Abnormal Auditory Processing and Underlying Structural Changes in 22q11.2 Deletion Syndrome

Abstract

The 22q11.2 deletion syndrome (22q11.2 DS), one of the highest genetic risk for the development of schizophrenia, offers a unique opportunity to understand neurobiological and functional changes preceding the onset of the psychotic illness. Reduced auditory mismatch negativity response (MMN) has been proposed as a promising index of abnormal sensory processing and brain pathology in schizophrenia. However, the link between the MMN response and its underlying cerebral mechanisms in 22q11.2 DS remains unexamined. We measured auditory-evoked potentials to frequency deviant stimuli with high-density electroencephalogram and volumetric estimates of cortical and thalamic auditory areas with structural T1-weighted magnetic resonance imaging in a sample of 130 individuals, 70 with 22q11.2 DS and 60 age-matched typically developing (TD) individuals. Compared to TD group, the 22q11.2 deletion carriers reveal reduced MMN response and significant changes in topographical maps and decreased gray matter volumes of cortical and subcortical auditory areas, however, without any correlations between MMN alteration and structural changes. Furthermore, exploratory research on the presence of hallucinations (H+\H-) reveals no change in MMN response in 22q11.2DS (H+ and H-) as compared to TD individuals. Nonetheless, we observe bilateral volume reduction of the superior temporal gyrus and left medial geniculate in 22q11.2DSH+ as compared to 22q11.2DSH- and TD participants. These results suggest that the mismatch response might be a promising neurophysiological marker of functional changes within the auditory pathways that might underlie elevated risk for the development of psychotic symptoms.

Keywords: DiGeorge Syndrome; auditory processing; hallucinations; medial geniculate volume reduction; psychosis.

Fig. 1.

(A) The amplitude across time of auditory ERPs and the difference waveform (red, the deviant sound; black, the standard sound; green, the difference waveform) over a cluster of 15 fronto-central channels (displayed in pink alongside) plotted across −100 to 400 ms poststimulation (left side, the 22q11.2 deletion syndrome [22q11.2 DS]; right side, typically developing [TD]). The scalp topographies are displayed for standard ERP, deviant ERP, and the difference waveform over 190–260 ms poststimulation. (B) The difference waveform. The mean amplitude across time (red, the 22q11.2 DS; black, the TD); the violin boxplot distribution of the mismatch negativity response (MMN) mean amplitude from 15 fronto-central electrodes calculated over 230–260 ms; the MMN scalp potential maps (230–260 ms poststimulus).