ReviewAnimal models of transcranial direct current stimulation: Methods and mechanisms
Section snippets
Meaningful animal studies of tDCS
This review is an update, with permission, of a previously published work (Bikson et al., 2012).
The basic motivation for tDCS research using animals is similar to other translational medical research efforts: to allow rapid and risk free screening of stimulation protocols in research and clinical settings, and to address the mechanisms of tDCS with the ultimate goal of informing clinical efficacy and safety of tDCS. To have a meaningful relevance for clinical tDCS, animal studies must be
The somatic doctrine and need for amplification
Since seminal clinical neurophysiology in 2000 (Nitsche and Paulus, 2000, Ardolino et al., 2005, Fregni et al., 2005, Fregni et al., 2007), there has been exponential growth in the exploration of tDCS for clinical and cognitive/neuroscience research. Broad adaptation has been encouraged by the apparent simplicity of the technique, and the perception that tDCS protocols can be designed for any application simply by placing an electrode over the targeted brain region. In the next sections,
Synaptic processing and plasticity
There is a clinical need for lasting changes by tDCS, as it is impractical to improve disease/injury by continuously stimulating with electrodes on the head. The desire for lasting change means tDCS should influence plasticity during or after stimulation in cognitively/therapeutically relevant ways (Yoon et al., 2012). This section addresses the contribution of animal studies to understanding plasticity generated by weak DC electric fields.
Animal studies, some decades old, have suggested
Network effects
The consideration of how weak DC electric fields interact with active neuronal networks (e.g. oscillations) is a compelling area of ongoing research. Just as networks of coupled, active neurons exhibit network activity not seen in isolated neurons, the application of electrical stimulation to active networks often produce responses not expected by single neurons. These responses are specific to the network’s architecture and level of activity. Neuronal networks also provide a mechanism for
Interneurons and non-neuronal effects
The role of interneurons and non-neuronal cells, such as glial and endothelial cells, during tDCS remains both an open and critical question. To address their role to tDCS, we distinguish between: (1) primary stimulation effects, reflecting direct membrane polarization and modulation of these cell types by DC electric fields; (2) secondary stimulation effects, reflecting secondary functional changes resulting from direct excitatory neuronal activation that then influence interneurons and other
Pain
tDCS has shown promising results for treating pain symptoms in humans, and studies using animal models of pain have also provided reason for optimism. Pain symptoms are mainly determined by alterations in excitability and connectivity of pain related neural networks (Knotkova and Cruciani, 2010, Knotkova et al., 2013) and increased expression of some pro inflammatory cytokines in the brain vascular system (Spezia Adachi et al., 2012). Recent studies (Laste et al., 2012, Spezia Adachi et al.,
Safety limits for tissue injury
Data for a tDCS lesion threshold in animal models have been used to support the significant safety factor between maximum tDCS and brain damage (Bikson et al., 2009, Liebetanz et al., 2009). As the use of tDCS increases, this data warrants updating. Modeling DC predictions across animal and human are specific to the electric field produced in the brain, so data from animal models are solely based on analysis of brain lesion in this section. In addition, our analyses in this section do not
Summary: 3 tier approach, beyond the somatic doctrine, experimental rigor and dose response
Implicitly or explicitly, tDCS protocols in humans, whether directed toward clinical application, neurophysiology, or cognitive function, continue to be interpreted and designed following what we have termed the somatic doctrine of tDCS. Under the somatic doctrine, brain regions under the anode or cathode electrode are assumed to increase or decrease in neuronal excitability as a result of the polarization of cortical pyramidal cell somas due to radial current flow. Even though this simple
Acknowledgements
Support for this review comes from the Department of Defense (Air Force Office of Scientific Research), The Wallace Coulter Foundation, The Epilepsy Foundation, The Andy Grove Fund, and NIH.
Conflict of interest: MB and LP have equity in Soterix Medical Inc. The City University of New York has patents on brain stimulation with MB and LP as inventors. This review is an update of a previously published chapter (Bikson et al., 2012); portions of that chapter are updated here with permission from
References (202)
- et al.
Effects of glucose and glutamine concentration in the formulation of the artificial cerebrospinal fluid (ACSF)
Brain Res
(2008) - et al.
Modulation of transmitter release by presynaptic resting potential and background calcium levels
Neuron
(2005) Skin microcirculation during tapwater iontophoresis in humans-cathode stimulates more than anode
Microvasc Res
(1997)Computational neurostimulation in basic and translational research
Prog Brain Res
(2015)- et al.
Establishing safety limits for transcranial direct current stimulation
Clin Neurophysiol
(2009) - et al.
Electrode montages for tDCS and weak transcranial electrical stimulation: role of “return” electrode’s position and size
Clin Neurophysiol
(2010) - et al.
The “quasi-uniform” assumption in animal and computational models of non-invasive electrical stimulation
Brain Stimul
(2013) - et al.
Modeling sequence and quasi-uniform assumption in computational neurostimulation
Prog Brain Res
(2015) - et al.
The effects of polarizing currents on cell potentials and their significance in the interpretation of central nervous system activity
Electroencephalogr Clin Neurophysiol
(1950) - et al.
Brain polarization of parietal cortex augments training-induced improvement of visual exploratory and attentional skills
Brain Res
(2010)
Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions
Brain Stimul
Flash visual evoked potentials in mice can be modulated by transcranial direct current stimulation
Neuroscience
The excitable cerebral cortex Fritsch G, Hitzig E. Uber die elektrische Erregbarkeit des Grosshirns. Arch Anat Physiol Wissen 1870;37:300–32
Epilepsy Behav
Influence of transcortical d-c currents on cortical neuronal activity
Exp Neurol
Transcranial direct current stimulation in patients with skull defects and skull plates: high-resolution computational FEM study of factors altering cortical current flow
Neuroimage
Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient
Brain Stimul
Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs
Brain Stimul
Targeted transcranial direct current stimulation for rehabilitation after stroke
Neuroimage
Cumulative benefits of frontal transcranial direct current stimulation on visuospatial working memory training and skill learning in rats
Neurobiol Learn Mem
From psychiatric disorders to animal models: a bidirectional and dimensional approach
Biol Psychiatry
Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: a basis for high-definition tDCS
Neuroimage
Beyond the silence: bilateral somatosensory stimulation enhances skilled movement quality and neural density in intact behaving rats
Behav Brain Res
Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression
Exp Neurol
Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning
Neuron
Endogenous electric fields may guide neocortical network activity
Neuron
Classification of methods in transcranial electrical stimulation (tES) and evolving strategy from historical approaches to contemporary innovations
J Neurosci Methods
Biphasic effects of polarizing current on adenosine-sensitive generation of cyclic AMP in rat cerebral cortex
Neurosci Lett
Anodal polarization induces protein kinase C gamma (PKC gamma)-like immunoreactivity in the rat cerebral cortex
Neurosci Res
Increase in the calcium level following anodal polarization in the rat brain
Brain Res
The “mirror” estimate: an intuitive predictor of membrane polarization during extracellular stimulation
Biophys J
Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats
Behav Brain Res
A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders
J Psychiatr Res
Considerations for safety in the use of extracranial stimulation for motor evoked potentials
Neurosurgery
Electric field-induced astrocyte alignment directs neurite outgrowth
Neuron Glia Biol
Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance
J Neurosci
The effect of spatially inhomogeneous extracellular electric fields on neurons
J Neurosci
Dendritic electrogenesis in rat hippocampal CA1 pyramidal neurons: functional aspects of Na and Ca currents in apical dendrites
Hippocampus
Oscillatory brain activity and transcranial direct current stimulation in humans
NeuroReport
Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain
J Physiol
Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex
Nature
Trains of transcranial Direct Current Stimulation antagonize motor cortex hypoexcitability induced by acute hemicerebellectomy
J Neurosurg
Modeling transcranial electric stimulation in mouse-a high resolution finite element study
Conf Proc IEEE Eng Med Biol Soc
Use of exogenous electric current in the treatment of delayed lesions in peripheral nerves
Plast Reconstr Surg
Modulation of burst frequency, duration, and amplitude in the zero-Ca2+ model of epileptiform activity
J Neurophysiol
Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro
J Physiol
Transcranial direct current stimulation for major depression-a general system for quantifying transcranial electrotherapy dosage
Curr Treat Options Neurol
Cellular and network effects of transcranial direct current stimulation-insights from animal models and brain slice
Long lasting changes in the level of the electrical activity of cerebral cortex produced by polarizing currents
Nature
The action of brief polarizing currents on the cerebral cortex of the rat during current flow and in the production of long-lasting after-effects
J Physiol
The effects of polarization upon the activity of vertebrate nerve
Am J Physiol
Cited by (199)
Transcranial direct current stimulation improves motor function in rats with 6-hydroxydopamine-induced Parkinsonism
2024, Behavioural Brain ResearchNon-invasive brain stimulation for functional recovery in animal models of stroke: A systematic review
2024, Neuroscience and Biobehavioral ReviewsA novel free-moving rat model of transcranial direct current stimulation
2023, Brain StimulationBoosting affective control with bifrontal transcranial direct current stimulation (tDCS): a proof-of-concept study in healthy individuals
2023, Behaviour Research and Therapy