Speaker:
Mirella Dapretto, University of California at Los Angeles

Highlights:

• Although children with ASD exhibit reduced preference for human faces and voices, evidence suggests that these responses can be boosted when their attention is actively focused.

• The lack of attention to these stimuli in ASD may in part result from a failure of the brain to perceive such socially-relevant input as ‘rewarding’.

• Reduced activity in mirror neuron centers, which help the brain to interpret the actions and mental states of others, may also contribute to these social attention deficits.

• These various brain regions appear to function properly at the local level in ASD, but lack the long-range connectivity and coordination necessary for normal social cognition.

Early in brain development, infants will preferentially focus their attention on human faces and voices—particularly that of their mother. However, this is not the case for children with ASD. As Dawson pointed out in her talk, face response is diminished in autistic children. These children also display a preference for neutral, computerized voices over a warm, tonally-rich human voice. Accordingly, several studies have revealed that individuals with ASD exhibit diminished activity in the fusiform ‘face area’ and the amygdala, key brain regions involved in the interpretation of emotional information.

Individuals with ASD exhibit diminished activity in key brain regions involved in interpretation of emotional information

Mirella Dapretto’s group has been exploring these phenomena in the context of understanding how neurological defects associated with autism disrupt brain activities associated with ‘theory of mind’ functions. “These are those skills we have that allow us to interpret other people’s intentions and actions, and to interpret their emotional state,” she said.
Some evidence suggests that these areas can be selectively activated under some conditions; for instance, familiar faces trigger normative fusiform activity in individuals with autism relative to the faces of complete strangers. [1] This suggests that this activity is at least partly dependent upon attention, and Dapretto’s team has performed studies that investigate the extent to which increased attention can improve the capacity of ASD-affected children to perceive subtle social cues.

In one series of experiments, she presented children with cartoon scenarios of social interaction in which a character makes the same remark in either a ‘positive’ and sincere or a ‘negative’ and ironic manner, and then asked them to characterize the nature of the remark. When told to simply ‘pay attention’, unaffected children showed healthy levels of activity in the ventromedial prefrontal cortex, a theory of mind area, while children with ASD did not. However, when these children were instructed to specifically pay attention to characters’ tone of voice or facial expressions, the affected children exhibited normal activity levels in this area. [2]

The rewards of attention
With this evidence that brain function is essentially intact in these areas, Dapretto shifted her focus to explore the lack of a bias for facial and vocal stimuli in ASD. “According to the social motivation hypothesis, this lack of an attentional preference for these stimuli may reflect that they’re not ‘rewarding’,” she said.

Her team has tested this model with a series of experiments in which children performed simple learning tasks with positive or negative feedback given ‘socially’ (with a picture of a smiling or frowning woman) or ‘monetarily’ (with pictures of gold coins or the same coins marked with red X’s). Unaffected children showed stronger activity in the reward circuitry, including the ventral striatum, in response to both types of reinforcement relative to children with ASD, but the differences were especially significant for social rewards.

A growing body of data suggests that the mirror neuron system is typically impaired in ASD

Various neuroimaging studies have suggested that activity in the so-called ‘mirror neuron’ system, which enables the brain to map and interpret the actions and intentions of others, may play an important role in social and emotional interactions. Accordingly, a growing body of data suggests that this system is typically impaired in ASD. Dapretto and colleagues previously performed an fMRI study in which autistic children were asked to mimic facial expressions conveying various emotions; although the children performed well at the physical task, they showed markedly reduced activity in mirror neuron centers of the brain. [3] The extent of these activity deficits was closely correlated with the severity of ASD symptoms related to social interaction.

Her group is also examining the role of a reduced attentional bias for speech and ASD-associated language deficits through experiments that make use of an artificially constructed language. Infants as young as 6 months old have already acquired the capacity to recognize word boundaries in a continuous stream of speech, and this ability has been correlated with subsequent language development (e.g., child’s vocabulary size). Dapretto’s team exposed children to streams of speech consisting of trisyllabic words with or without prosodic cues (e.g., stressed syllables), as well as a random syllable stream. Like normal adults, typically developing children selectively exhibited increasing activity in language centers—indicative of implicit learning—in response to repeated sequences of structured ‘words’. In children with ASD, only minimal increases in activity were observed in these regions—and intriguingly, the extent of activation observed in a given child could be directly correlated with their level of language impairment.

In accordance with other ASD models presented today, Dapretto concludes that social and emotional impairments might result largely from a lack of long-range integration between otherwise-functioning brain regions and be exacerbated by issues of reduced attentional bias, and her group is continuing to explore the potential impact of such deficits on linguistic development as well.

[1] Pierce, K. et al. Brain 127, 2703–16 (2004).
[2] Wang, A.T. et al. Arch. Gen. Psychiatry 64, 698–708 (2007).
[3] Dapretto, M. et al. Nat. Neurosci.9, 28–30 (2006).

Connecting the dots
According to Dapretto, there may be a link between mirror neuron activity and attentional bias, and ongoing experiments from her group are investigating this question. Preliminary data from her group offer evidence that autistic children lack coordinated activity between the reward centers and mirror neuron centers, a correlation that is strongly apparent in unaffected children. “Children who have highest activity in the ventral striatum when they were getting the smiling faces as positive feedback were also the children who showed greater activity in those mirroring regions that we think are important for interpreting another’s facial expression and how that person might feel,” she said.

More than words
Communication is based on much more than the transmission and reception of strings of sounds, and a great deal of meaning in social interactions is conveyed through a combination of facial expression and voice characteristics.