Abstracts

Rationale: Cathodal transcranial direct current stimulation (ctDCS) may suppress seizures by induction of DC stimulation-mediated long-term depression (DCS-LTD) of cortical excitability in human cortex. Yet, while most patients with focal epilepsy exposed to ctDCS experience seizure suppression, others experience seizure exacerbation. The instances of seizure exacerbation with ctDCS indicate that some individuals or some epileptic pathologies may not respond with depression of cortical excitability when exposed to ctDCS. Accordingly, we tested, in vitro: whether cDCS induce DCS-LTD of cortical excitability in human neocortex derived from patients with epilepsy (as it does in healthy mouse cortex in vitro or healthy human cortex in vivo).

Methods: Field excitatory postsynaptic potentials (fEPSPs) were evoked by single pulses (0.2 ms) delivered at 0.033Hz through 1 planar microelectrode (test stimulus site) of a 64-microelectrode array (MEA). fEPSP slope fold change obtained from 3 × 5 or 3 × 6 microelectrodes surrounding the test stimulus site were plotted as an interpolated two-dimensional map using a custom MATLAB algorithm. Values for the channel that delivered the test stimuli were interpolated as an average of the fEPSP slope changes from the 8 adjacent channels. Human neocortical tissues (from temporal lobe, insula, or occipital lobe) were isolated during surgical removal of the epileptogenic zone of patients (1–14 years old) with focal cortical dysplasia.

Results: In 5 of 7 (~71%) human epileptic neocortical slices we found that DCS-LTD was induced in a majority (≥50%) of MEA channels above test stimulus site, which is consistent with our previous mouse and human cDCS works (Sun et al., 2016 and 2020). Interestingly, in 2 of 7 (~29%) human epileptic neocortical slices, a large proportion of long-term potentiation (DCS-LTP) of the fEPSP slope, instead of cortical DCS-LTD was induced. The fraction of MEA channels above test stimulus site expressing DCS-LTD under cathode was 74 ± 9% in 5 human neocortical slices vs 17 ± 8% in 2 human neocortical slices (p < 0.05 as compared between the two groups).

Conclusions: ctDCS may potentiate (rather than depotentiate) excitatory synaptic strength in some epileptic tissue. The variable response to in vitro DC stimulation indicates that careful selection of cortical targets and specific epilepsies may be needed to optimize the ctDCS anti-seizure effect. Alternatively, as we have explored, drug-device coupling that facilitates DCS-LTD may improve the anti-seizure ctDCS capacity.

Funding: Please list any funding that was received in support of this abstract.: Boston Children’s Hospital Translational Research Program; Credit Unions Kids at Heart.