When they go low, we go high

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Science Translational Medicine  21 Jun 2017:
Vol. 9, Issue 395, eaan6193
DOI: 10.1126/scitranslmed.aan6193


High-frequency electrical interference can be used to drive activity deep in the brain.

Deep brain stimulation has emerged as a viable therapeutic option for several mood and cognitive disorders. This treatment is based on delivering electrical current through intracerebral electrodes implanted in a target brain region. However, given the invasive nature of such therapy, it is not a first-line treatment. Furthermore, many patients who fail more conventional therapies remain unable to benefit from this treatment due to neurosurgical contraindications. But what if it were possible to stimulate deep brain regions without the need for surgically implanted electrodes?

In this study, Grossman et al. developed a noninvasive method for location-specific deep brain stimulation induced by oscillating electric currents applied to the surface of the brain via external electrodes. In contrast to the lower stimulation frequencies utilized in clinical DBS applications (~120 Hz), the author’s noninvasive approach utilizes two independent high-frequency (>1000 Hz) electrical stimulations to induce electric fields within the brain. Whereas stimulation at lower frequencies directly modulates neuronal firing, the high-frequency stimulations applied in this study do not affect neuronal activity on their own. Rather, by applying principles of temporal interference, the authors demonstrate that two high-frequency electric fields can be patterned such that the interference generated by the frequency difference between the two electrical stimulations applied on the brain surface induces neuronal firing in specific deep brain locations.

The study demonstrates that this method can be applied to stimulate deep brain tissue without activating overlying areas. Additionally, the authors use computational modeling and in vivo testing to show that the brain stimulation site can be adjusted by simply modifying the current intensity delivered by the two surface electrodes. Critically, the high-frequency stimulation did not induce supraphysiological heating of brain tissue or cellular damage, as assessed using standard markers of inflammation and cell death.

Overall, this approach exploits electrical interference to directly drive deep brain activity. Future experiments will be needed to determine whether temporal electrical interference can be implemented in larger brains while still maintaining its fidelity in targeting even structures and its limited side effect profile. Nevertheless, because electrical stimulation has already been applied as a treatment for brain disorders, this method might be rapidly tested in clinical settings. If testing proves successful, noninvasive deep brain stimulation may soon become a standard first-line treatment for neurological and psychiatric disorders.

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