Dartmouth Researchers Examine the Mozart K448 Effect in Epilepsy

There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. But little is known about the mechanism underlying the beneficial “Mozart K448 effect” says a paper published today in Nature Scientific Reports: Musical Components Important for the Mozart K448 Effect in Epilepsy.

Led by researchers from Geisel School of Medicine, Dartmouth-Hitchcock Medical Center (DHMC), and Dartmouth College’s Bregman Music and Affective Sound Lab, this is the first study to systematically evaluate the relationship between musical segment boundaries and spectral power changes related to Mozart’s K448.

Mozart’s Sonata for Two Pianos in D Major (K448). Copyright (C) 2021 Bregman Music and Affective Sound Lab. Used by permission.

“Our work is aimed at trying to engineer music that is antiepileptic and reduces seizures. Identifying the features of music that have an effect on epileptic activity in the brain is a first step,” says Barbara C. Jobst, MD, Dr. med, the Louis and Ruth Frank Professor of Neuroscience at Geisel, and chair of the Department of Neurology and Neurocritical Care and director of the Epilepsy and Cognition Lab (ECoGlab) at Dartmouth-Hitchcock (D-H).

“Robert Quon, the lead author, worked on the antiepileptic properties of music in the brain as part of his PhD thesis. He has done an outstanding job bringing neurologists, engineers, data scientists, music professors, and musicians together to perform this work,” Jobst added.

Robert Quon

Quon, a PhD candidate in Geisel’s Quantitative Biomedical Sciences program, says, “There is a substantial body of research supporting the use of different sensory stimuli to treat various neurological conditions. Preeminent in epilepsy research is the use of Mozart’s K448 for reducing interictal and ictal events.”

Because its mechanism is unknown, he says their study “sought to untangle how auditory stimuli may exert its therapeutic effects, with the dream of creating novel, adjunctive therapies for medically resistant epilepsy.”

Michael Casey, PhD, a professor of music and of computer science at Dartmouth, and one of the investigators, says he likes how this study combined expertise in music analysis with clinical neurology in a deep way.

“We analyzed the musical structure of Mozart's K448 and the electrical brain response, using both human experts and machine listening algorithms, to determine the effects on the brain of specific musical features. Participants listened to songs selected from a range of musical genres, with acoustic features matching Mozart K448, to replicate the Mozart effect with a more diverse music selection,” Casey explains. “However, despite selecting genres to match participants' preferred listening habits, so far only 40-Hz auditory gamma-band tones and Mozart's piano sonata K448 were observed to be effective at reducing interictal epileptiform discharges.

“One explanation,” he says, “is that the Mozart sonata has a relatively constant repeated sixteenth-note rhythm (around 128 beats per minute in the recording that we used) that can evoke neural entrainment. Another would be that the classical sonata form is engaging attentional and emotional circuits by setting up and then playing with musical expectations. For these reasons in our search for effective music medicine, we must factor in music-theoretic elements of the selections, such as: tempo, onset density, timbre, key, and musical form.”

Their research data suggest a strategy for the noninvasive modulation of intracranial interictal epileptiform activity (IED) that, according to the paper, “may alleviate IED-related comorbidities and support future investigation of other sonatas with similar structural characteristics to Mozart’s K448, as they may hold therapeutic potential for epilepsy.” The research also provides insight into intracranial mechanisms that may be important for the anti-epileptic properties of Mozart’s K448.

Casey, who conducts research into how sound affects the body and brain, and also creates music for sound therapies and medical interventions, cites French otolaryngologist Alfred Tomatis’ 1991 book, Pourquoi Mozart?, whose essays on his decades of work using Mozart’s music for the treatment of a range of disorders he thought were connected to the ear—including dyslexia, depression, and severe schizophrenia—says, “amazingly, for now, we are left with the same question.”

Quon says he was fortunate to be a part of all aspects of this music study, including the experiment conception and design, data collection and analysis, and manuscript preparation. “I had a lot of help along the way, without which none of this would be possible. Our active collaborations with Professor Michael Casey’s Bregman Music and Affective Sound Lab at Dartmouth and Professor Grace Leslie’s Brain Music Lab at Georgia Tech were instrumental in generating and testing novel hypotheses about how music may be beneficial for epilepsy."

This work was supported by the National Institutes of Health [Grant Number 05-T32LM012204-03], the Burroughs Wellcome Fund [Grant Number 1014106], the National Science Foundation [Award Number 1632738], and by a Diamond Foundation Research Development Award.

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