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

Duchet B
Sermon JJ
Weerasinghe G
Denison T
Bogacz R

Brain stimulation can have unintended effects at different ratios of the stimulation frequency (e.g. half the stimulation frequency or twice the stimulation frequency). Here, we propose modified stimulation patterns in order to avoid these unintended effects which could be harmful to patients.

Scientific Abstract

While brain stimulation therapies such as deep brain stimulation for Parkinson's disease (PD) 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 behaviour 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 could be harmful to patients, for example by triggering debilitating involuntary movements in PD. We therefore seek 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.

Two panels showing regions of entrainment as a function of natural frequency and stimulation amplitude. Upper pane, entrainment regions around the stimulation frequency. Lower panel, our proposed stimulation pattern showing entrainment only around the stimulation frequency.
When stimulation is periodic, neural oscillators may be entrained at the stimulation frequency but also at sub- and super-harmonics of the stimulation frequency. Corresponding entrainment regions (Arnold tongues) are represented in panel A for uncoupled neural oscillators modelled using the sine circle map. Stimulation is provided at 130Hz (red dashed line), with stimulation amplitude shown on the vertical axis, and the natural frequency of oscillators on the horizontal axis. Entrainment is observed when the rotation number (color scale) is an integer ratio. With our proposed stimulation pattern, entrainment at sub- and super-harmonics of the stimulation frequency disappears, and only the 1:1 Arnold tongue persists (panel B, green tongue).

2023. J Neural Eng, 20(2).

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