The neuron mixer and its impact on human brain dynamics.

A signal mixer facilitates rich computation, which has been the building block of modern telecommunication. This frequency mixing produces new signals at the sum and difference frequencies of input signals, enabling powerful operations such as heterodyning and multiplexing. Here, we report that a neuron is a signal mixer. We found through ex vivo and in vivo whole-cell measurements that neurons mix exogenous (controlled) and endogenous (spontaneous) subthreshold membrane potential oscillations, producing new oscillation frequencies, and that neural mixing originates in voltage-gated ion channels. Furthermore, we demonstrate that mixing is evident in human brain activity and is associated with cognitive functions. We found that the human electroencephalogram displays distinct clusters of local and inter-region mixing and that conversion of the salient posterior alpha-beta oscillations into gamma-band oscillations regulates visual attention. Signal mixing may enable individual neurons to sculpt the spectrum of neural circuit oscillations and utilize them for computational operations.

Pulse-width modulated temporal interference (PWM-TI) brain stimulation.

BACKGROUND: Electrical stimulation involving temporal interference of two different kHz frequency sinusoidal electric fields (temporal interference (TI)) enables non-invasive deep brain stimulation, by creating an electric field that is amplitude modulated at the slow difference frequency (within the neural range), at the target brain region. OBJECTIVE: Here, we investigate temporal interference neural stimulation using square, rather than sinusoidal, electric fields that create an electric field that is pulse-width, but not amplitude, modulated at the difference frequency (pulse-width modulated temporal interference, (PWM-TI)). METHODS/RESULTS: We show, using ex-vivo single-cell recordings and in-vivo calcium imaging, that PWM-TI effectively stimulates neural activity at the difference frequency at a similar efficiency to traditional TI. We then demonstrate, using computational modelling, that the PWM stimulation waveform induces amplitude-modulated membrane potential depolarization due to the membrane's intrinsic low-pass filtering property. CONCLUSIONS: PWM-TI can effectively drive neural activity at the difference frequency. The PWM-TI mechanism involves converting an envelope amplitude-fixed PWM field to an amplitude-modulated membrane potential via the low-pass filtering of the passive neural membrane. Unveiling the biophysics underpinning the neural response to complex electric fields may facilitate the development of new brain stimulation strategies with improved precision and efficiency.