Investigating Disinhibitory Brain Mechanism in Tinnitus and Hearing Loss: Is There a Maladaptive Signature of Auditory Cortex GABA Loss and Dysconnectivity?
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Nottingham
- Enrollment
- 76
- Locations
- 3
- Primary Endpoint
- GABA neurotransmitter level measured using MRS and neural activity and connectivity strength in auditory resting-state networks using functional MRI scan.
Study Overview
Brief 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.
Detailed Description
SELECTION AND WITHDRAWAL OF PARTICIPANTS
Recruitment
- Clinical routes Suitable candidates may be identified by the sites, at Ropewalk House Nottingham Audiology Services and ear, nose, and throat (ENT) services at Nottingham University Hospitals National Health Service (NHS) trust, via searches of their clinical databases or opportunistically during routine clinical appointments. Candidates will only be approached by a member of staff at the site or NIHR Clinical Research Network (CRN) staff to whom recruitment activities have been delegated by the local PI. All patient contact information will be kept confidential and undisclosed to the research team. The initial approach will be providing the participant with the information packs, that will contain (i) an invitation letter, (ii) a participant information sheet explaining all aspects pertaining to participation in the study and (iii) a reply slip. Potential participants who wish to find out more about the study will then be able to opt to be contacted by the researcher by completing a reply slip attached to the invitation letter and returning it in a pre-paid and addressed envelope. Alternatively, potential participants can contact the researcher directly via email and phone number that is written on the participant information sheet.
It will be explained to the potential participant that entry into the trial is entirely voluntary and that their treatment and care will not be affected by their decision. It will also be explained that they can withdraw at any time, but attempts will be made to avoid this occurrence. In the event of their withdrawal, it will be explained that their data collected so far cannot be erased and the investigators will seek consent to use the data in the final analyses where appropriate.
Posters about the study will be on display in the relevant clinical areas. 2. Non-clinical routes:
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Are age 18-80 years.
- •Are eligible to be scanned using MRI and to undergo audiometry and psychometry.
- •Are able to give informed consent.
- •Must have a good comprehension of English in order to complete the hearing-related questionnaires
Exclusion Criteria
- •Pregnant women will be excluded based on MRI safety recommendations.
- •Past medical history of acoustic neuroma and Ménière's disease.
- •Significant past medical history that may affect brain GABA and functional metrics such as stroke, multiple sclerosis, epilepsy, diabetes, cardiovascular, major neurodegenerative or psychiatric conditions, cancer requiring systemic chemotherapy or brain radiotherapy.
- •Individuals who had in last 3 months and/or currently taking a sedating or GABA enhancing or psychoactive drugs (opioids, anti-depressants).
Arms & Interventions
People with tinnitus
People with tinnitus will undergo all interventions (audiology test, MRI scans, tinnitus-related questionnaires).
Intervention: MRI scanning (Other)
People without tinnitus
People with tinnitus will undergo most of all interventions (audiology test, MRI scans) except filling up the tinnitus-related questionnaires.
Intervention: MRI scanning (Other)
Outcomes
Primary Outcomes
GABA neurotransmitter level measured using MRS and neural activity and connectivity strength in auditory resting-state networks using functional MRI scan.
Time Frame: During 3-6 months after the data has been collected
Primary test: * Univariate group comparison between-group differences in imaging outcomes: auditory cortex GABA, local functional connectivity density (REHO), interhemispheric auditory cortices functional connectivity, cross-modal functional connectivity between auditory and visual cortex, auditory cortex neural activity (using BOLD response) to visual attention task. * Between-group test for differences in correlation: GABA and hearing loss, auditory cortex functional connectivity and hearing loss.
Secondary Outcomes
- Measures of GABA level in the auditory cortex and correlation with tinnitus severity scores and tinnitus negative affect scores.(During 3-6 months after the data has been collected)
- Measures of neural activity, and connectivity changes in brain-wide and correlation of these measures with tinnitus severity scores and tinnitus negative affect scores.(During 3-6 months after the data has been collected)