Effects of high‐frequency stimulation on epileptiform activity in vitro: ON/OFF control paradigm

Su, Yuzhuo; Radman, Thomas; Vaynshteyn, Jake; Parra, Lucas C.; Bikson, Marom

doi:10.1111/j.1528-1167.2008.01592.x

Cited by 22 publications

(18 citation statements)

References 47 publications

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“…Animal studies indicate that application of DC electric fields >20 V/m (corresponding to >60 mA tDCS) can trigger AP’s in the most sensitive quiescent cortical cells (Radman et al, 2009), while electric fields of ~100 V/m (corresponding to >500 mA tDCS) in the somatic depolarizing direction can trigger epileptiform activity in hippocampal slices (Bikson et al, 2004), although this threshold may decrease for already active neurons. In brain slices, weak DCS on the order of 1 V/m can modulate ongoing epileptiform activity, suggesting cathodal tDCS may control ongoing seizures while anodal tDCS may aggravate ongoing seizure activity (Gluckman et al, 1996, Ghai et al, 2000, Durand et al, 2001, Su et al, 2008, Sunderam et al, 2010). In a polarity specific fashion (consistent with somatic polarization) DCS can also modulate the propagation of epileptiform activity in slices (Gluckman et al, 1996), spreading depression in vivo (Liebetanz et al, 2006a), and perhaps clinical epileptiform activity (Varga et al, 2011).…”

Section: The Somatic Doctrine and Need For Amplificationmentioning

confidence: 99%

Animal models of transcranial direct current stimulation: Methods and mechanisms

Jackson

Rahman

Lafon

et al. 2016

Clinical Neurophysiology

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The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: 1) transcranial stimulation; 2) direct cortical stimulation in vivo and 3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching “quasi-uniform” assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the complexity of normal and pathological brain function, and how recent studies have already indicated more sophisticated approaches are necessary. One tDCS theory regarding “functional targeting” suggests the specificity of tDCS effects are possible by modulating ongoing function (plasticity). Use of animal models of disease are summarized including pain, movement disorders, stroke, and epilepsy.

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Section: The Somatic Doctrine and Need For Amplificationmentioning

confidence: 99%

Animal models of transcranial direct current stimulation: Methods and mechanisms

Jackson

Rahman

Lafon

et al. 2016

Clinical Neurophysiology

Self Cite

250

216

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“…In the case of low frequency and high frequency pulse trains, the effects of stimulation are often changes in activity patterns rather than complete suppression. For example, in Su et al88, disorganized high amplitude electrographic seizures were replaced with population spikes in phase with stimulation. Though stimulation changes activity away from the spontaneous epileptiform pattern, this does not necessarily reflect a net decrease in average firing rate or synchrony, nor does it reflect an improvement in the network’s performance of its normal cognitive computations.…”

Section: Clinical Aspects Of Epilepsy and Objectives For Electrothmentioning

confidence: 99%

Toward rational design of electrical stimulation strategies for epilepsy control

Sunderam¹,

Gluckman²,

Reato³

et al. 2010

Epilepsy & Behavior

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Electrical stimulation is emerging as a viable alternative for epilepsy patients whose seizures are not alleviated by drugs or surgery. Its attractions are temporal and spatial specificity of action, flexibility of waveform parameters and timing, and the perception that its effects are reversible unlike resective surgery. However, despite significant advances in our understanding of mechanisms of neural electrical stimulation, clinical electrotherapy for seizures relies heavily on empirical tuning of parameters and protocols. We highlight concurrent treatment goals with potentially conflicting design constraints that must be resolved when formulating rational strategies for epilepsy electrotherapy: namely seizure reduction versus cognitive impairment, stimulation efficacy versus tissue safety, and mechanistic insight versus clinical pragmatism. First, treatment markers, objectives, and metrics relevant to electrical stimulation for epilepsy are discussed from a clinical perspective. Then the experimental perspective is presented, with the biophysical mechanisms and modalities of open-loop electrical stimulation, and the potential benefits of closed-loop control for epilepsy.

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“…In addition, before the reappearance of PPD, when the PTX had not yet penetrated the tissue well, a period occurred where the neurons were sensitive to every stimulus. The distinct neuronal responses to stimulations in different epileptic stages may implicate the different antiepileptic effects of electrical stimulation (Schiller and Bankirer, 2007;Su et al, 2008) and provide important information for the development of new clinical treatments for epilepsy disease.…”

Section: P<0001 N=6 Student's T-testmentioning

confidence: 99%

Changes of paired-pulse evoked responses during the development of epileptic activity in the hippocampus

Feng

Zheng

Tian

et al. 2011

J. Zhejiang Univ. Sci. B

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Dysfunction of inhibitory synaptic transmission can destroy the balance between excitatory and inhibitory synaptic inputs in neurons, thereby inducing epileptic activity. The aim of the paper is to investigate the effects of successive excitatory inputs on the epileptic activity induced in the absence of inhibitions. Paired-pulse orthodromic and antidromic stimulations were used to test the changes in the evoked responses in the hippocampus. Picrotoxin (PTX), γ-aminobutyric acid (GABA) type A (GABA A ) receptor antagonist, was added to block the inhibitory synaptic transmission and to establish the epileptic model. Extracellular evoked population spike (PS) was recorded in the CA1 region of the hippocampus. The results showed that the application of PTX induced a biphasic change in the paired-pulse ratio of PS amplitude. A short latency increase of the second PS (PS2) was later followed by a reappearance of PS2 depression. This type of depression was observed in both orthodromic and antidromic paired-pulse responses, whereas the GABAergic PS2 depression [called paired-pulse depression (PPD)] during baseline recordings only appeared in orthodromic-evoked responses. In addition, the depression duration at approximately 100 ms was consistent with a relative silent period observed within spontaneous burst discharges induced by prolonged application of PTX. In conclusion, the neurons may ignore the excitatory inputs and intrinsically generate bursts during epileptic activity. The depolarization block could be the mechanisms underlying the PPD in the absence of GABA A inhibitions. The distinct neuronal responses to stimulations during different epileptic stages may implicate the different antiepileptic effects of electrical stimulation.

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Effects of high‐frequency stimulation on epileptiform activity in vitro: ON/OFF control paradigm

Cited by 22 publications

References 47 publications

Animal models of transcranial direct current stimulation: Methods and mechanisms

Animal models of transcranial direct current stimulation: Methods and mechanisms

Toward rational design of electrical stimulation strategies for epilepsy control

Changes of paired-pulse evoked responses during the development of epileptic activity in the hippocampus

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