Consistent linear and non-linear responses to invasive electrical brain stimulation across individuals and primate species with implanted electrodes

Abstract

a b s t r a c tBackground: Electrical neuromodulation via implanted electrodes is used in treating numerous neurological disorders, yet our knowledge of how different brain regions respond to varying stimulation parameters is sparse. Objective/Hypothesis: We hypothesized that the neural response to electrical stimulation is both regionspecific and non-linearly related to amplitude and frequency. Methods: We examined evoked neural responses following 400 ms trains of 10e400 Hz electrical stimulation ranging from 0.1 to 10 mA. We stimulated electrodes implanted in cingulate cortex (dorsal anterior cingulate and rostral anterior cingulate) and subcortical regions (nucleus accumbens, amygdala) of nonhuman primates (NHP, N ¼ 4) and patients with intractable epilepsy (N ¼ 15) being monitored via intracranial electrodes. Recordings were performed in prefrontal, subcortical, and temporal lobe locations. Results: In subcortical regions as well as dorsal and rostral anterior cingulate cortex, response waveforms depended non-linearly on frequency (Pearson's linear correlation r < 0.39), but linearly on current (r > 0.58). These relationships between location, and input-output characteristics were similar in homologous brain regions with average Pearson's linear correlation values r > 0.75 between species and linear correlation values between participants r > 0.75 across frequency and current values per brain region. Evoked waveforms could be described by three main principal components (PCs) which allowed us to successfully predict response waveforms across individuals and across frequencies using PC strengths as functions of current and frequency using brain region specific regression models. Conclusions: These results provide a framework for creation of an atlas of input-output relationships which could be used in the principled selection of stimulation parameters per brain region.

Decoding task engagement from distributed network electrophysiology in humans

“…We have successfully deployed this approach in other investigations, e.g. [76], as have other research groups using different approaches to assign electrodes to homologous regions [77].…”

Closed loop enhancement and neural decoding of human cognitive control

“…We did not test any other stimulation sites for their effects on MSIT performance, because we had a specific hypothesis regarding the internal capsule. Other sEEG electrodes were stimulated in separate experiments in these same participants, but those are reported elsewhere 59,68,69 and the outcomes of those experiments did not influence the present study.…”

Stimulation Mapping Using Stereoelectroencephalography: Current and Future Directions

“…One such area of research would include better defining the electrophysical properties most conducive to stimulation mapping, such as the biophysical properties of the cortical regions or the optimal charge density to minimize tissue damage (1,44). Other investigations into optimal stimulation paradigms and excitation properties of certain cortical or subcortical areas could benefit our understanding of both normal regional physiology and pathologic excitability (45)(46)(47)(48). Such investigations could include high-/low-frequency stimulation paradigms or rely on SPES (49)(50)(51)(52).…”