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 tDCS treatment, implanted brain medical devices, or the presence of metal implants in the head.</li>
		<li>Use the following inclusion criteria: subacute and chronic stroke patients with light to moderate upper-extremity hemiparesis. Other contraindications include skull defects, which could alter intensity and location of current flow, and subjects must be free of unstable medical conditions such as uncontrolled epilepsy.</li>
		<li>Inspect the patient&#39;s scalp thoroughly for cutaneous lesions, such as acute or chronic skin disorders, cuts, or other inflammatory signs. Avoid placing the electrodes and stimulating areas with such lesions as a safety precaution.</li>
	</ol>
	</li>
	<li>Materials for tDCS
	<ol>
		<li>Check if all the following listed materials are available (Figure 1) before starting the procedure: tDCS stimulator device, 9 V battery, 2 conductive electrodes, 2 sponge electrodes, cables, 2 rubber head bands (or Velcro straps, non-conductive straps), sodium chloride (NaCl) solution, measuring tape</li>
	</ol>
	</li>
	<li>Measurements
	<ol>
		<li>Electrode sites are usually defined as 10/20 EEG positions, as described in a previous publication20. Make sure the subject is comfortably seated.</li>
		<li>First, localize the vertex (Cz).
		<ol>
			<li>Measure the distance from the nasion (bridge of the nose or intersection of the frontal bone and two nasal bones) to the inion (external occipital protuberance or most prominent projection of the protuberance), and mark 50% of this length. Mark this preliminary Cz location as a line, using either an oil pencil or nontoxic water-based marker.</li>
			<li>Measure the left and right pre-auricular points distance (i.e., the area anterior to the tragus). Divide this distance in half and mark the calculated point with a line.</li>
			<li>Connect both lines to create a cross. The intersection of both lines will correspond to the vertex (Cz) (Figure 2).</li>
		</ol>
		</li>
		<li>Identify the target site on the head. 
		NOTE: Anodal stimulation increases the cortical excitability in the stimulated brain tissue, while cathodal stimulation decreases it. Previous studies have used anodal stimulation in the lesioned hemisphere or cathodal stimulation in the contralesional hemisphere in order to decrease cortical excitability in the unaffected motor cortex and increase it in the affected motor cortex. In this protocol, we will describe both bihemispheric stimulation (with both anodal and cathodal stimulation in the same session) and anodal stimulation over the primary motor cortex.
		<ol>
			<li>To locate the primary motor cortex (M1), use 20% of the distance from Cz to the left or right pre-auricular point (Figure 3). This area should correspond to the C3/C4 EEG location.</li>
			<li>Place the anode over the center of M1 motor cortex of the ipsilesional hemisphere and the cathode over the contralateral supraorbital region (Fp) (Figure 3).</li>
			<li>Alternatively, place the anode over the center of M1 motor cortex of the ipsilesional hemisphere and the cathode over the contralesional M1. The M1 positions for the tDCS electrodes are located at channels C3 and C4 (Figure 3).</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Skin Preparation
	<ol>
		<li>Inspect the skin and avoid stimulating over lesions or damaged skin.</li>
		<li>Move the hair away from the site of stimulation to improve conductance. Clean the surface of the skin, removing any signs of lotion and gel. For subjects with thicker hair, using conductive gel may be necessary.</li>
	</ol>
	</li>
	<li>Electrode positioning and device setup20
	<ol>
		<li>After preparing the skin and localizing the stimulation site, place one head strap under the inion, around the head circumference. Provide head straps made of non-conducting and non-absorbent material such as elastic, Velcro, or rubber straps.</li>
		<li>Soak the sponges with saline solution. For a 35 cm2 sponge, approximately 6 mL of solution per side may suffice. Avoid oversoaking the sponge. Avoid producing fluid leaks over the subject. If necessary, use a syringe to add more solution.</li>
		<li>Connect the cables to the tDCS device. Make sure the polarity of the cables is correct, since the effects of tDCS are polarity-specific (as standardized: red corresponds to the anode electrode, and black or blue corresponds to the cathode electrode).</li>
		<li>Insert the connector cord pin securely into the conductive rubber inset.</li>
		<li>Insert the conductive rubber inset into the sponge. Ensure that the entire conductive rubber inset is covered by the sponge and that the connector cord pin is not visible.</li>
		<li>Place the first sponge electrode under the head strap and ensure that excessive fluid is not released from the sponge.</li>
		<li>Connect both elastic head straps, according to the electrode montage planned.</li>
		<li>Place the second sponge electrode on the head over the area being stimulated, under the second elastic head strap.</li>
		<li>If the overall electrical resistance of the electrodes and body is high, it may indicate inadequate electrode set-up. Some devices provide resistance measuring, which should be under 5 k&#937;, ideally.</li>
		<li>Some devices provide a continuous indication of resistance during stimulation, which is a useful way to detect potentially hazardous situations (such as a dry electrode). In such cases, the device may finish or reduce the stimulation intensity if resistance increases beyond a certain threshold.</li>
	</ol>
	</li>
	<li>Stimulation
	<ol>
		<li>Make sure that the patient is awake, relaxed, and seated comfortably during the procedure21.</li>
		<li>Adjust the tDCS stimulator settings (intensity, time, and sham condition, if applicable). In accordance with previous studies, apply direct current for 20 minutes at an intensity of 1 mA. 
		NOTE: For sham intervention, the current is usually applied only for the first 30 s to give the subject the sensation of stimulation. This duration has been established in several studies as being effective in blinding them to the assigned intervention, without stimulating cortical excitability22.</li>
		<li>Initiate the tDCS stimulation. Start the current flow by ramping up the current to avoid the most adverse effects. Ramping up is automatically done on some devices, but if it is not, increase the current slowly during the initial 30 s to reach the maximum programmed current (in our protocol, up to 1 mA).</li>
		<li>After starting the electrical stimulation, some patients may perceive temporary slight itching sensations, dizziness, or vertigo. This can be avoided by ramping the current up and down at the start and end of each session.</li>
		<li>At the end of the procedure, gradually ramp off the current for 30 s.</li>
	</ol>
	</li>
	<li>After the procedure
	<ol>
		<li>To record and evaluate the safety of the stimulation, ask the patient to fill out a questionnaire of common adverse effects and their intensities after the procedure is done. These may include skin irritation, nausea, headaches, burning sensations, dizziness, tingling, or other discomforts.</li>
		<li>Explain to the patient that any possible side effects are usually of mild or moderate intensity and usually temporary.</li>
		<li>After tDCS, refer the patients to undergo robotic therapy. 
		NOTE: In the next sections of this protocol, we will describe the use of the commercial versions of the MIT-Manus and T-WREX.</li>
	</ol>
	</li>
</ol>
2. Robotic Therapy with MIT-Manus
<ol>
	<li>Positioning 
	NOTE: This robot is an interactive robot for rehabilitation of the upper limb. The version utilized in our study allows training of wrist movement in the horizontal plane (planar).
	<ol>
		<li>Make sure the subject is seated in a comfortable and ergonomic chair, secured by a four-point seatbelt, and facing the video screen.</li>
		<li>Make sure that a trained therapist is supervising the robotic training.</li>
		<li>Place the hand that will be subject to training into the grip of the robotic handle. Adjust both straps around the subject&#39;s arm. Adjust the support on the back of the arm so that it stays stable during training.</li>
		<li>Place the paretic upper extremity as indicated: shoulder in a 30&#176; flexion, 90&#176; elbow flexion, forearm in mid-prone position, wrist in neutral position.</li>
		<li>During machine operation, make sure movement of the shoulder joints and elbow range is limited to about 45&#176;. Make sure that the arm is immobilized, and the wrist has freedom of movement. Movement is possible in the horizontal plane (in all possible directions).</li>
	</ol>
	</li>
	<li>Training
	<ol>
		<li>The number of movements in a robotic training session is variable; however, it is common to perform about 320 repetitions in every possible direction of a plane within a same plane.</li>
		<li>The video screen shows cues of the tasks that the subject needs to perform and gives constant feedback of the position of the arm.</li>
		<li>The robot&#39;s software has several therapeutic exercise games for motor training. The visual feedback usually consists of a yellow ball that the patient must move between targets. Other training scenarios are available.</li>
		<li>The robot will only assist the patient if necessary; for example, if the subject cannot realize the intended movement within 2 s, the machine will help complete its movement. If the subject does not have enough motor coordination to carry out the intended movement, the robot will guide the subject&#39;s arm to perform the appropriate movement.</li>
	</ol>
	</li>
</ol>
3. Training with MIT-Manus Arm
Note: This robotic arm allows training of elbow flexion and extension, shoulder protraction and retraction, and shoulder internal and external rotation on a horizontal plane.
<ol>
	<li>Positioning
	<ol>
		<li>For the MIT-MANUS Arm, make sure the subject is seated comfortably. Adjust the seat belts accordingly. Position the patient&#39;s right or left arm on the robot and adjust both straps.</li>
		<li>Adjust the robot&#39;s height as necessary. Adjust the table height as necessary.</li>
		<li>If there is any discomfort or pain, press the emergency stop button to turn off the robot immediately.</li>
	</ol>
	</li>
	<li>Training
	<ol>
		<li>Calibrate the machine by asking the subject to move its arm along the lines.</li>
		<li>The robot will only assist the patient if necessary. For example, if the subject cannot realize the intended movement within 2 s, the machine will help complete its movement. If the subject does not have enough motor coordination to carry out the intended movement, the robot will guide the subject&#39;s arm to perform the appropriate movement. 
		NOTE: The robot&#39;s software has several therapeutic exercise games for motor training. The visual feedback usually consists of a yellow ball that the patient must move between targets. Other training scenarios are available.</li>
	</ol>
	</li>
</ol>
4. Training with T-WREX
<ol>
	<li>Positioning 
	NOTE: The T-WREX consists of an exoskeleton that fits the subject&#39;s arm and allows free movement of the shoulder, elbow, and wrist joints in a tridimensional setting.
	<ol>
		<li>Ensure that the subject is seated in a comfortable and ergonomic chair facing the video screen, which provides visual and auditory feedback in a virtual reality setting, helping the patient achieve his or her goal.</li>
		<li>Place the patient seated in front of the robot&#39;s main module. Use the provided remote control to adjust the exoskeleton&#39;s height accordingly. Adjust the robot&#39;s exoskeleton arm to the corresponding side of the patient&#39;s limb that will be trained (either left or right).</li>
		<li>Leave about 4 fingers of height above the shoulder.</li>
		<li>Adjust the patient&#39;s limb into the exoskeleton, adjusting the straps on the arm and forearm.</li>
		<li>Adjust the length of the exoskeleton&#39;s arm and forearm accordingly, as well as the weight (gravity) compensation necessary for the arm (A to I) and forearm (A to E). It consists of a linear scale of gravity support, where A has no gravity support.</li>
		<li>Input these measurements to the computer.</li>
		<li>Before starting the training, adjust and calibrate the range of motion limits of the robot, according to the patient&#39;s capabilities.</li>
		<li>To test the calibrated range of motion, ask the patient to move the cube in all directions of the screen.</li>
	</ol>
	</li>
	<li>Training
	<ol>
		<li>In each session, have the individual perform about 72 repetitions of the movement towards different functional targets (a T-WREX training session usually lasts about 60 min).</li>
		<li>Between each movement, allow a 10-second interval to prevent fatigue. The 72 repetitions are divided into 3 blocks of 24 movements each. Allow an interval of 5 min between each block of 24 movements.</li>
	</ol>
	</li>
</ol>

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<li>Timmermans, A. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effects+of+task-oriented+robot+training+on+arm+function%2C+activity%2C+and+quality+of+life+in+chronic+stroke+patients%3A+a+randomized+controlled+trial%5BTitle%5D)+AND+%22Journal+of+NeuroEngineering+and+Rehabilitation%22%5BJournal%5D)">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/pubmed?term=((Controversy%3A+noninvasive+and+invasive+cortical+stimulation+show+efficacy+in+treating+stroke+patients%5BTitle%5D)+AND+%22Brain+Stimulation%22%5BJournal%5D)">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/pubmed?term=((Optimizing+recovery+potential+through+simultaneous+occupational+therapy+and+non-invasive+brain-stimulation+using+tDCS%5BTitle%5D)+AND+%22Restorative+Neurology+and+Neuroscience%22%5BJournal%5D)">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/pubmed?term=((Modulation+of+cortical+excitability+by+transcranial+direct+current+stimulation%5BTitle%5D)+AND+%22Nervenarzt%22%5BJournal%5D)">Modulation of cortical excitability by transcranial direct current stimulation.</a> Nervenarzt. 73 (4), 332-335 (2002).</li>
</ol>

The authors declare that they have no competing financial interests.

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.

<table><tbody><tr><td>tDCS device</td><td>Soterix Medical</td><td></td><td>Soterix Medical 1x1</td></tr><tr><td>9V Battery (2x)</td><td></td><td></td><td></td></tr><tr><td>Two rubber head bands</td><td></td><td></td><td></td></tr><tr><td>Two conductive rubber electrodes</td><td></td><td></td><td></td></tr><tr><td>Two sponge electrodes</td><td></td><td></td><td></td></tr><tr><td>Cables</td><td></td><td></td><td></td></tr><tr><td>NaCl solution</td><td></td><td></td><td></td></tr><tr><td>Measurement tape</td><td></td><td></td><td></td></tr><tr><td>Armeo Spring Robot</td><td>Hocoma</td><td></td><td></td></tr><tr><td>inMotion ARM</td><td>Interactive Motion Technologies</td><td></td><td></td></tr></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...

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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 ...

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Research

JoVE Journal

Neuroscience

9.0K Views.  Instituto de Reabilitação Lucy Montoro. Neurologische aandoeningen zoals beroerte, cerebrale parese en traumatisch hersenletsel, zijn belangrijke oorzaken van langdurige instabiliteit vermindering van de kwaliteit van leven van een patiënt. Motorisch herstel wordt aangedreven door neuroplasticiteit. Dus, revalidatie therapieën zijn sterk gebaseerd op hoge dosis, intensieve training, en intense herhaling van bewegingen om het herstel van kracht en bereik van de beweging mogelijk te maken.De komst van robot ondersteunende th...

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

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 ...

Updated Technique for Reliable, Easy, and Tolerated Transcranial Electrical Stimulation Including Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of brain stimulation presents several potential advantages compared to other techniques, as it is noninvasive, cost-effective, broadly deployable, and well-tolerated provided proper equipment and protocols are administered. Even though tDCS is apparently simple to perform, correct administration of the tDCS session, especially the electrode positioning and preparation, is vital for ensuring reproducibility and tolerability. The electrode positioning and preparation steps are traditionally also the most time consuming and error-prone. To address these challenges, modern tDCS techniques, using fixed-position headgear and pre-assembled sponge electrodes, reduce complexity and setup time while also ensuring that the electrodes are consistently placed as intended. These modern tDCS methods present advantages for research, clinic, and remote-supervised (at home) settings. This article provides a comprehensive step-by-step guide for administering a tDCS session using fixed-position headgear and pre-assembled sponge electrodes. This guide demonstrates tDCS using commonly applied montages intended for motor cortex and dorsolateral prefrontal cortex (DLPFC) stimulation. As described, selection of the head size and montage-specific headgear automates electrode positioning. Fully assembled pre-saturated snap-electrodes are simply affixed to the set position snap-connectors on the headgear. The modern tDCS method is shown to reduce setup time and reduce errors for both novice and expert operators. The methods outlined in this article can be adapted to different applications of tDCS as well as other forms of transcranial electrical stimulation (tES) such as transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). However, since tES is application specific, as appropriate, any methods recipe is customized to accommodate subject, indication, environment, and outcome specific features.

When administering transcranial direct current stimulation (tDCS), reproducible electrode preparation and placement are vital for a tolerated and effective session. The purpose of this article is to demonstrate updated modern setup procedures for the administration of tDCS and related transcranial electrical stimulation techniques, such as transcranial alternating current stimulation (tACS).

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of ...

Medicine

Restoring Post-Stroke Motor Function by Motor Imagery Brain-Computer Interface

Motor Imagery Brain-Computer Interface in Rehabilitation of Upper Limb Motor Dysfunction After Stroke

The rehabilitation effect of patients with moderate or severe upper limb motor dysfunction after stroke is poor, which has been the focus of research owing to the difficulties encountered. Brain-computer interface (BCI) represents a hot frontier technology in brain neuroscience research. It refers to the direct conversion of the sensory perception, imagery, cognition, and thinking of users or subjects into actions, without reliance on peripheral nerves or muscles, to establish direct communication and control channels between the brain and external devices. Motor imagery brain-computer interface (MI-BCI) is the most common clinical application of rehabilitation as a non-invasive means of rehabilitation. Previous clinical studies have confirmed that MI-BCI positively improves motor dysfunction in patients after stroke. However, there is a lack of clinical operation demonstration. To that end, this study describes in detail the treatment of MI-BCI for patients with moderate and severe upper limb dysfunction after stroke and shows the intervention effect of MI-BCI through clinical function evaluation and brain function evaluation results, thereby providing ideas and references for clinical rehabilitation application and mechanism research.

Author Spotlight: Using Motor Imagery Brain-Computer Interface to Improve Motor and Cognitive Function in Stroke Patients

The purpose of this study is to provide an important reference for the standard clinical operation of motor imagery brain-computer interface (MI-BCI) for upper limb motor dysfunction after stroke.

The rehabilitation effect of patients with moderate or severe upper limb motor dysfunction after stroke is poor, which has been the focus of research ...

Treatment of Phantom Limb Pain by Remote Transcranial Direct Current Stimulation

Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical excitability. Previous trials have established the safety and tolerability of tDCS, and its potential to mitigate symptoms. However, the effects are cumulative, making it more difficult to have adherence to the treatment since frequent visits to the clinic or outpatient center are required. Moreover, the time needed for transportation to the center and the related expenses limit the accessibility of the treatment for many participants.
Following guidelines for remotely supervised transcranial direct current stimulation (RS-tDCS) implementation, we propose a protocol designed for remotely supervised and home-based participation that uses specific devices and materials modified for patient use, with real-time monitoring by researchers through an encrypted video conferencing platform. We have developed detailed instructional materials and structured training procedures to allow for self- or proxy-administration while supervised remotely in real time. This protocol has a specific design to have a series of checkpoints during training and execution of the visit. This protocol is currently in use in a large pragmatic study of RS-tDCS for phantom limb pain (PLP). In this article, we will discuss the operational challenges of conducting a home-based RS-tDCS session and show methods to enhance its efficacy with supervised sessions.

Author Spotlight: Insights into Remotely Supervised Neuromodulation Procedure for Phantom Limb Pain

The goal of this study is to describe a protocol for the home-based delivery of remotely supervised transcranial direct current stimulation (RS-tDCS) conserving the standard procedures of in-clinic practice, including safety, reproducibility, and tolerability. The participants included will be patients with phantom limb pain (PLP).

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical ...

Brain-Computer Interface-controlled Upper Limb Robotic System for Enhancing Daily Activities in Stroke Patients

This study introduces a Brain-Computer Interface (BCI)-controlled upper limb assistive robot for post-stroke rehabilitation. The system utilizes electroencephalogram (EEG) and electrooculogram (EOG) signals to help users assist upper limb function in everyday tasks while interacting with a robotic hand. We evaluated the effectiveness of this BCI-robot system using the Berlin Bimanual Test for Stroke (BeBiTS), a set of 10 daily living tasks involving both hands. Eight stroke patients participated in this study, but only four participants could adapt to the BCI robot system training and perform the postBeBiTS. Notably, when the preBeBiTS score for each item was four or less, the BCI robot system showed greater assistive effectiveness in the postBeBiTS assessment. Furthermore, our current robotic hand does not assist with arm and wrist functions, limiting its use in tasks requiring complex hand movements. More participants are required to confirm the training effectiveness of the BCI-robot system, and future research should consider using robots that can assist with a broader range of upper limb functions. This study aimed to determine the BCI-robot system's ability to assist patients in performing daily living activities.

This study introduces a brain-computer interface (BCI) system for stroke patients, which combines electroencephalography and electrooculography signals to control an upper limb robotic hand, enhancing daily activities. The evaluation used the Berlin Bimanual Test for Stroke (BeBiTS).

This study introduces a Brain-Computer Interface (BCI)-controlled upper limb assistive robot for post-stroke rehabilitation. The system utilizes ...

Integrated Robotic and Conventional Therapy for Post-Stroke Upper Limb Recovery

Enhancing Upper Limb Function and Motor Skills Post-Stroke Through an Upper Limb Rehabilitation Robot

Cerebrovascular accidents, commonly known as strokes, represent a prevalent neurological event leading to significant upper limb disabilities, thereby profoundly affecting individuals' activities of daily living and diminishing their quality of life. Traditional rehabilitation methods for upper limb recovery post-stroke are often hindered by limitations, including therapist and patient fatigue, reliance on singular training methodologies, and lack of sustained motivation. Addressing these challenges, this study introduces an upper limb rehabilitation robot, which uses intelligent feedback motion control to improve therapeutic outcomes. The system is distinguished by its capability to adjust the direction and magnitude of force feedback dynamically, based on the detection of spastic movements during exercises, thereby offering a tailored therapeutic experience. This system is equipped with four distinct training modes, intelligent assessment of joint range of motion, and the ability to personalize training programs. Moreover, it provides an immersive interactive gaming experience coupled with comprehensive safety measures. This multifaceted approach not only elevates the engagement and interest of participants beyond traditional rehabilitation protocols but also demonstrates significant improvements in upper limb functionality and the activities of daily living among hemiplegic patients. The system exemplifies an advanced tool in upper limb rehabilitation, offering a synergistic blend of precision, personalization, and interactive engagement, thereby broadening the therapeutic options available to stroke survivors.

Author Spotlight: Enhancing Post-Stroke Upper Limb Rehabilitation with Robotic Technologies for Improved Motor Recovery and Functional Outcomes

This protocol describes an upper limb rehabilitation robot that provides intelligent feedback through four modes. These modes enhance upper limb function and flexibility, thereby improving patients' quality of life.

Cerebrovascular accidents, commonly known as strokes, represent a prevalent neurological event leading to significant upper limb disabilities, thereby ...

Dual Upper Limb Robotic Training in Stroke Rehabilitation

Application of a Dual Upper Limb Task-Oriented Robotic System for the Functional Recovery of the Upper Limb in Stroke Patients

Highly repetitive and task-oriented training has been shown to promote the recovery of limb function in stroke patients. Additionally, bilateral arm training can help stroke survivors regain their upper limb function and improve their daily activities. The dual upper limb task-oriented robotic system is designed to assist the healthy side of the stroke patient in driving the affected side to perform bilateral arm training through the use of a robotic device. It can also guide the patient in carrying out dual upper limb coordinated movements and engage them in a task-oriented virtual game using force feedback and human-computer interaction technology. This study aimed to assess the efficacy of the system in enhancing upper limb function and activities of daily living in stroke patients. The assessment methods used included motor evoked potential (MEP), functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK), Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), and modified Barthel index (MBI). The results of the study indicate that the dual upper limb task-oriented robotic system can significantly improve the corticospinal pathway, upper limb function, and activities of daily living in stroke patients after 6 weeks of treatment. This system can serve as an effective adjunct to upper limb functional rehabilitation in stroke survivors, reducing the dependence on rehabilitation therapists. In conclusion, the dual upper limb task-oriented robotic system provides a new strategy for post-stroke limb functional rehabilitation and holds great potential for application, as it offers certain social and financial benefits.

Author Spotlight: Enhancing Upper Limb Rehabilitation in Stroke Patients Through Advanced Robotic and Neuromodulation Technologies

This experimental protocol outlines the use of a dual upper limb task-oriented robotic system for stroke patients with upper limb dysfunction. The findings indicate that this system can significantly improve stroke patients' upper limb function and daily living activities.

Highly repetitive and task-oriented training has been shown to promote the recovery of limb function in stroke patients. Additionally, bilateral arm ...

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

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