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Transcranial Direct Current Stimulation in Stroke Recovery

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Transcranial Direct Current Stimulation in Stroke Recovery NEUROLOGICAL REVIEW SECTION EDITOR: DAVID E. PLEASURE, MD Transcranial Direct Current Stimulation in Stroke Recovery Gottfried Schlaug, MD, PhD; Vijay Renga, MD; Dinesh Nair, MD, PhD ranscranial direct current stimulation (TDCS) is an emerging technique of noninva- sive brain stimulation that has been found useful in examining cortical function in healthy subjects and in facilitating treatments of various neurologic disorders. A better under- standing of adaptive and maladaptive poststroke neuroplasticity and its modulation Tthrough noninvasive brain stimulation has opened up experimental treatment options using TDCS for patients recovering from stroke. We review the role of TDCS as a facilitator of stroke recovery, the different modes of TDCS, and the potential mechanisms underlying the neural effects of TDCS. Arch Neurol. 2008;65(12):1571-1576 The concept of using therapeutic electric- interest in transcranial electric treat- ity on excitable tissues such as the brain is ments. However, several years later, the not new considering the attempts to cure effects of anodal direct currents on brain epileptic disorders with electric catfish as tissue in rats5 (such as increased accu- early as the 11th century as noted by Priori.1 mulation of calcium ions, leading to After a serendipitous discovery of abnor- increased cortical excitability, and evi- mal involuntary movements in patients dence for intracerebral currents during treated with high-voltage transcranial elec- electrosleep therapy studies in humans) tric currents, initial experiments by Hitzig prompted Priori and colleagues1,6 to in 1870 on dog cortex led to an interest in develop a novel approach of noninvasive using electric currents to identify the cor- brain stimulation using weak direct cur- tical representations of limb movements as rents, which came to be known as cited by Gross.2 Electrosleep therapy, men- “transcranial direct current stimulation” 3 tioned by Gilula and Barach, which later (TDCS). Subsequent experiments by came to be known as “cranial electric stimu- Nitsche and Paulus7,8 demonstrated lation,” has been used to treat sleep disor- modulating effects of anodal (increases ders and depression since 1902. cortical excitability) and cathodal (de- 4 In the 1960s, Bindman et al per- creases cortical excitability) TDCS on formed experiments that resulted in brain tissue in which the effects surpris- long-lasting polarization effects follow- ingly outlasted the duration of stimula- ing electric stimulation of the exposed tion. Residual electrophysiologic effects motor cortex of animals, which led to a were detectable up to 90 minutes and resurgence of studies exploring the clini- sensorimotor and cognitive effects up to cal applications of electric stimulation, 30 minutes after a 20- to 30-minute including the use of brain polarization in stimulation period.7,8 These early reports patients with depression. Although the and others during the past 8 to 10 years investigations showed some benefits, have renewed the interest in the use of replicating these beneficial effects in con- noninvasive regional brain polarization trolled settings yielded mixed results, for various neurologic disorders. Current which subsequently led to a diminished research studies make use of the block- Author Affiliations: Neuroimaging and Stroke Recovery Laboratories, Department ing and depressing effects of cathodal of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, TDCS to create temporary cortical dys- Boston, Massachusetts. functions (“virtual lesions”), which (REPRINTED) ARCH NEUROL / VOL 65 (NO. 12), DEC 2008 WWW.ARCHNEUROL.COM 1571 Downloaded from www.archneurol.com at Harvard University, on December 11, 2008 ©2008 American Medical Association. All rights reserved. A B Active electrode Reference electrode al od An al od th Ca Constant current stimulator Figure 1. Transcranial direct current stimulation setup and montage. A, The setup using a mobile battery-operated direct current stimulator connected with 2 electrodes. One electrode (active) is positioned over C3 (corresponding to the precentral gyrus), and the reference electrode is positioned over the contralateral supraorbital region. If current flows from C3 to the supraorbital region, then the tissue underlying C3 is subjected to anodal (increase in excitability) stimulation. If current is reversed, then the tissue underlying C3 is subjected to cathodal (decrease in excitability) stimulation. B, Regional cerebral blood increases in the motor region underlying the electrode positioned over C3 after anodal stimulation. Regional cerebral blood was determined using a noninvasive arterial spin-labeling technique.11 enables investigators to causally examine functions of becomes the cathode) (Figure 1A). Once switched on, cortical regions. Similarly, studies have examined the constant current stimulator produces a transient tin- whether anodal TDCS can be used to improve perfor- gling sensation under the electrode that fades off in 30 mance of certain sensorimotor or cognitive tasks (Vines to 60 seconds, thereby making it ideal for use in blinded et al9,10 provide an example of these 2 approaches). subjects (in sham-control studies) by turning it off after the initial sensory experience. McCreery et al12 found that MECHANISMS OF TDCS current densities below 25 mA/cm2 did not cause brain tissue damage, and the protocols that apply 1 to 2 mA as The components required for TDCS include a constant in present-day studies fall well within these limits. Re- current stimulator and surface electrodes soaked in iso- cent results of investigations on brain modeling and cur- tonic sodium chloride solution. While constantly moni- rent density distribution suggest that, despite a fraction toring the resistance in the system, a constant current of the direct current being shunted through the scalp, stimulator provides a steady flow of direct current (eg, TDCS carries adequate currents to the underlying cor- 0-4 mA). Electrodes soaked in isotonic sodium chloride tex that are sufficient for neuronal excitability shifts.13 solution, which are applied and secured onto the scalp Preliminary results of our ongoing studies have shown over desired areas such as the left or right precentral gy- that measures of cerebral blood flow can change in brain rus region (corresponding to C3 or C4 of the interna- regions that are targeted by transcranial anodal direct cur- tional 10-20 electroencephalographic system), form ter- rent, providing further proof that transcranially applied minals relaying currents across the scalp and through the direct currents can affect tissue excitability and regional underlying brain tissue. The direction of the current flow blood flow as an indirect marker of change in regional determines the effects on the underlying tissue. With an tissue excitability (Figure 1B). active electrode over C3 or C4, a reference electrode over The advantages of TDCS over other noninvasive brain a control region (eg, supraorbital region), and current stimulation methods include its ease of use, large elec- flowing from the active to the reference electrode, the ex- trode size allowing effect over a larger neural network, citability of the brain tissue under the anodal electrode sham mode allowing controlled experiments and ran- is increased, and when the current flow is reversed, the domized controlled clinical trials, and portability that excitability of the brain tissue under this electrode is de- makes it possible to apply stimulation while the patient creased (the electrode that was previously the anode now receives occupational or physical therapy. Neverthe- (REPRINTED) ARCH NEUROL / VOL 65 (NO. 12), DEC 2008 WWW.ARCHNEUROL.COM 1572 Downloaded from www.archneurol.com at Harvard University, on December 11, 2008 ©2008 American Medical Association. All rights reserved. less, TDCS is limited by its poor temporal resolution and to inhibition from the contralesional unaffected hemi- anatomical localization. Furthermore, interindividual sphere onto the lesional hemisphere that is not bal- variation in conductivity due to differences in hair, scalp, anced by a similar level of inhibition from the lesional and bone composition can interfere with the current that hemisphere onto the contralesional normal hemi- is carried to the brain. Finally, although single and mul- sphere. This abnormal and imbalanced interhemi- tiday sessions have been performed and found to be safe, spheric inhibition is the hypothetical model that under- the safety of prolonged periods of stimulation requires lies experimental therapy of applying anodal TDCS to the further studies. lesional hemisphere or cathodal TDCS to the nonle- By itself, TDCS provides a subthreshold stimulus that sional unaffected hemisphere. modulates the likelihood that neurons will fire by hy- perpolarizing or depolarizing the brain tissue, without EXPERIMENTAL ANIMAL STUDIES direct neuronal depolarization. The prolonged sensory, motor, and cognitive effects of TDCS have been attrib- Spontaneous, training-induced, and postpolarization neu- uted to persistent bidirectional modification of postsyn- roplasticity with or without physical rehabilitation has been aptic connections similar to long-term potentiation and studied in primates and in rodent brain models. Factors long-term depression effects.5,7 Dextromethorphan, an N- such as delay between the stroke and the time of initia- methyl-D-aspartate antagonist, suppressed anodal and tion of therapy—as well as the type (monopolar
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