Labree, Bas
(2024)
Transcranial Direct Current Stimulation for tinnitus: towards an improved understanding to facilitate clinical translation.
PhD thesis, University of Nottingham.
Abstract
Tinnitus is the perception of sound in the absence of an external source. It is a highly prevalent condition, comorbid with depression, anxiety, insomnia and reduced quality of life. There is no cure and existing management strategies tend to address the impact of tinnitus, rather than the percept itself. Transcranial Direct Current Stimulation (tDCS) is a potential treatment for tinnitus. TDCS works via a low-intensity direct current delivered through electrodes on the head. It is postulated to modulate tinnitus-associated neural activity in the affected region(s) of the brain, thereby reducing the severity of tinnitus symptoms. TDCS is used for various health conditions, but no optimal set of stimulation parameters exists for the treatment of tinnitus. This is a major hurdle to future large-scale clinical trials to assess its efficacy and safety.
This PhD aimed to optimise tDCS for tinnitus via three approaches. Firstly, it systematically evaluated the existing evidence for safety and effects of tDCS for tinnitus and related symptoms via a systematic review. The evidence suggested that tDCS may be an effective intervention improving tinnitus severity and depression, compared to sham. There was no significant effect of tDCS on anxiety and no serious adverse effects were detected. Data on quality of life and neurophysiological change were insufficient for meta-analysis. This review narrowed down the potentially optimal stimulation protocol (between 7-10 sessions of 20 minutes at 2mA with a frontal electrode montage) using network meta-analyses.
Secondly, specific changes in brain activity during a single session of tDCS were investigated, to improve understanding of the mechanisms by which tDCS might be effective for tinnitus. Magnetoencephalography (MEG) was used to record neural activity from participants with tinnitus before, during and after either active or sham tDCS. Tinnitus loudness ratings were also collected before and after the stimulation. Loudness ratings decreased after stimulation compared to before, but there was no statistically significant difference between tDCS and sham. However, the observed changes in neural activity provide meaningful insights into the effects of tDCS on people with tinnitus. Changes in the delta and theta frequencies localised to the frontal cortices indicate a localised response to tDCS, with more widespread changes in the gamma frequency band suggesting tDCS-related changes in activity in cortical areas beyond the stimulation site. This study shed further light on the technical challenges associated with combining tDCS and MEG, as well as providing new data on efficacy of blinding protocol and adverse effects associated with the stimulation.
Finally, to improve the quality and consistency of future clinical trials of tDCS for tinnitus, a Core Outcome Domain Set (CODS) for electrical stimulation for tinnitus was established, engaging both patients and professional stakeholders. Online Delphi methodology was used to achieve consensus on which outcomes should always be measured in clinical trials of those interventions. The final Core Outcome Domain Set included ability to ignore, concentration, treatment satisfaction, helplessness (lack of control), tinnitus intrusiveness and adverse effects in the Core Outcome Domain Set.
The studies reported in this thesis: (i) identified the optimal set of stimulation parameters based on the current literature; (ii) provided insight into the neural mechanisms by which tDCS can be effective for tinnitus; (iii) established the minimum reporting standards for future clinical trials of electrical stimulation for tinnitus. As such, the work described herein has provided a strong evidential foundation and improved methodological rigour for future studies that seek to investigate safety and efficacy of tDCS as a treatment for tinnitus.
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