Archive for June, 2013

Functional Brain Imaging of Autism Spectrum Disorder:

Current and Future Directions

(adapted in part from Dichter, 2012)

Gabriel S. Dichter

Departments of Psychiatry and Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC

Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC

Since Leo Kanner (1943) and Hans Asperger (1944) first described children with what we now call autism spectrum disorder (ASD), there has been widespread recognition of the brain basis of ASD.  Much of what is known about brain functioning in ASD is due to advances in modern brain imaging techniques.  It has been over twenty years since the first brain imaging studies of ASD (Carina Gillberg, Bjure, Uvebrant, Vestergren, & Gillberg, 1993), and nearly fifteen years since the first study using functional magnetic resonance imaging (fMRI)(Baron-Cohen, et al., 1999), arguably the most widespread technique to investigate brain functioning in ASD.  Incredibly, over 600 fMRI studies of ASD have been reported in the scientific literature.  Given this rapid growth in fMRI research, it is important to consider what these studies have taught us and what the future of this technology holds for helping to understand the brain basis of ASD and ultimately for improving the lives of those affected by ASD.


What we’ve learned so far:  Brain regions activate and co-activate differently in ASD

fMRI investigates what brain areas are “active” during specific conditions.  fMRI studies to date have addressed brain activation in ASD in the following areas:

Social Processing: A core feature of ASD is social impairment, and individuals with ASD are characterized by decreased activation in face-responsive brain areas, including the amygdala and fusiform gyrus, although directing attention to certain areas of a face may “normalize” face-responsive brain activation.  Responses to images, stories, or animations designed to elicit the attribution of mental states to other people reveal decreased activation in the amygdala, a region known to respond to the emotional relevance of social information, and the posterior superior temporal sulcus, a region responsive to animate motion.  Finally, decreased activity has been found in brain regions specialized for imitation (the so-called “mirror neuron system), including the pars opercularis in the inferior frontal gyrus.  Finally, a recent review of multiple studies highlights that a brain region called the anterior insula, an important information processing hub, consistently is under-activated in ASD across a wide variety of social tasks (Di Martino, et al., 2009).

Cognitive Control:  ASD is also characterized by restricted and repetitive behaviors and interests, which encompasses repetitive motor behaviors such as hand flapping, the need for predictability and routines, as well as extreme interest in certain topics or objects.  Brain imaging research into this symptom domain has used tasks requiring complex problem solving with reports of anomalous activation in the basal ganglia and the prefrontal cortex.  Most of these studies indicate relatively greater activation in these regions, suggesting compensatory activation in the context of a cognitively challenging task.

Communication: Studies of communication deficits in ASD have focused on responses to speech sounds and language.  Whereas in typical development the left side of the brain predominantly processes language, this pattern is less pronounced in ASD.  Additionally, brain regions typically not responsive to speech are active in ASD.  Anomalous responses to speech have also been demonstrated in 12-month old children with ASD during sleep, suggesting utility in studies of young children at risk for developing ASD.

Reward Processing: A growing area of research addresses responses of brain regions that process rewards in ASD.  These studies have shown generally lower activity in reward processing regions in response to social rewards, suggesting that cues and images of faces are less pleasing and motivating, respectively, in ASD.  Additionally, reward processing regions are over-active in response to restricted interests, suggesting a brain basis for the unusually strong interests, preoccupations, and attachments that are commonly observed in ASD.

ASD as a disorder of brain connectivity: fMRI is well suited to study whether different brain regions activate in unison.  Such studies of “functional connectivity” speak to the temporal dynamics of brain network activity.   Multiple studies indicate that ASD is characterized by decreased connectivity between brain regions that are far apart, including between areas at the front of the brain and regions towards the back of the brain that process social information.  Additionally, ASD is characterized by increased connectivity between brain regions that are close together, indicating inefficient information processing.

Where we’re headed: The future of functional brain imaging research in ASD

Most brain imaging studies of ASD to date have focused on adulthood or adolescence, and yet ASD is present from very early childhood.  It will be important to study the emergence and development of brain function in younger samples to separate early brain patterns characteristic of ASD from the effects of a lifetime of altered experiences due to ASD.

Brain imaging is expensive, and most studies include only small samples that impede the identification of meaningful subgroups with different developmental profiles.  Large publicly available brain imaging repositories with data from thousands of well-characterized individuals are being created, including the National Database for Autism Research (http://ndar.nih.gov/) and the Autism Brain Imaging Data Exchange (http://fcon_1000.projects.nitrc.org/indi/abide/), that will facilitate research into network-level brain function in large ASD samples.

Finally, the National Institute of Mental Health (NIMH) has developed a new initiative to support so-called Fast-Fail Trials (http://www.nimh.nih.gov/research-priorities/research-initiatives/fast-fast-fail-trials.shtml) designed to increase the pace of discovery of new psychiatric medications.  These trials focus intensively on the capacity of a novel compound to engage brain targets relevant to a disorder in a small sample of patients (about 10-30) rather than on more expensive and time-consuming clinical trials involving hundreds or thousands of patients (Insel, 2012).  Functional brain imaging is a key component of this new approach which holds the ultimate promise of bringing new effective treatments to market as soon as possible and of broadening the avenues available for development and screening of new candidate drugs to improve the lives of those with ASD and their families.


Asperger, H. (1944). Autistic Psychopathy in Childhood. In U. Frith (Ed.), Translated in Autism and Asperger’s Syndrome (pp. 37-92): Cambridge University Press, Cambridge.

Baron-Cohen, S., Ring, H. A., Wheelwright, S., Bullmore, E. T., Brammer, M. J., Simmons, A., et al. (1999). Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci, 11(6), 1891-1898.

Carina Gillberg, I., Bjure, J., Uvebrant, P., Vestergren, E., & Gillberg, C. (1993). SPECT (Single Photon Emission Computed Tomography) in 31 children and adolescents with autism and autistic-like conditions. Eur Child Adolesc Psychiatry, 2(1), 50-59.

Di Martino, A., Ross, K., Uddin, L. Q., Sklar, A. B., Castellanos, F. X., & Milham, M. P. (2009). Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biol Psychiatry, 65(1), 63-74.

Dichter, G. S. (2012). Functional magnetic resonance imaging of autism spectrum disorders. Dialogues Clin Neurosci, 14(3), 319-351.

Insel, T. R. (2012). Next-generation treatments for mental disorders. Sci Transl Med, 4(155), 155ps119.

Kanner, L. (1943). Autistic Disturbances of Affective Contact. Nervous Child 2 217-250.

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