Retrospectacle: A Neuroscience Blog

Over at Pharyngula, Mark Antimony posted this:

A friend of mine, who’s name won’t be mentioned, blacked out in class the other day. Since then, he’s been on a seizure drug. The drug is giving a very weird side effect. It must be affecting his auditory cortex, because he is hearing all audio roughly a half-octave lower than what it really is. In fact, he’s using a sound editing program to raise his entire music library up the ~half-octave to compensate. The name of the drug is Tegretol.

While I am not a medical doctor, my research is in auditory neuroscience so it might be interesting to postulate as to the cause of this patient’s odd shift in auditory perception. Tegretol is the trade name of carbamazepine (CBZ) and is a commonly prescribed drug in the treatment of epileptic seizures, such as the patient was experiencing. The experience of perceiving sounds lower (about a semitone, or ‘half-step’) in pitch than they really are is a known side effect of this drug, however its rare for people to notice it, so the patient might be considered unusual in that.

In the literature, case studies which described similar symptoms often involved patients which had absolute pitch and they hypothesized that these people might be more sensitive to pitch changes. The first published paper reporting this symptom was in 1993, and that was a single case, and perhaps only a few dozen more have been reported since then. (Sample free case study here.) So one thing I might ask would be, did the patient mentioned above have absolute pitch before taking CBZ?

Luckily, this hearing impairment is reversible if CBZ is stopped. There are other equally effective anti-convulsant drugs (like zonisamide) out there that the patient’s doctor could consider. Its important to emphasize that there is nothing *wrong* with the auditory cortex, auditory nerve, or the inner ear of these people. Auditory brain responses are all normal, so it seems to be the interpretation of auditory signals is what is temporarily impaired. For this reason, CBZ is sometimes given to people with chronic tinnitus to dampen the annoying, ongoing noise they perceive.

The mechanism of how CBZ interferes with auditory processing is not known, because this side effect is so rare it has not been extensively studied beyond case reports. My guess is that in an effort to reduce extraneous neuronal firings (to nix seizures) you change the way the auditory cortex processes incoming signals. CBZ works to stabilize the inactivated state of voltage-gated sodium channels in neurons to make these neurons ‘less exciteable’ and less likely to generate a seizure. So voltage-gated channels are also being inhibited in the auditory cotex as well as the rest of the brain, which may change how it responds to incoming sound stimuli. (Just my guess.)

Either way, probably best for your friend to get put on a different anti-convulsant if it keeps bothering him.


  1. #1 Benjamin Franz
    December 15, 2007

    You mis-understood the reported change. Her friend had a half-octave change in perception. That is around six tones (half of the twelve tone scale), not a half-tone. You wouldn’t need anything like perfect pitch to notice that much change. You would have to be darn near tone deaf to not notice it.

  2. #2 N.O.
    December 15, 2007

    She did not misunderstand. She reported what has been described in the literature.

  3. #3 Benjamin Franz
    December 15, 2007

    Hmmm…You are right.

    But her question is still odd about whether the friend had absolute pitch given the reported symptom. While you probably need absolute pitch (or close to it) to notice a half-tone change, you need only ordinary pitch to notice a half-octave change.

  4. #4 Charlie (Colorado)
    December 15, 2007

    It’s not that odd a qyuestion, you just misunderestimate how many people have close to absolute pitch. Since I do have near absolute pitch, I notice it quite a bit; there are a lot of people who literally can’t keep a tone and will slip a third or a fifth and not notice. It’s just there are more people than you’d think you won’t even if they can’t identify whether “that tone” is a B or a G. (Which is completely arbitrary, anyway.)

    Now, a half-octave is a little odd, since that’s approximately a sixth, which changes the music to a whole ‘nother mode.

  5. #5 Joel
    December 15, 2007

    The doctor could consider switching the patient to Trileptal.

    Trileptal (oxcarbazepine ) is similar to Tegretol (carbamazepine) but seems to cause side effects less often than Tegretol.

    I have heard of this class of drugs being prescribed to normalize hearing in a case where it was hypothesized that the patient was hearing a particular frequency (or frequencies) at too high a “gain,” adversely affecting the perception of adjacent frequencies.

  6. #6 Rebecca
    December 15, 2007

    Wow! This is really interesting — and it may explain a very odd thing about my husband’s ability to carry a tune.

    My husband has been taking Tegretol for quite a few years.

    When he’s singing alone, he has no difficulty at all singing the correct intervals, but when he’s singing with other people — or with instrumental accompaniment — it’s almost impossible for him to sing on pitch, though he doesn’t hear it himself.

    If the Tegretol is affecting his perception of pitch, that would explain why he has this problem.

    Thank you, thank you! This has been bugging me for years and finally I have what may be an explanation!

  7. #7 David
    December 15, 2007

    This is really fascinating side-effect, thanks for posting it! Pitch perception is quite poorly understood, so it would be interesting to see if this drug can elucidate some of the underlying physiology involved. I’m not entirely convinced that this is all auditory cortex and above, though. There are reports of CBZ altering auditory brain stem responses. This paper makes some interesting conjectures as the origin of the pitch shift, the most convincing being a Ca2+ related speeding up of oscillators in the brainstem, used for pitch detection. I’m surprised no-one has grabbed some rats, a vial of CBZ, and a microelectrode to try and figure this out.

  8. #8 Sloane Angel
    December 16, 2007

    Have either of you ever come across or dealt with Interferon (Peg-Intron) causing tinnitus? Or any info on using Gabapentin or other neuro drugs to help with tinnitus?

  9. #9 Bram Cohen
    December 16, 2007

    Charlie, the positioning of consonant intervals in the scale is due to properties of the sound produced by plucking a string (specifically where the overtones are) not properties of the human ear, so it isn’t all that strange that a neurological alteration does something which is non-sensical from a (western) musical standpoint.

  10. #10 Brian X
    December 18, 2007

    This reminds me of a thing I think I’ve experienced from time to time. Every once in a while, when I wake up to music after not having had enough sleep, the music seems to be going faster than it should. I’ve assumed that it has something to do with my brain being underclocked from fatigue — since hearing is the most time-sensitive of the senses (the reason why Morse code uses beeps rather than lights), it would seem that however my ears are “sampling” the sound I’m hearing, it’s doing it at too slow a rate, but the brain processes it as if it’s coming in at the normal rate, warping the perception of the sound…

    Does that make any sense?

  11. #11 carmen
    January 27, 2008

    sounds like DIPT. from Tihkal #4:

    “My wife’s voice is basso, as if she had a cold … Radio voices are all low, music out of key. Piano sounds like a bar-room disaster. The telephone ringing sounds partly underwater. In a couple more hours, music pretty much normal again.”"

  12. #12 Shawna
    May 6, 2009

    I have been on Tegretol (CBZ) for only a few days now and I have also noticed the change in pitch, which led me to this webpage when I was searching for info on it. I first noticed when my cell phone rang… I thought the battery must be weak or the sound file damaged because the tone sounded lower than usual, like it was dying. And then the microwave beeped and it sounded lower too. The dial tone on my regular phone also sounded weird…. and music is just too weird to listen too. Woman singers all sound mannish or like they have hoarse voices, and my own voice sounds nasal-y when I listen to myself speak. Everything is just a little bit off and I don’t like it at all.