Tuning out the noise: limbic-auditory interactions in tinnitus.

Neuronal plasticity, the process by which the human brain changes as a result of experience, is thought to be the source of several chronic neurological conditions, including tinnitus. Using a rodent model for noise-induced tinnitus, Engineer et al. find that reversing neural plasticity induced by the tinnitus can correct perceptual impairment. Repeatedly pairing tones with a brief stimulation of the vagus nerve sharpens auditory neuron tuning and eliminates the physiological and behavioural signs of tinnitus. This proof of principle suggests that simply restoring normal neural activity to circuits that have been pathologically modified could provide a benefit in conditions involving aberrant neural plasticity. Neuronal plasticity is thought to be the source of several chronic neurological conditions, including tinnitus. Using a rodent model for noise-induced tinnitus, this study finds that reversing neural plasticity induced by the tinnitus can correct perceptual impairments caused by the ailment. Pairing tones with stimulation of the vagus nerve sharpened auditory neuron tuning and eliminated the physiological as well as behavioural correlates of the tinnitus. This proof of principle suggests that simply restoring normal neural activity to circuits that have been pathologically modified could provide a benefit in those ailments involving aberrant neural plasticity. Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus1,2,3. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively1,4. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations5. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing tones with brief pulses of vagus nerve stimulation completely eliminated the physiological and behavioural correlates of tinnitus in noise-exposed rats. These improvements persisted for weeks after the end of therapy. This method for restoring neural activity to normal may be applicable to a variety of neurological disorders.

/pdf/reversing-pathological-neural-activity-using-targeted-5diyn6v9f4.pdf

Reversing pathological neural activity using targeted plasticity

Tinnitus is a phantom sound (ringing of the ears) that affects quality of life for millions around the world and is associated in most cases with hearing impairment. This symposium will consider evidence that deafferentation of tonotopically organized central auditory structures leads to increased neuron spontaneous firing rates and neural synchrony in the hearing loss region. This region covers the frequency spectrum of tinnitus sounds, which are optimally suppressed following exposure to band-limited noise covering the same frequencies. Cross-modal compensations in subcortical structures may contribute to tinnitus and its modulation by jaw-clenching and eye movements. Yet many older individuals with impaired hearing do not have tinnitus, possibly because age-related changes in inhibitory circuits are better preserved. A brain network involving limbic and other nonauditory regions is active in tinnitus and may be driven when spectrotemporal information conveyed by the damaged ear does not match that predicted by central auditory processing.

https://www.jneurosci.org/content/jneuro/30/45/14972.full.pdf

Ringing Ears: The Neuroscience of Tinnitus

Summary Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. With prevalence ranging from 10% to 15%, tinnitus is a common disorder. Many people habituate to the phantom sound, but tinnitus severely impairs quality of life of about 1–2% of all people. Tinnitus has traditionally been regarded as an otological disorder, but advances in neuroimaging methods and development of animal models have increasingly shifted the perspective towards its neuronal correlates. Increased neuronal firing rate, enhanced neuronal synchrony, and changes in the tonotopic organisation are recorded in central auditory pathways in reaction to deprived auditory input and represent—together with changes in non-auditory brain areas—the neuronal correlate of tinnitus. Assessment of patients includes a detailed case history, measurement of hearing function, quantification of tinnitus severity, and identification of causal factors, associated symptoms, and comorbidities. Most widely used treatments for tinnitus involve counselling, and best evidence is available for cognitive behavioural therapy. New pathophysiological insights have prompted the development of innovative brain-based treatment approaches to directly target the neuronal correlates of tinnitus.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(13)70160-1.pdf

Tinnitus: causes and clinical management

Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the temporal precision of the auditory system. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (18–30 years old) and older (60–67 years old) adult humans. Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Together, our results support the theory that older adults have a loss of temporal precision in the subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception.

https://www.jneurosci.org/content/jneuro/32/41/14156.full.pdf

Aging Affects Neural Precision of Speech Encoding

Age-Related Changes in Glycine Receptor Subunit Composition and Binding in Dorsal Cochlear Nucleus

Objectives Presbyacusis, one of the most common ailments of the elderly, is often treated with hearing aids, which serve to reintroduce some or all of those sounds lost to peripheral hearing loss. However, little is known about the underlying changes to the ear and brain as a result of such experience with sound late in life. The present study attempts to model this process by rearing aged CBA mice in an augmented acoustic environment (AAE). Design Aged (22-23 months) male (n = 12) and female (n = 9) CBA/CaJ mice were reared in either 6 weeks of low-level (70 dB SPL) broadband noise stimulation (AAE) or normal vivarium conditions. Changes as a function of the treatment were measured for behavior, auditory brainstem response thresholds, hair cell cochleograms, and gamma aminobutyric acid neurochemistry in the key central auditory structures of the inferior colliculus and primary auditory cortex. Results The AAE-exposed group was associated with sex-specific changes in cochlear pathology, auditory brainstem response thresholds, and gamma aminobutyric acid neurochemistry. Males exhibited significantly better thresholds and reduced hair cell loss (relative to controls) whereas females exhibited the opposite effect. AAE was associated with increased glutamic acid decarboxylase (GAD67) levels in the inferior colliculus of both male and female mice. However, in primary auditory cortex AAE exposure was associated with increased GAD67 labeling in females and decreased GAD67 in males. Conclusions These findings suggest that exposing aged mice to a low-level AAE alters both peripheral and central properties of the auditory system and these changes partially interact with sex or the degree of hearing loss before AAE. Although direct application of these findings to hearing aid use or auditory training in aged humans would be premature, the results do begin to provide direct evidence for the underlying changes that might be occurring as a result of hearing aid use late in life. These results suggest the aged brain retains significantly anatomical, electrophysiological, and neurochemical plasticity.

Jennifer L. Parrish

Papers

Age-Related Changes in Glycine Receptor Subunit Composition and Binding in Dorsal Cochlear Nucleus

Acoustic experience alters the aged auditory system.