Abstracts

Rationale:
Musical stimuli that are engineered for persons with epilepsy present a compelling alternative to current invasive neuromodulation techniques for regulating abnormal epileptiform brain rhythms, such as interictal epileptiform activity (IEA). IEA is associated with increased seizure frequency and impaired cognition, which are both predictive factors of a poor quality of life in persons with epilepsy. While there are many invasive neuromodulation techniques, there are noninvasive options for reducing IEA in refractory epilepsy. A novel noninvasive alternative is sensory stimulation that drives the neural activity of brain regions temporally, and thereby demonstrates a novel alternative to modulating IEA. We propose to engineer auditory stimuli to achieve gamma-frequency sensory stimulation and reduce IEA. Gamma-band auditory stimulation is known to exert a therapeutic effect on other neurological conditions, such as Alzheimer’s disease and Schizophrenia, but its effect on epilepsy remains unknown. 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 to temporally drive the neural activity of brain regions. Our study sought to determine the optimal carrier frequency and delivery method for this non-invasive auditory neuromodulation by assessing our ability to evoke 40-Hz auditory responses in intracranial ECoG patients.
Method:
We enrolled 10 patients that were admitted for intracranial (ECoG) monitoring at Dartmouth-Hitchcock Medical Center (DHMC) during this study. These patients were diagnosed with refractory epilepsy that was monitored using multiple electrode configurations, but with the predominant configuration covering the temporal lobe. We used various signal processing methods to engineer a set of auditory stimuli containing enhanced 40 Hz spectral power. We presented subjects with blocks of randomly shuffled 15 second clips of these stimuli in addition to 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 acoustic and visual stimuli presented during a 20-minute session, which presented approximately 20 different auditory and visual stimuli. 
Results:
We assessed  our ability to evoke 40Hz auditory responses in intracranial  patients by calculating the spectral power of the ECoG signal in the 40 Hz range. We were able to demonstrate neural responses to the engineered 40-Hz stimuli in 10 enrolled subjects. Our preliminary analysis was able to demonstrate an increase in 40-Hz event-related synchronization during trials containing specifically-engineered musical stimuli, as compared to baseline and rest periods.
Conclusion:
The effects that gamma-band music stimuli have on epileptiform activity has not been 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 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:
:EPIC Epilepsy Foundation of Long Island