Impairments in social interaction are a key feature of autism and are associated with atypical social information processing. Here we report functional magnetic resonance imaging (fMRI) results showing that individuals with autism failed to activate superior temporal sulcus (STS) voice-selective regions in response to vocal sounds, whereas they showed a normal activation pattern in response to nonvocal sounds. These findings suggest abnormal cortical processing of socially relevant auditory information in autism.

Cochlear implants may improve the medical and social prognosis of profound deafness. Nevertheless, some patients have experienced poor results without any clear explanations. One correlate may be an alteration in cortical voice processing. To test this hypothesis, we studied the activation of human temporal voice areas (TVA) using a well-standardized PET paradigm adapted from previous functional MRI (fMRI) studies. Methods: A PET H 2 15 O activation study was performed on 3 groups of adult volunteers: normal-hearing control subjects (n 5 6) and cochlearimplanted postlingually deaf patients with .2 y of cochlear implant experience, with intelligibility scores in the ''Lafon monosyllabic task'' .80% (GOOD group; n 5 6) or ,20% (POOR group; n 5 6). Relative cerebral blood flow was measured in 3 conditions: rest, passive listening to human voice, and nonvoice stimuli. Results: Compared with silence, the activations induced by nonvoice stimuli were bilaterally located in the superior temporal regions in all groups. However these activations were significantly and similarly reduced in both cochlear implant groups, whereas control subjects showed supplementary activations. Compared with nonvoice, the voice stimuli induced bilateral activation of the TVA along the superior temporal sulcus (STS) in both the control and the GOOD groups. In contrast, these activations were not detected in the POOR group, which showed only left unilateral middle STS activation. Conclusion: These results suggest that PET is an adequate method to explore cochlear implant benefits and that this benefit could be linked to the activation of the TVA.

Presbycusis, or age-related hearing loss (ARHL), is a major public health issue. About half the phenotypic variance has been attributed to genetic factors. Here, we assessed the contribution to presbycusis of ultrarare pathogenic variants, considered indicative of Mendelian forms. We focused on severe presbycusis without environmental or comorbidity risk factors and studied multiplex family age-related hearing loss (mARHL) and simplex/sporadic age-related hearing loss (sARHL) cases and controls with normal hearing by whole-exome sequencing. Ultrarare variants (allele frequency [AF] < 0.0001) of 35 genes responsible for autosomal dominant early-onset forms of deafness, predicted to be pathogenic, were detected in 25.7% of mARHL and 22.7% of sARHL cases vs. 7.5% of controls (P = 0.001); half were previously unknown (AF < 0.000002). MYO6, MYO7A, PTPRQ, and TECTA variants were present in 8.9% of ARHL cases but less than 1% of controls. Evidence for a causal role of variants in presbycusis was provided by pathogenicity prediction programs, documented haploinsufficiency, three-dimensional structure/function analyses, cell biology experiments, and reported early effects. We also established Tmc1N321I/+ mice, carrying the TMC1:p.(Asn327Ile) variant detected in an mARHL case, as a mouse model for a monogenic form of presbycusis. Deafness gene variants can thus result in a continuum of auditory phenotypes. Our findings demonstrate that the genetics of presbycusis is shaped by not only well-studied polygenic risk factors of small effect size revealed by common variants but also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment with emerging inner ear gene therapy.