S-89.3480 Acoustics Seminar 18.2.2015 Petteri Hyvärinen Tinnitus S-89.3480 Acoustics Seminar 18.2.2015 Petteri Hyvärinen

Outline Basic understanding of tinnitus How can tinnitus be studied? What it (probably) is and isn’t How can tinnitus be studied? Principles of clinical trials Some examples

Tinnitus basics

Tinnitus Tinnitus — from latin word tinnire (to ring) Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus1 Almost any kind of sound Indistinct & w/o meaning (vs. hallucinations) 1Langguth et al. Lancet Neurol. 2013;12:920–930

Tinnitus ~10–15% of the population affected 1–2% invalidated Risk factors Hearing impairment Age Male

Tinnitus Cause unknown, theories exist Earlier: thought to originate from cochlea Now: pathology of the central nervous system (CNS) Hearing loss can lead to tinnitus Maladaptive plasticity Compare to phantom pain

Tinnitus --- CNS Schaette. 2013. Hearing Research

Tinnitus --- CNS Where in the auditory pathway? What changes? Not possible to pinpoint Although changes due to tinnitus can be observed, proving causality is quite challenging What changes? Reorganization of neural maps Increased synchrony Not only auditory! Attention, anxiety, depression, stress, etc…

Tinnitus --- CNS

Tinnitus Still too straightforward … There’s tinnitus and then there’s tinnitus Objective tinnitus The sound can be heard by another person Blood vessels Somatosensory tinnitus Modulated by neck tension, head position, jaw ~20%–70% of tinnitus cases, depending on who you ask Other forms of subjective tinnitus What “tinnitus” usually refers to

Diagnosing tinnitus Three components of tinnitus Auditory features (pitch, loudness, location, masking, …) Emotional features (distress) Attentional features (awareness, cognitive load)

Diagnosing tinnitus No objective measures Instead, subjective questionnaires and scales Tinnitus Handicap Inventory (THI) Tinnitus Questionnaire (TQ) Tinnitus Handicap Questionnaire (THQ) Tinnitus Functional Index (TFI) Visual analogue scales (VAS) … Treatment effect measured by comparing these at different timepoints

Diagnosing tinnitus in the future … Neuroimaging (f)MRI Structural changes EEG / MEG Evoked responses Oscillatory activity Functional connectivity Require big datasets TINNET Collaboration on heterogeneity of tinnitus Aim: objective measures for tinnitus

Diagnosing tinnitus Big challenge: it’s never just the sound How to disentangle all possible confounding factors? Different components of tinnitus don’t correlate Louder not necessarily more irritating So what should you measure?

Tinnitus treatments Many approaches Counselling, CBT Hearing aids Sound therapy Pharmacotherapy Brain stimulation Many treatments aim at management of tinnitus Not necessarily abolishing tinnitus Stress reaction   tinnitus distress

Tinnitus treatments Exapmle: Sound therapy Just masking Loud enough to mask tinnitus Unnoticeable, relaxing Bedside sound generators Combined with CBT Tinnitus retraining therapy (TRT) Individualized Tailor-made notched music therapy (TMNMT) Promoting plasticity Lateral inhibition

Tinnitus treatments Poor evidence Placebo effect Heterogeneity of tinnitus Trial design flawed Placebo effect Remarkable No physiological explanation Why did it work? Does it matter?

Tinnitus recap A very diverse condition It’s not in the ear Many problems because all forms treated as same It’s not in the ear Hearing loss can lead to tinnitus There are treatments None of them work 100% They might not be what you’d expect

Designing experiments

Experiment design How would you design an experiment? “My tinnitus went away after I started wearing this healing crystal bracelet” You want to sell these bracelets to tinnitus patients  show that wearing one cures tinnitus

Clinical trials (in tinnitus) Key aspects in clinical trials (of tinnitus)1 Trial type (RCT, N, power calc.) Control condition* and blinding Trial duration Study population* Outcome measures* Statistical sig. vs. clinical relevance Trial reporting Ethical aspects 1Landgrebe et al. 2012 J Psychosom Res. 73:112–121

The scientific method Make hypotheses Derive predictions Make experiments based on predictions Analysis and conclusions

Experiment design RCT = randomized controlled trial Gold standard of clinical studies Control groups Blinding So why doesn’t everyone just do RCTs? You need a hypothesis You need a lot of subjects Specificity vs. generality: statistical power

Example of a study (tDCS) transcranial direct current stimulation (tDCS) Brain stimulation method Used successfully for depression Promising method for tinnitus neuroConn DC-STIMULATOR PLUS http://www.neuroconn.de/dc-stimulator_plus_en/

tDCS study Two electrode montages: LTA left temporal anode  targeting AC Bifrontal  targeting frontal areas Similar results for LTA and bifrontal in earlier studies However, targeting of stimulation is different So is it just a sham effect? Does tDCS work differently than what expected?

tDCS study Double-blind sham-controlled trial Comparing two electrode montages LTA vs. bifrontal 2 mA current, 20 min daily for 10 days Pre-treatment vs. 4 weeks after first treatment (18 days)

tDCS study Pre- and post-treatment measures: THI and mini-TQ Beck Depression Inventory Beck Anxiety Inventory VASs: loudness, irritability, overall effect on life MEG measurements High-freq audiometry Tinnitus pitch matching & masking levels

tDCS study Trial started in beginning of 2014 Now ~30 subjects have completed Preliminary results Subjects with low THI scores don’t improve Difference between pre and post treatment for sham vs. active LTA vs. bifrontal not so clear Aim is to increase N by 15–20 subjects Takes time

Questions?

Questions

Questions How to measure changes in tinnitus? Do auditory hallucinations and tinnitus differ? How? How does an RCT help you support causality of treatment  improvement?