TinnitusS-89.3480 Acoustics Seminar18.2.2015Petteri Hyvärinen

Outline

Basic understanding of tinnitus• 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?• 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• 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• 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 PLUShttp://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?