International Meeting for Autism Research: Gamma Band Oscillopathy: An Electrical Signature of Language Impairment in ASD That Impairs Active Listening

Gamma Band Oscillopathy: An Electrical Signature of Language Impairment in ASD That Impairs Active Listening

Thursday, May 20, 2010: 3:00 PM
Grand Ballroom AB Level 5 (Philadelphia Marriott Downtown)
1:30 PM
J. P. Welsh , Center for Integrative Brain Research, Seattle Childrens Research Institute/University of Washington, Seattle, WA
P. V. Rodrigues , Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA
J. C. Edgar , Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA
T. P. L. Roberts , Radiology / Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA
Background: It is often assumed that language impairment in autism spectrum disorders (ASDs) is secondary to an inability to develop a “theory of mind” necessary for social communication. An alternative is that children with ASD do not develop social communication due to an impairment of auditory processing that degrades the ability to understand spoken language. As clinical electrophysiology does not easily lend itself to understanding cellular mechanism, intracranial microelectrode array recordings of the primary auditory cortex (A1) in awake and behaving rats were compared to magnetoencephalography (MEG) of the A1 in children with ASD administered an auditory test that had no social or language content. The goal was to elucidate the circuit mechanisms responsible for language impairment in ASD (ASD+LI).

Objectives: To determine auditory disturbances in real-time processing in children with ASD+LI using a trans-species approach that lends itself to understanding electrophysiological correlates of language impairment and circuit abnormalities.

Methods:  Electrophysiology was carried out using whole-cortex MEG in children, and with intracranial arrays of microelectrodes in rats targeting A1.  Children and rats received sequences of 2 tones presented with a 200 ms intertone interval.  Seven rats were either: a) trained to actively listen to the tone pairs and report when they heard the second tone or, b) passive listeners with no prior experience with the tones.  For rats, local field potential recordings (LFPs) and single-unit spikes were obtained with a computer-guided microelectrode array from at least 8 sites within the left A1 (128 sites total). Ten children with ASD+LI and 25 typically-developing (TD) control children passively listened to the tone pairs while watching a movie (soundtrack off).  ASD in the children was confirmed by ADOS and SCQ, and language function quantified using the CELF-4.  In the children, MEG data were decomposed from sensor to source space, and activity in left and right superior temporal gyri (STG) examined.

Results: During silence, passively-listening rats showed dominant delta activity (0.7-3.9 Hz).  In contrast, during silence, actively listening rats showed dominant beta activity (12-30 Hz).  During active listening, identification of the second tone was associated with the magnitude of resting gamma activity (30-130 Hz) during the period immediately prior to the tones, as well as with the occurrence of gamma bursts following the second tone.  In the children with ASD+LI, an electrical signature of active listening was not observed at STG sources.  Specifically, in the baseline period, the ASD+LI children had greatly reduced gamma activity and elevated delta activity compared to the language-intact children.  Moreover, children with ASD+LI had a virtual absence of an induced gamma response to tone pairs despite obvious ERPs.  In contrast, the baseline and tone-evoked activity of TD children approximated that of actively-listening rats.

Conclusions: An unexpected pathophysiology underlying ASD+LI is an inability to transition from passive to active listening due to an inability to generate gamma oscillation within A1. The relative absence of resting and evoked gamma activity in A1 suggests an oscillopathy that can be used to assess ASD severity and monitor treatment efficacy.

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