Thesis
Neural signatures of tinnitus across the sleep-wake cycle
- Abstract:
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Subjective tinnitus is an internally generated auditory percept, most commonly taking the form of hissing or ringing. Especially long-lasting tinnitus is associated with anxiety, depression, and sleep impairments. There is no effective treatment for tinnitus, although research has made progress in uncovering its neural basis, including identifying hyperactivity in the central auditory pathway and several cortical regions, including those involved in brain state control. We have proposed that the occurrence of aberrant neural activity associated with tinnitus has important implications for natural brain state dynamics across sleep and wakefulness and vice versa (Milinski et al., 2022).
Our first prediction was that the neural representation of tinnitus interferes with global sleep maintenance, while a strong sleep drive (such as high homeostatic pressure) overrides aberrant tinnitus-related activity. To test this empirically, a longitudinal assessment of behavioural and neural markers of tinnitus across the sleep-wake cycle was conducted in a ferret model of tinnitus after noise overexposure (NOE) over a period of ~6 months. The changes in behavioural performance and auditory evoked activity after NOE differed between individuals and suggest distinct degrees of tinnitus and hearing impairment with early or late onset. The emergence of tinnitus symptoms was associated with disrupted and reduced sleep, corroborating the possibility that noise-induced tinnitus is linked to sleep disturbance. In addition, neural markers of tinnitus were reduced during sleep, suggesting that sleep may transiently mitigate tinnitus.
Our second prediction was that besides the interaction between sleep and tinnitus, sleep might facilitate tinnitus emergence. To test this, we assessed in mice the effect of acute sleep deprivation after NOE on tinnitus development. Sleep deprivation mitigated behavioural and hearing impairment after NOE, which indicates that sleep may play a role in mediating the consequences of noise-induced peripheral trauma.
Overall, these results highlight the potential of further research on the interactions between natural brain states dynamics and tinnitus to uncover new avenues for future treatments.
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- Files:
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(Preview, Dissemination version, pdf, 63.9MB, Terms of use)
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Authors
Contributors
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- Physiology Anatomy & Genetics
- Role:
- Supervisor
- ORCID:
- 0000-0002-3612-2048
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- Physiology Anatomy & Genetics
- Role:
- Supervisor
- ORCID:
- 0000-0002-4336-6681
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- Physiology Anatomy & Genetics
- Role:
- Supervisor
- ORCID:
- 0000-0002-1039-6032
- Funder identifier:
- http://dx.doi.org/10.13039/501100020172
- Funding agency for:
- Rodriguez Nodal, F
- Bajo Lorenzana, V
- Vyazovskiy, V
- Milinski, L
- Grant:
- RNID Bajo_S52 'Neural signatures of tinnitus across the sleep-wake cycle'
- DOI:
- Type of award:
- DPhil
- Level of award:
- Doctoral
- Awarding institution:
- University of Oxford
- Language:
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English
- Keywords:
- Subjects:
- Pubs id:
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2004456
- Local pid:
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pubs:2004456
- Deposit date:
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2023-09-13
- ARK identifier:
Terms of use
- Copyright holder:
- Milinski, L
- Copyright date:
- 2022
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