Age-related hearing loss is associated with cognitive decline and has been proposed as a risk factor for dementia. However, the mechanisms that relate hearing loss to cognitive decline remain elusive. Here, we propose that the impairment of the cochlear amplifier mechanism is associated with structural brain changes and cognitive impairment. Ninety-six subjects aged over 65 years old (63 female and 33 male) were evaluated using brain magnetic resonance imaging, neuropsychological and audiological assessments, including distortion product otoacoustic emissions as a measure of the cochlear amplifier function. All the analyses were adjusted by age, gender and education. The group with cochlear amplifier dysfunction showed greater brain atrophy in the cingulate cortex and in the parahippocampus. In addition, the atrophy of the cingulate cortex was associated with cognitive impairment in episodic and working memories and in language and visuoconstructive abilities. We conclude that the neural abnormalities observed in presbycusis subjects with cochlear amplifier dysfunction extend beyond core auditory network and are associated with cognitive decline in multiple domains. These results suggest that a cochlear amplifier dysfunction in presbycusis is an important mechanism relating hearing impairments to brain atrophy in the extended network of effortful hearing.

Evidence shows that selective attention to visual stimuli modulates the gain of cochlear responses, probably through auditory-cortex descending pathways. At the cerebral cortex level, amplitude and phase changes of neural oscillations have been proposed as a correlate of selective attention. However, whether sensory receptors are also influenced by the oscillatory network during attention tasks remains unknown. Here, we searched for oscillatory attention-related activity at the cochlear receptor level in humans. We used an alternating visual/auditory selective attention task and measured electroencephalographic activity simultaneously to distortion product otoacoustic emissions (a measure of cochlear receptor-cell activity). In order to search for cochlear oscillatory activity, the otoacoustic emission signal, was included as an additional channel in the electroencephalogram analyses. This method allowed us to evaluate dynamic changes in cochlear oscillations within the same range of frequencies (1–35 Hz) in which cognitive effects are commonly observed in electroencephalogram works. We found the presence of low frequency (<10 Hz) brain and cochlear amplifier oscillations during selective attention to visual and auditory stimuli. Notably, switching between auditory and visual attention modulates the amplitude and the temporal order of brain and inner ear oscillations. These results extend the role of the oscillatory activity network during cognition in neural systems to the receptor level.

21 Evidence shows that selective attention to visual stimuli modulates the gain of 22 cochlear responses, probably through auditory-cortex descending pathways. At the cerebral 23 cortex level, amplitude and phase changes of neural oscillations have been proposed as a 24 correlate of selective attention. However, whether sensory receptors are also influenced by 25 the oscillatory network during attention tasks remains unknown. Here, we searched for 26 oscillatory attention-related activity at the cochlear receptor in humans. We used an 27 alternating visual/auditory selective attention task and measured electroencephalographic 28 activity simultaneously to distortion product otoacoustic emissions (a measure of cochlear 29 receptor-cell activity). In order to search for cochlear oscillatory activity, the otoacoustic 30 emission signal, was included as an additional channel in the electroencephalogram 31 analyses. This method allowed us to study dynamic changes of cochlear oscillations in the 32 same range of frequencies (1-35 Hz) in which cognitive effects are commonly observed in 33 electroencephalogram works. We found the presence of low frequency (<10 Hz) brain and 34 cochlear amplifier oscillations during periods of selective attention to visual and auditory 35 stimuli. Notably, switching between auditory and visual attention modulates the amplitude 36 and the temporal order of brain and inner ear oscillations. These results extend the role of 37 the oscillatory activity network during cognition in neural systems to the receptor level.38

Belkhiria et al. Neurobehavioral Impairment in Presbycusis that (i) the neuropsychiatric symptoms had a major effect on functional loss in subjects with presbycusis, (ii) cochlear dysfunction is relevant for the association between hearing loss and behavioral impairment, and (iii) atrophy of the insula and amygdala among other temporal areas are related with hearing loss and behavioral impairment.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (thirteen males, mean age 25.3 years) with normal hearing performed a visual change detection task with different VWM load conditions (high load= 4 visual objects; low load= 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAE) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n=21) compared to control experiments (n=10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.