Name: High-Definition Transcranial Direct Current Stimulation During Sleep (Video) | JoVE Journal
Uploaded: 2025-12-05T12:45:00.000+00:00
Duration: 9 min 23 s
Description: Learn high-definition transcranial direct current stimulation during sleep with simultaneous EEG monitoring. This method investigates causal relationships between targeted brain regions and sleep physiology.

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5 minutes

We gratefully acknowledge the Beth Israel Deaconess Medical Center Clinical Research Coordinator Core Facility (RRID:SCR_027579) for their invaluable support of this work, including dedicated research space and infrastructure. We also thank the Core for their generous support that enabled the publication of this manuscript.

The study was approved and conducted following our institute&#39;s ethical guidelines. Informed consent with full explanations about the procedures, risks, and benefits was obtained from the participants of the study.
1. Contraindications and safety considerations
<ol>
	<li>Prior to experimental set-up, confirm that the participant does not have any contraindications for HD-tDCS based on current safety guidelines16,17 (Table 1).</li>
	<li>Inspect the participant&#39;s scalp thoroughly for skin lesions. Avoid stimulating areas with damage or inflammation.</li>
	<li>Review the participant&#39;s medications, as central nervous system-acting drugs might alter the effects of stimulation.</li>
	<li>Procure informed consent with full explanations about the procedures, risks, and benefits.</li>
	<li>Screen baseline symptoms16 for pre-existing symptoms that might be confused with stimulation-related effects16,17. These include: headache, scalp discomfort, tingling, itching, burning sensation, skin redness, sleepiness, trouble concentrating, and mood changes.</li>
</ol>
2. Equipment preparation
NOTE: This protocol describes the use of separate, independent devices for HD-tDCS and EEG recording (Figure 1). Some commercially available systems integrate both stimulation and recording capabilities within a single device. Users of such integrated systems should consult manufacturer-specific instructions.
<ol>
	<li>Gather all necessary equipment and materials (Table 2, Figure 2, and Figure 3).</li>
	<li>Ensure the conventional tDCS device has an adequate power supply.
	<ol>
		<li>Turn on both devices and check the power status according to the manufacturer&#39;s specifications.</li>
		<li>For battery-powered devices: If low battery indicators illuminate, replace batteries (for user-replaceable systems) or recharge the device (for integrated battery systems).</li>
		<li>For software-controlled devices: Verify power status through the control interface.</li>
		<li>For mains-powered devices: Ensure proper connection to the power outlet with appropriate medical-grade isolation.</li>
	</ol>
	</li>
	<li>Inspect all electrodes for signs of unusual wear or damage.
	<ol>
		<li>For Ag/AgCl sintered ring electrodes: Check for deposits of electrolysis products on the electrode surface.</li>
		<li>For carbon rubber electrodes: Check for cracks, brittleness, or uneven wear.</li>
		<li>For disposable electrodes: Verify they have not exceeded single-use or recommended usage limits.</li>
		<li>Replace any damaged or excessively used electrodes following the manufacturer&#39;s guidelines for replacement frequency.</li>
	</ol>
	</li>
	<li>Connect the cables of the Ag/AgCl sintered ring electrodes to the matching receivers on the 4 x 1 adapter output cable.
	<ol>
		<li>Connect the center electrode lead to the center receiver plug.</li>
		<li>Connect the remaining electrodes to the surrounding plugs.</li>
	</ol>
	</li>
</ol>
3. EEG cap and HD-tDCS electrode preparation (Figure 2 and Figure 3)
<ol>
	<li>Select the appropriate size EEG cap for the participant based on the head circumference. Refer to the manufacturer&#39;s manual for the EEG cap size selection.</li>
	<li>Determine HD-tDCS electrode polarity configuration based on study objectives. For anodal stimulation, the center electrode serves as the anode (positive) with the surrounding electrodes as cathodes (negative). For cathodal stimulation, the center electrode serves as the cathode (negative) with the surrounding electrodes as anodes (positive). Common placements (and expected brain targets) include:
	<ol>
		<li>Use the bilateral frontolateral (F3/F4) placement to target the prefrontal cortex6.</li>
		<li>Use the central (Cz) placement to target sensorimotor areas18.</li>
		<li>Use the occipital (Oz) placement to target the visual cortex19.</li>
		<li>Use the parietal (P3/P4) to target association cortices20.</li>
		<li>Optional) Use computational field modeling to visualize and optimize current distribution ( Figure 4):
		<ol>
			<li>Obtain the participant&#39;s structural MRI if available, or use a standard head model.</li>
			<li>Use field modeling software (e.g., SIMNIBS, ROAST, or manufacturer-specific tools like HD-Explore) to simulate current flow21,22.</li>
			<li>Input electrode positions and stimulation parameters (current intensity, polarity).</li>
			<li>Evaluate the predicted field distribution to ensure adequate targeting of the intended region of interest.</li>
			<li>Adjust the electrode positions as needed to optimize field focality and intensity at the target.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Remove the EEG recording electrodes at the chosen stimulation location from the EEG cap. This allows the HD-tDCS stimulation electrodes to occupy these positions so that they have direct scalp contact through the same openings in the cap. The removed EEG electrodes cannot record meaningful data from these locations during stimulation due to saturation from the stimulation current.</li>
	<li>Insert the HD-tDCS electrodes or electrode holders into the cap (Figure 2). 
	&#8203;NOTE: Some HD-tDCS systems use electrodes that are directly inserted into the cap without separate holders. Follow manufacturer-specific instructions.
	<ol>
		<li>For systems with electrode holders: Position and secure the holders so that the side containing a cap faces the EEG cap&#39;s exterior and the opposite side (lacking a cap) faces the EEG cap&#39;s interior, such that it will contact the participant&#39;s scalp.</li>
		<li>For systems with direct-insertion electrodes: Follow manufacturer guidelines for proper electrode orientation and securing mechanism.</li>
	</ol>
	</li>
	<li>Apply adhesive conductive paste (high viscosity, chloride-free; Ten-20) paste to prepare the EEG cap, as recommended by the manufacturer.
	<ol>
		<li>Reverse the EEG cap inside-out and place it on a foam head.</li>
		<li>Flatten any wrinkles in the fabric of the cap.</li>
		<li>Using a tongue depressor, cover the EEG electrodes with paste. Do not use paste on HD-tDCS stimulation electrodes.</li>
		<li>Shape the paste into domes. Apply less paste in the front where there is less hair and more at the crown and back of the head.</li>
		<li>Avoid applying too much paste to each electrode site and getting paste on the fabric, as excessive spillage can cause bridging.</li>
	</ol>
	</li>
</ol>
4. Participant set-up
<ol>
	<li>Seat the participant comfortably in a chair.</li>
	<li>Apply the facial and ground reference electrodes with adhesive conductive paste using gold cup electrodes. Secure the electrodes with medical-grade tape.
	<ol>
		<li>Clean sites with an alcohol swab, exfoliate with mildly abrasive preparation gel (e.g., Nuprep) on a cotton swab (e.g., Q-tip), and remove all fluids with a dry gauze square. Electrode sites follow standard polysomnography montage requirements for sleep staging according to American Academy of Sleep Medicine (AASM) criteria23 and include: 
		Reference (forehead); serve as reference electrodes 
		A1/A2 (mastoids, bone behind ears); serve as reference electrodes. 
		LOC/ROC (right and left outer canthi near eyes, right raised, left lowered); record eye movements. 
		EMGs (2 on chin); record muscle tone for distinguishing sleep stages. 
		&#8203;Ground (clavicle/collar bone); stabilizes the amplifier and reduces common-mode noise.</li>
		<li>Fill electrodes with adhesive conductive paste and apply to the site while avoiding exposing the paste on the back of the electrode.</li>
		<li>For the HD-tDCS return electrode, place the relevant stimulation electrode on the collar bone and secure it with tape. Apply saline solution or gel per the manufacturer&#39;s specifications.</li>
	</ol>
	</li>
	<li>Locate and mark the central point for EEG cap placement.
	<ol>
		<li>First, localize the vertex (Cz).
		<ol>
			<li>Measure the distance from the nasion (junction of the forehead and nasal bones) to the inion (most prominent point of the occipital bone). Mark the halfway point with a line.</li>
			<li>Measure the distance between the left and right pre-auricular points. Mark the halfway point with a line.</li>
			<li>Cz lies at the intersection of these lines. Lightly spray the hair with water using a spray bottle ( Figure 3) to facilitate EEG cap placement.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Invert the prepared EEG cap snugly and comfortably on the participant&#39;s head, targeting the Cz electrode with the marked Cz site. Secure the EEG cap on the participant&#39;s head with the chin straps.</li>
	<li>Using a syringe, fill the electrode sites with conductive gel (e.g., e-gel).
	<ol>
		<li>Pull up the electrode slightly and insert the large-gauge, blunt-tip needle tip into the center of the electrode. Gently wiggle the needle to move hair out of the way and apply conductive gel (~0.5 mL). Gently push the electrode down to ensure a strong connection between the gel, adhesive conductive paste, and scalp.</li>
		<li>Avoid spreading gel beyond the circumference of the electrode site to prevent shunting of current.</li>
		<li>Apply more conductive gel on the crown and back of the head to compensate for the higher density of hair.</li>
		<li>Press each electrode down against the scalp.</li>
	</ol>
	</li>
	<li>Position the Ag/AgCl sintered ring electrodes in each HD-tDCS electrode holder ( Figure 2, right panel).
	<ol>
		<li>Place with the rough surface facing down and the smooth, rounded surface facing up.</li>
		<li>Lower the ring electrode until it rests on the base of the holder.</li>
		<li>Add more high-viscosity conductive gel (e.g., HD-gel) to cover the electrode.</li>
		<li>Use the caps provided to lock the electrodes in place.</li>
	</ol>
	</li>
</ol>
5. HD-EEG system setup
<ol>
	<li>Prepare the appropriate software for the recording computer.</li>
	<li>If a high-density headbox (or similar hardware) is involved, ensure all electrodes are connected to the appropriate amplifiers. This stage may involve using a fiber-optic connector cable, and variations may exist in the set-up of the recording hardware.</li>
	<li>Do not plug in the stimulation electrodes at this stage.</li>
	<li>Turn on the amplifier and launch the EEG recording software.
	<ol>
		<li>After creating a new study file, select the profile option appropriate for a high-density montage.</li>
		<li>Verify the destination for file storage and filters appropriate for the montage.</li>
	</ol>
	</li>
	<li>Check impedances.
	<ol>
		<li>Set the impedance limit to 25 k&#937; and aim for impedances below 10 k&#937;.</li>
		<li>For electrodes with high impedance, consider the following adjustments:
		<ol>
			<li>If all or most are high, check if all the electrodes are properly connected. Check the reference electrode and, if necessary, redo the reference electrodes.</li>
			<li>If all or most are unusually low, check that the ground is connected.</li>
			<li>If half are completely red, check the snugness of the cap and amplifier.</li>
			<li>If an individual electrode is high, press down on the electrode. If the impedance remains high, add more conductive gel with the syringe, gently scrape the scalp with the syringe tip for the scalp electrode, or redo the facial electrode. If the problem persists or excess impedance is detected, check the connection between the cap, the connector, and the amplifier.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Begin recording EEG.</li>
	<li>Perform biocalibrations.
	<ol>
		<li>Ask the participant to open and close their eyes for ~10 s. Observe for alpha activity in most participants. Expect larger amplitudes at posterior channels than at anterior channels. Monitor for amplitude variations across the scalp.</li>
		<li>Ask the participant to look left, right, up, and down. Subsequently, ask the participant to clench their teeth. Observe movements in the eye and chin electrode recordings.</li>
		<li>Ask the participant to blink a few times. 
		&#8203;NOTE: Blink artifacts should appear as large deflections in the frontal electrodes (e.g., Fp1, Fp2), as these are closest to the eyes. Electrodes further from the eyes may show smaller deflections.</li>
		<li>Add additional biocalibrations as dictated by study protocol (e.g., respiration, limb movement, etc.)</li>
	</ol>
	</li>
</ol>
6. HD-tDCS stimulator set-up
<ol>
	<li>Prepare the HD-tDCS stimulation electrodes and stimulator. Connect the electrodes to the stimulator only after the following have been completed first.
	<ol>
		<li>Ensure that the stimulator is connected to a power outlet, or its batteries are fully charged and properly installed.</li>
		<li>Switch on the stimulator.</li>
	</ol>
	</li>
	<li>After the device is on, plug the electrode cable into the back of the device. 
	NOTE: Failure to turn the device on before plugging could lead to a mild shock. A long or specially ordered electrode cable may be necessary so that the stimulation can be triggered from the control room or location outside the sleeping space to decrease the likelihood of disrupting the participant&#39;s sleep.</li>
	<li>Set stimulation parameters based on study design. Settings include the intensity, waveform (this will be DC for tDCS protocols), duration, and ramp times. 
	NOTE: These parameters will vary depending on the intended target and physiology within the brain. Most devices also possess settings to separate stimulation and sham protocols. At this stage, the current distribution for the stimulation montage should be configured. For a typical 4 x 1 configuration, the center electrode receives 100% of the programmed current intensity, while this current is distributed across the four return electrodes (25% each).</li>
	<li>Set active stimulation or sham mode as per the study protocol. If the study involves blinding, appropriate steps are warranted to prevent participants or researchers from knowing which mode is being used. Some stimulators have built-in stimulation/sham functions to help with this.</li>
	<li>If the HD-tDCS electrodes exhibit high impedance (e.g., greater than 600 k&#937;), deliver a brief test stimulation (5-10 s at programmed intensity) under the SHAM setting to check the connectivity. Ideally, complete this prior to the participant falling asleep.
	<ol>
		<li>Under the SHAM setting, deliver the pulse. Expect to see the impedance drop 3-5 s after delivering the pulse. Once impedance reduction is confirmed, immediately abort the stimulation (total test duration should not exceed 10 s).</li>
		<li>Add more high-viscosity conductive gel and/or check the connections until the impedance falls to less than 20-25 k&#937; when a sham pulse is applied.</li>
	</ol>
	</li>
</ol>
7. Sleep monitoring and stimulation protocol
<ol>
	<li>Prepare the sleep environment.
	<ol>
		<li>Minimize ambient light and noise.</li>
		<li>Ensure the participant&#39;s reported comfort.</li>
		<li>Offer the participant earplugs.</li>
		<li>Mark the time in the EEG recording when the lights are turned off.</li>
	</ol>
	</li>
	<li>Monitor the EEG for sleep onset and specific stages to initiate the stimulation protocol based on the study design. Decisions regarding the stimulation protocol and its point of initiation should consider the duration/continuity of stimulation (i.e., continuous vs intermittent) as well as the targeted physiology/sleep architecture.</li>
	<li>Mark the start of stimulation in the EEG recording with an appropriate notation.</li>
	<li>If the participant awakens during stimulation:
	<ol>
		<li>Abort the stimulator.</li>
		<li>Mark the time point with an appropriate notation on the EEG recording.</li>
		<li>Monitor for the participant to return to the sleep stage of interest per study design and stimulation protocol.</li>
		<li>Resume the stimulation protocol as appropriate. If using an intermittent stimulation design, the aborted stimulation period is typically considered over, and the next stimulation would be the next one in the schedule (e.g., if Stimulation #3 is aborted, the protocol picks up with Stimulation #4 once resumed).</li>
		<li>Complete the stimulation protocol.
		<ol>
			<li>Once the final stimulation period ends, unplug the stimulation cord (connecting the HD-tDCS electrodes) from the stimulator before turning off the stimulator. 
			&#8203;NOTE: Again, failure to unplug before turning the device off could result in a minor shock, potentially waking the participant.</li>
			<li>Allow the participant to continue sleeping (as appropriate), undisturbed, depending on the study design.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
8. Session completion and equipment removal
<ol>
	<li>Wake the participant at the appropriate time.
	<ol>
		<li>Mark the time in the EEG recording when the lights are turned on.</li>
		<li>Gently wake the participant.</li>
	</ol>
	</li>
	<li>Stop the EEG recording.</li>
	<li>Disconnect the equipment.
	<ol>
		<li>Remove the caps from the HD-tDCS electrode holders.</li>
		<li>Gently remove the Ag/AgCl ring electrodes, using a blunt tool if necessary to avoid pulling on cables.</li>
		<li>Clean the electrodes with a damp paper towel and dry them for storage.</li>
	</ol>
	</li>
	<li>Remove the EEG cap and clean the electrode sites to remove the gels.</li>
	<li>Offer the participant cleaning products to remove gel from their hair and skin.</li>
	<li>Evaluate post-stimulation adverse event assessment (similar to the screen in step 1.5). Document severity (e.g., mild, moderate, or severe) and probable relationship to stimulation to compare responses to baseline screening. 
	NOTE: Most HD-tDCS adverse events are mild and transient, typically resolving within hours following stimulation16,17. If this is not the case, institutional protocols should be invoked for serious adverse events reporting.</li>
</ol>

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<li>da Silva, R., de, M. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Transcranial+direct+current+stimulation+in+obsessive-compulsive+disorder%3A+an+update+in+electric+field+modeling+and+investigations+for+optimal+electrode+montage%5BTitle%5D)+AND+%22Expert+Rev+Neurother%22%5BJournal%5D)">Transcranial direct current stimulation in obsessive-compulsive disorder: an update in electric field modeling and investigations for optimal electrode montage.</a> Expert Rev Neurother. 19 (10), 1025-1035 (2019).</li>
<li>Farnell Sharp, A., Witney, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Optimising+electrode+montages+in+conventional+transcranial+direct+current+stimulation+and+high-definition+transcranial+direct+current+stimulation+of+the+cerebellum+for+pain+modulation%5BTitle%5D)+AND+%22Brain+Sci%22%5BJournal%5D)">Optimising electrode montages in conventional transcranial direct current stimulation and high-definition transcranial direct current stimulation of the cerebellum for pain modulation.</a> Brain Sci. 15 (4), 344(2025).</li>
<li>Troester, M., et al. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aTroester%2C+M+%22The+AASM+Manual+for+the+Scoring+of+Sleep+and+Associated+Events%22">The AASM Manual for the Scoring of Sleep and Associated Events</a>. , American Academy of Sleep Medicine. Darien, IL. (2023).</li>
<li>Fertonani, A., Ferrari, C., Miniussi, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((What+do+you+feel+if+I+apply+transcranial+electric+stimulation%3F+safety%2C+sensations+and+secondary+induced+effects%5BTitle%5D)+AND+%22Clin+Neurophysiol%22%5BJournal%5D)">What do you feel if I apply transcranial electric stimulation? safety, sensations and secondary induced effects.</a> Clin Neurophysiol. 126 (11), 2181-2188 (2015).</li>
<li>Khorrampanah, M., Seyedarabi, H., Daneshvar, S., Farhoudi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Optimization+of+montages+and+electric+currents+in+tDCS%5BTitle%5D)+AND+%22Comput+Biol+Med%22%5BJournal%5D)">Optimization of montages and electric currents in tDCS.</a> Comput Biol Med. 125, 103998(2020).</li>
<li>Im, C., Lee, J., Kim, D., Jun, S. C., Seo, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Seeking+optimal+montage+for+single-pair+transcranial+direct+current+stimulation+using+Bayesian+optimization+and+Hyperband-A+feasibility+study%5BTitle%5D)+AND+%22Neuromodulation%22%5BJournal%5D)">Seeking optimal montage for single-pair transcranial direct current stimulation using Bayesian optimization and Hyperband-A feasibility study.</a> Neuromodulation. 28 (1), 86-94 (2025).</li>
<li>Alam, M., Truong, D. Q., Khadka, N., Bikson, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Spatial+and+polarity+precision+of+concentric+high-definition+transcranial+direct+current+stimulation+%28HD-tDCS%29%5BTitle%5D)+AND+%22Phys+Med+Biol%22%5BJournal%5D)">Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS).</a> Phys Med Biol. 61 (12), 4506-4521 (2016).</li>
<li>Khanmohammadi, R., Inanlu, M., Manesh, V. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Region-specific+cognitive+effects+of+HD-tDCS+in+older+adults%3A+M1%2C+DLPFC%2C+and+cerebellum%5BTitle%5D)+AND+%22Behav+Brain+Res%22%5BJournal%5D)">Region-specific cognitive effects of HD-tDCS in older adults: M1, DLPFC, and cerebellum.</a> Behav Brain Res. 486 (1), 115571(2025).</li>
<li>Batsikadze, G., Moliadze, V., Paulus, W., Kuo, M. -F., Nitsche, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Partially+non-linear+stimulation+intensity-dependent+effects+of+direct+current+stimulation+on+motor+cortex+excitability+in+humans%5BTitle%5D)+AND+%22J+Physiol%22%5BJournal%5D)">Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.</a> J Physiol. 591 (7), 1987-2000 (2013).</li>
<li>Lerner, O., Friedman, J., Frenkel-Toledo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+effect+of+high-definition+transcranial+direct+current+stimulation+intensity+on+motor+performance+in+healthy+adults%3A+a+randomized+controlled+trial%5BTitle%5D)+AND+%22J+Neuroeng+Rehabil%22%5BJournal%5D)">The effect of high-definition transcranial direct current stimulation intensity on motor performance in healthy adults: a randomized controlled trial.</a> J Neuroeng Rehabil. 18 (1), 103(2021).</li>
<li>Effects of electrode configurations and injected current intensity on the electrical field of transcranial direct current stimulation: a simulation study. Mackenbach, C., Tian, R., Yang, Y. Conf Proc IEEE Eng Med Biol Soc, 2020, 3517-3520 (2020).</li>
<li>Evans, C., Zich, C., Lee, J. S. A., Ward, N., Bestmann, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Inter-individual+variability+in+current+direction+for+common+tDCS+montages%5BTitle%5D)+AND+%22Neuroimage%22%5BJournal%5D)">Inter-individual variability in current direction for common tDCS montages.</a> Neuroimage. 260, 119501(2022).</li>
<li>Klaus, J., Schutter, D. J. L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Electrode+montage-dependent+intracranial+variability+in+electric+fields+induced+by+cerebellar+transcranial+direct+current+stimulation%5BTitle%5D)+AND+%22Sci+Rep%22%5BJournal%5D)">Electrode montage-dependent intracranial variability in electric fields induced by cerebellar transcranial direct current stimulation.</a> Sci Rep. 11 (1), 22183(2021).</li>
<li>Laakso, I., Tanaka, S., Koyama, S., De Santis, V., Hirata, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Inter-subject+variability+in+electric+fields+of+motor+cortical+tDCS%5BTitle%5D)+AND+%22Brain+Stimul%22%5BJournal%5D)">Inter-subject variability in electric fields of motor cortical tDCS.</a> Brain Stimul. 8 (5), 906-913 (2015).</li>
<li>Saita, M., Ikenaka, T., Matsushima, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Isolation+and+characterization+of+-D-mannosidase+from+soy+bean%5BTitle%5D)+AND+%22J+Biochem%22%5BJournal%5D)">Isolation and characterization of -D-mannosidase from soy bean.</a> J Biochem. 70 (5), 827-833 (1971).</li>
<li>Noury, N., Hipp, J. F., Siegel, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Physiological+processes+non-linearly+affect+electrophysiological+recordings+during+transcranial+electric+stimulation%5BTitle%5D)+AND+%22Neuroimage%22%5BJournal%5D)">Physiological processes non-linearly affect electrophysiological recordings during transcranial electric stimulation.</a> Neuroimage. 140, 99-109 (2016).</li>
<li>Kasten, F. H., Herrmann, C. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Recovering+brain+dynamics+during+concurrent+tACS-M%2FEEG%3A+an+overview+of+analysis+approaches+and+their+methodological+and+interpretational+pitfalls%5BTitle%5D)+AND+%22Brain+Topogr%22%5BJournal%5D)">Recovering brain dynamics during concurrent tACS-M/EEG: an overview of analysis approaches and their methodological and interpretational pitfalls.</a> Brain Topogr. 32 (6), 1013-1019 (2019).</li>
<li>Fehér, K. D., Morishima, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Concurrent+electroencephalography+recording+during+transcranial+alternating+current+stimulation+%28tACS%29%5BTitle%5D)+AND+%22J+Vis+Exp%22%5BJournal%5D)">Concurrent electroencephalography recording during transcranial alternating current stimulation (tACS).</a> J Vis Exp. (107), e53527(2016).</li>
<li>Helfrich, R. F., Schneider, T. R., Rach, S., Trautmann-Lengsfeld, S. A., Engel, A. K., Herrmann, C. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Entrainment+of+brain+oscillations+by+transcranial+alternating+current+stimulation%5BTitle%5D)+AND+%22Curr+Biol%22%5BJournal%5D)">Entrainment of brain oscillations by transcranial alternating current stimulation.</a> Curr Biol. 24 (3), 333-339 (2014).</li>
<li>Lafon, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Low+frequency+transcranial+electrical+stimulation+does+not+entrain+sleep+rhythms+measured+by+human+intracranial+recordings%5BTitle%5D)+AND+%22Nat+Commun%22%5BJournal%5D)">Low frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings.</a> Nat Commun. 8 (1), 1199(2017).</li>
</ol>

This protocol provides a standardized yet flexible methodological framework for delivering HD-tDCS during sleep with simultaneous EEG monitoring. The technique&#39;s primary strength lies in its focal, parameter-controlled neuromodulation and the ability to directly monitor its neurophysiological effects. This allows for tests of causality between targeted brain activity and sleep-related processes.
Successful and reliable execution of HD-tDCS during sleep requires attention to certain paramet...

Sleep is essential for brain health and cognition, and specific sleep oscillations have key supportive and restorative roles. The ability to modulate these sleep oscillations offers unique opportunities to establish causality between sleep, brain activity, and cognition. Various neuromodulation techniques have emerged in recent years, with transcranial direct current stimulation (tDCS) showing promise as a non-invasive approach to modulate neural activity during sleep1,2,3,4.
Conventional tDCS applies direct electrical current through large pad electrodes, typically 25-35 cm2, resulting in relatively diffuse stimulation5. The efficacy and specificity of tDCS during sleep depend on several key parameters that can be systematically manipulated. Electrode placement fundamentally determines which cortical regions receive stimulation; bifrontal configurations can either enhance slow oscillations and sleep spindles6,7 or reduce total sleep time8, depending on the montage and polarity. Current intensity (typically 0.2-2.0 mA) exhibits dose-dependent effects on both the magnitude of neurophysiological responses and participant tolerability9. Temporal parameters, including total stimulation duration, ramp duration, and protocol structure (continuous vs. intermittent with specific inter-stimulation intervals), determine both immediate effects and after-effects; for example, intermittent protocols with stimulation-free intervals can enhance motor cortex excitability while reducing adaptation10. Additionally, the timing of stimulation relative to sleep architecture impacts outcomes; for instance, Stage 2 (N2) sleep stimulation primarily affects spindles and slow oscillations6,7 while rapid eye movement (REM) sleep stimulation influences self-awareness during dreams11. This diversity in outcomes from such subtleties in parameter selection exemplifies the exquisite sensitivity of sleep architecture-and related processes such as cognition-to targeted neuromodulation.
High-definition tDCS (HD-tDCS) employs smaller electrodes, such as the 4 x 1 ring montage (approximately 0.95 cm&#178; surface area vs 2-35 cm&#178; for conventional rubber electrodes), which allows for more focal targeting of brain regions with enhanced spatial precision-defined as the ability to concentrate electrical current within a specific target while minimizing spread to adjacent areas-compared to larger rubber electrodes used a priori12. HD-tDCS also produces a more circumscribed electric field distribution, and the generated current is largely confined to cortical areas directly beneath the electrodes13. This advanced spatial specificity minimizes off-target effects and paves the way for high precision functional correlations between the stimulation sites and observed outcomes14. This selectivity allows for more accurate testing of brain region-specific hypotheses while reducing confounding influences from unintended stimulation of adjacent cortical areas5,12,13,14,15. The improved focal precision and accuracy of HD-tDCS enable mechanistic interrogations of specific brain regions and their associations with distinct aspects of sleep physiology and cognition. The adaptability of HD-tDCS is amplified when coupled with continuous neurophysiological recordings, such as continuous high-definition electroencephalography (EEG). Hence, a platform with such translational promise is capable of advancing both basic neuroscience research and the development of clinical interventions for sleep and neuropsychiatric conditions4.
This protocol describes a comprehensive methodology for applying HD-tDCS during sleep using a 4 x 1 ring configuration while simultaneously recording EEG to monitor sleep architecture and stimulation effects. The approach is designed to be versatile, allowing researchers to customize stimulation parameters to address various research questions related to sleep neuroscience.

<table><tbody><tr><td>Ag/AgCl sintered ring electrodes</td><td>Soterix Medical</td><td>HD-1AGE-12&amp;nbsp;</td><td>For stimulation set-up</td></tr><tr><td>Alcohol swabs</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr><tr><td>Ear plugs&amp;nbsp;</td><td>NA</td><td>NA</td><td>For helping participant to fall asleep&amp;nbsp;</td></tr><tr><td>EC2</td><td>Natus</td><td>CR-003</td><td>For EEG set-up</td></tr><tr><td>EEG recording cap (with attached electrodes)</td><td>Natus</td><td>21114</td><td>For EEG set-up</td></tr><tr><td>Electro-gel</td><td>Electro-Cap International, Inc.&amp;nbsp;</td><td>E11</td><td>For EEG set-up</td></tr><tr><td>Gauze squares&amp;nbsp;</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr><tr><td>Gold cup electrodes&amp;nbsp;</td><td>Natus</td><td>F-E5GH-48</td><td>For electrooculography (EOG) and electromyography (EMG) collection</td></tr><tr><td>HD-EEG system with 64-channel capability&amp;nbsp;</td><td>Natus</td><td>Brain Monitor EEG Amplifier</td><td>For EEG set-up</td></tr><tr><td>HD-gel&amp;nbsp;</td><td>Soterix Medical</td><td>HD-1GEL</td><td>For stimulation set-up</td></tr><tr><td>HD-tDCS electrode holders</td><td>Soterix Medical</td><td>HD-1A.2&amp;nbsp;</td><td>For stimulation set-up</td></tr><tr><td>HD-tDCS stimulation adapter</td><td>Soterix Medical 4x1 Multichannel Stimulation Adapter</td><td>Model 4X1-C3A&amp;nbsp;</td><td>For stimulation set-up</td></tr><tr><td>HD-tDCS stimulation system&amp;nbsp;</td><td>Soterix Medical M&amp;times;N HD Transcranial Stimulation System</td><td>Model 9002&amp;nbsp;</td><td>For stimulation set-up</td></tr><tr><td>Head model for securing and preparing gel on EEG recording cap (if needed)</td><td></td><td>For EEG set-up</td><td></td></tr><tr><td>Nuprep</td><td>Weaver and Company</td><td>10-30</td><td>For EEG set-up</td></tr><tr><td>Q-tips</td><td>Q-tips</td><td>https://www.qtips.com/</td><td>For EEG set-up</td></tr><tr><td>Scissors</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr><tr><td>Specialized connector cable/cord&amp;nbsp;</td><td>Soterix Medical</td><td>CUS_MxN_CBL&amp;nbsp;</td><td>For stimulation electrodes</td></tr><tr><td>Spray bottle (and cup) with water</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr><tr><td>Tape</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr><tr><td>Ten cc syringe with 16-gauge blunt tip</td><td>NA</td><td>NA</td><td>For EEG/stimulation set-up</td></tr><tr><td>Ten-20</td><td>Weaver and Company</td><td>10-20-8</td><td>For EEG set-up</td></tr><tr><td>Tongue depressor</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr><tr><td>Towels</td><td>NA</td><td>NA</td><td>For EEG set-up</td></tr></tbody></table>

high-definition transcranial direct current stimulation during sleep

High-Definition Transcranial Direct Current Stimulation During Sleep

High-definition transcranial direct current stimulation (HD-tDCS) enables high spatial precision modulation of neural activity during sleep. This protocol presents a comprehensive methodology for applying HD-tDCS using a 4 x 1 ring electrode configuration while simultaneously recording high-definition electroencephalography (HD-EEG) to monitor sleep architecture and stimulation effects. The technique enables systematic tuning of multiple parameters, where each parameter selection produces distinct neurophysiological outcomes. This provides opportunities to target specific brain regions and oscillatory patterns specifically tailored to the research question. Successful implementation of this protocol requires attention to electrode placement, impedance management, and real-time sleep staging capability. The versatility of this methodology and its capacity to address causal relationships in sleep physiology invite a broad range of applications from basic neuroscience to clinical interventions based on sleep optimization. The standardized yet flexible framework described here establishes HD-tDCS as a robust platform for systematic investigations of sleep neurobiology as well as its clinical ramifications.

When the protocol is implemented correctly, HD-tDCS during sleep produces measurable and reproducible changes in sleep architecture and physiology that vary systematically with the chosen stimulation parameters. The focal distribution from bilateral frontolateral stimulation in Figure 4-one possible montage-exemplifies the spatial precision of 4 x 1 ring electrodes. Successful protocol implementation is confirmed through several key indicators. Optimal electr...

This protocol describes high-definition transcranial direct current stimulation during sleep with simultaneous electroencephalography monitoring to investigate causal relationships between targeted brain regions and sleep as well as its related processes.

High-definition transcranial direct current stimulation (HD-tDCS) enables high spatial precision modulation of neural activity during sleep. This protocol ...

We use neuromodulation during sleep to investigate the relationships between targeted brain regions and sleep physiology. High-definition transcranial direct current stimulation with simultaneous electroencephalography advances research on regulation of and restoration from sleep. To begin, gather all necessary equipment and materials required for the procedure.Ensure the conventional tDCS device has an adequate power supply, and if required, change the batteries. Turn on HD-tDCS and EEG devices and verify the power status according to the manufacturer's specifications. Select an appropriately sized EEG cap based on the participant's head circumference.Use bilateral frontal lateral positions F3 and F4 to target the prefrontal cortex. Next, input the electrode positions and stimulation parameters. Insert the HD-tDCS electrodes or the electrode holders into the designated positions on the EEG cap and reverse the EEG cap inside out and place it on a foam head for better access.Then, apply the high viscosity, chloride-free adhesive conductive paste to the cap. Using a tongue depressor, cover each EEG electrode with paste, avoiding application on HD-tDCS stimulation electrodes. Shape the conductive paste into dome-like structures.Apply a smaller amount of paste in the front of the scalp, where there is less hair, and a greater amount at the crown and back of the head, where hair density is higher. Now, clean each electrode site using an alcohol swab. Exfoliate the site with mildly abrasive preparation gel using a cotton swab, then remove any residual fluid with a dry gauze square.Target sites include the forehead and mastoids behind the ears for reference electrodes. Outer canthi near the eyes to record eye movements, chin for electromyography electrodes, and clavicle for the ground electrode. Then, fill each electrode with adhesive conductive paste and apply it to the prepared site.Secure each electrode in place using medical grade tape. Similarly, apply all the facial and ground reference electrodes using gold cup electrodes filled with adhesive conductive paste. For the HD-tDCS ground electrode, position the stimulation electrode on the collarbone and secure it with tape.Now, measure the distance from the nasion to the inion and mark the halfway point along this line. Then, measure the distance between the left and right preauricular points, and mark the halfway point on this line with a visible line. Identify the CZ location at the intersection of the nasion, inion and preauricular lines.After that, lightly spray the participant's hair with water using a spray bottle to assist in EEG cap placement. Invert the prepared EEG cap and place it snugly on the participant's head, aligning the CZ electrode with the marked CZ site. Secure the cap in place using the chin straps for a comfortable and stable fit.To fill each electrode site with conductive gel, pull up each electrode slightly and insert the large gauge blunt tip needle into its center. Gently wiggle the needle to displace hair and dispense approximately 0.5 milliliters of conductive gel. Push the electrode back down to establish firm contact between the gel, paste and scalp.Position the silver or silver chloride centered ring electrodes into each HD-tDCS electrode holder with the rough surface facing downward and the smooth rounded surface facing upward. Add more high viscosity conductive gel over each inserted electrode to fully cover its surface. Lock each electrode in place using the caps provided.Turn on the amplifier after connecting the required cords and launch the EEG recording software on the connected computer. Check the electrode impedances using the software. Set the impedance limit to 25 kiloohms and aim to achieve values below 10 kiloohms for all electrodes.Ask the participant to open and close their eyes for approximately 10 seconds. Observe the presence of alpha wave activity, typically more prominent in posterior channels than in anterior ones. Monitor the scalp for amplitude variations.Ask the participant to look to the left, right, up and down, then instruct them to clench their teeth while observing the recordings from the eye and chin electrodes for movement signals. Ask the participant to blink several times. Connect the cables of the silver or silver chloride centered ring electrodes to the corresponding receivers on the 4x1 adapter output cable Switch on the stimulator using its power button.Once the stimulator is on, plug the electrode cable securely into the back of the device. Set the stimulation parameters according to the study design. Configure the intensity.Select the waveform as direct current for transcranial direct current stimulation protocols, and set the duration and ramp times. Select either active stimulation or sham mode as directed by the study protocol. If the HD-tDCS electrodes show high impedance, deliver a brief test stimulation under the sham setting to verify connectivity.Start the recording and mark the time in the EEG recording when the lights are turned off. Monitor the EEG for signs of sleep onset and specific sleep stages to trigger stimulation according to the study protocol. Mark the start of stimulation in the EEG recording with a clear notation.Once the final stimulation period ends, unplug the stimulation cord from the device. Mark the time in the EEG recording when the lights are turned on. After waking the participant from sleep, stop the EEG recording using the software interface.Gently remove the silver or silver chloride ring electrodes from the participant's scalp. Clean the used electrodes with a damp paper towel and allow them to air dry before storing them. Once the EEG cap is removed from the participant's head, clean all electrode sites thoroughly to remove residual conductive gels.Bilateral frontal lateral HD-tDCS produced a focal electric field distribution, highlighting the spatial precision achievable with a 4x1 ring electrode montage. Clean EEG signals with minimal artifacts were observed during the ramp-up phase, confirming correct protocol implementation with optimal electrode preparation. HD-tDCS provides enhanced spatial precision and focal targeting versus conventional tDCS, minimizing off-target effects during sleep.This enables mechanistic studies of region-specific sleep physiology and development of targeted interventions for neuropsychiatric disorders. Future research will develop adaptive closed-loop systems and refine computational models for improved targeting.

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Neuroscience

Source: Shaw, M. T. et al. Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability. J. Vis. Exp. (2017)This video demonstrates the process of self-administering transcranial direct current stimulation (tDCS) for cognitive enhancement. It outlines the steps for electrode placement, stimulation setup, tolerability assessment, and the neuroplastic effects induced by tDCS.

Self-Administration of Transcranial Direct Current Stimulation for Enhancing Cognitive Functions

Source: Chen, W., et al. Stimulation Location Determination using a 3D Digitizer with High-Definition Transcranial Direct Current Stimulation. J. Vis. Exp. (2019)This video demonstrates the procedure for delivering high-definition transcranial direct current stimulation (HD-tDCS) by accurately positioning electrodes using the 10–10 system, mapping their locations with a 3D digitizer, and applying stimulation to modulate neuronal activity in a targeted brain region.

High-Definition Transcranial Direct Current Stimulation for Activation of the Target Brain Region

High-definition transcranial direct current stimulation (HD-tDCS), with its 4x1-ring montage, is a noninvasive brain stimulation technique that combines both the neuromodulatory effects of conventional tDCS with increased focality. This article provides a systematic demonstration of the use of 4x1 HD-tDCS, and the considerations needed for safe and effective stimulation.

Technique and Considerations in the Use of 4x1 Ring High-definition Transcranial Direct Current Stimulation (HD-tDCS)

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has shown initial therapeutic effects in several neurological conditions. The main mechanism underlying these therapeutic effects is the modulation of cortical excitability. Therefore, online monitoring of cortical excitability would help guide stimulation parameters and optimize its therapeutic effects. In the present article we review the use of a novel device that combines simultaneous tDCS and...

Simultaneous EEG Monitoring During Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. It has successfully been used in basic research and clinical settings to modulate brain function in humans. This article describes the implementation of tDCS and simultaneous functional magnetic resonance imaging (fMRI), to investigate the neural basis of tDCS effects.

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) over the cerebellum exerts a remote effect on the prefrontal cortex, which can modulate cognition and performance. This was demonstrated using two information-processing tasks of varying complexity, whereby only cathodal tDCS improved performance when the task was difficult, but not easy.

Modulating Cognition Using Transcranial Direct Current Stimulation of the Cerebellum

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's disease.

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

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.

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

This protocol describes the method of neuronavigated electrode placement for focal, transcranial direct current stimulation (tDCS) administered during functional magnetic resonance imaging (fMRI).

Neuronavigated Focalized Transcranial Direct Current Stimulation Administered During Functional Magnetic Resonance Imaging

This study presents a novel transcranial direct current stimulation (tDCS) protocol combined with cognitive stimulation to address post-stroke hemispatial neglect. Initial data from a pilot patient ensure the procedure's feasibility and suggest potential efficacy, providing a foundation for a future parallel, triple-blind, controlled clinical trial.

Randomized, Triple-Blind, and Parallel-Controlled Trial of Transcranial Direct Current Stimulation for Cognitive Rehabilitation after Stroke

This study proposed an experimental paradigm that applies High-Definition Transcranial Direct Current Stimulation (HD-tDCS) to improve human metacognition in human-AI delegation tasks. The results demonstrated the effectiveness of HD-tDCS in enhancing metacognitive sensitivity.

High-definition Transcranial Direct Current Stimulation over Right Dorsolateral Prefrontal Cortex to Enhance Metacognitive Sensitivity

Learn high-definition transcranial direct current stimulation during sleep with simultaneous EEG monitoring. This method investigates causal relationships between targeted brain regions and sleep physiology.

High-Definition Transcranial Direct Current Stimulation During Sleep

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