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Translational use of event-related potentials to assess circuit integrity in ASD

Nature Reviews Neurology volume 13, pages 160–170 (2017)Cite this article

Subjects

Key Points

  • Autism spectrum disorder (ASD) can be characterized as a disorder of connectivity that disrupts the spatially diffuse neural social circuit to cause characteristic deficits in social interaction

  • Event-related potentials (ERPs) are EEG-based readouts of time-locked circuit activation, alterations of which reflect circuit dysfunction

  • Sensory-evoked ERPs can be measured in patients with ASD and animal models of the disorder

  • Socially-evoked ERPs are abnormal in humans with ASD, suggesting that ERPs could represent a quantitative biomarker of social impairment

  • Characterization of socially evoked ERPs in animal models of ASD could provide a translational biomarker of social cognition that could aid forward and backward translational research

Abstract

Deficits in social cognition are the defining characteristic of autism spectrum disorder (ASD). Social cognition requires the integration of several neural circuits in a time-sensitive fashion, so impairments in social interactions could arise as a result of alterations in network connectivity. Electroencephalography (EEG) has revealed abnormalities in event related potentials (ERPs) evoked by auditory and visual sensory stimuli in humans with ASD, indicating disruption of neural connectivity. Similar abnormalities in sensory-evoked ERPs have been observed in animal models of ASD, suggesting that ERPs have the potential to provide a translational biomarker of the disorder. People with ASD also have abnormal ERPs in response to auditory and visual social stimuli, demonstrating functional disruption of the social circuit. To assess the integrity of the social circuit and characterize biomarkers of circuit dysfunction, novel EEG paradigms that use social stimuli to induce ERPs should be developed for use in animal models. The identification of a socially-relevant ERP that is consistent in animal models and humans would facilitate the development of pharmacological treatment strategies for the social impairments in ASD and other neuropsychiatric disorders.

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Figure 1: Auditory event-related potentials in humans and rodents.
Figure 2: Similar alterations in sensory event-related potentials in humans and rodents in syndromic and idiopathic autism spectrum disorder.
Figure 3: Forward and backward translation of an identified event-related potential biomarker of autism spectrum disorder.

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Acknowledgements

The authors thank Dr April Levin (Boston Children's Hospital, Massachusetts, USA) for critical reading of the manuscript and helpful discussions. The authors were supported by the Nancy Lurie Marks Family Foundation, the Boston Children's Hospital Translational Research Program NIH U01 NS082320 and the Developmental Synaptopathies Consortium (U54NS092090), which is a part of the National Center for Advancing Translational Sciences (NCATS). Rare Diseases Clinical Research Network (RDCRN) to M.S. RDCRN is an initiative of the Office of Rare Diseases Research, NCATS, funded through collaboration between NCATS, National Institute of Mental Health (NIMH), National Institute of Neurological Diseases and Stroke (NINDS), and National Institute of Child Health and Human Development (NICHD).

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Authors and Affiliations

  1. Department of Neurology, Translational Neuroscience Center, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Meera E. Modi & Mustafa Sahin

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  1. Meera E. Modi
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  2. Mustafa Sahin
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Both authors contributed equally to the preparation of the manuscript.

Corresponding author

Correspondence to Mustafa Sahin.

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Competing interests

M.S. has received research support from Novartis, Pfizer, Roche and Shire, and is on the Scientific Advisory Board of Sage Pharmaceuticals. M.M. has received research support from Pfizer.

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Coherence

The degree of association in phase of neural oscillations across brain regions; high coherence is associated with functional connectivity.

Auditory gating

Neural phenomenon evident in ERP and characterized by suppression of the P1 component of the evoked response to the second auditory stimulus in a pair, resulting from habituation to repetitive stimuli at a neuronal level.

Mismatch negativity

Neural phenomenon evident in ERPs as an increased negative deflection in response to a novel stimulus among trains of standard stimuli; mismatch negativity is calculated as the difference in wave responses to standard versus novel stimuli.

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Modi, M., Sahin, M. Translational use of event-related potentials to assess circuit integrity in ASD. Nat Rev Neurol 13, 160–170 (2017). https://doi.org/10.1038/nrneurol.2017.15

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