Autism Spectrum Disorders nimh.nih/publicat/autism.cfm

2. Understanding Emotions in Others: Mirror Neuron Dysfunction in Children with Autism Spectrum Disorders Mirella Depretto, Mari S. Davies, Jennifer H. Pfeifer, Ashley A. Scott, Marian Sigman, Susan Y. Bookheimer, & Marco Iacoboni Published online 4 December 2005. Nature Neuroscience. Volume 9, Number 1, January 2006. Nature Publishing Group. Summarized by Shannon Juedes

3. Autism Spectrum Disordershttp://www.nimh.nih.gov/publicat/autism.cfm • A recent study of a U.S. metropolitan area estimated that 3.4 of every 1,000 children 3-10 years old had autism. • ASD is often dismissed. The child is just a little slow and “will catch up.” • All children with ASD demonstrate deficits in • 1) social interaction • 2) verbal and nonverbal communication • 3) repetitive behaviors or interests. • In addition, they will often have unusual responses to sensory experiences, such as certain sounds or the way objects look. • Each of these symptoms runs the gamut from mild to severe. They will present in each individual child differently.

5. Autism Spectrum Disorder (Cont.) http://www.nimh.nih.gov/publicat/autism.cfm • Postmortem and MRI studies have shown that many major brain structures are implicated in autism. • Other research is focusing on the role of neurotransmitters such as serotonin, dopamine, and epinephrine.

6. Mirror Neurons • Rizzolatti et al. found that neurons in an area of the rostral part of the ventral premotor cortex in the monkey brain became active when monkeys saw people or other monkeys perform various movements or when they performed these movements themselves. These neurons were also found in the inferior parietal lobule which is connected with the ventral premotor cortex. • Mirror neuron system activity in the human homolog of area F5—the pars opercularis in the inferior frontal gyrus—has been consistently reported during imitation, action observation, and intention understanding. • Mirror Neurons: Neurons located in the ventral premotor cortex and inferior parietal lobule that respond when the individual makes a particular movement or sees another individual making that movement.

8. Mirror Neurons • The “What” System—recognition of objects involves the ventral stream of the visual association cortex including the inferior temporal cortex • The “Where” System—perception of location and movement involves the dorsal stream of the posterior parietal cortex. This system includes the mirror neuron circuit (The “How” system.) • The “Why” System—The Intent of the Action/Mediation of Understanding of Emotional States of Others • “[A]n action is understood when its observation causes the motor system of the observer to ‘resonate.’ So, when we observe a hand grasping an apple, the same population of neurons that control the execution of grasping movements becomes active in the observer’s motor areas…In other words, we understand an action because the motor representation of that action is activated in our brain.” • The neurons responded to either the sight or the execution of particular movements. • Sight and Sound

9. Prelude • Dysfunction of the mirror neuron system (MNS) early in development could give rise to the cascade of impairments that are characteristic of ASD. • Using fMRI, a neural network in which the insula acts as an interface between the frontal component of the MNS and the limbic system was described, thus enabling the translation of an observed or imitated facial emotional expression into its internally felt emotional significance.

10. Previous Studies • Three recent studies used different electrophysiological techniques have each reported preliminary evidence for abnormal MNS functioning during action imitation and observation in adults with ASD. • A more definitive test of MNS theory of autism would involve examining MNS activity in the content of a socio-emotional task and in a sample of children.

11. The Experiment • An event-related fMRI design was used to investigate neural activity during the imitation and observation of facial emotional expressions. • Subjects: • 9 high-functioning children with ASD (12.05+/- 2.50 years) • 9 typically-developing children matched by age and IQ (12.38+/- 2.22 years)

12. The Experiment (Cont.) • Stimuli: • 80 faces expressing five different emotions: • Anger, Fear, Happiness, Neutrality, or Sadness • Presented for two seconds with optimized random sequence that included null events (blank screens with fixation crosses at eye level) and temporal jittering to increase statistical efficacy

13. The Experiment (Cont.) • In two separate scans (with the order counterbalanced within each group), subjects either imitated or simply observed the faces via high-resolution, magnet-compatible goggles. • All children practiced the tasks outside the scanner to demonstrate that they were willing and able to comply with the task requirements. • Half the children in each group also performed both tasks during a video-taped session with an eye tracker.

14. Observations • Imitation of Emotional Expressions vs. Null Events: • The typically developing children activated a neural network very similar to that previously observed in adults. • Extensive bilateral activation of striate and extra striate cortices, primary motor and premotor regions, limbic structures (amygdala, insula, and ventral striatum) and the cerebellum. • Showed strong bilateral activity within the pars opercularis of the inferior frontal gyrus (Brodmann’s area 44) as well as in the neighboring pars triangularis (Brodmann’s area 45), with strongest peaks in the right hemisphere.

15. Observations (Cont.) • Observations of the ASD group: • Robust activation in visual cortices, premotor and motor regions of the face and the amygdala. • Indicates that these children attend to the stimuli and imitated the facial expressions. • Failed to show any activity in the mirror area in the pars opercularis

16. Observations (Cont.) • Direct Comparisions between the ASD group and the typically developing children confirmed that activity in the anterior component of the MNS was reliably greater in typically developing children. • TD children showed reliably greater activity in insular and periamygdaloid regions as well as in the ventral striatum and thalamus. • ASD children showed greater activity in left anterior parietal and right visual association areas.

17. Findings • Individuals with ASD typically show deficits in understanding the emotional states of others. • Dysfunction in the MNS should be manifest not only when these individuals imitate emotional expressions but when they observe others’ emotions • Activity in the right pars opercularis during the observation of facial expressions was stronger in the TD group then the ASD group • Difference is not attributed to the failure of the children with ASD to attend to the face stimuli as both groups showed activation in regions implicated in face processing.

20. To Further Test the Hypothesis: • Examined the relationship between activity in regions with MN properties and symptom severity, as indexed by children’s scores on the ADOS-G and the ADI-R. • Controlled for IQ

21. Observations • Negative correlations between activity in the pars opercularis and the children’s scores on the social subscales of the ADOS-G and ADI-R. • The greater the activity in this critical component of the MNS during imitation, the higher a child’s level of functioning in the social domain • Activity in components of the normative network underlying emotion understanding via action representation was also negatively correlated with symptom severity.

23. Analysis of Experiment • Although they were unable to monitor gaze fixation during scanning, a variable shown to affect brain activity in ASD, it is unlikely that their findings reflect between-group differences in the amount of time spent looking at the eye region. 1. During neither the imitation or observation of facial expressions did they find group differences in the fusiform region. • Activity in the fusiform gyrus did not correlate with activity in MNS areas in either condition. • In the children with ASD for whom eye-tracking data were available, there was no indication of a positive relationship between MNS activity in the pars opercularis and time spent fixating the eyes.

24. Analysis of the Experiment (Cont.) • Despite the fact that they were unable to monitor task performance during scanning and imitation deficits in ASD, they believe that their findings reflect the children with ASD not performing the imitation task or not performing it well. • All the children were willing and able to perform the task before scanning. • Children with ASD performed the task outside the scanner as well as TD children. • Observations of the ASD group show robust activity in primary motor and premotor areas of the face during the imitation task, with no evidence of between group differences in these regions. • The ASD children showed greater activity than the typically developing children in right visual and left anterior parietal areas.

25. Conclusions • The neural strategies adopted by the TD and ASD groups are quite different. • TD children rely upon a right hemisphere-mirroring neural mechanism—interfacing with the limbic system via the insula. • ASD children must adopt an alternative strategy of increased visual and motor attention. In effect, the internally felt emotional significance of the imitated facial expression is not probably not experienced.

26. Conclusions (Cont.) • The fact that TD children showed increased MNS activity even when simply observing an emotional expression indicates that this mirroring mechanism underlies the ability to read others’ emotional states from a glance. • The lack of MNS activity during both the imitation and the observation of emotional expressions in their sample of children with ASD provides support that early dysfunction in the MNS may be at the core of the social deficits that are typical of ASD.