This research was supported by the Science Fund of the Republic of Serbia, PROMIS, grant no. #6058808, MEMORYST

This procedure has been approved by the Institutional Ethics Committee and is in line with the Declaration of Helsinki and guidelines for human research.
1. Materials
NOTE: For each tDCS session prepare the following materials (Figure 1).
<ol>
	<li>Obtain a tDCS device - use only a battery driven tDCS device or a mains-connected optically isolated tDCS device. The device should function as a constant current stimulator with a maximum output limited preferably to a few milliampere range. The device must have regulatory approval for human use.</li>
	<li>Obtain rubber electrodes - use either 5 cm x 5 cm square-shaped or 25 cm2 round-shaped electrodes. These electrodes will have the current densities between 0.06 mA/cm2 and 0.08 mA/cm2 for currents of 1.5 mA-2 mA, respectively.</li>
	<li>Prepare sponge pockets that fit the rubber electrodes. If the sponge pocket is too large it will increase the contact surface to the skin.</li>
	<li>Prepare saline solution (standard 0.9% NaCl).</li>
	<li>Prepare alcohol (70%).</li>
	<li>Obtain an adjustable silicone cap - head straps can be used as well, however EEG silicone caps can be better adjusted to the size and the shape of participants&#39; head and are therefore more comfortable for electrode placement.</li>
	<li>Obtain measuring tape (flexible; plastic or ribbon).</li>
	<li>Obtain a skin marker - skin marker pencils or various makeup products (e.g., eye pencil or eyeshadow crayon), the later can be even more convenient as they are dermatologically tested and easily removable.</li>
	<li>Obtain cotton pads.</li>
	<li>Obtain comb and single-use mini silicon hair bands.</li>
	<li>Obtain a syringe or plastic pipette.</li>
	<li>Prepare a protocol sheet - fill-in form for basic information about the session i.e., participants ID, study ID, date, times, notes, etc (see Appendix for an example).</li>
	<li>Prepare a table with pre-calculated head measures to help with electrodes&#39; placement. 
	&#8203;NOTE: To speed-up the process and to reduce the possibility for errors, it is advisable to have this table ready in advance. The measurement is based on 10-20 EEG electrode placement system; the values used for calculations are nasion-inion/left-right-preauricular distances (see below). The table gives 20% values for a range of distance values. We have found it as the most convenient to have the table embedded into the protocol sheet (Appendix).</li>
	<li>Prepare questionnaires. For each session, collect data on sensations and side effects before and after tDCS; sensations and the level of (un)pleasantness during tDCS; mood and general subjective state i.e., freshness/tiredness.</li>
</ol>
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/62681/62681fig01.jpg" /> 
Figure 1: Materials for tDCS experiment (see text for details). 1) tDCS device; 2) electrodes; 3) sponges; 4) saline solution; 5) alcohol; 6) silicone cap; 7) measuring tape; 8) skin pencil; 9) cotton pads; 10) combs and silicon hairbands; 11) syringe <a href="https://www.jove.com/files/ftp_upload/62681/62681fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
2. Programing stimulation protocols
NOTE: Exact steps in programming tDCS protocol differ across tDCS systems/devices. However, all tDCS devices provide basic features - the ability to produce constant current with desired stimulation intensity, the ability to gradually ramp up and down, and a method to set the duration of stimulation. The more advanced protocols such as theta-oscillatory tDCS require devices/systems that allow for custom-built stimulation protocols.
<ol>
	<li>Constant anodal tDCS
	<ol>
		<li>Define the standard constant anodal tDCS protocol (Figure 2A) as: (1) fade-in period of 30 seconds, when current intensity is gradually ramped up from 0 mA to the target intensity (we typically use 1.5 mA, but other intensities can be used as well, providing they stay within safety limits); (2) stimulation period during which the constant current of the target intensity (e.g., 1.5 mA) is delivered; and (3) fade-out period of 30 seconds when current intensity is gradually decreased to 0 mA.</li>
	</ol>
	</li>
</ol>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/62681/62681fig02.jpg" /> 
Figure 2: tDCS protocols: (A) Constant anodal tDCS; (B) Theta oscillatory tDCS; (3) Sham tDCS. Fade in period is marked orange; fade out period is marked green. <a href="https://www.jove.com/files/ftp_upload/62681/62681fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<ol fo:break-after="page" start="2">
	<li>Theta oscillatory tDCS
	<ol>
		<li>Theta-oscillatory tDCS delivers current of varying intensity but does not switch polarities (Figure 2B). Therefore, define the waveform in which the current is delivered as following: (1) fade-in period of 30 seconds, when current intensity is gradually ramped up from 0 mA to the target intensity (e.g., 1.5 mA); (2) the stimulation period of 19 minutes in which the current oscillates around the target intensity within a pre-defined amplitude range (we use oscillations of &#177; 0.5 mA of the target intensity) in a selected frequency (we typically use 5 Hz frequency as representative for theta rhythm); and (3) fade-out period of 30 seconds to bring the current intensity to 0 mA. 
		NOTE: This protocol can be generated by any experimental control software (e.g., CED Signal) and delivered through an intelligent interface (e.g., CED 1401 range of devices) that is compatible with tDCS device which is to be used. Some more advanced dedicated transcranial electric stimulation (tES) systems besides tDCS can deliver alternating current (tACS) and random noise stimulation (tRNS) too. They can also be used to generate the oscillatory tDCS protocol. For example, in StarStim the theta-oscillatory tDCS protocol are defined as a linear combination of tDCS (1.5 mA) and tACS (&#177;0.5 mA, 5 Hz). This type of protocol can be personalized in a sense that not all participants receive oscillatory stimulation in the same frequency (i.e., 5 Hz), but that the frequency is adjusted to the dominant frequency within theta band for each person (e.g., Person 1: 5 Hz, Person 2: 6 Hz, Person 3: 4.5 Hz, etc.).</li>
	</ol>
	</li>
</ol>
&#160; &#160;
<ol start="3">
	<li>Sham tDCS
	<ol>
		<li>Use a sham protocol with the same duration as constant/oscillatory tDCS (Figure 2C). Namely, define it as: (1) first fade in/out period in which the current is gradually ramped up to target intensity (e.g., 1.5 mA) and gradually ramped down to 0 mA during the first 60 seconds (2) 18 minutes of 0 mA, and (3) the second fade in/out period which again lasts 60 seconds. 
		NOTE: An alternative approach would be to use very low current intensity over the entire stimulation period (20 min). This type of sham protocol is programmed the same as the anodal stimulation (only the current intensity is set to (0.1 mA) and is designed to produce cutaneous sensations but the intensity is too week to produce any physiological effects33.</li>
	</ol>
	</li>
</ol>
3. Electrode placement&#160;(Figure 3)
<ol>
	<li>DLPFC electrode montage: For stimulation of the DLPFC, place the target (anodal) electrode on either F3 (left) or F4 (right) of the international 10-20 EEG system. Place the return electrode (cathodal) on the contralateral cheek - i.e., right cheek for F3 anode and left cheek for F4 anode.</li>
	<li>PPC electrode montage: For stimulation over PPC, place the target (anodal) electrode on either P3 (left) or P4 (right) of the international 10-20 EEG system. Place the return electrode (cathodal) on the contralateral cheek same as in DLPFC montage.</li>
	<li>The target electrode placement
	<ol>
		<li>To locate F3 on participants&#39; head
		<ol>
			<li>Use the measuring tape to measure the distance between nasion (the deepest point of the nasal bridge) and inion (the most pronounced point of the external occipital protuberance) going over the top of the head. Mark the halfway distance with the skin marker with a thin line.</li>
			<li>Measure the distance between the ears (use preauricular points as references) going over the top of the head and mark the halfway distance with a thin line.</li>
			<li>Find the vertex or midline central position, referred as Cz, at the intersections of the two midlines. Mark it clearly with the skin marker.</li>
			<li>Measure again the nasion-inion distance, but this time going over Cz, and note the distance as measure A. Measure again the distance between the ears, this time going over Cz, and note the distance as measure B.</li>
			<li>Calculate 20% of distance A, and 20% of distance B (or see Protocol sheet for pre-calculated values).</li>
			<li>Move 20% of distance A forward from Cz along the nasion-inion line to reach Fz (midline frontal) and mark the spot.</li>
			<li>Move 20% of distance B leftward from Cz along the inter-auricular line to reach C3 (left central) and mark the spot.</li>
			<li>Move 20% forward form C3 (in parallel with the nasion-inion line), and 20% leftward form Fz (in parallel with the inter-auricular line), to reach F3 at the intersection. Mark F3 with the skin-marker and place the center of the electrode at the spot.</li>
		</ol>
		</li>
		<li>To locate F4, follow the same procedure only on the right side of the head.</li>
		<li>To locate P3 on participants&#39; head
		<ol>
			<li>Follow the steps 3.3.1.1-3.3.1.5 as outlined above (find Cz, note distance A and B, calculate 20%).</li>
			<li>Move 20% of distance A backward from Cz along the nasion-inion to reach Pz (midline parietal) and mark the spot.</li>
			<li>Move 20% of distance B leftward from Cz along the inter-auricular line to reach C3 and mark the spot.</li>
			<li>Move 20% backward from C3 (in parallel with the nasion-inion line), and 20% leftward from Pz (in parallel with the inter-auricular line), to reach P3 at their intersection. Mark P3 with the skin-marker and place the center of the electrode at the spot.</li>
		</ol>
		</li>
		<li>To locate P4, follow the same procedure only on the right side of the head.</li>
	</ol>
	</li>
	<li>Return electrode placement
	<ol>
		<li>After securing the target electrode with the adjustable silicon cap (see step-by step procedure), insert the return electrode below the chin band to secure the contact of the electrode with the contralateral cheek.</li>
	</ol>
	</li>
</ol>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/62681/62681fig03.jpg" /> 
Figure 3: Electrode placement scheme. <a href="https://www.jove.com/files/ftp_upload/62681/62681fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
4. Step-by-step procedure
<ol>
	<li>Before the tDCS session
	<ol>
		<li>Check if each participant satisfies the inclusion criteria as defined in ethical approval for the study (see Appendix for the most common inclusion/exclusion criteria).</li>
		<li>Ask the participant to fill in the Participant information sheet (including all the relevant information such as age, gender, nicotine/alcohol consumption, etc.34).</li>
		<li>Follow&#160;the institutional review board ethical guidelines, and ask participant to sign informed consent. Use this opportunity to explain the basic aspects of the procedure they will undergo and answer any questions the participants may have.</li>
		<li>Depending on the study design, perform baseline cognitive assessment (memory and/or other cognitive functions).</li>
	</ol>
	</li>
	<li>tDCS set-up and stimulation
	<ol>
		<li>Seat the participant comfortably in a chair.</li>
		<li>Ask participant to fill out pre-tDCS sensations checklist and to report on overall state (i.e., current mood; freshness/tiredness - these can be assessed either as a single Likert-type item or using standardized questionnaires such as Brief Mood Introspection Scale35).</li>
		<li>Take head measures using a measuring tape.</li>
		<li>For locating the DLPFC or PPC follow the procedure described above (electrode placement). Write down the measures in the Protocol sheet for each participant. These can be used to check against when taking measurements in subsequent sessions.</li>
		<li>To increase conductance, move away participant&#39;s hair from stimulation site (use comb and hair bands for participants with long hair).</li>
		<li>Inspect for any signs of skin damage at the place of stimulation. Avoid positioning electrodes over damaged skin.</li>
		<li>Clean the surface of the skin where electrodes will be placed using alcohol-soaked cotton pads to remove grease, dirt, etc. and let it dry (use a makeup removal product if the participant has heavy makeup on the cheek).</li>
		<li>Put the silicon cap on the participant&#39;s head and secure it with the chinstrap. Do not make the cap tight (this will be done later).</li>
		<li>Soak the sponge pockets with saline solution and put the electrodes inside them. The sponges should be moist but not dripping; usually 10-15 mL of saline solution per sponge is enough. If the sponges are too dry this will cause high resistance and result in poor conductivity, even losing the circuit connection. 
		NOTE: Most of the tDCS devices have the resistance indicators; however, the sponges should be occasionally inspected for moisture. On the other hand, if the sponges are excessively wet it can cause the current to shift across the head during stimulation. It is recommend having sponges medium wet and use a syringe to add more saline solution during the experiment if the sponges become too dry.</li>
		<li>Put the sponge electrode under the silicon straps and position the center of the target electrode on the marked head-location. Set the return electrode on the contralateral cheek. Use the silicon straps to adjust the cap to the participant&#39;s head-size and shape. The cap should be tight so the electrodes cannot move, but still comfortable for the participant.</li>
		<li>Turn on the stimulator, select and run predefined tDCS protocol (active anodal stimulation or sham).</li>
		<li>Ask the participant to relax and let them report how they feel during the first few minutes of stimulation (1-3 minutes). Explain that the sensations will slowly fade away as they get used to it or when they start focusing their attention on some other activity.</li>
		<li>To avoid unstructured activities that can interfere with the stimulation effects, use light cognitive engagement during tDCS. For example, participants can perform practice trials of cognitive tasks or engage in easy memory games during stimulation (starting after 3-5 minutes of stimulation). This type of cognitive engagement during stimulation has the potential to promote tDCS effects and will help participants to keep the mind off the tDCS-induced skin sensations.</li>
		<li>Ask the participant to report how they feel multiple times during stimulation (e.g., to report the level of unpleasantness on a 10-point scale every 5 minutes of stimulation, 1 - completely absent, 10 - very intensive). Higher levels of unpleasantness (&#62;6) could be expected during fade-in fade-out periods in some participants. If the level of unpleasantness remains high after 5 minutes abort the stimulation.</li>
		<li>After the pre-defined protocol run has elapsed, turn off the stimulator.</li>
		<li>Remove the sponge electrodes first, and then remove the silicon cap.</li>
		<li>Ask the participant to fill out post-tDCS sensations checklist and to report for any side effects not already listed.</li>
		<li>Clean the skin on the places where it was marked and inspect the skin for any changes. If there is a skin reaction (e.g., local vasodilation i.e., skin redness on the cheek), monitor as it fades away as it is usually a transient reaction in participants with sensitive skin, and should disappear within 10-15 minutes.</li>
	</ol>
	</li>
	<li>Memory assessment
	<ol>
		<li>To standardize the assessment across participants, use computerized assessment tools i.e., memory tasks with automatic scoring. Several WM tasks (e.g., verbal and spatial 3-back task) and AM tasks (verbal paired learning; face-word cued recall, object location, etc.) can be found here: https://osf.io/f28ak/?view_only=f8d5e8dd71d24127b3668ac3d8769408</li>
		<li>To evaluate the specificity of tDCS effects on memory it is advisable to include control task(s) i.e., tasks tapping other cognitive or motor function.</li>
	</ol>
	</li>
	<li>Ending the experimental session/study
	<ol>
		<li>After the (last) experimental session in the study ask participant to try to guess the sessions in which they have received real and sham stimulation. Note all responses and see whether obtained proportions are higher than chance probability. If not, the blinding was successful. If participants were able to differentiate real from sham stimulation analyze the data for those that guessed correctly and those that did not to check if the unsuccessful blinding affected the tDCS effects.</li>
		<li>In line with ethical guidelines, debrief the participants in detail after their involvement is completed.</li>
	</ol>
	</li>
	<li>After the experimental session
	<ol>
		<li>Wash the sponges with running water and soap so that the saline solution is fully washed away. Let the sponges to dry completely before putting them away.</li>
		<li>Use warm water and alcohol to clean all reusable materials including comb, silicone cap and measuring tape.</li>
		<li>Make notes on all unusual, unexpected, or unplanned events that might have happened during the session - including any equipment malfunctions, relevant comments made by the participant, interruptions, etc.</li>
	</ol>
	</li>
</ol>

Authors have no conflicting interests to disclose

The outcome of the tDCS study on memory depends on number of factors, and some of which e.g., homogeneity/heterogeneity of the sample, sufficient statistical power, the difficulty of the memory tasks and motivation of the participants have been previously discussed (see Berryhill, 2014). Several excellent papers on tDCS method, as well as more general tutorials on the application of tDCS to study cognitive functions are available and can be well applied to the memory research too (see17,43,44,45,46,47). Here we will focus on the aspects of the protocol which, based on our experience, are relevant but often overlooked or not discussed in sufficient detail elsewhere.
Placement of the return electrode. It is important to keep in mind that the return electrode is not passive but negative-polarity terminal (i.e., cathode). Therefore, it can induce physiological effects that are opposite to the target electrode. Furthermore, the current flow, depends on the positioning of the return as much as it depends on the target electrode. Moreover, since the current flows along the path of the least resistance, if the anode and cathode are located too close to each other, the current may flow only over the skin surface and/or through the cerebrospinal fluid between the electrodes, thus leaving the cortical tissue unaffected. For these reasons, the careful choice of the return electrode is as relevant as the position of the target electrode. There is meta-analytic evidence to suggest that extracranial cathodes are more likely to produce significant effects48. Positioning of the return electrode on contralateral cheek for memory enhancement was based on current flow modeling and selected to avoid potential confounding effects of generating negative polarity over function-irrelevant brain areas. The positioning of return electrode on the contralateral cheek has successfully been used in previous WM studies (see36,37,38,49, as well as in AM studies27,39,40), and has been highlighted as a good choice for tDCS montages aiming to modulate other cognitive functions as well45.
Blinding. In single blind experiments, to ensure blinding of the participant, the position of the stimulator and/or monitoring display should be out of participant&#39;s sight. This is especially important when using stimulators that have lights indicating when the unit is on and/or delivering current. For double-blind designs (when both participant and experimenter are unaware of the protocol which is administered), one should use the double-blind option, or similar option that is available for a given device. If such option is not available, the good practice is to have two-experimenter procedure. That is, one experimenter comes in only to run the stimulation protocol, while the other experimenter who runs the participant through the experiment, including the subsequent memory task and analyzes the data, leaves the room just before and during the stimulation. By methodological standards, double-blind experiments are preferred to the single-blind designs because they reduce the bias or the &#34;experimenter&#34; effects. This is highly relevant when conducting clinical trials and/or using the interview-based assessments of cognitive functions. However, blinding of the experimenter is less of an issue when participants are highly motivated to maximize their performance (which is mostly the case in memory assessment or cognitive enhancement in general), and when the task is administrated as well as scored automatically (i.e., when experimenter has little to no intervention in the assessment phase).
Activity during tDCS. Authors of tDCS papers rarely report on what were the participants doing during stimulation. When the activity is not reported it is usually implied that the participants were instructed to sit comfortably and relax. However, the absence of structured activity represents source of the uncontrollable &#34;noise&#34; in the experiments. Namely, 20 minutes is rather long time, so some participants may use the time to relax (with possibility to even fall asleep) while others may focus on tDCS sensations or start ruminating or excessively thinking about some tDCS unrelated topics. There is evidence to suggest that function-relevant but not tiring activity performed during tDCS has the potential to promote tDCS effects50. For these reasons, in our experiments, participants perform either practice trials of the memory tasks to be used as outcome measures or similar memory tasks. Practice trials are good choice because they engage the same neural networks as the target function but are easier and therefore not frustrating or tiring for the participants. Besides that, performing practice trials during stimulation is economical in a sense that it cuts down the testing time following tDCS, which comes as a benefit especially when the study design includes multiple tasks to be completed post-tDCS. However, the practice trials are usually much shorter than 20 minutes, thus alternative activity needs to be presented too. For this purpose, we have used common memory games40, that keep the participants focused, help them pass the time and keep the mind off the tDCS induced sensations and make them overall more comfortable in the testing setting. A few things to keep in mind when choosing the memory task to be performed during tDCS are that the task should not be difficult but also not boring (adaptive tasks set at 80% success rate are good in this context); the task should not have the material that might interfere with subsequent memory assessment (e.g., when assessing memory for faces and words, one can use abstract images/shapes pairs). Another important issue is the duration of the &#34;habituation period&#34; i.e., how long after the beginning of stimulation should participants start to perform the &#34;distraction activity&#34;. There are individual differences in the intensity of the sensation and habituation times, but majority of participants will be ready to start the activity after 3-5 minutes of stimulation.
Cutaneous sensations. Some participants may be more sensitive to cutaneous tDCS effects, thus reporting elevated levels of discomfort, although this does not happen very often. It is important to inform participants about potential sensations they might experience prior the experiment. If someone is afraid of the procedure, we often let participants &#34;feel&#34; the current on their hand before putting the sponges on their head. The participants should be continuously monitored and asked to provide feedback on their level of comfort and sensations at regular intervals. If the participant reports increased level of discomfort, always offer to abort the experiment. It is essential that the participants are aware that the stimulation can be stopped at any time if they ask. If participant decides to stop the stimulation, the current should be slowly turned down (abrupt cancelation of the stimulation protocol may induce even stronger sensations). It is often recommended that in the case of unpleasant sensations the current intensity is temporarily lowered to the highest comfortable level, until participant adjusts, and then gradually returned to the target intensity. This seems like an appropriate alternative to stopping the stimulation protocol, especially if tDCS is used in clinical setting. However, when tDCS is used for the research purposes, and especially in relatively small samples, it is essential that all participants undergo the same procedure. Therefore, stopping the experiment is preferred to lowering the intensity of the stimulation for some participants for some time.
Reporting tDCS methodology and monitoring for potential confounds. The tDCS research field is highly heterogeneous regarding methods and measures, thus it is important to clearly report all aspects of the tDCS procedure, including blinding procedure and assessment; the head-positioning of the target as well as the position of the return electrode; the size and shape of the electrodes; type of conducting substance used (saline or gel); the current intensity (mA) and density (mA/cm2) as well as the duration of fade-in/out period; the impedance levels if measured; the duration of the stimulation (including the fade-in/out period); the detailed account of the activities participants were engaged in during the stimulation; the timing and the duration of the cognitive tasks following the stimulation (including break-times, if any). This type of information facilitates standardization and systematic analysis of the published studies (see recent review for example51). The aspects that are rarely reported on are the effect of potentially moderating/confounding variables such as time of the day of tDCS session, level of tiredness/mood reported by the participants, successfulness of blinding (i.e., beliefs about the type of stimulation they are receiving), the order of experimental sessions in within-subject designs, etc. Most of these variables have been reported to modulate the effects of tDCS, but their effect remains understudied and inconsistently reported. Therefore, tDCS studies should ensure to collect and report on any potentially confounding variables; for details on good practices see Tables 10A, 10B, 11 by Antal and colleagues34.
Application of the described protocol for anodal tDCS either in its standard or, even more, in its advanced form (i.e., oscillatory-modulated tDCS) provides a mean not only for enhancement of memory functions (and prospective use in clinical populations), but also allows for investigation of the neurobiology of the functional neural networks behind these functions.

Memory plays a vital role in everyday functioning as it enables one to remember information about people and places, recall past events, learn new facts and skills, as well as to make judgments and decisions. Here we focus on two types of memory - working memory (WM) and associative memory (AM). WM provide us with the ability to temporarily maintain and store information for ongoing cognitive processing1, while AM enables us to remember multiple pieces of experience or information bound together. Therefore, these two types of memory underline almost all daily activities. Unfortunately, memory is one of the most vulnerable functions as it declines with normal ageing as well as due to various pathological states and conditions. Both WM and AM decline is prominent in mild cognitive impairment2,3 and dementia4,5 as well as in normal ageing6,7. Since memory deficits are associated with a high disease burden level8,9 and significantly affect quality of life10,11,12,13, there is a growing need for novel approaches to prevention and treatment of memory decline.
Transcranial direct current stimulation (tDCS) is a promising tool for tackling memory decline14,15,16 and gaining better understanding of brain functions in general17. tDCS is a non-invasive brain stimulation technique that uses weak electric currents (usually between 1 mA and 2 mA) to modulate brain activity by affecting neuronal membrane excitability. The effects of tDCS are polarity-dependent, such that anodal stimulation increases while cathodal decreases neuronal excitability. Namely, anodal tDCS increases the likelihood for action potentials to fire through depolarization of neuronal membranes, thus facilitating spontaneous brain activity under the anode18. Moreover, it is shown that the effect of increased activation does not remain localized but tends to spread to other functionally connected areas of the central nervous system. Anodal tDCS is thus expected to promote cognitive functions that rely on targeted brain regions and functionally interconnected brain areas, while cathodal tDCS is expected to have the opposite effect.
The tDCS has several advantages over other brain stimulation techniques: (1) tDCS is safe, i.e., does not pose health risks and does not produce any negative short or long term structural or functional changes19; (2) tDCS is characterized by highest tolerability among brain stimulation techniques as it causes minimal discomfort to participants in a form of a mild tingling and itching sensations under the stimulating electrodes20; (3) tDCS is cost-effective - the price of tDCS devices and application are ten to hundred times lower than other treatment options, which makes it attractive for patients and healthcare system; (4) tDCS is easy to use, and therefore has a high potential to be applied even in home-based settings, which can lead to higher compliance of patients and reduced cost for medical staff and facilities.
The main challenges for using tDCS for memory enhancement are finding the optimal electrode montage and stimulation protocol that will produce reliable effects on memory. Here we use the term electrode montage to refer to the configuration and the positions of the electrodes (i.e., the placement of the target and reference (return) electrode). Due to the nature of the electrical fields, the reference (return) electrode is not neutral - it has the polarity opposite to the target electrode - and thus can also exercise biological (neuromodulatory) effects on the underlying neural tissue. Therefore, careful choice of the reference electrode is essential for avoiding unwanted additional effects of the stimulation.
When using the term stimulation protocol, we refer to the tDCS parameters such as the duration and the intensity of the current being applied as well as the way current intensity changes over time (i.e., whether the intensity is constant throughout the stimulation or changes following a sinusoidal waveform with certain amplitude and frequency). Different stimulation protocols can be applied using the same electrode montage, and the same protocol can be used across different montages.
To optimize the electrode montage, we look at the function-relevant brain areas and how the electric fields induced by various positions of the electrodes would affect those brain areas and consequentially cognitive functions. Several different cortical and subcortical structures play a significant role in memory functions - including areas of the frontal, temporal, and parietal cortex. Namely, WM is supported by a widespread neural network that includes dorsolateral (DLPFC) and ventral lateral prefrontal cortex (VLPFC), premotor and supplementary motor cortices, as well as posterior parietal cortex (PPC)21. For AM and episodic memory in general, structures within medial temporal lobe are essential22. However, associative areas of the parietal, frontal, and temporal cortices, with their convergent pathways to the hippocampus also play a significant role. Due to its anatomical position, the hippocampus cannot be directly stimulated using tDCS, and thus the enhancement of hippocampus-dependent memory functions is done using the cortical targets with high functional connectivity to hippocampus such as posterior parietal cortex. For these reasons, DLPFC and PPC are most frequently used as stimulation targets to enhance memory. Positioning of the electrodes can be further refined based on current flow modeling23 and validated in studies that combine tDCS with neuroimaging techniques24.
The most usual stimulation protocol is a constant anodal current of 1-2 mA that lasts between 10-30 minutes. The assumed mechanism behind this protocol is that the electrode with a positive charge will increase the excitability of the underlying cortical tissue which will than result in enhanced subsequent memory performance. Unlike the constant anodal tDCS, where current intensity stays the same during the whole stimulation period, in the oscillatory tDCS protocol the intensity of the current fluctuates at the given frequency around a set value. Therefore, this type of protocol modulates not only excitability but also entrains neural oscillations of the relevant brain areas. It is important to note that for both constant and oscillatory tDCS the electrodes retain the same current polarity for the whole duration of the stimulation.
Here we present tDCS montages that target nodes within fronto-parieto-hippocampal network to promote memory - both WM and AM: specifically, two electrode montages with the target electrode over either left/right DLPFC or left/right PPC. In addition to constant anodal tDCS protocol we outline a theta oscillatory tDCS protocol.
Study design 
Before providing a detailed guide on how to use tDCS for memory enhancement, we will outline a few essential properties of the experimental design that are important to consider when planning a tDCS study on memory.
Sham control 
To assess the effects of tDCS on memory, the study needs to be sham controlled. This implies that in one of the experimental conditions the protocol resembles a real stimulation session, but no treatment is given. This fake or sham session serves as a reference point to compare performance following real tDCS and make inferences about its effectiveness. Commonly, in the sham protocol the current is applied only for a brief period - usually up to 60 seconds at the beginning and at the end of the sham stimulation as a ramp-up followed by immediate ramp-down (i.e., fade-in/fade-out, up to 30 seconds each) fashion. This way it is ensured that the duration of the stimulation is insufficient to produce any behavioral or physiological effects. Since local skin/scalp sensations are usually most pronounced at the beginning and at the end of stimulation (due to changes in the current intensity), the sensations induced in all protocols are comparable and difficult to distinguish25. This way, the participant is blinded on whether the stimulation is real or not, which is especially important in within-subject designs.
In addition to sham-control, to assess the specificity of the effects of oscillatory protocols, it is advisable to have an active control condition, too. For instance, the active control for oscillatory protocol can be constant anodal stimulation of the same intensity26,27, or oscillatory stimulation in different frequency e.g. theta vs gamma28.
Within- or between-subjects design. 
In within-subjects design each participant undergoes both real and sham tDCS, while in between-subjects design one group of participants receives real, and the other group receives sham tDCS. The main advantage of within-subject design is better control of subject-specific confounds. That is, individual differences in anatomy and cognitive abilities are best controlled for when each participant is compared to their self. However, since within-subject design needs to be applied in cross-over fashion (i.e., half of the participants receive real tDCS in the first session and sham in the second session, while the other half of participants receive sham first and real tDCS second) this design may not be optimal for clinical and training studies as well as studies involving several tDCS sessions over consecutive days, because crossover design may result in unequal baselines between crossover arms. Therefore, within-subject design is suited the best when assessing either behavioral or physiological effects of a single tDCS session, and when unequal baselines are not considered an issue for the research hypothesis. In within-subject design assessing the effects of single tDCS session, it is a good practice to keep 7 days between real and sham tDCS session to avoid carryover effects (however some studies suggest even shorter wash-out periods do not significantly affect the outcomes29,30) and to use parallel forms of memory tasks in counterbalanced order to minimize training and between-session learning effects.
When between-subjects design is used, the control group should be carefully matched for baseline performance, as well as other relevant characteristics known to be of relevance for tDCS effectiveness. Random group assignment may not be the best approach in small sample sizes (e.g., &#60;100) as it may lead to suboptimal matching. In either case, baseline performance should be accounted for in statistical analysis.
Sample size. 
One of frequently asked questions is &#34;how many participants does one need to detect tDCS effects&#34;. The answer to this question depends on several aspects of the study including experimental design, expected effects sizes, type of statistical analysis, etc. The sample sizes in the brain stimulation experiments are often too small, and it is estimated that studies in this field miss around 50% of true positive results because they are underpowered31. Power analysis enables determining adequate sample size for each specific experiment based on the study design and expected effect size for planned statistical analysis. The power analysis can be performed in R environment or using free specialized software such as G*Power32, and it should always be performed a priori (i.e., before the experiment). The power should be set at &#62;.80 (ideally .95) and expected effect size on memory tasks following a single tDCS session is usually between .15-.20 (&#951;2) i.e., Cohen f 0.42-0.50. Therefore, one typically needs to enroll 20-30 participants in total for within-subject experiment and 30-40 participants per group for between-subject study, to achieve satisfactory power and thus diminish type II error. However, the sample size depends on the number of other factors including the planned analysis, and sensitivity of the behavior measures that are used. Therefore ideally, one would run an initial experiment to understand the effect sizes for the specific design and use those data as an input for power analysis. However, it is important to note that running a pilot experiment on just a few participants will lead to faulty and unreliable estimates of the effect sizes. Therefore, if resources are limited it is better to rely on the previous studies with comparable outcomes, and take slightly more conservative approach i.e., by estimating for somewhat smaller effect sizes than reported in the literature.
Outcome measures 
To assess the effectiveness of tDCS on memory one needs to select adequate behavioral tasks. In fact, the choice of the memory task is one of the crucial aspects of the study design, because the ability to detect the tDCS effect directly depends on the sensitivity of the task. The challenge here is that most standardized memory assessment tools or classical neuropsychological tasks may not be sensitive enough to detect tDCS effects in specific populations. Furthermore, most of the standardized tasks are not available in two or more parallel forms and therefore cannot be used in within-subjects designs. For that reason, most of the tDCS memory studies use custom-build tasks. When designing or selecting outcome measure one should ensure that the task is: (1) focal/selective measure of the memory function of interest; (2) sensitive (i.e., that the scale is fine enough to detect even small changes); (3) challenging for the participants (i.e., that the task difficulty is sufficient and thus to avoid celling effects); (4) reliable (i.e., that the measurement error is minimized as much as possible). Therefore, one should use empirically validated strictly parallel forms of memory tasks, which have a sufficient number of trials - both to ensure sensitivity of the measure as well as to maximize its reliability. Ideally, the tasks should be pre-tested on a group sampled from the same population as the experiment participants to ensure that maximum performance is not achievable, and that the task-forms have equal indices of difficulty. Finally, it is best to use computerized tasks whenever possible as they allow for controlled duration and precise timing. This way researchers can ensure that all participants undergo memory assessment at the same time in respect to the timing of stimulation (either during or following tDCS). The duration of each task or task block should not be longer than 10 minutes, to avoid fatigue and fluctuation in attention levels; the cognitive assessment should not be longer than 90 minutes in total (including tasks both during and after tDCS).

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
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			<td>Adjustable silicone cap</td>
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			<td>Alcohol</td>
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			<td>Comb</td>
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			<td>Cotton pads</td>
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			<td>Measuring tape</td>
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			<td>Rubber electrodes</td>
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			<td>Saline solution</td>
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			<td>Single-use mini silicon hair bands</td>
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			<td>Skin marker</td>
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			<td>Sponge pockets</td>
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			<td>Syringe</td>
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			<td>tDCS device</td>
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</table>

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.

The described protocol has been successfully used to enhance memory performance in several studies in our laboratory. However, similar protocols have been used in other research laboratories as well (e.g., see36,37).
When it comes to working memory, our results have shown that 20-minutes of right frontal tDCS (F4 location; constant current of 1.8 mA) enhanced verbal WM, while the same stimulation protocol applied over left parietal cortex (P3 location) resulted in better spatial WM performance. In contrast, no significant effects were found when the same stimulation protocol was applied over the left frontal (F3) and right parietal (P4) cortices. Figure 4 shows the representative results of modeling of the electric field generated by tDCS as well as the performance measures following active and sham tDCS based on the data reported in &#381;ivanovi&#263; et al., 202138.
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/62681/62681fig04.jpg" /> 
Figure 4: (A) Effects of constant anodal tDCS of left PPC (P3-contralateral cheek montage) on spatial working memory performance (spatial 3-back task); (B) Effects of constant anodal tDCS of right DLPFC (F4-contralateral cheek montage) on verbal WM performance (verbal 3-back task). The figure shows simulation of electric fields induced by tDCS, outline of the task trials, and the within-subjects performance across active and sham condition (the values are centered to the order of the session to account for counterbalancing i.e., positive values indicate above-average performance, while negative values indicate below average performance at session). The simulation of local electric fields generated by the electrode set up is performed using COMETS2 MATLAB toolbox 41. <a href="https://www.jove.com/files/ftp_upload/62681/62681fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
The effects of parietal tDCS on associative memory have been consistent and robust. That is, in the series of within-subject experiments we have shown that 20 minutes of tDCS over left PPC (P3 location; constant current of 1.5 mA) improves memory for face-word associations27,39,40. Figure 5 shows representative task and results. In addition, comparable effects were observed on AM task assessing the object-location associations when right PPC (P4 location) is stimulated using the same constant tDCS protocol40.
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/62681/62681fig05.jpg" /> 
Figure 5: Effects of constant anodal tDCS of left PPC (P3-contralateral cheek montage) on associative memory performance (A) Face-word pairs task; (B) Effects of constant anodal tDCS of left PPC (P3-contralateral cheek montage) on associative memory performance (proportion of correctly recalled words on cue). <a href="https://www.jove.com/files/ftp_upload/62681/62681fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
The more advanced protocols such as theta-oscillatory tDCS have been less extensively studied, however the study by Lang and colleagues26 as well as recent study conducted in our laboratory27 showed improvement in face-word AM following theta-oscillatory tDCS protocol in comparison to sham. The animated figure shows simulation of the electric field induced by theta oscillatory tDCS over left PPC.
Video 1. <a href="https://www.jove.com/files/ftp_upload/62681/Video1.mp4" target="_blank">Please click here to download this Video.</a>
Appendix.&#160;<a href="https://www.jove.com/files/ftp_upload/62681/Appendix.zip" target="_blank">Please click here to download these files.</a>

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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.

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-for-memory-enhancement

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13.2K Views.  University of Belgrade. 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. 

Video: Transcranial Direct Current Stimulation tDCS for Memory Enhancement

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 ...

Using Affordable LED Arrays for Photo-Stimulation of Neurons

Standard slice electrophysiology has allowed researchers to probe individual components of neural circuitry by recording electrical responses of single cells in response to electrical or pharmacological manipulations1,2. With the invention of methods to optically control genetically targeted neurons (optogenetics), researchers now have an unprecedented level of control over specific groups of neurons in the standard slice preparation. In particular, photosensitive channelrhodopsin-2 (ChR2) allows researchers to activate neurons with light3,4. By combining careful calibration of LED-based photostimulation of ChR2 with standard slice electrophysiology, we are able to probe with greater detail the role of adult-born interneurons in the olfactory bulb, the first central relay of the olfactory system. Using viral expression of ChR2-YFP specifically in adult-born neurons, we can selectively control young adult-born neurons in a milieu of older and mature neurons. Our optical control uses a simple and inexpensive LED system, and we show how this system can be calibrated to understand how much light is needed to evoke spiking activity in single neurons. Hence, brief flashes of blue light can remotely control the firing pattern of ChR2-transduced newborn cells.

Adult-born neurons expressing ChR2 can be manipulated in slice electrophysiological preparations in order to examine their contribution towards the function of olfactory neural circuits.

Standard slice electrophysiology has allowed researchers to probe individual components of neural circuitry by recording electrical responses of single ...

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 ...

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.

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 ...

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 ...

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.