Investigating Disinhibitory Brain Mechanism in Tinnitus and Hearing Loss

Summary

Tinnitus, the perception of sound in the absence of an external acoustic stimulus. Tinnitus is often perceived inside the head rather than the ear and is a common condition with a prevalence estimated between 10 and 15% in adults. Between 1 and 3% of this population are having a significant impact on their quality of life. Despite its high prevalence, the underlying mechanisms of tinnitus still remain unclear.

The majority of tinnitus cases associated with some degree of hearing loss, making hearing loss the biggest risk factor for tinnitus. Recently, it has been suggested that hearing deficits, such as speech-in-noise difficulty, can exist in the absence of any overt hearing loss within the audiometric range (0.125-8 kHz). This is referred to as "hidden hearing loss" and has been suggested to be associated with hearing loss at above-audiometric (\> 8 kHz) frequencies.

This project is aimed at studying the underlying mechanisms of tinnitus and the possible relation with overt or hidden hearing loss. Specifically, the investigators want to test the hypothesis that tinnitus is caused by maladaptive plasticity arising as a result of auditory input deprivation. This idea is supported by the finding that tinnitus may disappear when the hearing, and thus auditory input, recover. Disruptions at lower levels of the auditory pathway could lead to alterations in synaptic transmission and neurotransmitter release in more central regions of the auditory system (e.g., in the auditory cortex). This may create an imbalance between neuronal excitation and inhibition, and re-routing of auditory pathways, leading to abnormal neural excitability and connectivity.

In this study, the investigators question whether auditory cortex disinhibition is specifically related to tinnitus, or is a consequence of hearing loss. To answer this question, the investigators propose to conduct a study that aims to investigate the inhibition mechanism by quantifying GABA concentration level, neural activity and functional connectivity strength of auditory cortex using non-invasive imaging techniques, namely Magnetic Resonance Spectroscopy (MRS) and functional Magnetic Resonance Imaging (fMRI). The investigators expected to possibly provide a tinnitus biomarker, and this may help to direct future treatments.

Conditions

• Tinnitus
• Hearing Loss

Interventions

OTHER

MRI scanning

In the audiological assessment, participants will undergo various audiometric test, such as pure tone audiometry with extended high-frequency range, speech audiometry, tympanometry, and auditory reflex threshold. These tests are all noninvasive and aim to assess participants hearing threshold, speech-in-noise difficulty, whether or not they have conductive hearing loss, and test efferent auditory function. The appointment will take around 60-90 minutes. An experienced audiologist on-site will be in charge of this procedure. In the MRI appointment, participant will undergo MRI scanning. Before the MRI scan, a researcher with experienced radiographer will re-check that the participant is safe to be scanned, with the standard University of Nottingham safety questionnaire. This rechecking step is necessary to make sure that participants are still eligible for the scanning. An experience radiographer will be in charge of this procedure.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust

  collaborator OTHER

• University of Nottingham

  lead OTHER

Principal Investigators

• Dorothee Auer, Prof. · University of Nottingham

• Anissa Ramadhani · University of Nottingham

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-08-09

Primary Completion

2022-10-31

Completion

2022-10-31

Countries

• United Kingdom

Study Locations