Name: the combined use of transcranial direct current stimulation and robotic therapy for the upper limb
Uploaded: 2018-09-23T13:30:00
Description: Watch this Scientific Journal Video about The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb at JoVE.com

The authors would like to thank the Spaulding Laboratory of Neuromodulation and Instituto de Reabilita&#231;&#227;o Lucy Montoro for their generous support on this project.

This protocol follows the guidelines of our institution&#39;s human research ethics committee.
1. tDCS
<ol>
	<li>Contraindications and Special Considerations 
	Note: tDCS is a safe technique that sends constant and low direct current through the electrodes, inducing changes in neuronal excitability of the area being stimulated.
	<ol>
		<li>Prior to device setup, confirm that the patient does not have any contraindications to tDCS, such as adverse reactions to previous t...

<ol>
	<li>Miller, E. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comprehensive+overview+of+nursing+and+interdisciplinary+rehabilitation+care+of+the+stroke+patient:+A+scientific+statement+from+the+American+Heart+Association.">Comprehensive overview of nursing and interdisciplinary rehabilitation care of the stroke patient: A scientific statement from the American Heart Association.</a> Stroke. 41 (10), 2402-2448 (2010).</li><li>Adeyemo, B. O., Simis, M., Macea, D. D., Fregni, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+review+of+parameters+of+stimulation,+clinical+trial+design+characteristics,+and+motor+outcomes+in+noninvasive+brain+stimulation+in+stroke.">Systematic review of parameters of stimulation, clinical trial design characteristics, and motor outcomes in noninvasive brain stimulation in stroke.</a> Front Psychiatry. 3 (8), 1-27 (2012).</li><li>Johansson, B. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+trends+in+stroke+rehabilitation.+A+review+with+focus+on+brain+plasticity.">Current trends in stroke rehabilitation. A review with focus on brain plasticity.</a> Acta Neurologica Scandinavica. 123 (3), 147-159 (2011).</li><li>Hummel, F., Cohen, L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improvement+of+motor+function+with+noninvasive+cortical+stimulation+in+a+patient+with+chronic+stroke.">Improvement of motor function with noninvasive cortical stimulation in a patient with chronic stroke.</a> Neurorehabilitation Neural Repair. 19 (1), 14-19 (2005).</li><li>Lo, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robot-assisted+therapy+for+long-term+upper-limb+impairment+after+stroke.">Robot-assisted therapy for long-term upper-limb impairment after stroke.</a> New England Journal of Medicine. 362 (19), 1772-1783 (2010).</li><li>Mehrholz, J., Haedrich, A., Platz, T., Kugler, J., Pohl, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electromechanical+and+robot-assisted+arm+training+for+improving+generic+activities+of+daily+living,+arm+function,+and+arm+muscle+strength+after+stroke.">Electromechanical and robot-assisted arm training for improving generic activities of daily living, arm function, and arm muscle strength after stroke.</a> Cochrane Database of Systematic Reviews. , (2012).</li><li>Maciejasz, P., Eschweiler, J., Gerlach-Hahn, K., Jansen-Troy, A., Leonhardt, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+survey+on+robotic+devices+for+upper+limb+rehabilitation.">A survey on robotic devices for upper limb rehabilitation.</a> Journal of NeuroEngineering and Rehabilitation. 11 (3), 10-1186 (2014).</li><li>Ang, K. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facilitating+effects+of+transcranial+direct+current+stimulation+on+motor+imagery+brain-computer+interface+with+robotic+feedback+for+stroke+rehabilitation.">Facilitating effects of transcranial direct current stimulation on motor imagery brain-computer interface with robotic feedback for stroke rehabilitation.</a> Archives of Physical Medicine and Rehabilitation. 96 (3), S79-S87 (2015).</li><li>Chang, W. H., Kim, Y. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robot-assisted+therapy+in+stroke+rehabilitation.">Robot-assisted therapy in stroke rehabilitation.</a> Journal of Stroke. 15 (3), 174-181 (2013).</li><li>Volpe, B. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+approach+to+stroke+rehabilitation:+robot-aided+sensorimotor+stimulation.">A novel approach to stroke rehabilitation: robot-aided sensorimotor stimulation.</a> Neurology. 54 (10), 1938-1944 (2000).</li><li>Volpe, B. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+devices+as+therapeutic+and+diagnostic+tools+for+stroke+recovery.">Robotic devices as therapeutic and diagnostic tools for stroke recovery.</a> Archives of Neurology. 66 (9), 1086-1090 (2009).</li><li>Nitsche, M. A., Paulus, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Excitability+changes+induced+in+the+human+motor+cortex+by+weak+transcranial+direct+current+stimulation.">Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.</a> TheJournal of Physiology. 527 (3), 633-639 (2000).</li><li>Fregni, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+of+the+unaffected+hemisphere+in+stroke+patients.">Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.</a> Neuroreport. 16 (14), 1551-1555 (2005).</li><li>Kim, D. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+transcranial+direct+current+stimulation+on+motor+recovery+in+patients+with+subacute+stroke.">Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke.</a> American Journal of Physical Medicine and Rehabilitation. 89 (11), 879-886 (2010).</li><li>Giacobbe, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+(tDCS)+and+robot+practice+in+chronic+stroke:+the+dimension+of+timing.">Transcranial direct current stimulation (tDCS) and robot practice in chronic stroke: the dimension of timing.</a> NeuroRehabilitation. 33 (1), 49-56 (2013).</li><li>Hesse, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+transcranial+direct+current+stimulation+and+robot-assisted+arm+training+in+subacute+stroke+patients:+a+pilot+study.">Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: a pilot study.</a> Restorative Neurology and Neuroscience. 25 (1), 9-16 (2007).</li><li>Hesse, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+transcranial+direct+current+stimulation+and+robot-assisted+arm+training+in+subacute+stroke+patients:+an+exploratory,+randomized+multicenter+trial.">Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: an exploratory, randomized multicenter trial.</a> Neurorehabilitation and Neural Repair. 25 (9), 838-846 (2001).</li><li>Edwards, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Raised+corticomotor+excitability+of+M1+forearm+area+following+anodal+tDCS+is+sustained+during+robotic+wrist+therapy+in+chronic+stroke.">Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke.</a> Restorative Neurology and Neuroscience. 27 (3), 199-207 (2008).</li><li>Ochi, M., Saeki, S., Oda, T., Matsushima, Y., Hachisuka, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+anodal+and+cathodal+transcranial+direct+current+stimulation+combined+with+robotic+therapy+on+severely+affected+arms+in+chronic+stroke+patients.">Effects of anodal and cathodal transcranial direct current stimulation combined with robotic therapy on severely affected arms in chronic stroke patients.</a> Journal of Rehabilitation Medicine. 45 (2), 137-140 (2013).</li><li>DaSilva, A. F., Volz, M. S., Bikson, M., Fregni, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrode+positioning+and+montage+in+transcranial+direct+current+stimulation.">Electrode positioning and montage in transcranial direct current stimulation.</a> Journal of Visualized Experiments. (51), (2011).</li><li>Antal, A., Terney, D., Poreisz, C., Paulus, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Towards+unravelling+task-related+modulations+of+neuroplastic+changes+induced+in+the+human+motor+cortex.">Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex.</a> European Journal of Neuroscience. 26 (9), 2687-2691 (2007).</li><li>Williams, J. A., Pascual-Leone, A., Fregni, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interhemispheric+modulation+induced+by+cortical+stimulation+and+motor+training.">Interhemispheric modulation induced by cortical stimulation and motor training.</a> Physical Therapy. 90 (3), 398-410 (2010).</li><li>Zimerman, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+training+by+single-session+transcranial+direct+current+stimulation+to+the+intact+motor+cortex+enhances+motor+skill+acquisition+of+the+paretic+hand.">Modulation of training by single-session transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand.</a> Stroke. 43 (8), 2185-2191 (2012).</li><li>Nitsche, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmacological+modulation+of+cortical+excitability+shifts+induced+by+transcranial+direct+current+stimulation+in+humans.">Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.</a> The Journal of Physiology. 553 (1), 293-301 (2003).</li><li>Lindenberg, R., Renga, V., Zhu, L. L., Nair, D., Schlaug, G. M. D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bihemispheric+brain+stimulation+facilitates+motor+recovery+in+chronic+stroke+patients.">Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients.</a> Neurology. 75 (24), 2176-2184 (2010).</li><li>Fusco, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+ineffective+role+of+cathodal+tDCS+in+enhancing+the+functional+motor+outcomes+in+early+phase+of+stroke+rehabilitation:+an+experimental+trial.">The ineffective role of cathodal tDCS in enhancing the functional motor outcomes in early phase of stroke rehabilitation: an experimental trial.</a> BioMed Research International. , (2014).</li><li>Kwakkel, G., Kollen, B. J., Krebs, H. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+robot-assisted+therapy+on+upper+limb+recovery+after+stroke:+a+systematic+review.">Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review.</a> Neurorehabilitation and Neural Repair. 22 (2), 111-121 (2008).</li><li>Gilliaux, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Upper+limb+robot-assisted+therapy+in+cerebral+palsy:+a+single-blind+randomized+controlled+trial.">Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.</a> Neurorehabilitation and Neural Repair. 29 (2), 183-192 (2015).</li><li>Timmermans, A. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+task-oriented+robot+training+on+arm+function,+activity,+and+quality+of+life+in+chronic+stroke+patients:+a+randomized+controlled+trial.">Effects of task-oriented robot training on arm function, activity, and quality of life in chronic stroke patients: a randomized controlled trial.</a> Journal of NeuroEngineering and Rehabilitation. 11 (1), 45 (2014).</li><li>Hummel, F. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controversy:+noninvasive+and+invasive+cortical+stimulation+show+efficacy+in+treating+stroke+patients.">Controversy: noninvasive and invasive cortical stimulation show efficacy in treating stroke patients.</a> Brain Stimulation. 1 (4), 370-382 (2008).</li><li>Nair, D. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimizing+recovery+potential+through+simultaneous+occupational+therapy+and+non-invasive+brain-stimulation+using+tDCS.">Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS.</a> Restorative Neurology and Neuroscience. 29 (6), 411-420 (2011).</li><li>Nitsche, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+cortical+excitability+by+transcranial+direct+current+stimulation.">Modulation of cortical excitability by transcranial direct current stimulation.</a> Nervenarzt. 73 (4), 332-335 (2002).</li></ol>

In this protocol, we describe a standard therapy protocol for combined tDCS stimulation associated and robotic therapy, used as a complement to conventional rehabilitation programs in patients with arm impairments. The protocol&#39;s goal is to improve motor function and mobility. It is important to observe the ramping-on and ramping-off of the tDCS machine to avoid any risk of adverse effects. tDCS is a safe technique with few side effects described in the literature2.
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Neurological disorders such as stroke, cerebral palsy, and traumatic brain injury are leading causes of long-term disability, due to lesions and subsequent neurologic symptoms that can lead to severe incapacity and restriction of daily activities1. Movement disorders significantly reduce a patient's quality of life. Motor recovery is fundamentally driven by neuroplasticity, the basic mechanism underlying the reacquisition of motor skills lost due to brain lesions2,3. Thus, rehabilitation therapies are strongly based on high-dose intensive training and intense repetition of movements to recover strength and range of motion. These repetitive activities are based on daily life movements, and patients may become less motivated due to the slow motor recovery and repetitive exercises, which can impair the success of neurorehabilitation4. Intensive physical and occupational therapy are still considered main treatments, but newer adjunct therapies to standard rehabilitation are being studied to optimize functional outcomes1.
The advent of robotic-assisted therapies has been shown to have great value in stroke rehabilitation, influencing processes of neuronal synaptic plasticity and reorganization. They have been investigated for the training of patients with damaged neurological functions and assisting people with disabilities5. One of the most important advantages of adding robot technology to rehabilitive interventions is its ability to deliver high-intensity and high-dosage training, which otherwise would be a very labor-intensive process6. The use of robotic therapies, along with virtual reality computer programs, allows for an immediate perception and evaluation of motor recovery and can change repetitive actions into meaningful, interactive functional tasks such as cleaning a stovetop7. This can elevate patients' motivation and adherence to the long rehabilitation process and allows, through the possibility of measuring and quantifying movements, tracking of their progress5. Integration of robotic therapy into current practices may increase the efficacy and effectiveness of rehabilitation and enable the development of novel modes of exercise8.
Therapeutic rehabilitation robots provide task-specific training and can be divided into end-effector-type devices and exoskeleton-type devices9. The difference between these classifications is related to how movement is transferred from the device to the patient. End-effector devices have simpler structures, contacting the patient's limb only at its most distal part, making it more difficult to isolate movement of one joint. Exoskeleton-based devices have more complex designs with a mechanical structure that mirrors the skeletal structure of the limb, so a movement of the device's joint will produce the same movement on the patient's limb7,9.
The T-WREX is an exoskeleton-based robot that assists whole arm movements (shoulder, elbow, forearm, wrist, and finger movements). The adjustable mechanical arm allows variable levels of gravity support, enabling patients who have some residual upper limb function to achieve a larger active range of motion in a tridimensional spatial therapy7,9. The MIT-MANUS is an end-effector-type robot that works in a single plan (x- and y-axis) and allows a two-dimensional gravity compensated therapy, assisting shoulder and elbow movements by moving the patient's hand in the horizontal or vertical plane9,10. Both robots have built-in position sensors that can quantify upper extremity motor control and recovery and an interface for computer integration that allows 1) the training of meaningful functional tasks simulated in a virtual learning environment and 2) therapeutic exercise games, which help the practice of motor planning, eye-hand coordination, attention, and visual field defects or neglects7,9. They also allow for the compensation of gravity effects on the upper limb and are capable of offering support and assistance to repetitive and stereotyped movements in severely impaired patients. This progressively reduces assistance as the subject improves and applies minimal assistance or resistance to movement for mildly impaired patients9,11.
Another new technique for neurorehabilitation is transcranial direct current stimulation (tDCS). tDCS is a non-invasive brain stimulation technique that induces cortical excitability changes through the use of low amplitude direct currents applied via scalp electrodes12,13. Depending on the polarity of the current flow, brain excitability can be increased by anodal stimulation or decreased by cathodal stimulation2.
Recently, there has been increased interest in tDCS, as it has been shown to have beneficial effects on a wide range of diseases such as stroke, epilepsy, Parkinson's disease, Alzheimer's disease, fibromyalgia, psychiatric disorders such as depression, affective disorders, and schizophrenia2. tDCS has some advantages, such as its relatively low cost, ease of use, safety, and rare side effects14. tDCS is also a painless method and can be reliably blinded in clinical trials, as it has a sham mode13. tDCS is likely not optimal for functional recovery on its own; however, it is showing increased promise as an associated therapy in rehabilitation, as it enhances brain plasticity15.
In this protocol, we demonstrate combined robot-assisted therapy (with two state-of-the-art robots) and non-invasive neuromodulation with tDCS as a method for improving rehabilitation outcomes, in addition to conventional physical therapy. Most studies involving robotic therapies or tDCS have used them as isolated techniques, and few have combined both, which may enhance the beneficial effects beyond each intervention alone. These smaller trials demonstrated a possible synergistic effect between the two procedures, with improved motor recovery and functional ability8,15,16,17,18,19. Therefore, novel multi-modal therapies may enhance movement recovery beyond the current possibilities.

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			<td height="21" style="height:21px;width:216px;">tDCS device</td>
			<td style="width:241px;">Soterix Medical</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Soterix Medical 1x1</td>
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			<td height="21" style="height:21px;width:216px;">9V Battery (2x)</td>
			<td style="width:241px;"></td>
			<td style="width:119px;"></td>
			<td></td>
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			<td height="21" style="height:21px;width:216px;">Two rubber head bands</td>
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			<td style="width:119px;"></td>
			<td></td>
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			<td height="42" style="height:42px;width:216px;">Two conductive rubber electrodes</td>
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			<td></td>
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			<td height="21" style="height:21px;width:216px;">Two sponge electrodes</td>
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			<td></td>
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			<td height="21" style="height:21px;width:216px;">Cables</td>
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			<td></td>
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			<td height="21" style="height:21px;width:216px;">NaCl solution</td>
			<td style="width:241px;"></td>
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			<td></td>
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			<td height="21" style="height:21px;width:216px;">Measurement tape</td>
			<td style="width:241px;"></td>
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			<td></td>
		</tr>
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			<td height="21" style="height:21px;width:216px;">Armeo Spring Robot</td>
			<td style="width:241px;">Hocoma</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">inMotion ARM</td>
			<td style="width:241px;">Interactive Motion Technologies</td>
			<td style="width:119px;"></td>
			<td></td>
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	</tbody>
</table>

the combined use of transcranial direct current stimulation and robotic therapy for the upper limb

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

Non-invasive brain stimulation with tDCS has recently generated interest due to its potential neuroplastic effects, comparatively inexpensive equipment, ease of use, and few side effects22. Studies have shown that neuromodulation by tDCS has the potential to modulate cortical excitability and plasticity, thus promoting improvements in motor performance through synaptic plasticity by stimulating the primary motor cortex4. Anodal stimulation i...

Watch this Scientific Journal Video about The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb at JoVE.com

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

Neurological disorders such as stroke, cerebral palsy and traumatic brain injury, are leading causes of long term instability reducing a patient's quality of life. Motor recovery is driven by neuroplasticity. Thus, rehabilitation therapies are strongly based on high dose, intensive training, and intense repetition of movements as to allow the recovery of strength and range of motion.The advent of robot assistive therapy has been shown of great value to the rehabilitation, influencing process of neuroplasticity and heregonization. The most important advantage of using robot technology and rehabilitation intervention is the ability to deliver high dosage and high intensity training which otherwise would be a very labor-intensive process. It also allows an immediate perception and evaluation of motor recovery, and can also turn repetitive actions into meaningful interactive functional tasks.Another new technique being developed for rehabilitation is the tDCS, which is the shorter for transcranial direct current stimulation. tDCS is a low-evasive brain stimulation technique which allows the changes in current excitability through the use of low-intensity electrical cortical stimulation applied over this count. tDCS, transcranial direct current stimulation, has generated much attention lately from researchers and also clinicians.There are several reasons to explain. The main reason is due to its effects on neuroplasticity, and the other reasons are because tDCS device is cheap and also because tDCS is an easy technique to use. tDCS has been studied for several types of diseases, such as epilepsy, Parkinson's, depression and stroke.However, tDCS is unlikely optimal for functional recovery on its own, but it is showing increasing promise as an adjunct therapy in rehabilitation as it enhances brain plasticity. Most studies involving robotic therapies or tDCS use them isolated. Few studies were done combining both of them which could possibly enhance their beneficial effects beyond each intervention alone.These few small trials demonstrated a possible synergistic effect between these two procedures with improved motor recovery and functional ability. In this video, we describe the combined methods used in our institute for improving motor performance after stroke. tDCS can be used either before or during robotic rehabilitation as demonstrated in the medical literature.Equipments needed:tDCS device, cables, rubber bands, sponges, sodium chloride solution, measuring tape, electrodes, battery. The stimulation location will be found through the measurement of scalp. Using the convention of the EEG 10/20 system, as described in our previous article.In this protocol, we will stimulate the primary motor cortex, or M1.To locate this point, calculate 20%of the auricular measurement. This spot should correspond to C3/C4 EEG location. Place the electrode on the center of this spot, and the secondary electrode over the contralateral super orbital region.After preparing the skin and localizing the stimulation site, After tDCS, refer patients to undergo robotic therapy. In this protocol, we will describe the use of the commercial of the MIT-Manus and T-WREX. The robot has several therapy protocols, allowing patients to practice motor-planning, eye-hand coordination, attention and mass practice.The therapeutic exercises and games practice both wrist flexion and extension, along with radial and ulnar deviation. The video screen shows cues of the tasks that the subject needs to perform and constantly gives feedback of the position of the arm. On a robotic therapy session, the therapist selects the appropriate treatment protocol and the robot may provide real-time assistance if necessary.The MIT-Manus arm allows the training of the elbow flexion and extension, shoulder protraction and retraction, and shoulder internal and external rotation on a horizontal plane. The robot will only assist the patient if necessary. For example, if the subject cannot realize the intended movement within two seconds, the machine will help complete its movement.If the subject has not enough motor coordination to carry out the intended movement, the robot will guide the subject's arm to do the appropriate movement. The robot software has several therapeutic exercise games for motor training. The visual feedback usually consists in a yellow ball that the patient must move between targets.Other training scenarios are available. The T-WREX consists of an exoskeleton that fits the subject's arm and allows him to move his shoulder, elbow, and wrist joints freely in a tri-dimensional setting. The adjustable mechanical arm allows variable levels of gravity support by means of a spring mechanism, enabling patients with residual upper limb function to achieve a larger active range of motion.The compensation for the arm goes from A to I and A to E for the forearm. It consists of a linear scale of gravity support where A has no gravity support. Therapy protocols and games included allows the training of task-specific functions by moving the exoskeleton across a 3D workspace.By combining movements of the shoulder, forearm, elbow, and wrist, the robot allows a task-specific repetitive training. A training session usually lasts about 60 minutes. In each session, the individual performs about 72 repetitions of the movement towards different functional targets.Between each movement, allow a 10-second interval in order to prevent fatigue. The robots demonstrated on this video can be used as part of the rehabilitative program for several neurological injuries, including stroke, cerebral palsy, and spinal cord injury. They offer the ability of even severely impaired users to train independently and benefit from highly intensive repetitive and self-initiated movement therapy with increased user motivation.Non-invasive brain stimulation with tDCS has generated much interest recently due its potential neuroplasticity effects, comparatively inexpensive equipment, ease of use, and few side effects. Studies have shown that neuromodulation with tDCS has the potential to modulate cortical excitablity and plasticity, thus promoting additional improvements in motor performance through long-term potentiation by stimulating the primary motor cortex. Previous studies have reported electrophysiological effects of tDCS lasting up to 90 minutes, and behavioral effects lasting up to 30 minutes after a single tDCS session of 20 minutes.The evidence is still, however, controversial, as the positive findings are not consistent. A previous trial found functional motor improvement after bihemispheric stimulation that outlasted the intervention period. The evidence for robotic therapy in rehabilitation is more prominent, demonstrating clear incremental reductions of motor impairment.However, due to the large number of manufacturers and several types of robotic devices, each machine has their own properties, qualities and limitations. A multi-center, randomized controlled trial found that chronic stroke patients with moderate to severe upper limb impairment had significant but modest improvement in arm function, movement, and quality of life after robotic training over the 36-week study period as compared to usual care, but not with intensive physical therapy. While trials of neurorehabilitation with separate tDCS or robotic therapies have been done before, few trials were conducted combining these therapies.A previous trial evaluated the dimension of timing in combined robotic therapy with tDCS for wrist rehabilitation in chronic stroke patients. The authors found that wrist movement speed and smoothness was improved over 15%when tDCS was delivered prior to a 20-minute session of robotic training. The present paper aimed to describe a standard therapy protocol for combined noninvasive brain stimulation and robot-assisted movement therapy, used as an adjunct to conventional therapy, in patients with deficits in arm function in order to improve motor skill.tDCS and robotics show significant motor effects but most of these studies show these effects when these techniques are used in isolation. What is important to explore is when we combine these two techniques it is possible to enhance their effects on more recovery. Robotic therapy endues an increase of cortical excitability in the brain and an increase of afferent input to the brain.These combined with tDCS may result in a better motor outcome due to the synergetic effect of those therapies combined.

the-combined-use-transcranial-direct-current-stimulation-robotic

Research

JoVE Journal

Neuroscience

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

Electrode Positioning and Montage in Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability2. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation6. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders &#x2013; especially when applied over several consecutive sessions4. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks3,5. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex7. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.

Transcranial direct current stimulation (tDCS) is an established technique to modulate cortical excitability1,2. It has been used as an investigative tool in neuroscience due to its effects on cortical plasticity, easy operation, and safe profile. One area that tDCS has been showing encouraging results is pain alleviation 3-5.

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while maintaining clinical standards. The current consensus regarding the efficacy of tDCS is that multiple treatment sessions are needed to observe targeted behavioral reductions in symptom burden. However, the requirement for patients to travel to clinic daily for stimulation sessions presents a major obstacle for potential participants, due to work or family obligations or limited ability to travel. This study presents a protocol that directly overcomes these obstacles by eliminating the need to travel to clinic for daily sessions.
This is an updated protocol for remotely supervised self-administration of tDCS for daily treatment sessions paired with a program of computer-based cognitive training for use in clinical trials. Participants only need to attend clinic twice, for a baseline and study-end visit. At baseline, participants are trained and provided with a study stimulation device, and a small laptop computer. Participants then complete the remainder of their stimulation sessions at home while they are monitored via videoconferencing software.
Participants complete computerized cognitive remediation during stimulation sessions, which may serve a therapeutic role or as a &#34;placeholder&#34; for other computer-based activity. Computers are enabled for real-time monitoring and remote control by study staff.
Outcome measures that assess feasibility and tolerance are administered remotely with the aid of visual analogue scales that are presented onscreen. Following completion of all RS-tDCS sessions, participants return to clinic for a study end visit in which all study equipment is returned.
Results support the safety, feasibility, and scalability of the RS-tDCS protocol for use in clinical trials. Across 46 patients, 748 RS-tDCS sessions have been completed. This protocol serves as a model for use in future clinical trials involving tDCS.

This manuscript provides an updated remote supervision protocol that enables participation in transcranial direct current stimulation (tDCS) clinical trials while receiving treatment sessions from home. The protocol has been successfully piloted in both patients with multiple sclerosis and Parkinson&#39;s disease.

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major depression.

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Transcranial Direct Current Stimulation (tDCS) in Mice

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for several neuropsychiatric diseases. The biological effects of tDCS are not fully understood, which is in part explained due to the difficulty in obtaining human brain tissue. This protocol describes a tDCS mouse model that uses a chronically implanted electrode allowing the study of the long-lasting biological effects of tDCS. In this experimental model, tDCS changes the cortical gene expression and offers a prominent contribution to the understanding of the rationale for its therapeutic use.

Transcranial Direct Current Stimulation tDCS in Mice

Transcranial direct current stimulation (tDCS) is a therapeutic technique proposed to treat psychiatric diseases. An animal model is essential for understanding the specific biological alterations evoked by tDCS. This protocol describes a tDCS mouse model that uses a chronically implanted electrode.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for ...

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles&#39; corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject&#39;s structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it&#160;can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

The present protocol describes the simultaneous, bilateral assessment of the corticomotor response of the tibialis anterior and soleus during rest and tonic voluntary activation using a single pulse transcranial magnetic stimulation and neuronavigation system.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

Stimulation Location Determination using a 3D Digitizer with High-Definition Transcranial Direct Current Stimulation

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, causal evidence of brain area activation leading to a behavior is often left missing. Transcranial direct current stimulation (tDCS), which can temporarily alter brain cortical excitability and activity, is a noninvasive neurophysiological tool used to study causal relationships in the human brain. High-definition transcranial direct current stimulation (HD-tDCS) is a noninvasive brain stimulation (NIBS) technique that produces a more focal current compared to conventional tDCS. Traditionally, the stimulation location has been roughly determined through the 10-20 EEG system, because determining precise stimulation points can be difficult. This protocol uses a 3D digitizer with HD-tDCS to increase accuracy in determination of stimulation points. The method is demonstrated using a 3D digitizer for more accurate localization of stimulation points in the right temporo-parietal junction (rTPJ).

Presented here is a protocol to achieve higher accuracy in determination of stimulation location combining a 3D digitizer with high-definition transcranial direct current stimulation.

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, ...

Simultaneous Application of Transcranial Direct Current Stimulation during Virtual Reality Exposure

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that changes the likelihood of neuronal firing through modulation of neural resting membranes. Compared to other techniques, tDCS is relatively safe, cost-effective, and can be administered while individuals are engaged in controlled, specific cognitive processes. This latter point is important as tDCS may predominantly affect intrinsically active neural regions. In an effort to test tDCS as a potential treatment for psychiatric illness, the protocol described here outlines a novel procedure that allows the simultaneous application of tDCS during exposure to trauma-related cues using virtual reality (tDCS+VR) for veterans with posttraumatic stress disorder (NCT03372460). In this double-blind protocol, participants are assigned to either receive 2 mA tDCS, or sham stimulation, for 25 minutes while passively watching three 8-minute standardized virtual reality drives through Iraq or Afghanistan, with virtual reality events increasing in intensity during each drive. Participants undergo six sessions of tDCS+VR over the course of 2-3 weeks, and psychophysiology (skin conductance reactivity) is measured throughout each session. This allows testing for within and between session changes in hyperarousal to virtual reality events and adjunctive effects of tDCS. Stimulation is delivered through a built-in rechargeable battery-driven tDCS device using a 1 (anode) x 1 (cathode) unilateral electrode set-up. Each electrode is placed in a 3 x 3 cm (current density 2.22 A/m2) reusable sponge pocket saturated with 0.9% normal saline. Sponges with electrodes are attached to the participant&#8217;s skull using a rubber headband with the electrodes placed such that they target regions within the ventromedial prefrontal cortex. The virtual reality headset is placed over the tDCS montage in such a way as to avoid electrode interference.

This manuscript outlines a novel protocol to allow the simultaneous application of transcranial direct current stimulation during exposure to warzone trauma-related cues using virtual reality for veterans with posttraumatic stress disorder.

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that changes the likelihood of neuronal firing through ...

Transcranial Direct Current Stimulation (tDCS) for Memory Enhancement

Memory enhancement is one of the great challenges in cognitive neuroscience and neurorehabilitation. Among various techniques used for memory enhancement, transcranial direct current stimulation (tDCS) is emerging as an especially promising tool for improvement of memory functions in a non-invasive manner. Here, we present a tDCS protocol that can be applied for memory enhancement in healthy-participant studies as well as in aging and dementia research. The protocol uses weak constant anodal current to stimulate cortical targets within cortico-hippocampal functional network engaged in memory processes. The target electrode is placed either on the posterior parietal cortex (PPC) or the dorsolateral prefrontal cortex (DLPFC), while the return electrode is placed extracranially (i.e., on the contralateral cheek). In addition, we outline a more advanced method of oscillatory tDCS, mimicking a natural brain rhythm to promote hippocampus-dependent memory functions, which can be applied in a personalized and non-personalized manner. We present illustrative results of associative and working memory improvement following single tDCS sessions (20 minutes) in which the described electrode montages were used with current intensities between 1.5 mA and 1.8 mA. Finally, we discuss crucial steps in the protocol and methodological decisions that must be made when designing a tDCS study on memory.

Transcranial Direct Current Stimulation tDCS for Memory Enhancement

A protocol for memory enhancement by using transcranial direct current stimulation (tDCS) targeting dorsolateral prefrontal and posterior parietal cortices, as core cortical nodes within hippocampo-cortical network, is presented. The protocol has been well evaluated in healthy-participant studies and is applicable to aging and dementia research as well.

Memory enhancement is one of the great challenges in cognitive neuroscience and neurorehabilitation. Among various techniques used for memory enhancement, ...