent trials to a significantly greater degree than unaffected siblings. The two differential waveforms correspond to two distinct definitions of congruency. The blue line is the waveform for the same definition used throughout the study (congruency is based on the intention derived from the emotional expression of the actor). The green line disregards emotion and defines intention by head turn, such that looking at a cup and reaching for it is labeled a congruent action, regardless of the preceding emotion.

Figure 7

Peak BOLD response values in the pSTS (defined empirically via activation likelihood-estimation meta-analysis) to intentional biological motion in the ASD group and the sub-group of control children, matched on age, gender, sample size, and IQ.