Abstract
Neurostimulation is an emerging treatment for drug-resistant epilepsies when surgery is contraindicated. Recent clinical results demonstrate significant seizure frequency reduction in epileptic patients, however the mechanisms underlying this therapeutic effect are largely unknown. This study aimed at gaining insights into local direct current stimulation (LDCS) effects on hyperexcitable tissue, by i) analyzing the impact of electrical currents locally applied on epileptogenic brain regions, and ii) characterizing currents achieving an “anti-epileptic” effect (excitability reduction). First, a neural mass model of hippocampal circuits was extended to accurately reproduce the features of hippocampal paroxysmal discharges (HPD) observed in a mouse model of epilepsy. Second, model predictions regarding current intensity and stimulation polarity were confronted to in vivo mice recordings during LDCS (n = 8). The neural mass model was able to generate realistic hippocampal discharges. Simulation of LDCS in the model pointed at a significant decrease of simulated HPD (in duration and occurrence rate, not in amplitude) for cathodal stimulation, which was successfully verified experimentally in epileptic mice. Despite the simplicity of our stimulation protocol, these results contribute to a better understanding of clinical benefits observed in epileptic patients with implanted neurostimulators. Our results also provide further support for model-guided design of neuromodulation therapy.
Highlights
Drug-resistant epilepsies are most often ‘partial’ or ‘focal’, i.e. characterized by an epileptogenic zone (EZ) that is relatively circumscribed in one of the two cerebral hemispheres
We studied LDCS effects on interictal epileptiform hippocampal discharges using a computational model of the hippocampus
The major originality of this work is that the computational model guided us towards an LDCS protocol able to suppress HPD in silico, which was experimentally tested and validated in vivo through dentate gyrus (DG) stimulation, motivated by the key role of this hippocampal subfield in epileptiform activity generation
Summary
Drug-resistant epilepsies are most often ‘partial’ or ‘focal’, i.e. characterized by an epileptogenic zone (EZ) that is relatively circumscribed in one of the two cerebral hemispheres. As in open resective surgery, contraindications still concern the majority of individuals due to a possibly low patient benefit vs a significant risk of functional deficits. In this context of refractory focal-onset epilepsy, neuromodulation techniques based on electrical stimulation have slowly developed over the past decades and they still represent a potentially-valuable therapeutic option[16]. Long-term results reported a seizure frequency decrease at 2 years (median percent reduction: 53%), this multicentric study concludes with two major points It remains unknown how excitability is altered by electric stimulation. There is still a large margin for improvement of therapeutic effects through the optimization of stimulation protocols
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
