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.