For several decades, scientists have struggled to explain why one particular Mozart composition appears to alleviate epileptic brain activity. Known as Sonata for Two Pianos in D Major, K. 448, the piece is the only musical arrangement known to produce this effect, and new research may have finally revealed the secret behind its therapeutic properties.

Writing in the journal Scientific Reports, the study authors state that their findings “may enable us to replicate the “Mozart K448 effect” with other musical stimuli,” suggesting that an entire genre of anti-epileptic music could now be created.

To conduct their investigation, the researchers played the song to 16 participants with refractory epilepsy, all of whom had been fitted with brain implants to measure their neural activity. This enabled the authors to monitor a particular type of electrical impulse known as interictal epileptiform discharges (IEDs), which are strongly associated with epilepsy and can provoke seizures.

Listening to K448 for just 30 seconds produced a noticeable decrease in IEDs, particularly within brain regions that coordinate emotion, such as the bilateral frontal cortices.

Interestingly, however, when participants listened to their personal favorite songs, no such effect was seen. According to the researchers, this suggests that K448 produces an effect on brain activity that is totally independent of subjective emotional response. Such a theory is supported by a study from the 90s which showed that the Sonata reduces IED activity even in comatose individuals.

To understand how the piece achieves this, the study authors analyzed its musical structure, noting that it is “organized by contrasting melodic themes, each with its own underlying harmony.” Intriguingly, they found that reductions in IED were particularly pronounced during the transitions between these musical phrases.

Based on this observation, the researchers hypothesize that the transitions between extended melodies generate “positive emotional responses” within the brain, which appears to attenuate epileptic activity. To test this theory, they asked participants to listen to a separate piece by Wagner, which “has no recognizable melodies” and “is organized by subtle and gradual changes instead of contrasting melodic themes.”

Listening to Wagner had no effect on IED activity, bolstering the conclusion that melodic changes are the key anti-epileptic ingredient in Mozart’s K448. By harnessing this property and composing other musical arrangements that mirror the structure of the Sonata, the researchers say it may be possible to develop new, non-invasive treatments for epilepsy – something that will be music to the ears of those who suffer from the condition.