BALTIMORE — Exposure to specifically engineered auditory tones in music may offer a noninvasive option to reduce seizures in patients with refractory epilepsy, early research suggests.
Investigators found this novel therapy regulated abnormal interictal epileptiform activity (IEA) in patients who had failed other treatments such as antiepileptic drug (AED) therapy, and was particularly effective in participants with a high baseline rate of interictal spikes.
For these patients, "we showed that the stimuli that we specifically engineered for this experiment had a greater effect on their spiking rate," study investigator Grace Leslie, PhD, assistant professor at the School of Music, Georgia Institute of Technology, Atlanta, told Medscape Medical News.
The findings were presented here at the American Epilepsy Society (AES) 2019 Annual Meeting.
Auditory Theory
About 40% of patients with epilepsy are resistant to antiepileptic medications. Although several neuromodulation techniques can reduce IEA, these options tend to be invasive and include surgical resections, and implantation of neurostimulation devices such as responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS).
Low frequency auditory tones have previously been tested in neurodegenerative diseases, such as Alzheimer's disease, with some success at alleviating disease pathology, said coinvestigator Robert J. Quon, a PhD candidate at Dartmouth Geisel School of Medicine, Hanover, New Hampshire.
The mechanism underlying these therapeutic benefits remains unknown, although experts have put forward some theories. For example, the intervention might enhance blood flow in certain brain regions and recruit helpful blood cells, said Leslie.
In the area of epilepsy, there is limited evidence for exactly how low tones improve seizures.
"Our theory is that it may help reduce interictal spikes in patients with epilepsy, but our ongoing research is exploring potential physiologic mechanisms underlying these benefits," said Quon.
To test this approach, researchers enrolled nine adult patients with refractory epilepsy who were admitted for intracranial (ECoG) monitoring at Dartmouth-Hitchcock Medical Center.
"Electrodes were implanted in the brain for presurgical monitoring to determine which specific brain is involved with seizure onset and propagation," Quon said.
Study investigators Robert Quon, PhD candidate, and Grace Leslie, PhD
The investigators monitored brain activity of participants during exposure to random selections of short acoustic stimuli. One piece of music was Mozart's Sonata for Two Pianos in D Major (K448). This piece was chosen, in part, because it had been used in experiments by Taiwanese researchers studying the impact of music on epileptiform activity in children, Quon noted.
The lowest frequency that humans can detect is about 20Hz. The slightly higher frequencies used in the study may sound like a buzzing or background "white noise," he added.
"We were trying to see how these tones affect spike rates and if there's a form of entrainment in the brain, such that the brain aligns to these types of external auditory tones," he added.
Using an automated spike detector developed in another investigator's ECoG lab, the researchers separated patients into high and low interictal spike-rate groups.
Dramatic Response
Results showed the exposure to low frequency auditory stimulation significantly reduced interictal spikes compared with the visual control.
"We found that in the low spike rate group there was a dramatic spectral response," Quon said.
"Interestingly, in the high spike rate group, we found a significant reduction in 3 of the 4 subjects during exposure to this stimulus, meaning that when we played them this tone, there was a reduction in spikes, he added.
Quon believes that the group with the high baseline spike rates allowed him to detect alterations in spike rates, which are otherwise hidden in subjects with low overall spike rates.
The reduction in interictal spikes was generalized to the right hemisphere, specifically to the superior temporal cortex and the hippocampus — brain regions that scientists believe are involved in music processing in the brain.
Reducing epileptiform activity could enhance cognitive processes in patients with refractory epilepsy, Leslie said.
One of the next research steps is to determine whether there's added benefit to more persistent exposure to these low frequency tones.
The current results "represent a new avenue" for epilepsy management, Leslie noted.
"Our research advances the understanding of the intricate relationship that exists between music and epilepsy, and will generate critical knowledge for future applications of noninvasive sensory neuromodulation," she said.
"I believe that we can compose, engineer, and scientifically validate new kinds of music that will bring health and well-being to patients. In 5 to 10 years, we may envision a doctor being able to prescribe a music intervention to address a patient's specific needs," she added.
Helping Patients With Headphones?
Commenting for Medscape Medical News, Daniel Goldenholz, MD, PhD, Division of Epilepsy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, described the results as "tantalizing."
The authors raise the question of whether patients with epilepsy could be helped with headphones, said Goldenholz.
"If so, that would be great as it involves no drugs and no intracranial wires," said Goldenholz, who was not involved with the current research.
He noted that there have been case reports of using Mozart's music to stop seizures in patients with status epilepticus.
However, Goldenholz wondered if paying attention to anything that is engaging might also have a short-term anti-IED effect. He pointed to anecdotal evidence of reduced IED activity while driving.
"Perhaps there's a benefit to patients simply doing a demanding task that requires their attention," he said. Goldenholz also said he was curious about what happens in the brain after exposure to auditory stimuli stops.
"Do the patients go back to their baseline rate again?" he asked.
Leslie said that many of these questions would be addressed in future research.
The study had no specific funding. The study authors and Goldenholz have disclosed no relevant financial relationships.
American Epilepsy Society (AES) 2019 Annual Meeting. Abstract 3.185. Presented December 9, 2019.
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