Safety of slow‐pulsed transcranial electrical stimulation in acute spike suppression

Holmes, Mark; Feng, Rui; Wise, Mackenzie V.; Ma, Chengxin; Ramon, Ceon; Wu, Jinsong; Luu, Phan; Hou, Jing; Pan, Li; Tucker, Don M.

doi:10.1002/acn3.50934

Cited by 11 publications

(14 citation statements)

References 20 publications

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“…Finally, despite the vast number of studies investigating the effects of tACS in memory, sleep and other functions, there is little account for tACS effects on epilepsy. One study conducted by Holmes et al ( 2019 ) implemented a slow-pulsed tACS protocol in seven adult DRE patients with MRI-based personalized head models. The study consisted of 5 consecutive days of tES protocol combined with 256-channel dense EEG recordings before and after stimulation.…”

Section: Resultsmentioning

confidence: 99%

“…The use of tACS in epilepsy is promising but relatively under-examined. The safety of this technique has been assessed in epileptic patients (Opitz et al, 2016 ; Lafon et al, 2017 ) and a recent study obtained interesting preliminary studies of tACS in epilepsy (Holmes et al, 2019 ). To design optimal stimulation protocols for patients, it is necessary to investigate the underlying physiological mechanisms of tACS, via cell cultures, animal, or computational models.…”

Section: Discussionmentioning

confidence: 99%

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

Simula

Daoud

Ruffini³

et al. 2022

Front. Neurosci.

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PurposeTranscranial 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.MethodsA 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)”.ResultsA 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.ConclusionBoth 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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Simula

Daoud

Ruffini³

et al. 2022

Front. Neurosci.

View full text Add to dashboard Cite

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“…Though similar in nature, these techniques have different physiological and behavioral effects (Ali, Sellers, & Frohlich, 2013; Daa, Atc, Gbsc, et al, 2019; Laakso, Mikkonen, Koyama, Hirata, & Tanaka, 2019) due to the different temporal profiles of the applied currents. In view of its safe and inexpensive features, tCS has been used for pain relief (O'Connell, Marston, Spencer, DeSouza, & Wand, 2018), depressive symptom relief (Mutz, Edgcumbe, Brunoni, & Fu, 2018), stroke (Fujimoto et al, 2016) and Parkinson's disease recovery (Elsner, Kugler, Pohl, & Mehrholz, 2016; Fregni et al, 2006; Kaski, Allum, Bronstein, & Dominguez, 2014; Kaski, Dominguez, Allum, Islam, & Bronstein, 2014), and in the treatment of epilepsy (Holmes et al, 2019). Over the last several years, new tCS approaches using multiple kHz currents have been proposed to stimulate deep targets (Grossman et al, 2017) or increase the intensity of stimulation (Voroslakos et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Influence of layered skull modeling on the frequency sensitivity and target accuracy in simulations of transcranial current stimulation

Wang

Sun

Zhang

et al. 2021

Human Brain Mapping

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With the development of electrical stimulation technology, especially the emergence of temporally interfering (TI) stimulation, it is necessary to discuss the influence of current frequency on stimulation intensity. Accurate skull modeling is important for transcranial current stimulation (tCS) simulation prediction because of its large role in dispersing current. In this study, we simulated different frequencies of transcranial alternating current stimulation (tACS) and TI stimulation in single‐layer and layered skull model, compared the electric field via error parameters such as the relative difference measure and relative magnification factor. Pearson correlation analysis and t‐test were used to measure the differences in envelope amplitude. The results showed that the intensity of electric field in the brain generated by per unit of stimulation current will increase with current frequency, and the layered skull model had a better response to frequency. An obvious pattern difference was found between the electric fields of the layered and single‐layer skull individualized models. For TI stimulation, the Pearson correlation coefficient between the envelope distribution of the layered skull model and the single‐layer skull was only 0.746 in the individualized model, which is clearly lower than the correlation coefficient of 0.999 determined from the spherical model. Higher carrier frequencies seemed to be easier to generate a large enough brain electric field envelope in TI stimulation. In conclusion, we recommend using layered skull models instead of single‐layer skull models in tCS (particularly TI stimulation) simulation studies in order to improve the accuracy of the prediction of stimulus intensity and stimulus target.

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“…In contrast to typical tDCS where sustained direct current stimulation is administered for at least 20 min, a slow-pulsed transcranial electrical stimulation protocol applied short cathodal direct current pulses of 100 ms duration with a frequency of 0.5 Hz to patients with pharmacoresistant focal epilepsies (Holmes et al 2019 ). In all 7 subjects accurate targeting of the cortical focus of epileptic spikes was achieved by the combination of a high-resolution head conductivity model and a 256-channel dense EEG system.…”

Section: Introductionmentioning

confidence: 99%

“…Noninvasive cathodal tDCS is suggested to provoke transient and long-term effects on cortical excitability (Antal et al 2017 ; Luu et al 2016 ; Nitsche et al 2003 ; Nitsche and Paulus 2000 ; Stagg et al 2018 ) and epileptiform discharges (Holmes et al 2019 ; VanHaerents et al 2020 ; Yang et al 2020 ). Whereas acute effects of cathodal tDCS are due to transient hyperpolarization of cortical neurons (Nitsche et al 2003 ; Nitsche and Paulus 2000 ), human experimental studies provide evidence that long-term effects base upon LTD (Stagg et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Cortical stimulation in pharmacoresistant focal epilepsies

Ellrich

2020

Bioelectron Med

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Pharmacoresistance and adverse drug events designate a considerable group of patients with focal epilepsies that require alternative treatments such as neurosurgical intervention and neurostimulation. Electrical or magnetic stimulations of cortical brain areas for the treatment of pharmacoresistant focal epilepsies emerged from preclinical studies and experience through intraoperative neurophysiological monitoring in patients. Direct neurostimulation of seizure onset zones in neocortical brain areas may specifically affect neuronal networks involved in epileptiform activity without remarkable adverse influence on physiological cortical processing in immediate vicinity. Noninvasive low-frequency transcranial magnetic stimulation and cathodal transcranial direct current stimulation are suggested to be anticonvulsant; however, potential effects are ephemeral and require effect maintenance by ongoing stimulation. Invasive responsive neurostimulation, chronic subthreshold cortical stimulation, and epicranial cortical stimulation cover a broad range of different emerging technologies with intracranial and epicranial approaches that still have limited market access partly due to ongoing clinical development. Despite significant differences, the present bioelectronic technologies share common mode of actions with acute seizure termination by high-frequency stimulation and long-term depression induced by low-frequency magnetic or electrical stimulation or transcranial direct current stimulation.

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Safety of slow‐pulsed transcranial electrical stimulation in acute spike suppression

Cited by 11 publications

References 20 publications

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

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

Influence of layered skull modeling on the frequency sensitivity and target accuracy in simulations of transcranial current stimulation

Cortical stimulation in pharmacoresistant focal epilepsies

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