Abnormal Lateralization of Auditory Magnetic Fields Evoked by Clicks In Autism Spectrum Disorders (ASD)

Background: Rightward lateralization for processing of sounds with sharp ramps, such as clicks, has been previously reported in adults and may relate to functional specialization of the right hemisphere (RH) for certain types of information processing, such as rapid, global detection of stimulation and spatial attention.  We have previously found rightward lateralization of the N1c(Tb) component of auditory evoked responses to clicks in typically developing children (TDC). Such lateralization was absent in children with autism, who had reduced N1c in the RH.  We proposed that this finding reflects abnormal functioning of the RH networks responsible for arousal and initial orienting that, in turn, could affect later stages of information processing in autism.

Objectives: We sought to localize brain sources of the abnormal reaction to clicks in ASD using MEG. We also tested the hypothesis that these auditory processing abnormalities correlate with severity of autism or contribute to sensory difficulties observed in the majority of ASD individuals.

Methods: MEG and structural MRIs were obtained in 14 ASD children aged 8-13 years and 15 age-matched TDC.  Presence of sensory abnormalities was assessed with Sensory Profile.  Parents also answered questionnaire concerning autism symptoms during the first years of life, including sensory behavioral abnormalities.  Children watched a movie while passively listening to clicks presented either binaurally or monaurally in pairs, with 1 sec ISI within a pair and 8-10 sec ISIs between the pairs. We applied distributed source modeling using minimal norm estimate (MNE) and defined regions of interest (ROIs) in the vicinity of the auditory cortex where significant activation was observed in a majority of subjects.  MNE current timecourses in the ROIs were analyzed.

Results: In both groups the most prominent component of the auditory field response was P100m at approx. 100 ms.  The amplitude of P100m was significantly higher in response to binaural, then monaural clicks and  only in response to binaural clicks the P100m was detected in all subjects.  Therefore, only binaural responses were analyzed.  P100m strongly decreased upon stimulus repetition in both groups.  In control subjects the P100m was right-lateralized, while no lateralization was evident in ASD children, who had tendency (p=0.06) for P100m reduction in the right hemisphere.  After correction for IQ, the RH reduction of P100m correlated with greater severity of autism, assessed by child version of the Autism Quotient.  Moreover, greater leftward lateralization of P100m in ASD was associated with greater severity of sensory abnormalities assessed by Sensory Profile, as well as with severely abnormal auditory behavior during the 1^st year of life. 

Conclusions: The P100m is thought to originate from thalamo-cortical input to infragranular cortical layers (Eggermont&Ponton, Acta Otolaryngol 2003; 123:249–52).  Its reduction in the RH in ASD children suggests disturbance of RH thalamo-cortical afferents or their cortical targets that in turn may contribute to abnormal arousal and attention orienting in ASD.  The correlation between sensory abnormalities and atypical leftward P100m suggests that a shift of activation balance to the left hemisphere ‘non-optimal’ for the initial orienting, may contribute to bizarre sensory behaviors in ASD.