How to entrain a selected neuronal rhythm but not others: open-loop dithered brain stimulation for selective entrainment

Abstract

While brain stimulation therapies such as deep brain stimulation for Parkinson's disease can be effective, they have yet to reach their full potential across neurological disorders. Entraining neuronal rhythms using rhythmic brain stimulation has been suggested as a new therapeutic mechanism to restore neurotypical behavior in conditions such as chronic pain, depression, and Alzheimer's disease. However, theoretical and experimental evidence indicate that brain stimulation can also entrain neuronal rhythms at sub- and super-harmonics, far from the stimulation frequency. Crucially, these counterintuitive effects can be harmful to patients, for example by triggering debilitating involuntary movements in Parkinson's disease. We therefore propose a principled approach to selectively promote rhythms close to the stimulation frequency, while avoiding potential harmful effects by preventing entrainment at sub- and super-harmonics. Our open-loop approach to selective entrainment, dithered stimulation, consists in adding white noise to the stimulation period. We theoretically establish the ability of dithered stimulation to selectively entrain a given brain rhythm, and verify its efficacy in simulations of uncoupled neural oscillators, and networks of coupled neural oscillators. Furthermore, we show that dithered stimulation can be implemented in neurostimulators with limited capabilities by toggling within a finite set of stimulation frequencies. Likely implementable across a variety of existing brain stimulation devices, dithering-based selective entrainment has potential to enable new brain stimulation therapies, as well as new neuroscientific research exploiting its ability to modulate higher-order entrainment.

Irregular optogenetic stimulation waveforms can induce naturalistic patterns of hippocampal spectral activity

“…We observed that the Poisson waveform, when compared to standard pulse stimulation at an equivalent central frequency, increases power at the central frequency while obscuring the effects of harmonics. These empirical observations support recent theoretical work showing that adding noise to the inter-pulse interval of a constant-frequency stimulation waveform ('dithering') can suppress harmonic stimulation effects [64]. There may be a quantitative tradeoff between these two properties: having low inter-pulse noise produces greater entrainment at the central frequency, but at the cost of increased harmonics; higher inter-pulse noise might lead to reduced harmonics, but also decreased entrainment at the central frequency.…”

Mean-Field Approximations With Adaptive Coupling for Networks With Spike-Timing-Dependent Plasticity

“…Here we have focused predominantly on the Kuramoto model with adaptivity rules that mimic the adaptation between individual neural cells. However, as a prototypical model to study synchronization in neuroscience, the Kuramoto model has also found application on different scales including whole-brain modeling, epilepsy, and Parkinson's disease (Cumin & Unsworth, 2007;Breakspear et al, 2010;Cabral et al, 2014;Schmidt et al, 2015;Ponce-Alvarez et al, 2015;Finger et al, 2016;Asllani et al, 2018;Weerasinghe et al, 2019Weerasinghe et al, , 2021Bick et al, 2020;Duchet et al, 2022). While here each Kuramoto oscillator typically represents neural populations rather than individual cells, our results may still help understand the role of adaptivity in such networks-albeit with potentially different adaptivity rules on different timescales.…”

Irregular optogenetic stimulation waveforms can induce naturalistic patterns of hippocampal spectral activity

“…These empirical observations support recent theoretical work showing that adding noise to the inter-pulse interval of a constant-frequency stimulation waveform ("dithering") can suppress harmonic stimulation effects. 48 There may be a quantitative tradeoff between these two properties: having low inter-pulse noise produces greater entrainment at the central frequency, but at the cost of increased harmonics; higher inter-pulse noise might lead to reduced harmonics, but also decreased entrainment at the central frequency.…”