31339
Effects of Age, Gender, and Genotype on Auditory Processing in Phelan-Mcdermid Syndrome
Objectives: This study uses a standard auditory gating task that measures attenuation of neural activity to repetitive auditory responses in PMS and typically-developing (TD) controls, with a focus on age, genotype, and deletion-size effects in PMS. Auditory gating deficits are commonly associated with abnormal sensory responsiveness and speech processing; understanding variations contributing to auditory gating abnormalities may provide insight into observed variations in clinical phenotype.
Methods: Thirty-seven PMS (age range 46-216 months, 20 females) and 14 TD participants (age range 76-178 months, 6 females) completed 150 trials of a two-stimulus auditory gating task while undergoing dense-array EEG. Gating, amplitude, and latency measures of the P50, N1, and P2 were compared using ANCOVA, examining spatial topography, gender, and genotype (TD, deletion, mutation) for adolescent and adult PMS (n=20 out of 37) matched to TD (n=13 out of 14). Additional analyses included within-PMS comparisons for the full available age range and deletion size.
Results: Gating. PMS showed a significantly decreased p50 gating response compared to TD. TD showed stronger gender effects on the N1 gating response than PMS. When variations in topography were examined using global field power, mutations (n=6) could also be differentiated as showing gating deficits intermediate between TD and deletions. Within PMS, an age by deletion size interaction for the N1 gating response indicated there were fewer age differences in gating with small deletion sizes, but as deletion size increased, younger individuals tended toward poorer gating. Amplitude. A significant effect of deletion size for PMS indicated that as deletion size increased, P50 and N1 amplitudes decreased. Latency. Within PMS, there was a gender by deletion size interaction for the P2 response latency to the repeated stimulus. Males and females with small deletion sizes did not differ, but males had longer latencies than females as deletion sizes increased.
Conclusions: Here we demonstrate differences in age, gender and genotype findings between and within PMS and TD. The most notable differences between PMS and TD were in genotype, where PMS showed worse gating than TD for P50. Within PMS, larger deletion sizes were associated with increased auditory processing abnormalities, especially in younger individuals, suggesting the possibility for developmentally-regulated involvement of additional genes in this region. Auditory gating deficits are commonly associated with deficits filtering irrelevant sensory information and can lead to difficulty with sensory responsiveness and speech development. Results suggest that PMS exhibit auditory processing abnormalities that show complex variation by deletion-size, gender and age, which may provide valuable insight into clinical characterization of sensory and speech behaviors in future studies.