Fundamentals of transcranial electric and magnetic stimulation dose: Definition, selection, and reporting practices

Peterchev, Angel V.; Wagner, Timothy; Miranda, Pedro C.; Nitsche, Michael A.; Paulus, Walter; Lisanby, Sarah H.; Pascual‐Leone, Álvaro; Bikson, Marom

doi:10.1016/j.brs.2011.10.001

Cited by 355 publications

(310 citation statements)

References 131 publications

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“…This observation is consistent with the understanding that individual anatomical differences (eg, head shape and size, scalp and skull thickness and conductivity) affect the electric field strength in the brain (Deng et al, 2014;Edwards et al, 2013;van Waarde et al, 2013a, b), and that pulse amplitude individualization can normalize it across individuals, as the electric field strength is directly proportional to the pulse amplitude (Deng et al, 2013;Peterchev et al, 2012).…”

Section: Interindividual Threshold Variation and Stimulus Individualisupporting

confidence: 86%

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

Peterchev

Krystal

Rosa³

et al. 2015

Neuropsychopharmacol

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Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

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Section: Interindividual Threshold Variation and Stimulus Individualisupporting

confidence: 86%

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

Peterchev

Krystal

Rosa³

et al. 2015

Neuropsychopharmacol

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“…Nevertheless, future studies should investigate new ways of enhancing the antidepressant effects of LF-rTMS, such as the identification of more clinically relevant stimulation parameters/protocols (eg, preconditioning paradigms/priming, different rTMS waveforms, frequencies, intensities, number of sessions, brain targets) George and AstonJones, 2010;Peterchev et al, 2011), as well as the use of baseline electrophysiological and/or neuroimaging evaluations to better predict which patients might benefit from LF-rTMS (Arns et al, 2012). Furthermore, novel developments in the field of neuromodulation, such as the H-coil (Levkovitz et al, 2010), might enhance the efficacy of LFrTMS by allowing the direct stimulation of deeper brain structures.…”

Section: Discussionmentioning

confidence: 99%

Clinically Meaningful Efficacy and Acceptability of Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Primary Major Depression: A Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials

Berlim

Eynde

Daskalakis

2012

Neuropsychopharmacol

245

141

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Clinical trials on low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the right dorsolateral prefrontal cortex have yielded conflicting evidence concerning its overall efficacy for treating major depression (MD). As this may have been the result of limited statistical power of individual trials, we have carried the present systematic review and meta-analysis to examine this issue. We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on LF-rTMS for treating MD from 1995 through July 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses, and from October 2008 until July 2012 using MEDLINE. The main outcome measures were response and remission rates as well as overall dropout rates at study end. We used a random-effects model, odds ratios (ORs) and number needed to treat (NNT). Data were obtained from eight RCTs, totaling 263 subjects with MD. After an average of 12.6±3.9 rTMS sessions, 38.2% (50/131) and 15.1% (20/132) of subjects receiving active LF-rTMS and sham rTMS were classified as responders (OR ¼ 3.35; 95% CI ¼ 1.4-8.02; p ¼ 0.007). Also, 34.6% (35/101) and 9.7% (10/103) of subjects receiving active LF-rTMS and sham rTMS were classified as remitters (OR ¼ 4.76; 95% CI ¼ 2.13-10.64; po0.0001). The associated NNT for both response and remission rates was 5. Sensitivity analyses have shown that protocols delivering 41200 magnetic pulses in total as well as those offering rTMS as a monotherapy for MD were associated with higher rates of response to treatment. No differences on mean baseline depression scores and dropout rates for active and sham rTMS groups were found. Finally, the risk of publication bias was low. In conclusion, LF-rTMS is a promising treatment for MD, as it provides clinically meaningful benefits that are comparable to those of standard antidepressants and high-frequency rTMS. Furthermore, LF-rTMS seems to be an acceptable intervention for depressed subjects.

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“…Therefore we monitored the safety and tolerability of tES used repeatedly (three to five days per week) in a naturalistic setting for up to six weeks by healthy volunteer research subjects. The tolerability of any tES technique is specific to: 1) dose, namely electrical waveform properties and electrode montage [34]; 2) electrode design [27,35]; and 3) subject exclusion and treatment protocols. We tested two waveforms of limited output tES including tDCS and tPCS, as well as an active sham waveform.…”

Section: Introductionmentioning

confidence: 99%

The tolerability of transcranial electrical stimulation used across extended periods in a naturalistic context by healthy individuals

Paneri

Khadka

Patel

et al. 2015

Preprint

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Transcranial electrical stimulation (tES) is one of the most widely implemented forms of non-invasive neuromodulation in basic and clinical neuroscience. Further, the use of tES by healthy populations for various purposes is growing widespread daily. The effects of tES protocols on the skin and other tissues has remained uncharacterized when used across extended periods of time by healthy individuals. Therefore, we examined the basic safety and tolerability profile of two distinct tES protocols used repeatedly across an extended period of time by healthy subjects and report our findings here for the first time. The safety and tolerability profile previously accumulated regarding extended use of tES in clinical populations is compelling and supports a low-risk or non-significant risk designation. In the present study, we tested the tolerability (safety) and compliance, compared to sham, of two common tES approaches having a current density < 2 mA/cm 2 ; transcranial Direct Current Stimulation (tDCS) or transcranial Pulsed Current Stimulation (tPCS) used by healthy subjects three to five days (17 -20 minutes per day) per week for up to six weeks in a naturalistic environment. In this study 100 healthy subjects were randomized to one of three treatment groups: tDCS (n = 33), tPCS (n = 30), or sham (n = 37) and blinded to the treatment condition. The tES and sham waveforms were delivered through self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 treatment sessions (636 sham, 623 tDCS, and 646 tPCS sessions) on study volunteers over a six-week period. There were no serious adverse events in any treatment condition. Common side effects were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in active tES treatment arms (tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham treatment arm. Other adverse events had a rarity (< 5% incidence) that could not be statistically distinguished across the treatment groups. Some subjects withdrew early from the study for atypical headache (sham n = 2, tDCS n = 2, and tPCS n = 3), atypical discomfort (sham n = 0, tDCS n = 1, and tPCS n = 1), or atypical skin irritation (sham n = 2, tDCS n = 8, and tPCS n = 1). The compliance (elected sessions completed) for tPCS was significantly greater when compared to sham (p = 0.007). The present study represents the most comprehensive analysis of tES tolerability and safety in healthy subjects to date. Limited to the hardware, electrodes, and protocols tested here, we conclude that repeated use of limited output tES across extended periods, is well tolerated and poses no significant risks to healthy subjects, as previously observed in clinical studies.

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Fundamentals of transcranial electric and magnetic stimulation dose: Definition, selection, and reporting practices

Cited by 355 publications

References 131 publications

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

Clinically Meaningful Efficacy and Acceptability of Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Primary Major Depression: A Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials

The tolerability of transcranial electrical stimulation used across extended periods in a naturalistic context by healthy individuals

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