Atypical Language Lateralization Mediated by Development of the Corpus Callosum

Background:  

While over 90% of typical individuals have language lateralized to the left hemisphere, individuals with autism are reported to show a higher rate of right hemisphere language lateralization.  In autism, atypical development of the corpus callosum (a large white matter structure that serves to transfer information between the left and right hemispheres) has been reported and the role of the corpus callosum in language lateralization remains unclear.  Intriguingly, clinical language impairments reported in autistic individuals are observed in individuals with callosal abnormalities, including agenesis of the corpus callosum (AgCC).

Objectives:  

Here, we quantify language lateralization in patients with AgCC and matched healthy controls using magnetoencephalography (MEG) during a verb generation task.  This task has been shown to produce patterns of left hemisphere dominant activation in typical individuals.  Both hemispheric dominance as well as temporal and oscillatory differences were assessed and compared between groups.

Methods:  

27 participants with AgCC and 20 IQ and age-matched healthy control (HC) subjects enrolled in this study.  Of the 27 AgCC participants, 10 have complete agenesis of the corpus callosum (cAgCC) and 17 have partial agenesis of the corpus callosum (pAgCC).  MEG data were collected using a 275-channel whole-head biomagnetometer (MISL) at a sampling rate of 1200Hz.  At the beginning of every trial, a single noun was presented at a comfortable volume through earphones every four seconds (100 trials).  Subjects were instructed to think of a verb or “action word” associated with the noun and to speak into a megaphone attached to a microphone at the foot of the bed.  Data were analyzed in the time-frequency domain using an adaptive spatial filtering technique implemented in Nutmeg (nutmeg.berkeley.edu).  Changes in beta oscillatory power (12-30Hz) were used to compute an index of language lateralization (laterality index; LI).  Tomographic reconstructions were spatially normalized and entered into a second-level group analysis using SnPM and multiple comparisons corrections were performed using a Family-Wise Error rate (FWE).  

Results:  

While we found the expected leftward language lateralization in 90% of our healthy controls (mean LI=0.6), only 20% (mean LI=-0.06) of individuals with complete AgCC showed left hemisphere language dominance. The partial AgCC group demonstrated an intermediate left lateralization at 47% (mean LI=0.08).  Further investigation reveals that individuals with AgCC have greater activation of the right middle frontal gyrus (MFG; p<0.05, FWE corrected) that occurs in the beta frequency.  This increase in neural activity occurs immediately prior to the vocal response (750ms post-stimulus, -450ms pre-response).

Conclusions:  

Language deficits are a core feature of autism spectrum disorders and may be a result of atypical hemispheric specialization.  The cause of this disruption may be related to abnormal interhemispheric communication mediated by the corpus callosum.  This report shows a direct relationship between the preservation of the corpus callosum and language lateralization. With the overlap in communication deficits seen in both autism and AgCC, identification of this level of neural specification can facilitate the development of targeted treatment interventions that focus on remediating language impairments.