Neurofeedback for Tinnitus - Does Frequency Specificity Matter?

Study Overview
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Brief Summary
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This study will evaluate the efficacy of an alpha/delta ratio (ADR) neurofeedback training protocol on tinnitus distress. 1/3 of the participants in the study will undergo ADR neurofeedback training, 1/3 an active comparator, beta/theta ratio (BTR) neurofeedback training, whilst the final 1/3 of participants will fill in daily diaries of tinnitus complaints and symptoms for two weeks.

Detailed Description
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Tinnitus is hypothesized to originate as a result of a disturbance in the balance of excitatory and inhibitory neurons in central auditory structures. More specifically, inhibitory neurons hyperpolarize, by which their functional role is weakened . Consequently, this allows auditory neurons, deprived of input from a lesioned auditory system, to spontaneously synchronize their activity, resulting in the tinnitus percept. In the normal functioning auditory system, neurons firing synchronously in the alpha frequency region (8 - 12 Hz) have a gating function of inhibiting task-irrelevant regions in the brain. In people with chronic tinnitus, it has been observed, that alpha activity over temporal regions is weakened, thus leading to the spontaneous activity characterizing the condition. By upregulating alpha activity with neurofeedback training, it is hypothesized that the excitatory/inhibitory balance in temporal regions can be restored, thus minimizing the tinnitus percept. The coupling or exchange of information of distinct brain regions, leading to an integrated conscious perception, is assumed to be mediated by delta oscillations. In tinnitus, the distress associated with the condition arises as a consequence of coupling prefrontal areas, responsible for allocation of attentional resources with limbic (arousal) and temporal (auditory processing) regions. In neurofeedback, the downregulation of delta activity is hypothesized to lead to a de-coupling of the communication between the areas associated with the distress. No studies to date have tested the specific role of alpha and delta in the origin and perpetuation of tinnitus distress and intrusiveness. The present study seeks to compensate for this, by comparing an alpha and delta neurofeedback ratio training protocol with one assumed to have no direct association with the pathophysiology of tinnitus. In addition to the ten neurofeedback training sessions, all participants undergo diagnostic assessments at three time points throughout the trial (pre-neurofeedback training, post-neurofeedback training and at three months follow-up). For the first 40 participants, electroencephalographic (EEG) activity is recorded and cognitive capacity assessed with two attention tests, the Attention Network Test and Sustained Attention Response Task, respectively at all three time points. For the remaining 80 participants, the EEG recording is abandoned, and only cognitive capacity assessed in the pre- post, and follow-up phase of the study. EEG recording and attention processes is similarly measured in a control group (n=40) at the pre-neurofeedback training stage. The group is comprised of healthy, age and gender matched participants. Their inclusion serve the purpose of comparing the brain activity, both at rest and during cognitive activity between people with- and people without tinnitus.

Official Title
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Study Protocol for a Single-blind Randomized Controlled Trial, Assessing the Specificity of an Alpha/Delta Ratio Neurofeedback Training Protocol in Chronic Tinnitus.

Conditions
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Tinnitus, Subjective Tinnitus, Chronic Tinnitus

Intervention / Treatment
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* Behavioral: alpha/delta neurofeedback
* Behavioral: beta/theta neurofeedback
* Other: Diary completion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic subjective tinnitus, i.e. tinnitus with a duration > 6 months At least mild tinnitus distress, corresponding to a score of ≥ 18 on the Tinnitus Handicap Inventory Exclusion Criteria: Moderately severe or severe depression Objective tinnitus, where causes are classified according to whether they are vascular or non-vascular in origin Current use of psychotropic drugs for a mental health condition Bipolar disorder, Attention Deficit Hyperactivity Disorder (ADHD), Psychosis Substance abuse Current psychotherapeutic treatment for tinnitus, previous biofeedback- or neurofeedback treatment A history of seizures, strokes and/or brain hemorrhages

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADR neurofeedback<br>Ten ADR neurofeedback training sessions. The first five sessions comprise four training blocks. The latter five sessions consists of five training blocks each. All training blocks are seven minutes in duration. Participants take between two to three sessions each week. | Behavioral: alpha/delta neurofeedback<br>* neurofeedback training protocol seeking to decrease the alpha/delta ratio, by simultaneous rewarding alpha and inhibiting delta activity.<br>|
| Active Comparator: BTR neurofeedback<br>Ten BTR neurofeedback training sessions. The first five sessions comprise four training blocks. The latter five sessions each consists of five training blocks. All training blocks are seven minutes in duration. Participants take between two to three sessions each week. | Behavioral: beta/theta neurofeedback<br>* neurofeedback training protocol seeking to decrease the beta/theta ratio, by simultaneous rewarding beta and inhibiting theta activity.<br>|
| Active Comparator: Diary Control Group<br>Daily diary completion for two weeks in the period between baseline and end-point assessments (total period baseline to end-point = four weeks). | Other: Diary completion<br>* completion of diary relating to participants' experience of tinnitus intensity, interference, coping, harm and disability. Rated three times daily on numerical scale (0 - 10) for two weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tinnitus Handicap Inventory (THI; Newman, Sandridge, & Jacobson, 1998) | Self-report measure of tinnitus handicap assessed pre-intervention, mid-treatment (five sessions), post-intervention and at three month follow-up. The Tinnitus Handicap Inventory is a 25 item questionnaire. Each item is scored 0 - 4 (0 = No, 2 = Sometimes, 4 = Yes), yielding a total between 0 (no handicap) - 100 (catastrophic impact). | 16 weeks | 
| Tinnitus Magnitude Index (TMI; Schmidt, Kerns, Griest, Theodoroff, Pietrzak, & Henry, 2014). | TMI measures tinnitus intensity, three-item scale assessing self-reported severity, loudness and awareness. - Visual analogue scale ranges from 0-10 or 0-100, respectively: item 1 (loudness): Range 0 (not at all strong or loud) to 10 (extremely strong or loud) item 2 (awareness): 0 to 100 in increments of 10, with verbal anchors of 0=never aware and 100=always aware item 3 (severity): 0-100 with verbal anchors of 0=no tinnitus present to 100=the worst tinnitus you can imagine for all items higher values indicate higher tinnitus magnitude values of the three items can be summed up to a total score. For standardisation, items are converted from 0-100 to 0-10. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tinnitus Functional Index (TFI; Brüggemann, Szczepek, Kleinjung, Ojo, & Mazurek, 2017) | The Tinnitus Functional Index (TFI) is a self-report measure of both perceived severity and negative impact of tinnitus. It covers multiple severity domains including but not exclusively quality of sleep, relaxation, sense of control. The TFI questionnaire consists of 25 items, predominantly scored between 0 - 10 bar item 1 and 3, which are expressed as percentages from 0 - 100%. | 16 weeks | 
| Brief Illness Perception Questionnaire (B-IPQ; Broadbent, Petrie, Main, & Weinman, 2006) | The B-IPQ is a nine item self-report measure of individual cognitive and emotional representations of illness. It includes the following domains: consequences of the illness; perception of duration of illness; control over illness; treatment control; symptoms; understanding of illness; emotional response and causes. | 4 weeks | 
| Insomnia Severity Index (ISI; Bastien, Vallières, & Morin, 2001) | A brief scanning measure of insomnia. It consists of 7 items assessing insomnia severity, interference in daily functioning, noticeability of impairment and distress/concern about sleep problems. | 4 weeks | 
| Credibility and Expectancy Questionnaire (CEQ; Devilly & Borkovec, 2000) | a quick and easy-to-administer scale for measuring treatment expectancy and rationale credibility for use in clinical outcome studies | 4 weeks | 
| Sustained Attention Response Task (SART; Robertson, Manly, Andrade, Baddeley, & Yiend, 1997) | measures the ability to sustain attention | 16 weeks | 
| Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002) | assesses orienting, alerting and executive attention processing respectively | 16 weeks | 
| Patient Health Questionnaire (PHQ-9; Gräfe, Zipfel, Herzog, & Löwe, 2004) | Assessment of depressive symptoms | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tinnitus distress, tinnitus intrusiveness, synchronization by loss of inhibition model (SLIM), neurofeedback, alpha/delta neurofeedback, beta/theta neurofeedback, electroencephalography (EEG), tinnitus intensity, tinnitus loudness