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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    049—Human Biomarkers of Autism

    Saturday, November 09, 2013, 1:00 pm - 5:00 pm

    49.01: Altered spontaneous gamma-band functional connectivity in adolescents with autism spectrum disorder

    Location: Halls B-H

    *A. X. YE1,2, R. C. LEUNG1,3, C. B. SCHAEFER1,4, M. J. TAYLOR1,2,3, S. M. DOESBURG1,2;
    1Neurosciences and Mental Hlth., Hosp. For Sick Children, Toronto, ON, Canada; 2Inst. of Med. Sci., 3Psychology, Univ. of Toronto, Toronto, ON, Canada; 4Heidelberg Univ., Heidelberg, Germany

    Abstract Body: Individuals with autism spectrum disorder (ASD) demonstrate deficits in social cognition, including difficulty recognizing emotions and social gestures. These deficits could reflect a dysmaturation of structural and functional network connectivity. Systems-level approaches, such as network analysis using graph theory, are well suited to assessing altered brain connectivity. Resting-state fMRI studies of ASD populations have found disruptions in frontal circuits which are related to social cognition and executive function. Magnetoencephalography (MEG) can measure the synchrony of fast neural oscillations known to be critical for cognition, providing complementary information to fMRI-based approaches. The present research used MEG imaging to test the hypothesis that inter-regional oscillatory synchrony is altered in adolescents with ASD. We recorded five minutes of spontaneous brain activity using 151-channel whole-head CTF system while participants (16 adolescents with ASD and 15 typically developing controls) viewed a centrally presented fixation cross. Atlas-guided reconstruction of brain activity was performed for 90 regions of interest using beamformer analysis, data were frequency filtered into five bands (θ, α, β, low γ, high γ) and inter-regional synchrony was calculated. We employed Network Based Statistics to investigate group differences in inter-regional connectivity. Using graph theoretical measures, the regions expressing significant connectivity differences were treated as nodes and network measures were quantified. We observed increased functional connectivity in the low gamma-band (30-80 Hz) in ASD adolescents. Specifically, fifteen brain regions showed increased inter-connectivity in the ASD group, the majority of which were in the frontal lobes. Graph analysis supported this increased gamma-band connectivity in adolescents with ASD, reflected by higher network strength and clustering. This study is the first demonstration of altered functional connectivity in ASD using a MEG phase coherence approach. Considered in concert with the recent literature, our findings indicate atypical frontal lobe networks in adolescents with ASD, which may contribute to difficulties in social cognition.

    Lay Language Summary: Our research uses recent advances in magnetoencephalographic (MEG) brain imaging and brain network analysis to provide new insights into the biological basis of autism. We found that adolescents with autism have altered communication among brain areas.
    Until recently, most evidence contributing to our understanding of communication in the brain has come from studies using functional magnetic resonance imaging (fMRI). fMRI provides millimetre-scale functional images of brain activity, but is unable to track them in 'real time' (ie. can only provide information on the order of seconds). This study, to our knowledge, is the first to use MEG brain imaging to show that communication in the autistic brain is altered (even when the brain is not involved in a task) using an approach based on 'real time' fluctuations in brain waves.
    We report differences in functional connectivity, which describe how brain areas communicate with one another. In particular, frontal areas appear hyperconnected (communicating too much with each other) in adolescents with autism when we looked at brain waves at fast frequencies (ie. gamma-band rhythms, which alternate at 30 to 80 cycles per second). This effect was not seen when we looked at brain waves at lower frequencies.
    Gamma-band brain rhythms have received much attention from neuroscientists in recent years. Experimental data suggest that brain areas involved in processes such as working memory and perceptual awareness express this type of rhythm when at work. Moreover, gamma rhythms are thought to be disrupted in abnormal brain states. Thus, our findings suggest that brain waves critical for mental processes are disturbed in adolescents with autism.
    Many of the stronger connections we found in adolescents with autism were between brain areas responsible for higher order cognitive control, emotions, and social interactions. These stronger connections could explain some of the behavioural deficits associated with autism: a more highly connected area of the brain is prone to information overload, which could mean that signals become too overwhelming to parse apart and feed to other brain areas. This suggests that the frontal areas of the brain may be processing the information locally, but not sending it out to the rest of the brain.
    We used a helmet-shaped device called an MEG to record brain waves in our participants. We scanned the brains of 16 autistic adolescents who ranged in age from 12 to 15 years and also recorded brain waves from 15 typically developing age and sex-matched adolescents for comparison. MEG allows changes in brain activity to be followed with millisecond timing accuracy, and is also a direct measure of brain activity (unlike fMRI). MEG can provide information on brain waves from the slowest (one or two cycles per second) to the fastest (150 cycles per second) frequencies, hence complementing information we know from fMRI and other brain imaging technologies.
    Our next step is to look at how altered brain communication develops in autism throughout childhood and adolescence. This will provide us with a better picture of brain development in autism and its role in social and communication deficits in this group.
    The prevalence of autism is about 1% in Asia and Europe, with one in 88 children diagnosed in the United States. People with autism face every day challenges with social, communication, and emotional skills. The symptoms of autism appear by the age of three years, and last throughout their lifetime. A better understanding of the autistic brain will help in developing strategies for earlier diagnosis, leading to the possibility of earlier interventions.