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(Abst. 3.185), 2019

Engineering Music to Mitigate Epilepsy
Authors: Grace Leslie Ph.D., Georgia Institute of Technology; Robert J. Quon, Dartmouth Geisel School of Medicine; Barbara C. Jobst, Dartmouth-Hitchcock Medical Center
Content: Rationale: Musical stimuli engineered for persons with epilepsy is an exciting noninvasive option for regulating abnormal epileptiform brain rhythms, such as interictal epileptiform activity (IEA). IEA is associated with seizure frequency and cognition, both factors that predict a poor quality of life in persons with epilepsy. While antiepileptic medications are a noninvasive option, approximately 40% of patients are drug-resistant. Currently, there are many neuromodulation techniques that are shown to reduce IEA, but most of these methods are invasive. A novel, noninvasive alternative is sensory stimulation for temporally driving the neural activity of brain regions. Our study seeks to determine the optimal carrier frequency and delivery method for reducing interictal spikes through non-invasive auditory neuromodulation.  Methods: We enrolled 9 patients diagnosed with refractory epilepsy that were admitted for intracranial (ECoG) monitoring at Dartmouth-Hitchcock Medical Center (DHMC). Their brain activity was monitored using multiple electrode configurations, but with the predominant configuration covering the temporal lobe. We presented subjects with blocks of randomly shuffled 15 second clips of 40-Hz pure tones and other musical samples modulated at 40-Hz. Each auditory stimulus was followed by a 15 second visual control stimulus, which is shown to reset the effects of the previous acoustic stimulus. Prior to the task, each subject was instructed to attend to the 20 different acoustic and visual stimuli presented during a 20-minute experiment session. We analyzed the total spectral power of the ECoG data in the frequency ranges of the auditory stimuli, with the region of interest located in the temporal lobe. We then identified interictal spikes with a template-based spike detector that was previously developed and validated by our lab, and compared the mean difference in baseline-normalized spikes between the different stimuli groups, with the visual stimuli serving as the control.  Results: We were able to demonstrate robust responses to 40-Hz stimuli by comparing spectral activity generated in response to these targeted stimuli, as compared to a pre-experiment baseline. Our analysis of interictal epileptiform activity compared the total number of IEDs detected during trials consisting of a pure 40-Hz tone, to those detected during a 440-Hz tone amplitude modulated to 40-Hz. Both tones were baseline normalized and re-referenced to a visual control, in order to assess the percent change in spike reduction from this visual control. Our results demonstrated significantly reduced interictal spikes after exposure to 40-Hz auditory stimulation, as compared to the visual control.  Conclusions: The effects that gamma-band music stimuli have on epileptiform activity have not been previously investigated in persons with refractory epilepsy. There is limited research that examines how certain types of music exert antiepileptic benefits, and even less on the antiepileptic effects of gamma-band auditory responses. The present research represents a new avenue for epilepsy management that shifts the classical application of invasive gamma-band electrophysiological stimulation to sensory modalities. Our data suggests that this approach will be effective at modulating IEA, which we predict will enhance cognitive processes by reducing epileptiform activity. 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.  Funding: No funding