What's new in tinnitus research

he main theory about tinnitus today is that it's a phantom sound caused by (1) spontaneous neural firing and (2) synchronization of circuits in the auditory cortex of the brain. Beneath it all is ‘synaptic plasticity’, what laymen call learning, that has somehow gone wrong due to noise exposure. ^[1]

What does this mean for treatment? The standard answer is cognitive behavioral therapy (CBT) and neuro­modu­lation. CBT is intended to make the noise less objectionable. Neuromodulation means electrically stimulating the auditory cortex in the brain to disrupt the bad circuits. This theory wasn't pulled out of thin air: even patients whose middle ear has been effectively destroyed can sometimes experience tinnitus, which implies that the auditory cortex might be involved. And over the past decade, a flurry of papers waxed optimistic about such things as transcranial magnetic stimulation and transcranial direct current electrical stimulation (tDCS) ^[2][3] whose job it was to rewire the auditory cortex, either by classical conditioning by pairing it with vagus nerve stimulation, or by brute force. Although some successes were reported (e.g. ^[4]), this new paradigm has come and gone with little demonstrable success.

The current dogma for tinnitus assumes noise exposure and brain plasticity are the cause of tinnitus. It's a kitchen sink of neuronal phenomena, which has the advantage of being nearly impossible to falsify (redrawn from [1])

As a theory hangs on for dear life it gets more and more complicated, marshalling more overlapping mechanisms to defend itself against falsification. That seems to be the current state of the synaptic plasticity theory (see diagram at right).

Probably the only solid therapy is the old standby lidocaine, usually given i.v., sometimes intra­tympan­ically, which the authors of a recent study claim is a “safe, efficacious” treatment for sudden sensorineural hearing loss.^[5] Intravenous lidocaine has been known for years to benefit tinnitus, but the effects are transient. There is little evidence that administering lidocaine intratympanically works any better, and it is an invasive method that punctures the eardrum and risks otitis media and eardrum damage.

A problem found with tDCS was that using patient reaction times, which are needed to determine whether the tDCS is working, generates false positive results. Patients experience a practice effect, and the tDCS interferes with this, suggesting that it somehow interferes with some types of motor learning.^[6] This is a very worrying side effect and it's a clear example of the danger of meddling with synaptic plasticity.

The main challenge is that there are many different types, symptomatically speaking: for instance, hissing tinnitus, pulsatile tinnitus, and single tone or ringing tinnitus. Most authors treat hissing and ringing tinnitus as if the cause is the same: sensorineural hearing loss. If that isn't really true, it would hinder progress even more.

We had the same situation in my field. People would recruit patients with Alzheimer's disease with no consideration of their genetic background, so patients with familial AD were mixed with other patients. The assumption was that the biological mechanism was the same. Then, after a hugely expensive clinical trial, they'd try to separate the groups out. The goal was to find some way of partitioning the results that would make them statistically significant so they could turn it over to Marketing and go work on something else.

A few researchers are still trying combinations. For instance, one group claimed some temporary success of combined cognitive behavioral therapy with matched sound therapy.^[7] But again, they did not distinguish among the various types. Then there are a few improbable experiments, like combining sound therapy with electrical tongue stimulation.^[8] This seemed to work a little, or so the authors claimed.

Animal experiments

Another more radical idea—so far in animals only—is that mid-infrared photons, aka heat, alleviate tinnitus by increasing KCNQ2 [potassium] ion current in neurons in the brain.^[9] The challenge here is in knowing whether the mice really have tinnitus that is comparable to humans and how to know when they've cured it.

Patients might not like the idea of a 7.5 milliwatt quantum cascade laser stereotaxically blasting “photons” with a wavelength of 8.8 microns directly into their auditory cortex, but if it worked, future refinements might make the treatment less invasive and maybe even a little safer.

New untested observations

All these failures are of course disappointing to patients, and reading the accounts gives one the impression that most of these researchers don't suffer from tinnitus themselves, so to them it's an abstract problem. The bias toward sensorineural hearing loss practically guarantees that no treatment will be considered unless it fits the hearing loss paradigm.

This is especially true for cervicogenic somatic tinnitus ^[10], which is more often of the ringing type. Imagine playing an instrument and suddenly there's an extra note—say an A-flat—that's louder than everything else. It would be incredibly annoying and would probably stop you instantly. It's well known that if the patient makes facial contortions, like eating a piece of toffee, it can often be stopped. In my experience, if it's not stopped within a few seconds after it starts, it can last for hours.

Last month I was casually checking on an old beat-up piano to determine whether the ringing frequency is always the same. It's not, but I discovered by accident that hitting the correct note caused the ringing to stop almost instantaneously. The ringing sometimes starts up again after a few seconds, but at a different pitch. In one case it changed from A-flat (1864.7 Hz) to G-flat (1661.2 Hz). The sound has to be in the same octave as the ringing; a lower or higher octave has no effect. Following the ringing with a second tone when it shifts to a new frequency stopped it for good.

I have no idea whether this works for anyone else, and it likely would have little effect on hissing tinnitus or pulsatile tinnitus. But the question is: why would it work at all? It's what we in science call a Big Clue.

oct 30 2024, 10:45 am. edited for readability oct 30 2024, 4:20 pm