Newswise — For people with drug-resistant epilepsy, treatment options can seem few and far between. Over the past two decades, several studies have suggested that listening to music—specifically, Mozart’s K448, Sonata for Two Pianos—is associated with seizure reduction.

Most recently, a one-year study from the Krembil Brain Institute in Toronto followed 13 people with drug-resistant epilepsy. Results showed that three months of daily listening to Mozart K448, compared with listening to a “scrambled” K448 lacking the rhythmicity of the original, was associated with a 35% reduction in seizures.

The study saw no differences in effects between people with normal and abnormal MRI results. The group’s next steps include attempts to tease out the mechanism or mechanisms behind the effect.

It’s music to your ears – and brain

Listening to music can change brain activity in so many ways,” said Marjan Rafiee, research assistant at Krembil and first author of the study. “We know that Mozart is different in some ways, compared with other classical composers. Mozart pieces are famous in terms of having long-term periodicity, and they have some of the most unpredictable rhythmic structures mathematically.”

The study length and strict criteria meant that of more than 1,100 potential participants, only 13 met the criteria and opted in.

“We had a wide range of exclusion criteria because we wanted to make sure it was controlled,” said Rafiee. For the yearlong study, participants could not change medication types or dosing, or pursue other treatment options. They also had to be willing to complete multiple follow-up visits at the hospital.

The concept of music therapy for epilepsy raises some eyebrows, of course, but as a noninvasive form of neuromodulation, it has sparked interest. A recent review of 12 studies in this area conducted nine meta-analyses, which “showed significant reductions in seizures and interictal epileptiform discharges after long-term music treatment, and in [interictal epileptiform discharge] frequency during and after a single music stimulus.”

The origin of the “Mozart effect”

Yet many are still skeptical that music could have any effect on seizures, let alone that there’s something about Mozart K448 that sets it apart from other compositions.

Why has this one piece of music been studied so intensively? The interest appears to stem from a 1993 study of college students: Some listened to 10 minutes of silence, some to 10 minutes of a monotone lecture, and some to 10 minutes of K448. The students completed spatial reasoning tests before and after the intervention. The study results asserted that listening to Mozart was associated with improved results on the tests.

The term “Mozart effect” became shorthand for the apparent association between Mozart K448 and changes in the brain; the idea has been extrapolated and distorted to the point of absurdity, which likely contributes to skepticism in the field of epilepsy, said Philip Pearl, professor of neurology at Harvard Medical School and a trained jazz musician.

The studies of spatial reasoning, said Pearl, “morphed into the belief that if a baby in the womb listened to Mozart during pregnancy, its IQ would go up. Or if you gave children music lessons very young, their IQs would go up. The skepticism has to do with extrapolating these limited studies to infancy and before we’re born.”

The original findings also were difficult to replicate, and any relationship between listening to music and improved cognition seemed farfetched to many, leading to widespread skepticism and outright dismissal of the entire concept (such as in the 2010 publication “Mozart effect, Shmozart effect: A meta-analysis”).

Some also have noted that listening to Mozart may simply be enjoyable, which could reduce stress and improve sleep patterns and potentially lead to decreased seizure frequency. However, studies of Mozart and seizure frequency have included participants who were exposed to Mozart K448 while asleep, in a coma, or experiencing status epilepticus, all states that preclude conscious music appreciation. Those studies have included work in mouse models (and there’s no consensus on whether rodents appreciate Mozart).

Music and lower mortality

Cameron Metcalf, Grzegorz Bulaj and colleagues at the University of Utah recently published work using mouse models of pain, suggesting that exposure to Mozart compositions could enhance the analgesic and anti-inflammatory effects of certain drugs, including ibuprofen and levetiracetam. The group also tested the music exposure in several kindling models of epilepsy, but did not see an effect on seizures.

“We hypothesized that the animals exposed to music would have fewer seizures, that they would take longer to kindle, and we didn’t see that,” said Metcalf, a research assistant professor in pharmacology and toxicology. “What was remarkable, though, is that we saw improved survivability.”

The group plans to probe this finding further in the future. “Because I’m interested in SUDEP, my interest is why the mortality was so much lower in the animals exposed to music,” said Metcalf. “It may be unique to the animal strain, or there may be an indication of an anti-inflammatory effect or behavioral effects…These are things we’re going to follow up on.”

“Everything in our lives is neuromodulation”

Taufik Valiante is a neurosurgeon at Toronto Western Hospital and senior author of the Krembil Brain Institute study. Valiante said that he did not expect to see any effect of listening to Mozart on seizure frequency.

“What Marjan and I were particularly surprised at was how much of an effect size we saw,” he said. “But everything in our lives is neuromodulation. We know the brain follows patterns in the environment – that’s what our senses are for. And there’s always the question, why this piece? What’s special about this piece?”

That’s the next step for the group, which is working to extract the unique features of K448 and capitalize on them for seizure reduction. Creating a “better K448” could provide another option for people whose seizures are not responding to medication, and who may not be candidates for other treatments.

Said Metcalf, “One day you might be able to imagine a digital therapy platform where you could put together a playlist, customized for the patient – you intermix patient preferences with proven therapeutic pieces of music and eventually you can say, particularly to someone with pharmacoresistant epilepsy, that this platform has been shown to have an added benefit.”

The idea is not a novel stand-alone therapy, but an adjunct. “We want something that can be useful to patients and providers and show that biologically, there’s something here that goes beyond relaxing and destressing,” said Metcalf.

Valiante agreed. “What I love about this project is that this is something you can add on top of something else; there will be people who don’t benefit from surgery, and there are people I can’t offer surgery to,” he said. “So as a clinician it’s wonderful feeling, because sometimes we don’t have much else to offer.”

Referenced articles

M Rafiee, et al. 2020. Daily listening to Mozart reduces seizures in individuals with epilepsy: A randomized controlled study. Epilepsia Open, May 2020 doi.10.1002. epi4.12400

M. Bodner, et al. 2012. Reduction of seizure occurrence from exposure to auditory stimulation in individuals with neurological handicaps: A randomized controlled trial.(Plos One doi100.137.pone.0045303

C.S. Metcalf, et al. 2019. Music-enhanced analgesia and antiseizure activities in animal models of pain and epilepsy: Toward preclinical studies supporting development of digital therapeutics and their combinations with pharmaceutical drugs Frontiers in Neurology March 2019. doi.10.3389/fneur.2019.00277

G. Sesso & F. Sicca. 2020. Meta-analyzing the Mozart effect on epilepsy. Clinical Neurophysiology. Vol131, Issue 7, July 2020, pp. 1610-1620

Music’s effects on the brain: Talk and piano performance by Philip Pearl. 2016. (video)

 

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Founded in 1909, the International League Against Epilepsy (ILAE) is a global organization with more than 120 national chapters.

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