We 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.
Bibliographical noteFunding Information:
E.S.B. was funded by NIH Director's Pioneer Award 1DP1NS087724 and NIH Director's Transformative Research Award 1R01MH103910-01, the New York Stem Cell Foundation-Robertson Investigator Award, the MIT Center for Brains, Minds, and Machines (NSF CCF-1231216), Jeremy and Joyce Wertheimer, Google, NSF CAREER Award CBET 1053233, the MIT Synthetic Intelligence Project, the MIT Media Lab, the MIT McGovern Institute, and the MIT Neurotechnology Fund. N.G. was funded by a Wellcome Trust MIT fellowship (097443/Z/11/Z). L.H.-T. was funded by NIH grants 1RF1AG047661 and NS051874, the Belfer Neurodegeneration Consortium, the Glenn Foundation for Aging Research, the Alana Foundation, Cure Alzheimer's Fund, and the JBP Foundation. A.R. was funded by a NARSAD grant. A.P.L. was partly supported by the?Sidney?R. Baer Jr. Foundation, the NIH (R01MH100186, R01HD069776, R01NS073601, R21 NS082870, R21 MH099196, R21 NS085491, R21 HD07616), the Football Players Health Study at Harvard University, and Harvard Catalyst | The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH, UL1 RR025758). We acknowledge, for helpful discussions, A.C. Singer. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University or its affiliated academic health care centers, MIT, the NIH, or the Sidney R. Baer Jr. Foundation. N.G., E.S.B., and D.B. have applied for a patent on the technology, assigned to MIT. N.G. is a founder of a medical device company that licensed the patent from MIT. A.P.L. serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Neuroelectrics, Axilum Robotics, Magstim, and Neosync and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging.
- deep brain stimulation
- transcranial direct current stimulation
- transcranial magnetic stimulation