Investigating the Feasibility of Epicranial Cortical Stimulation Using Concentric-Ring Electrodes: A Novel Minimally Invasive Neuromodulation Method

Abstract

Background Invasive cortical stimulation (ICS) is a neuromodulation method in which electrodes are implanted on the cortex to deliver chronic stimulation. ICS has been used to treat neurological disorders such as neuropathic pain, epilepsy, movement disorders and tinnitus. Noninvasive neuromodulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation (TES) show great promise in treating some neurological disorders and require no surgery. However, only acute stimulation can be delivered. Epicranial current stimulation (ECS) is a novel concept for delivering chronic neuromodulation through subcutaneous electrodes implanted on the skull. The use of concentric-ring ECS electrodes may allow spatially focused stimulation and offer a less invasive alternative to ICS. Objectives Demonstrate ECS proof-of-concept using concentric-ring electrodes in rats and then use a computational model to explore the feasibility and limitations of ECS in humans. Methods ECS concentric-ring electrodes were implanted in 6 rats and pulsatile stimulation delivered to the motor cortex. An MRI based electro-anatomical human head model was used to explore different ECS concentric-ring electrode designs and these were compared with ICS and TES. Results Concentric-ring ECS electrodes can selectively stimulate the rat motor cortex. The computational model showed that the concentric-ring ECS electrode design can be optimized to achieve focused cortical stimulation. In general, focality was less than ICS but greater than noninvasive transcranial current stimulation. Conclusion ECS could be a promising minimally invasive alternative to ICS. Further work in large animal models and patients is needed to demonstrate feasibility and long-term stability.

Rapid, Dose-Dependent Enhancement of Cerebral Blood Flow by transcranial AC Stimulation in Mouse

“…As we have shown with CBF, effective modulation of other intracranial biomarkers may also require a field strength of >2.5 mV/mm [21]. Potentially, this amplitude of stimulation could be achieved with direct intracranial stimulation or, alternatively, pericranial stimulation [49], with directional current focused directly against the skull rather than across the scalp. Thus, there are potential translational paths towards applying modified forms of stimulation to enhance CBF, to overcome the limitation of the electric field mismatch noted between rodent and human applications.…”

“…Still, these focused approaches may not lead to substantially increased field strength or tolerability at the levels apparently needed for CBF enhancement as demonstrated here. But, if stimulation is needed long-term (i.e., more than 6e8 weeks) a modified subcutaneous or pericranial stimulation through percutaneous implants (under the scalp, stimulation contacts facing the skull) may be a better solution to avoid side effects of scalp stimulation [48,49]. These could be left in indefinitely, controlled through wireless stimulation, and allow EEG recordings if needed to estimate physiological brain effects in response to the stimulation, but removable percutaneously as required.…”

A Computational Modeling Study to Investigate the Use of Epicranial Electrodes to Deliver Interferential Stimulation to Subcortical Regions

“…Furthermore, co-stimulation of peripheral nerves in the scalp means that TES becomes painful if amplitudes are increased above 2 mA ( Bikson et al, 2016 ; Antal et al, 2017 ). In a recent study, we introduced a novel technique, epicranial cortical stimulation (ECS), and demonstrated its potential at overcoming some of the limitation of TES ( Khatoun et al, 2019 ). In Our computational modeling and animal studies ECS induced stronger and more focused electric fields in the cortex than TES ( Khatoun et al, 2019 ).…”

“…In a recent study, we introduced a novel technique, epicranial cortical stimulation (ECS), and demonstrated its potential at overcoming some of the limitation of TES ( Khatoun et al, 2019 ). In Our computational modeling and animal studies ECS induced stronger and more focused electric fields in the cortex than TES ( Khatoun et al, 2019 ). Yet, ECS requires a minimally invasive surgical intervention to place stimulation electrodes under the scalp and directly over the skull.…”

Cortical stimulation in pharmacoresistant focal epilepsies

“…Preclinical experiments in rodents applied epicranially implanted electrodes in order to selectively stimulate the motor cortex. Experiments demonstrated focused limb movements by ECS with a design of concentric ring electrodes according to Laplace (Khatoun et al 2019 ). The combination of a minimally invasive epicranial electrode and an internal pulse generator recently made the first move into clinical development (Schulze-Bonhage 2019 ).…”