Electrophysiological Interference for Deep Brain Modulation

In this paper, we present a novel framework for electrophysiological interference (EI) as a means of modulating neural activity in deep brain regions. The motor and cerebellar cortices were targeted at subthreshold current levels by transcranial alternating current stimulation (tACS) at 100 Hz and 110 Hz respectively. The goal was to induce an interference pattern within a subcortical region of the brain, the motor thalamus (Mthal), which receives convergent projections from these cortical regions. The proposed EI method fundamentally contrasts with the previously proposed temporal interference (TI) in that the interference takes place between the synaptic inputs to the target cell rather than by summation of the electrical fields (e-fields) at the overlapping regions inside the brain. We demonstrate, in anesthetized rats, that the cortical projections from the motor and the cerebellar areas can entrain the spiking activity of the Mthal neurons both individually and synergistically. The interference pattern is predominantly a linear superposition of the two inputs, and modulation at the difference frequency (10 Hz) was much less than that at individual input frequencies. The results also demonstrate multi-synaptic entrainment of Mthal neurons by cerebellar tACS. EI has a potential to entrain neural activity in deep brain regions using non-invasive AC stimulation and it has the advantage over TI of not exposing the superficial layers of the brain to extreme electric fields.Clinical Relevance-Transsynaptic AC stimulation may find clinical applications for entrainment of spiking activity in deep brain regions while keeping the stimulation currents within safety limits at the cortical level.