Abstract
SummaryWe report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.
Highlights
Physical means of brain stimulation, such as the use of implanted electrodes for deep brain stimulation (DBS), have led to widespread excitement about the possibility of repairing neural dysfunction through direct control of brain circuit dynamics, including multiple FDA-approved therapies for previously intractable brain disorders (Greenberg et al, 2010; Kalia et al, 2013)
As a result of this complexity, physical means of brain stimulation are often used in a phenomenological way, especially because the excitability properties of neurons vary across different cell types, and understanding how a given brain stimulation method impacts a given brain function may require analyzing many factors
temporal interference (TI) Stimulation: Concept and Validation of Neural Firing Recruitment We first set out to examine whether the TI concept could result in well-defined low-frequency envelope modulated electric fields
Summary
Physical means of brain stimulation, such as the use of implanted electrodes for deep brain stimulation (DBS), have led to widespread excitement about the possibility of repairing neural dysfunction through direct control of brain circuit dynamics, including multiple FDA-approved therapies for previously intractable brain disorders (Greenberg et al, 2010; Kalia et al, 2013). Electrical stimulation via implanted electrodes sparsely activates distributed sets of neurons (Histed et al, 2009), in a fashion different from direct optogenetic control of local cells (Gradinaru et al, 2009). If we apply high-frequency oscillating electric fields at multiple sites outside the brain, neurons in the brain will not be able to follow these high-frequency fields directly. If two such electric fields are applied at high frequencies that differ by a small amount, which corresponds to a low frequency that neurons can follow, neurons in the brain
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