Targeted and optimized multi-channel transcranial direct current stimulation for focal epilepsy: An N-of-1 trial

Abstract

Transcranial direct current stimulation (tDCS) has been used to noninvasively reduce epileptic activity in focal epilepsy. In this proof-of-principle N-of-1 trial in a patient with drug-resistant focal epilepsy, we propose distributed constrained maximum intensity (D-CMI) for individually targeted and optimized multi-channel (mc-)tDCS to reduce epileptic activity. Combined electro- and magnetoencephalography (EMEG) source analysis in a realistic calibrated head model defines location and orientation of the target epileptogenic source. Converging evidence for this determination is achieved by retrospective identification of a cortical malformation in magnetic resonance imaging and by successful EMEG-guided invasive EEG. We applied D-CMI in a double-blind, sham-controlled stimulation experiment. In two stimulation weeks, either D-CMI or sham stimulation with 4 mA injection current were applied twice every week-day for 20 min each, with a 20 min pause in between. EEG was recorded 1 h before and after stimulation. For D-CMI, we find a highly significant reduction in IED frequency (p < 0.0001) marked by three experts of on average 37% to 81% over the five days of stimulation (mean +- SD: 58% +- 19%), while this is not the case for sham. The proposed procedure was well-tolerated and parameterizes a group clinical trial (Study registration number: DRKS00029384).