Authors :
Presenting Author: Sara Simula, MSc – Aix Marseille Univ, INSERM, INS, Int Neurosci Syst, Marseille, France
Giada Damiani, Eng – Neuroelectrics Barcelona, Barcelona, Spain; Elodie Garnier, Eng – Aix Marseille Univ, INSERM, INS, Int Neurosci Syst, Marseille, France; Julia Makhalova, MD – APHM, Timone Hospital, Epileptology and Cerebral Rhythmology, Marseille, France; Aix Marseille Univ, INSERM, INS, Int Neurosci Syst, Marseille, France; Samuel Medina-Villalon, Eng – Aix Marseille Univ, INSERM, INS, Int Neurosci Syst, Marseille, France; Giulio Ruffini, PhD – Neuroelectrics Barcelona, Barcelona, Spain; Fabrice Wendling, PhD – Univ Rennes, INSERM, LTSI-U1099, Rennes, France; Christian G. Bénar, PhD – 1Aix Marseille Univ, INSERM, INS, Int Neurosci Syst, Marseille, France; Fabrice Bartolomei, MD, PhD – APHM, Timone Hospital, Epileptology and Cerebral Rhythmology, Marseille, France; Aix Marseille Univ, INSERM, INS, Int Neurosci Syst, Marseille, France
Rationale:
The application of weak currents to the scalp via transcranial electrical stimulation has been shown to decrease seizure frequency and spike rate (SR) in focal epilepsy patients. However, the field lacks a quantification of the neurophysiological changes following stimulation in the human brain. Moreover, although stimulation can employ either direct (transcranial Direct Current Stimulation, tDCS) or alternating (transcranial Alternating Current Stimulation, tACS) currents, only tDCS has been studied in epilepsy so far. This study investigates the immediate effects of tACS and tDCS on local and network brain activity via simultaneous stimulation and stereoelectroencephalography (SEEG) recordings. Methods:
Nine patients with drug-resistant focal epilepsy have been recruited and randomised in either tACS (n=4) or tDCS (n=5) group (GALVANI PS2 study, NCT NCT05250713). Anatomical and functional data were used to reconstruct individualized brain models. Personalzed stimulation montages were obtained via simulation of intracranial electric field in order to maximise inhibition on the target. On the last day of SEEG investigation, we performed 20 min of sham stimulation followed by 20 min of active stimulation. We then analysed the spike rate, functional connectivity (FC, via the non-linear correlation coefficient h²) and power spectral density in the following five minute long windows: sham, postA, postB, postAll (starting respectively at min 0, min 5, min 20 after active stimulation). These values were then compared to baseline measurements via Wilcoxon rank-sum test.
Results:
Regarding SR changes, only four subjects had enough spike events at baseline and were thus analyzed. In the tDCS group, SR decreased after stimulation in one tDCS subject compared to baseline (but not sham) and increased in another subject. In the tACS group, one subject presented a significant SR decrease 10 min and 20 min after stimulation compared to baseline and sham. Two subjects presented significant SR changes during sham. Regarding FC changes, one subject receiving tDCS showed an increase in the total node strength compared to baseline and sham. Among tACS subjects, 1/4 subject presented a node strength increase, while 2/4 subjects presented a decrease compared to baseline and sham. In two subjects, we observe an opposite trend in FC changes for postA compared to postB periods. Node strength during sham was significantly different from baseline values in 6/9 subjects across the two groups.
Conclusions:
Neither tDCS nor tACS seem to have a univocal effect on immediate changes in interictal events or functional connectivity. This could be due to i) having a single 20 min session versus multiple sessions used in clinics; ii) the difficulty in reaching the epileptogenic zone (often mesial and surrounded by SEEG leads); iii) the changes in treatment that could cause changes in SR and FC. This study highlights the need for further analysis of neuromodulation mechanisms, which could act in longer time scales, and the importance of a sham protocol to control for possible placebo effects of stimulation.
Funding: This work was supported by the European Research Council: Galvani Project ERC-SyG 2019, Grant Agreement No. 855109.