A contribution to the debate on tinnitus definition.

Tinnitus is generally defined as an auditory perception in the absence of environmental sound stimulation. However, this definition is quite incomplete as it omits an essential aspect, the patient's point of view. This point of view constitutes, first and foremost, a global and unified lived experience, which is not only sensory (localization, loudness, pitch and tone), but also cognitive (thoughts, attentiveness, behaviors) and emotional (discomfort, suffering). This experience can be lived in a very unpleasant way and consequently have a very negative impact on quality of life. This article proposes and justifies a new definition for tinnitus elaborated by a group of French clinicians and researchers, which is more in line with its phenomenology. It also provides a minimum knowledge base, including possibilities for clinical care, hoping to eradicate all misinformation, misconceptions and inappropriate attitudes or practices toward this condition. Here is the short version of our definition: Tinnitus is an auditory sensation without an external sound stimulation or meaning, which can be lived as an unpleasant experience, possibly impacting quality of life.

Arterial spin labeling brain MRI study to evaluate the impact of deafness on cerebral perfusion in 79 children before cochlear implantation.

Age at implantation is considered to be a major factor, influencing outcomes after pediatric cochlear implantation. In the absence of acoustic input, it has been proposed that cross-modal reorganization can be detrimental for adaptation to the new electrical input provided by a cochlear implant. Here, through a retrospective study, we aimed to investigate differences in cerebral blood flow (CBF) at rest prior to implantation in children with congenital deafness compared to normally hearing children. In addition, we looked at the putative link between pre-operative rest-CBF and the oral intelligibility scores at 12 months post-implantation. Finally, we observed the evolution of perfusion with age, within brain areas showing abnormal rest-CBF associated to deafness, in deaf children and in normally hearing children. In children older than 5 years old, results showed a significant bilateral hypoperfusion in temporal regions in deaf children, particularly in Heschl's gyrus, and a significant hyperperfusion of occipital regions. Furthermore, in children older than 5 years old, whole brain voxel-by-voxel correlation analysis between pre-operative rest-CBF and oral intelligibility scores at 12 months post-implantation, showed significant negative correlation localized in the occipital regions: children who performed worse in the speech perception test one year after implantation were those presenting higher preoperative CBF values in these occipital regions. Finally, when comparing mean relative perfusion (extracted from the temporal regions found abnormal on whole-brain voxel-based analysis) across ages in patients and controls, we observed that the temporal perfusion evolution was significantly different in deaf children than in normally hearing children. Indeed, while temporal perfusion increased with age in normally hearing children, it remained stable in deaf children. We showed a critical period around 4 years old, where in the context of auditory deprivation, there is a lack of synaptic activity in auditory regions. These results support the benefits of early cochlear implantation to maximize the effectiveness of auditory rehabilitation and to avoid cross-modal reorganization.

Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis.

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.

Effects of noise reduction on AM perception for hearing-impaired listeners.

Noise reduction (NR) systems are commonplace in modern digital hearing aids. Though not improving speech intelligibility, NR helps the hearing-aid user in terms of lowering noise annoyance, reducing cognitive load and improving ease of listening. Previous psychophysical work has shown that NR does in fact improve the ability of normal-hearing (NH) listeners to discriminate the slow amplitude-modulation (AM) cues representative of those found in speech. The goal of this study was to assess whether this improvement of AM discrimination with NR can also be observed for hearing-impaired (HI) listeners. AM discrimination was measured at two audio frequencies of 500 Hz and 2 kHz in a background noise with a signal-to-noise ratio of 12 dB. Discrimination was measured for ten HI and ten NH listeners with and without NR processing. The HI listeners had a moderate sensorineural hearing loss of about 50 dB HL at 2 kHz and normal hearing (≤ 20 dB HL) at 500 Hz. The results showed that most of the HI listeners tended to benefit from NR at 500 Hz but not at 2 kHz. However, statistical analyses showed that HI listeners did not benefit significantly from NR at any frequency region. In comparison, the NH listeners showed a significant benefit from NR at both frequencies. For each condition, the fidelity of AM transmission was quantified by a computational model of early auditory processing. The parameters of the model were adjusted separately for the two groups (NH and HI) of listeners. The AM discrimination performance of the HI group (with and without NR) was best captured by a model simulating the loss of the fast-acting amplitude compression applied by the normal cochlea. This suggests that the lack of benefit from NR for HI listeners results from loudness recruitment.

Brain voice processing with bilateral cochlear implants: a positron emission tomography study.

Most cochlear implantations are unilateral. To explore the benefits of a binaural cochlear implant, we used water-labelled oxygen-15 positron emission tomography. Relative cerebral blood flow was measured in a binaural implant group (n = 11), while the subjects were passively listening to human voice sounds, environmental sounds non-voice or silence. Binaural auditory stimulation in the cochlear implant group bilaterally activated the temporal voice areas, whereas monaural cochlear implant stimulation only activated the left temporal voice area. Direct comparison of the binaural and the monaural cochlear implant stimulation condition revealed an additional right temporal activation during voice processing in the binaural condition and the activation of a right fronto-parietal cortical network during sound processing that has been implicated in attention. These findings provide evidence that a bilateral cochlear implant stimulation enhanced the spectral cues associated with sound perception and improved brain processing of voice stimuli in the right temporal region when compared to a monaural cochlear implant stimulation. Moreover, the recruitment of sensory attention resources in a right fronto-parietal network allowed patients with bilateral cochlear implant stimulation to enhance their sound discrimination, whereas the same patients with only one cochlear implant stimulation had more auditory perception difficulties.

Processing of voices in deafness rehabilitation by auditory brainstem implant.

The superior temporal sulcus (STS) is specifically involved in processing the human voice. Profound acquired deafness by post-meningitis ossified cochlea and by bilateral vestibular schwannoma in neurofibromatosis type 2 patients are two indications for auditory brainstem implantation (ABI). In order to objectively measure the cortical voice processing of a group of ABI patients, we studied the activation of the human temporal voice areas (TVA) by PET H(2)(15)O, performed in a group of implanted deaf adults (n=7) with more than two years of auditory brainstem implant experience, with an intelligibility score average of 17%+/-17 [mean+/-SD]. Relative cerebral blood flow (rCBF) was measured in the three following conditions: during silence, while passive listening to human voice, and to non-voice stimuli. Compared to silence, the activations induced by voice and non-voice stimuli were bilaterally located in the superior temporal regions. However, compared to non-voice stimuli, the voice stimuli did not induce specific supplementary activation of the TVA along the STS. The comparison of ABI group with a normal-hearing controls group (n=7) showed that TVA activations were significantly enhanced among controls group. ABI allowed the transmission of sound stimuli to temporal brain regions but lacked transmitting the specific cues of the human voice to the TVA. Moreover, among groups, during silent condition, brain visual regions showed higher rCBF in ABI group, although temporal brain regions had higher rCBF in the controls group. ABI patients had consequently developed enhanced visual strategies to keep interacting with their environment.

Cochlear implant benefits in deafness rehabilitation: PET study of temporal voice activations.

UNLABELLED: 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 = 6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear implant experience, with intelligibility scores in the "Lafon monosyllabic task" >80% (GOOD group; n = 6) or <20% (POOR group; n = 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.