Sensorineural hearing loss (SNHL), which affects more than 270 million people worldwide, is a permanent sensory impairment that impairs hearing. SNHL is found in 4/1000 in newborns, 8/1000 children aged 3-17 years, and 33% of adults 65-74 years old. Current treatments (hearing aids and cochlear implants) improve the symptoms of SNHL by increasing Corti’s damaged organ. These treatments do not reverse either the underlying pathology of SNHL or the loss of sensory inner hair cells within the Corti organ.
Internal and external cochlear hair cells are needed to hear sound waves and convert them into electrical impulses transmitted to the brain. Loss of hair cells reduces auditory input to the brain, and hearing impairment develops with sufficient hair cell loss. In mammals, the Corti organ is postmitotic at birth and spontaneous hair cell regeneration does not occur later.
Typical language development requires typical hearing. With sensorineural hearing loss (SNHL), damaged hair cells of the Corti organ in the cochlea block typical hearing and consequently cause impaired tongue development. Untreated SNHL causes significant neurocognitive differences in affected children. SNHL is a persistent sensory disorder that affects more than 270 million people worldwide. Congenital SNHL is found in 4 out of 1000 newborns. About half of congenital SNHL is inherited and is the result of genetic mutations that cause improper development of cochlear hair cells.
Non-genetic congenital SNHL is typically thought to be the result of premature birth, infection, or damage to the cochlea from exposure to ototoxic drugs or noise. In mammals, the cochlea is postmitotic at birth, and there is no spontaneous repair later. Current treatments for SNHL (hearing aids and cochlear implants) function by strengthening the damaged organ of Corti. Restorative therapy is currently not available. In preclinical and clinical studies, progenitor cell therapy (cord blood and mesenchymal stem cells) has shown promise in reversing the underlying pathology of SNHL, the loss of cochlear sensory hair cells.
Hearing Loss and Auditory Development
Spoken language is learned, and its development depends on both the innate ability found in the human cortex and the environmental stimulation. The time frame in which the cortex can learn the first spoken language is limited by neuroplasticity. Neuroplasticity refers to changes in neural connections, pathways, and networks as a result of maturation and development, sensory deprivation, injury, disease, dysfunction, and learning. Although neuroplasticity exists to some extent throughout life, it is particularly strong in early life when neuronal groups are most capable of tuning input-based function.
This higher education window, known as the critical period, lasts roughly 3 years and 6 months. The critical period is when the brain reconnects effortlessly in response to the environment and eventually there is a definite reduction in neuroplasticity. Auditory development is particularly sensitive to the critical period. Auditory learning begins when synapses form in utero and then becomes stronger at a noticeable rate. At about 4 years of age, the abundant neurons in the auditory cortex enter a rapid decline phase where neurons and synapses disappear when not used and are therefore considered unnecessary.
This reduction fundamentally alters the auditory cortex, which typically equates to improved language efficiency for the hearing child. Conversely, for the un-grown child with SNHL, pruning results in an inability to develop spoken language. If auditory stimulation was not delivered in the early optimal period of cortical plasticity, deficits were observed even after the child was amplified. A biomarker for auditory cortical maturation is the latency rates of the P1 component of cortical auditory evoked potentials (CAEP). The P1 component of CAEP has been shown to show age-related decreases in delay in children without hearing loss, meaning faster transmission. Sharma and Dorman found that in a series of 245 children with congenital deafness, the P1 CAEP delay fell within normal limits in children who received cochlear implants up to the age of 3.5. Children implanted after age 7 show abnormal P1 CAEP responses that persist even after years of experience with implant use.
Implanted children aged 3.5 to 7 years showed mixed auditory cortical development. Supporting this finding are studies that describe the developmental outcomes of speech and language skills in children implanted at various ages and show significantly improved results with younger age of implantation. The improved results are particularly true in the improvement of spoken language.
In summary, when a child with SNHL is given timely auditory access through hearing aids or a cochlear implant during the critical period, auditory development and language acquisition can occur normally. In contrast, children with prolonged auditory deprivation are susceptible to large-scale rearrangement of the auditory cortex areas responsible for speech and language perception. When this reorganization occurs, there is evidence that various areas of the auditory cortex are assigned for visual and tactile input under the condition of auditory deprivation.
To date, the only thing that has been proven to have a task-specific rearrangement of the auditory cortex has been in deaf cats. Meredith and Lumber show that different auditory regions support peripheral visual localization and visual motion detection in cats with SNHL, and the same regions support auditory localization in hearing cats.
Progenitor cell therapy may also allow functional reorganization of the auditory pathways, including the primary auditory cortex (Heschl’s gyrus). Here is a summary of the impact of hearing loss on auditory development, available preclinical and clinical data on progenitor cell therapy, and its potential role in (re) habilitation of non-genetic SNHL.
Current treatments for SNHL (hearing aids and cochlear implants) function by strengthening the damaged organ of Corti. Restorative therapy is currently not available. In preclinical and clinical studies, progenitor cell therapy (cord blood and mesenchymal stem cells) has shown promise in reversing the underlying pathology of SNHL, the loss of cochlear sensory hair cells.
Author: Ozlem Guvenc Agaoglu