Dysfunction of sensory oscillations in Autism Spectrum Disorder
Introduction
Autism Spectrum Disorder (ASD) is a developmental disability characterized by persistent deficits in social communication and interaction, restricted interests, and repetitive behaviors (American Psychiatric Association, 2013). An estimated 1 in 68 children born in the United States will receive a diagnosis of ASD, and the disorder carries enormous social and economic costs (Buescher et al., 2014, Developmental Disabilities Monitoring Network Surveillance Year Principal et al., 2014, Karst and Van Hecke, 2012). This high prevalence and socioeconomic cost have motivated numerous investigations to better understand the brain bases of ASD. Studies utilizing functional magnetic resonance imaging (fMRI) have consistently indicated that patterns of structural (Shukla et al., 2010) and functional (Dinstein et al., 2011) connectivity are significantly altered in individuals with ASD. Postmortem anatomical inquiries have likewise indicated that the microstructure of cortical circuitry is fundamentally altered in ASD (Casanova et al., 2006, McKavanagh et al., 2015). Investigations examining connectivity on more rapid time scales utilizing electroencephalography (EEG) (Coben et al., 2014) and magnetoencephalography (MEG) (Ye et al., 2014) have similarly indicated that connectivity alterations are a characteristic feature of ASD. These connectivity alterations have been proposed as both a leading biomarker and the origin of the behavioral dysfunction characteristic of the disorder (Geschwind and Levitt, 2007). Network-based analyses have revealed that the nature of connectivity differences among individuals with ASD is highly individualized (Hahamy et al., 2015). However, how these changes in network structure impact neural processing and emerge as the collection of phenotypes that characterize ASD is poorly understood, and consequently has become an area of important investigation. Studies using EEG and MEG have uncovered differences in rhythmically modulated networks known as oscillators. This oscillatory dysfunction in ASD may form the bridge between dysfunction at the cellular and local levels, changes in large-scale network organization, and the sensory and perceptual processing differences that represent a core feature of the disorder.
Section snippets
Sensory and perceptual function in ASD
Alterations in sensory and perceptual processes have long been recognized to be present in ASD (Marco et al., 2011). Recent revisions to diagnostic criteria have now acknowledged that these sensory and perceptual dysfunctions constitute a core feature of ASD (American Psychiatric Association, 2013). Intriguingly, investigations focused on sensory function in ASD have revealed that, even within a single sensory modality such as vision, both strengths and weaknesses can be present. For example,
Oscillatory contributions to sensory encoding
The rhythmic nature of neural activity has been recognized since the earliest attempts at non-invasive measurement (Berger, 1929). These rhythmic fluctuations are referred to as oscillations, and have been characterized over a large range of frequencies (here denoted as delta: δ, 1–4 Hz, theta: θ, 4–8 Hz, alpha: α, 8–14 Hz, beta: β, 15–30 Hz, and gamma: γ, >30 Hz, although the exact ranges vary in the literature). The role of these oscillations in neural computation is of great interest and has
Gamma abnormalities in ASD and their role in sensory and perceptual processing
Gamma (γ, >30 Hz) band responses have been proposed to play a key role in the encoding of sensory evidence in local networks and are strongly modulated in response to sensory stimulation. Importantly, the physiological origins of γ oscillations in sensory cortices are well known; high γ (>80 Hz) oscillations largely correspond with spiking activity while low γ (<80 Hz) oscillations primarily correspond with localized network synchronization (Ray and Maunsell, 2011). Activity in the 30–45 Hz range
Alpha abnormalities in ASD and their role in sensory and perceptual processing
Alpha (α, 8–14 Hz) is one of the most distinct frequency ranges in human neural activity, notable for its significant deviation from the expected relationship between frequency and power. For most oscillatory neural activity, total power is inversely related to frequency, but human alpha power is notably higher than would be expected from this relationship (Buzsaki and Draguhn, 2004). This atypical power distribution implies additional functional significance for this frequency band, which has
Oscillatory organization is disrupted in ASD
The presence of consistent deficits in ASD in both the α and γ frequency ranges suggests that these may be coupled in meaningful ways and that these changes may result in reduced flexibility of moderate and high frequency synchronization. Such a mechanism is offered by oscillatory hierarchies, in which low frequency δ and θ oscillations play an instrumental role in shaping higher frequency oscillations. One of the best studied of these hierarchical relationships is the entrainment of θ
Methodological challenges and opportunities
The finding of increased power over a wide range of frequencies highlights an important methodological challenge for oscillatory research in ASD. If intrinsic broadband power is chronically elevated then procedures which determine power changes compared to baseline systematically underestimate both evoked and induced power. This effect may account for some of the notable discrepancies between task based and resting state investigations of oscillatory function in ASD. A striking example of this
Mechanistic account of altered oscillator function in ASD
The consistent finding of impaired power modulation and reduced phase synchronization across multiple frequency bands suggests that disruption of oscillatory processes is a strong contributor to the neurobiological differences that underpin ASD. In attempting to link these more network-based changes to cellular and microcircuit substrates, disruption of the balance between excitation and inhibition has received substantial attention (Rubenstein and Merzenich, 2003). High frequency oscillations
Oscillatory function and neurobiologically inspired theories of autism
Theoretical perspectives on ASD have long recognized that the basis of neurologic impairment may lie in disruption of processes related to information transfer and information integration. The Weak Central Coherence (WCC) model, for example, posits that processing differences in ASD result from deficits of information integration across distributed and distant cortical circuits while localized processing remains intact (Happe and Frith, 2006). From a biological perspective, such processes would
Diagnostic and treatment implications of oscillator dysfunction
Perturbations in sensory and perceptual function are being increasingly recognized as core features of ASD that contribute to lifelong disability (American Psychiatric Association, 2013). The recognition of brain oscillations and synchronization as playing an important role in pathology raises two critical questions. First, whether oscillations can be utilized for evaluation of treatment regimes, and second, whether oscillatory function itself is a potential avenue of treatment. There is
Conclusions and future directions
Disruptions in oscillatory synchronization are ubiquitous during sensory and perceptual processing in ASD. While synchronization alterations in ASD are not limited to these processes, deficits in these areas are particularly important given the renewed emphasis on sensory dysfunction as a core impairment that potentially emerges early in development (and that may then underpin the develop of more complex and higher-order functions). These disruptions have been found in multiple sensory
Acknowledgements
This work was supported by NIH U54 HD083211, NIH DC010927, CA183492, HD83211, and by the Wallace Foundation and the Simons Foundation Autism Research Initiative. The funding sources played no role in the writing or submission of this article. The authors declare no competing interests.
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