Phase-Dependent Stimulation For Modulating Phase-Amplitude Coupling: A Computational Modeling Approach

Phase-amplitude coupling (PAC), in which the amplitude of a faster neural oscillation couples to the phase of a slower rhythm, is one of the most common representations of complex neuronal rhythmic activities. In a healthy brain, PAC accompanies cognitive function, and abnormal patterns of PAC have been linked to several neurological disorders. Among the various brain neuromodulation techniques, phase-dependent stimulation has a strong potential to modulate PAC levels. In this study, we utilize a computational model in the NEURON environment based on a detailed mathematical model of neuronal populations, consisting of networks with both excitatory and inhibitory neurons, to simulate PAC generation. The model was then used to investigate the modulatory effects of phase-dependent stimulation on the generated PAC. Simulated data from the model shows that stimulation locked to the phase of slower rhythms increased PAC level during stimulation. These results demonstrate the capacity of phase-dependent stimulation to modulate PAC, which could allow for applications in the treatment of neurological disorders associated with abnormal PAC, such as Parkinson's disease.