Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro

Radman, Thomas; Ramos, Raddy L.; Brumberg, Joshua C.; Bikson, Marom

doi:10.1016/j.brs.2009.03.007

Cited by 591 publications

(654 citation statements)

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“…Physiological effects of weak electric fields have been found in in vitro slice preparations at 0.5 mV/mm (14,15), and even at 0.2 mV/mm (16). A minimum threshold of 1 mV/mm has been suggested on the basis of in vivo measurements in rodents (17).…”

Section: Discussionmentioning

confidence: 99%

Limitations of ex vivo measurements for in vivo neuroscience

Opitz

Falchier

Linn

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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A long history of postmortem studies has provided significant insight into human brain structure and organization. Cadavers have also proven instrumental for the measurement of artifacts and nonneural effects in functional imaging, and more recently, the study of biophysical properties critical to brain stimulation. However, death produces significant changes in the biophysical properties of brain tissues, making an ex vivo to in vivo comparison complex, and even questionable. This study directly compares biophysical properties of electric fields arising from transcranial electric stimulation (TES) in a nonhuman primate brain pre-and postmortem. We show that pre-vs. postmortem, TES-induced intracranial electric fields differ significantly in both strength and frequency response dynamics, even while controlling for confounding factors such as body temperature. Our results clearly indicate that ex vivo cadaver and in vivo measurements are not easily equitable. In vivo examinations remain essential to establishing an adequate understanding of even basic biophysical phenomena in vivo.biophysical | electric field | nonhuman primate T he use of cadavers to study human anatomy has a long history in medicine and science. For the neurosciences, centuries of postmortem examination have provided a fundamental understanding of human brain structure and organization, as well as the effect of a range of disease processes (1). With the advent of powerful in vivo imaging methods (2), the study of cadavers has become less important in modern-day neuroscience research. However, cadavers are still regularly used to examine possible methodological artifacts in brain imaging studies because of the complete absence of neuronal activity with largely preserved anatomical structures (3, 4). Numerous studies have relied on cadavers to establish the conductivity of differing tissue types, with notable discrepancies compared with in vivo measurements (5-8). Similarly, in developing noninvasive transcranial electric stimulation (TES) procedures, some have suggested the use of cadavers for measuring electric fields generated in the brain during stimulation. Such knowledge is crucial to efforts aiming to optimize brain stimulation, whether focusing on the spatial accuracy of stimulation, the magnitude of a dose actually delivered to an individual, or the possible variations in delivery across individuals. The most recent of these gained widespread attention because of its conclusion that TES-induced currents have poor penetration through the scalp and skull (9). These findings seem to reinforce concerns about the effectiveness of current dosing levels (10); however, to understand their implications, it is first important to determine how well cadaver-based conductivity measurements approximate in vivo conditions.Death initiates a cascade of biochemical processes affecting the biophysical properties of body and brain tissues, which can make the generalization from ex vivo results to the in vivo case problematic. However, it is not clear how in...

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Section: Discussionmentioning

confidence: 99%

Limitations of ex vivo measurements for in vivo neuroscience

Opitz

Falchier

Linn

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Plasticity effects have been demonstrated only at higher field intensities of~20 V/m (Ranieri et al, 2012;Kronberg et al, 2017). It is possible that network effects amplify electric field effects (Reato et al, 2010) and that larger neurons will be more strongly polarized (Radman et al, 2009) and thus, in vivo effects in human may be stronger than the effects demonstrated for animal in vitro experiments. Future in vivo animal work may shed light on this fundamental question of the required electric field intensities for various physiological effects (e.g., Kar and Krekelberg, 2016).…”

Section: Stimulation Intensitymentioning

confidence: 99%

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

et al. 2017

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Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r = 0.86) and depth (r = 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials.

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“…These electrodes are placed over the scalp with the goal of, respectively, increasing and decreasing cortical excitability (Nitsche et al, 2003;Nitsche & Paulus, 2000); although tDCS effects on neuronal processing are in fact more complex (Rahman et al, 2013) and may even invert according to the nature of ongoing activity (Batsikadze, Moliadze, Paulus, Kuo, & Nitsche, 2013). TDCS generates low-intensity electric fields (Datta et al, 2009) in the brain leading to small changes (<1 mV) (Radman, Ramos, Brumberg, & Bikson, 2009) in the membrane potential, thus influencing the frequency of spike timing and modifying net cortical excitability (Purpura & McMurtry, 1965) without triggering action potentials per se (Brunoni et al, 2012;Nitsche et al, 2008). In turn, rTMS causes disruptions in brain activity by delivering strong magnetic pulses to the cortex that pass through the skull and depolarize the underlying neurons of particular areas in the brain Repetitive TMS over the motor cortex facilitates or inhibits brain excitability according to the frequency of stimulation (respectively >1Hz and <1Hz) (Fregni & Pascual-Leone, 2007;George & Aston-Jones, 2010;Hallett, 2007) For cognitive functions, however, there are also other factors that determine rTMS effects, particularly the baseline activity state of the stimulated region ("state-dependency") (Sandrini, Umilta, & Rusconi, 2011;Silvanto, Cattaneo, Battelli, & Pascual-Leone, 2008;van de Ven & Sack, 2013).…”

Section: Introductionmentioning

confidence: 99%

Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis

Brunoni

Vanderhasselt

2014

Brain and Cognition

558

411

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Recent studies have used non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), to increase dorsolateral prefrontal cortex (DLPFC) activity and, consequently, working memory (WM) performance.. However, such experiments have yielded mixed results, possibly due to small sample sizes and heterogeneity of outcomes. Therefore, our aim was to perform a systematic review and metaanalyses on NIBS studies assessing the n-back task, which is a reliable index for WM. From the first data available to February 2013, we looked for sham-controlled, randomized studies that used NIBS over the DLPFC using the n-back task in PubMed/MEDLINE and other databases. Twelve studies (describing 33 experiments) matched our eligibility criteria. Active vs. sham NIBS was significantly associated with faster response times (RT), higher percentage of correct responses and lower percentage of error responses. However, meta-regressions showed that tDCS (vs. rTMS) presented an improvement only in RT. This could have occurred in part because almost all tDCS studies employed a crossover design (possibly more employed in tDCS over rTMS due to the reliable tDCS blinding) -this factor (study design) was also associated with no improvement in correct responses in the active vs. sham groups. To conclude, rTMS over the DLPFC significantly improved all measures of WM performance whereas tDCS significantly improved RT, but not the percentage of correct and error responses. Mechanistic insights on the role of DLPFC in WM are further discussed, as well as how NIBS techniques could be used in neuropsychiatric samples presenting WM deficits, such as major depression, dementia and schizophrenia.

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Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro

Cited by 591 publications

References 84 publications

Limitations of ex vivo measurements for in vivo neuroscience

Limitations of ex vivo measurements for in vivo neuroscience

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis

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