Secondary outcome measures
The Dutch validated version of the TQ is used to differentiate between emotional and cognitive distress, auditory difficulties, and self-experienced intrusiveness caused by tinnitus [
33]. The total score can be in the range of 0–84, assigning a subject to a distress category: slight (score = 0–30, grade 1); moderate (score = 31–46, grade 2); severe (score = 47–59, grade 3); and very severe (score = 60–84, grade 4) [
34].
The SSQ12 is a short form of the Speech, Spatial and Qualities of Hearing scale [
35,
36]. The questionnaire is used in clinical research to measure several aspects of hearing ability, such as: speech comprehension in quiet and noise; localization of sound, distance, and movement; segregation; and listening effort. Responders rate their ability to do or experience the situation described in each question by marking a 1–10 scale (1 = not at all, 10 = perfectly). Scores of all 12 questions are averaged to obtain a global SSQ-12 score.
The HADS is used to detect states of anxiety or depression [
37]. Patients must answer a total of 14 questions, of which seven belong to the subscale “depression” and seven pertain to the subscale “anxiety.” Scores of 7 or less on each subscale indicate non-cases. Scores of 8–10 are borderline abnormal (borderline case), while scores of 11–21 are abnormal (case).
The VAS enquires the mean loudness and maximum loudness of the tinnitus. The patient must score their tinnitus loudness on a scale of 0 (absence of tinnitus) to 100 (cannot be any louder).
The patient’s hypersensitivity to sound is investigated using the 14-item HQ [
38]. The 14 questions assess three dimensions (attentional, social, and emotional). The answer categories are: “no” (score of 0 points); “yes, a little” (1 point); “yes, quite a lot” (2 points); and “yes, a lot” (3 points). A total score of 28 or more indicates clinically significant hyperacusis.
The HUI23 is a family of generic health profiles and preference-based systems for the purposes of measuring health status, reporting health-related quality of life (QoL), and producing utility scores [
39]. The HUI23 comprises a 15-item questionnaire. The resulting total health-related QoL score ranges from 0.00 (dead) to 1.00 (perfect health).
Pure-tone linear audiometry will be performed according to current clinical standards (International Organization for Standardization [ISO] 8253–1:2010), using a two-channel AC-40 audiometer (Interacoustics, Assens, Denmark) in a soundproof booth. Air conduction thresholds will be measured at 125 Hz, 250 Hz, 500 Hz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 6 kHz, and 8 kHz using headphones. When air conduction thresholds between 250 Hz and 4 kHz exceed normality levels of 20 dB HL, the bone conduction threshold will be measured at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 3 kHz, and 4 kHz in order to distinguish between conductive and sensorineural hearing loss.
Participants are asked whether they perceive the tinnitus unilaterally, bilaterally, or centrally, and whether the tinnitus sound is a pure tone, a noise, or a mixture of different sounds (polyphonic). Psychoacoustic characteristics of the tinnitus sound are assessed in a soundproof booth. As a psychoacoustic equivalent of frequency, the tinnitus pitch is obtained by use of a pitch matching technique. A two-alternative forced choice procedure will be employed using the contralateral ear as the reference ear. In cases where tinnitus is perceived bilaterally, the choice of ear is made arbitrarily. Using this technique, an attempt is made to identify the center pitch of the tinnitus. When multiple tinnitus sounds are perceived, patients are asked to focus on the most troublesome tinnitus sound. Pairs of pure tones (or noises in case of noise-like tinnitus), differing by one or more octaves, are presented to the individual, who has to indicate which of the stimuli best resembles the tinnitus sound. This procedure is repeated and finer adjustments are made to obtain the closest possible match of the tinnitus pitch.
Loudness is the perceptual correlate of sound intensity. The tone or noise defined as the pitch match is presented to the ipsilateral ear (when appropriate) and a loudness match is made by use of an alternating procedure. Because of compressed dynamic range frequently present at the tinnitus frequency, final loudness measurements are made with 1-dB steps. The absolute level of tinnitus loudness is measured in dB hearing level (dB HL). In addition, a calculation is made to provide a measurement of relative loudness expressed in dB sensation level (dB SL), which is defined as the level of the loudness match minus the auditory threshold at the tinnitus frequency.
Speech comprehension in quiet is investigated using the Dutch NVA lists, which were developed by the Dutch Society for Audiology (Nederlandse Vereniging voor Audiologie, NVA) [
40]. Each of the four lists consists of 12 monosyllabic words (consonant-vowel-consonant), of which the first one is used for training. The percentage of correctly identified items determines the speech recognition score. The lists are presented through headphones.
The Leuven Intelligibility Sentences Test (LIST) is used to measure speech reception in noise [
41]. The long-term average frequency spectrum of the speech signal matches the spectrum of the noise. The noise level is constant at 65 dB SPL, while the sound level of the speech signal is changed according to the individual’s response. Lists of 10 sentences are presented through headphones. If the individual correctly repeats the keywords of a sentence, the sound level of the next sentence is decreased by 2 dB SPL. In case of an incorrect response, the level is increased by 2 dB SPL. The levels of the last five sentences of the list and the imaginary 11th sentence are averaged to acquire the speech reception threshold (SRT).
Cognitive functioning will be evaluated by use of the RBANS-H [
42]. The RBANS assesses five cognitive domains, i.e. Immediate Memory, Visuospatial / constructional, Language, Attention, and Delayed Memory, and consists of 12 subtests.
The domain Immediate Memory consists of two subtests. In the subtest List Learning, the same list of 10 words is presented over four trials, whereas the subtest Story Memory consists of a 12-item short story that is presented twice. After each presentation, the individual must recall as much of the words or the story as possible. Two subtests belong to the domain Visuospatial / constructional: a Figure Copy test, in which the individual is asked to copy a geometric figure, and the subtest Line Orientation, during which the individual needs to match two lines according to their orientation. The domain Language includes the subtests Picture Naming and Semantic Fluency. In the first subtest, 10 line drawings are to be named by the individual. In the second subtest, the individual is given 1 min to generate as many examples as possible from a certain semantic category. The subtests Digit Span and Coding contribute to the domain Attention. In the first subtest, a string of digits is presented, after which the individual is asked to repeat the digits in the correct order. In the subtest Coding, the individual is asked to complete a page of symbols with the corresponding digits according to a key on top of the page. The last domain, Delayed Memory, enquires how many items the individual recalls from the subtests List Learning, Story Memory, and Figure Copy.
The RBANS-H is developed especially for the purpose of examining the cognitive function of individuals with hearing impairment. To reach this purpose, a number of adjustments to the original RBANS have been made. By means of an accompanying PowerPoint presentation, written explanations are given to support the oral instructions and ascertain that the participant understands the instruction. In addition, all relevant stimuli are not only presented orally but also visually. All adjustments were made in accordance to the RBANS guidelines [
43]. The total score before and after therapy will be compared in order to reveal any changes in different aspects of cognition due to HD-tDCS.
Exploratory research is performed towards CAEP as a potential objective measure of therapy effect. Brain potentials will be elicited using an oddball paradigm during which the patient is instructed to press a button every time a rare stimulus (2 kHz) is presented in between frequent stimuli (1 kHz) through shielded headphones (Audio Technica ATH M30x Refaeds). Rare and frequent stimuli will occur with a probability of 20% and 80%, respectively, and the rise and fall time of the presented stimuli are both 5 ms. Stimuli are delivered by use of the Software Presentation™ (Neurobehavioral Systems, Inc). During this task, EEG is recorded (Micromed™ SD LTM 64 Express) using the interface “Gilat Medical TM Event Related Potentials system.” In total, 31 silver/silver chloride (Ag/AgCl) electrodes are placed according to the 10–20 Standard International Electrode System referenced to a chin electrode, with the ground electrode placed on the right mastoid. Vertical electrooculogram (EOG) is recorded using one electrode located below the right eye. After recording the EEG is sampled at 1024 Hz with 22-bit A/D resolution and band passed in the range of 0.02–450 Hz (Micromed™ SD LTM 64 Express).
All data will be analyzed by one researcher using Gilat Medical™ analysis software (Karkur, Israel). Recordings will be segmented into time epochs of 2 s which are time-locked to the stimuli. Baseline correction for each trial will be performed using the average of the 200 ms before stimuli onset for each channel separately. For each patient, all trials will be averaged according to the condition (target and non-target). An Independent Component Analysis (ICA) algorithm will be used to correct for external artefacts, such as eye blinks.
The analysis software will be used to calculate the area below the curve and the center of gravity of peaks within specific time windows in the average trace for the target condition. The time window for the different components is determined according to visual inspection of the average trace over all electrodes. Furthermore, latency average of the correct response is calculated as the time from stimulus onset to the time of the button press. Finally, a group average for the target and non-target records of the baseline measurement and the follow-up measurement is performed in order to compare the averaged response at baseline with the averaged response at the follow-up at three months.