Non-invasive brain stimulation to target specific network activity patterns, e.g. transcranial alternating current stimulation (tACS), has become an essential tool to understand the causal role of neuronal oscillations in cognition and behavior. However, conventional sinusoidal tACS limits the ability to record neuronal activity during stimulation and lacks spatial focality. One particularly promising new tACS stimulation paradigm uses amplitude-modulated (AM) high-frequency waveforms (AM-tACS) with a slow signal envelope that may overcome the limitations. Moreover. AM-tACS using high-frequency carrier signals is more tolerable than conventional tACS, e.g. in terms of skin irritation and occurrence of phosphenes, when applied at the same current intensities (e.g. 1-2 mA). Yet, the fundamental mechanism of neuronal target-engagement by AM-tACS waveforms has remained unknown. We used a computational model of cortex to investigate how AM-tACS modulates endogenous oscillations and compared the target engagement mechanism to the case of conventional (unmodulated) low-frequency tACS. Analysis of stimulation amplitude and frequency indicated that cortical oscillations were phase-locked to the envelope of the AM stimulation signal, which thus exhibits the same target engagement mechanism as conventional (unmodulated) low frequency tACS. However, in the computational model substantially higher current intensities were needed for AM-tACS than for low-frequency (unmodulated) tACS waveforms to achieve pronounced phase synchronization. Our analysis of the carrier frequency suggests that there might be a trade-off between the use of high-frequency carriers and the stimulation amplitude required for successful entrainment. Together, our computational simulations support the use of slow-envelope high frequency carrier AM waveforms as a tool for noninvasive modulation of brain oscillations. More empirical data will be needed to identify the optimal stimulation parameters and to evaluate tolerability and safety of both, AM- and conventional tACS.
Keywords: Amplitude modulation; Brain stimulation; Computer simulation; Target engagement; Transcranial alternating current stimulation; tACS.
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