Impact of transcranial electrical stimulation on simultaneous stereoelectroencephalography recordings: A randomized sham-controlled study.

OBJECTIVE: Clinical exploitation of transcranial electrical stimulation for focal epilepsy treatment lacks quantification of the underlying neurophysiological changes. This study explores the immediate effects of transcranial alternating (tACS) and direct (tDCS) current stimulation on local and network brain activity using simultaneous stereoelectroencephalography (SEEG) recordings. METHODS: Patients were randomized for personalized tACS (n = 5) or tDCS (n = 6). Active stimulation (20 min) was preceded by sham stimulation (20 min). Changes in interictal epileptiform discharges (IED), functional connectivity (FC) and power spectral density (PSD) were quantified against baseline. RESULTS: Results demonstrated variable responses. Spike rate decreased in 2/6 subjects following sham and tDCS, while 2/6 showed an increase. Alpha power and aperiodic PSD components generally increased during and after tDCS but decreased following tACS. FC changes varied among subjects and were detectable even during sham sessions. CONCLUSIONS: Strong variability suggests that tES does not have a univocal effect on immediate changes in IED or FC, possibly due to the single session format and challenges in affecting subcortical areas. SIGNIFICANCE: This is the first study to examine intracranial FC changes during tACS and tDCS, highlighting the importance of sham comparisons and individual variability in tES response, offering valuable insights into its application for epilepsy treatment.

Changes in local and network brain activity after stereotactic thermocoagulation in patients with drug-resistant epilepsy.

OBJECTIVE: Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) aims to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative lesions. Although RF-TC is hypothesized to functionally modify brain networks, reports of changes in functional connectivity (FC) following the procedure are missing. We evaluated, by means of SEEG recordings, whether variation in brain activity after RF-TC is related to clinical outcome. METHODS: Interictal SEEG recordings from 33 patients with drug-resistant epilepsy (DRE) were analyzed. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 1 month following RF-TC. Local (power spectral density [PSD]) and FC changes were evaluated in 3-min segments recorded shortly before (baseline), shortly after, and 15 min after RF-TC. The PSD and FC strength values after thermocoagulation were compared with baseline as well as between the responder and nonresponder groups. RESULTS: In responders, we found a significant reduction in PSD after RF-TC in channels that were thermocoagulated for all frequency bands (p = .007 for broad, delta and theta, p <.001 for alpha and beta bands). However, we did not observe such PSD decrease in nonresponders. At the network level, nonresponders displayed a significant FC increase in all frequency bands except theta (broad, delta, beta band: p <.001; alpha band: p <.01), although responders showed a significant FC decrease in delta (p <.001) and alpha bands (p <.05). Nonresponders showed stronger FC changes with respect to responders exclusively in TC channels (broad, alpha, theta, beta: p >.05; delta: p = .001). SIGNIFICANCE: Thermocoagulation induces both local and network-related (FC) changes in electrical brain activity of patients with DRE lasting for at least 15 min. This study demonstrates that the observed short-term modifications in brain network and local activity significantly differ between responders and nonresponders and opens new perspectives for studying the longer-lasting FC changes after RF-TC.

Transcranial current stimulation in epilepsy: A systematic review of the fundamental and clinical aspects.

Purpose: Transcranial electrical current stimulation (tES or tCS, as it is sometimes referred to) has been proposed as non-invasive therapy for pharmacoresistant epilepsy. This technique, which includes direct current (tDCS) and alternating current (tACS) stimulation involves the application of weak currents across the cortex to change cortical excitability. Although clinical trials have demonstrated the therapeutic efficacy of tES, its specific effects on epileptic brain activity are poorly understood. We sought to summarize the clinical and fundamental effects underlying the application of tES in epilepsy. Methods: A systematic review was performed in accordance with the PRISMA guidelines. A database search was performed in PUBMED, MEDLINE, Web of Science and Cochrane CENTRAL for articles corresponding to the keywords "epilepsy AND (transcranial current stimulation OR transcranial electrical stimulation)". Results: A total of 56 studies were included in this review. Through these records, we show that tDCS and tACS epileptic patients are safe and clinically relevant techniques for epilepsy. Recent articles reported changes of functional connectivity in epileptic patients after tDCS. We argue that tDCS may act by affecting brain networks, rather than simply modifying local activity in the targeted area. To explain the mechanisms of tES, various cellular effects have been identified. Among them, reduced cell loss, mossy fiber sprouting, and hippocampal BDNF protein levels. Brain modeling and human studies highlight the influence of individual brain anatomy and physiology on the electric field distribution. Computational models may optimize the stimulation parameters and bring new therapeutic perspectives. Conclusion: Both tDCS and tACS are promising techniques for epilepsy patients. Although the clinical effects of tDCS have been repeatedly assessed, only one clinical trial has involved a consistent number of epileptic patients and little knowledge is present about the clinical outcome of tACS. To fill this gap, multicenter studies on tES in epileptic patients are needed involving novel methods such as personalized stimulation protocols based on computational modeling. Furthermore, there is a need for more in vivo studies replicating the tES parameters applied in patients. Finally, there is a lack of clinical studies investigating changes in intracranial epileptiform discharges during tES application, which could clarify the nature of tES-related local and network dynamics in epilepsy.