The authors would like to thank collaborators at City College of New York and Soterix Medical for their assistance and support.

All procedures and device protocols have been approved for human subjects by institutional review boards at both Stony Brook University and New York University Langone Medical Center.
1. Participant Recruitment and Screening
<ol>
	<li>Recruit potential participants via referrals from IRB approved study physicians.</li>
	<li>Contact participants and perform a pre-screening to confirm basic eligibility before the baseline study visit (see Supplemental File 1).
	<ol>
		<li>Assess cognitive competency via remote administration of a cognitive functioning test, (e.g. the symbol digit modalities test or SDMT)14. Exclude participants who score below three standard deviations of the healthy normative mean in their age group due to concerns regarding their cognitive capacity to comply with the study protocol.</li>
		<li>Briefly assess the potential participant&#39;s medical history over the phone. Assess inclusion and exclusion criteria. Exclusion criteria can be broad based on a recent consensus safety paper1. Assess the following portion of the inclusion criteria, including that patients must be 18 years or older and have the following: the understanding and ability to give consent, adequate home facilities to store equipment and perform RS-tDCS sessions, clearance for all study procedures by a study physician, and stable internet access at home. 
		NOTE: Allot sufficient time for the baseline visit so that the study physician may clear the potential participant. At least 3 hours are typically needed to complete all baseline procedures, questionnaires, and neuropsychological tests in the current iteration of this study protocol.</li>
		<li>Rate each patient&#39;s disease related disability (e.g., the Expanded Disability Status Scale (EDSS)15 score for MS patients only). Participants with severe disability (e.g. an EDSS score above&#160;6.5) will complete daily tDCS sessions with the aid of a healthcare proxy. The healthcare proxy will complete, on behalf of the participant, the device and headstrap preparation steps that require more advanced ambulation.</li>
		<li>In sham-control studies, randomize the participant to either the active or sham condition, as dictated by the blocked stratification table. The table stratifies participants based on the cognitive functioning and disability ratings collected during pre-screening16. Any study using sham should be double-blinded and have an un-blinded study technician, who will not supervise the participant&#39;s daily sessions, assign the condition, and prepare study devices for participants and study personnel.</li>
	</ol>
	</li>
</ol>
2. Baseline Study Visit
<ol>
	<li>Administer neuropsychological assessments and self-report questionnaires.
	<ol>
		<li>Choose relevant neuropsychological assessments (such as the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)17, based on the respective patient population. Administer measures and assess the motor and cognitive abilities of participants.</li>
		<li>Administer self-report questionnaires relevant to symptoms that are specific to the patients&#39; disease. For example, the Unified Parkinson&#39;s Disease Rating Scale (UPDRS)18 is a widely used clinical self-assessment questionnaire measuring Parkinson&#39;s specific symptoms. Likewise, the Multiple Sclerosis Neuropsychology Questionnaire (MSNQ) is designed and validated to measure neuropsychological competence in daily living specifically in patients with multiple sclerosis19,20. Administer universal symptom rating inventories (such as the Patient-Reported Outcomes Measurement Information System (PROMIS)21 and the Positive and Negative Affect Schedule (PANAS)22) to allow for comparison between patient populations.</li>
	</ol>
	</li>
</ol>
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56211/56211fig1.jpg" /> 
Figure 1: Left anodal DLPFC montage used in both studies.&#160;The red and blue patches are modeled representations of the left anode and right cathode, respectively, placed upon a scalp. <a href="//cloudfront.jove.com/files/ftp_upload/56211/56211fig1large.jpg">Please click here to view a larger version of this figure.</a>
<ol start="2">
	<li>Instruct and train participants to self-administer tDCS.
	<ol>
		<li>Show participants an instructive tDCS training video that details the entire step-by-step process of administering the stimulation.</li>
		<li>Ask participants to prepare the headstrap with guidance from study personnel. The headstrap holds the sponge electrodes in position throughout the duration of the stimulation session.
		<ol>
			<li>Have participants attach the sponges, which are pre-moistened with 5-mL of saline solution, to the cable electrodes.</li>
			<li>Instruct participants to place the headstrap upon their head, taking care to align the nasion marker on the front of the headstrap with the bridge of their nose.</li>
			<li>Have participants pull the back the headstrap towards the posterior end of their heads so the back of the headstrap rests over their inion. The Dorsolateral Prefrontal Cortex (DLPFC), left anodal tDCS montage is used23,24,25,26,27.</li>
			<li>Confirm that the participant has achieved optimal or moderate contact quality before continuing. 
			NOTE: The device dynamically adjusts its voltage depending on the entire resistive path between the anodal and cathodal electrodes (including skin and skull impedance) to deliver consistent amperage. The device will not unlock to release the stimulation if the contact quality is poor or the impedance is too high.</li>
			<li>If a participant has a poor or moderate contact quality then suggest methods to improve contact quality, such as adding saline to the sponges, adjusting headstrap placement, or brushing hair away from electrode sites. The participant can monitor their own contact quality by looking at the device&#39;s interface screen.</li>
			<li>Assess the participant&#39;s aptitude to complete study procedures to determine whether they understand and can replicate the procedures competently at home.</li>
		</ol>
		</li>
		<li>Participants complete a tolerability test lasting 90 seconds to determine whether they are able to comfortably tolerate 2.0 mA of direct current. If a participant finds they are unable to handle 2.0 mA, lessen the amperage to 1.5 mA, and further to 1.0 mA if deemed necessary. If a participant finds 1.0 mA intolerable, they must be discontinued from the study.</li>
	</ol>
	</li>
	<li>Conducting the first tDCS session in-clinic.
	<ol>
		<li>Ask the participant, after preparing the headstrap and prior to beginning the stimulation session, to report the duration of sleep from the previous night as well as any pain experienced due to the stimulation, disease specific pain, fatigue, and mood before the session with the aid of visual analogue scales.</li>
		<li>Confirm that the contact quality is still optimal or moderate. Provide the device unlock code to begin the participant&#39;s stimulation session.</li>
		<li>Begin stimulation and deliver a tolerable amount of stimulation (as detailed above) for an intended twenty minutes. The stimulation&#39;s length depends upon the parameters set by the study; for all studies presented herein, the stimulation length was twenty minutes. Should the participant be randomized to the sham condition, the participant receives only one minute of stimulation at the beginning of the session and at the end of the session, during which the amperage ramps up to the target tolerable amount of stimulation during the first thirty seconds and then ramps back down to 0 mA in the final thirty seconds, in order to convince participants that they are receiving stimulation. Aside from the first and last minute, sham participants receive no stimulation for 18 minutes.</li>
		<li>Participants complete cognitive remediation with guidance from the study technician. The cognitive remediation may be swapped out for a different remediation strategy depending on the intended goals of the study. Similarly, the length of the remediation strategy may be modified. 
		NOTE: Stimulation can be halted at any time by pressing &#34;zero&#34; on the device which immediately begins to abort stimulation by ramping down to 0 mA. Study technicians instruct participants to abort the session and end stimulation when any pain is reported above a 7 on a 1-10 visual analogue scale or if any other emergency situation occurs.</li>
		<li>After ten minutes, ask the participant whether they are experiencing any pain from the stimulation. Study technicians monitor placement through the videoconferencing software to determine that electrode placement does not shift and remains acceptable during the stimulation session.</li>
		<li>After an additional ten minutes, the pre-programmed tDCS device powers down and stimulation ceases. The device makes a loud beeping noise to notify the participant that the stimulation has ended. Should the participant have the sham condition, then the device ramps up once again during the final minute of the twenty-minute session to provide thirty seconds of the target stimulation current and then ramps down to 0 mA during the final thirty seconds of the session.</li>
		<li>Ask the participant once more to report their pain due to the device, disease specific pain, fatigue, and mood following the session, as well as any adverse events that may have been experienced during the course of the session.</li>
		<li>Plan a regular time for the remaining study sessions to ensure daily consistency for standardization purposes. Additionally for PD patients, coordinate session times so that stimulation takes place within 1-3 hours of their last dose of PD medication - a time window that study-approved physicians determined would provide maximum benefit in accordance with previous evidence showing greater improvement among Parkinson&#39;s patients in cognitive and motor dimensions (as measured by the Unified Parkinson&#39;s Disease Rating Scale, or UPDRS) when tDCS was delivered during participants&#39; &#34;on&#34; drug state vs. &#34;off&#34; drug state11.</li>
	</ol>
	</li>
</ol>
3. At-home tDCS Sessions
<ol>
	<li>Participants complete computer preparation prior to study sessions.
	<ol>
		<li>Participants connect to the internet in their homes prior to any further study procedures. Participants without stable internet in their homes are excluded from all study procedures.</li>
		<li>Connect to a participant&#39;s computer with the use of remote desktop software28 and engage in HIPAA-compliant video conferencing with the participant29.</li>
		<li>Study technicians administer study outcome measures wherein participants report the amount of sleep they received the previous night and rate pain due to the device, disease specific pain, fatigue, and mood before the stimulation session with the aid of visual analogue scales. Ask the participant to report any adverse events that may have occurred following the previous day&#39;s session (see supplemental files 2 and 3).</li>
	</ol>
	</li>
	<li>Participants remotely activate the stimulation.
	<ol>
		<li>Participants prepare the headstrap by attaching the pre-moistened sponges to the electrodes on the inside of the frontal headstrap. The sponge electrodes easily snap into the headstrap to minimize preparation.</li>
		<li>Participants place the headstrap upon their heads as study technicians monitor placement. Participants report the contact quality, which is tested by the device and assesses the sponge placement and sponge saturation measured by the tDCS device. As previously described, moderate and poor contact quality is remedied by suggestions from study personnel such as adding additional saline solution or checking sponge placement.</li>
		<li>Verbally state the stimulation code that unlocks the device to the participant and allow administration of the stimulation for twenty minutes.</li>
		<li>Should a participant have an EDSS score above 6.5, the healthcare proxy completes the above steps in lieu of the participant.</li>
	</ol>
	</li>
	<li>Participants complete computerized cognitive remediation during the twenty-minute stimulation period. The remediation includes cognitive training tasks that specifically target working memory systems. A previous publication of ours details the cognitive results concerning our first pilot study8.
	<ol>
		<li>After 10 min of stimulation, ask participants to report any pain they may be experiencing.</li>
	</ol>
	</li>
	<li>Participants complete post-session procedures.
	<ol>
		<li>Participants take off the headstrap and dispose of study sponges.</li>
		<li>Ask participants to report any pain due to the device, disease specific pain, fatigue, and mood after the session as well any adverse events that they may have experienced during the session. Record any adverse events that occurred along with their intensity and duration.</li>
		<li>Plan the session for the following day.</li>
	</ol>
	</li>
</ol>
4. Post-stimulation Visit
<ol>
	<li>Administer neuropsychological assessments and self-report questionnaires.
	<ol>
		<li>Schedule the final study visit as soon as possible after the final stimulation session.</li>
		<li>Administer study outcome measures that were completed during the baseline visit a second time to assess whether patients experienced benefit as a result of the stimulation17.</li>
		<li>Obtain and sanitize all study equipment.</li>
	</ol>
	</li>
	<li>Offer participants who were assigned the sham condition the option to complete an additional ten active, open-label, RS-tDCS sessions. This open label study period is modeled after our first tDCS pilot study6.</li>
</ol>
5. One Month Follow-up Survey
<ol>
	<li>Reach out to participants about a month after their study end to ask if they would remotely complete an online survey asking whether they believe benefits received from the stimulation persisted.</li>
</ol>

<ol>
	<li>Bikson, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+of+Transcranial+Direct+Current+Stimulation:+Evidence+Based+Update+2016.">Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.</a> Brain Stimul. , (2016).</li><li>Bashir, S., Yoo, W. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cheap+Technology+Like+Transcrinal+Direct+Current+Stimulation+(tDCS)+Could+Help+in+Stroke+Rehabilitation+in+South+Asia.">Cheap Technology Like Transcrinal Direct Current Stimulation (tDCS) Could Help in Stroke Rehabilitation in South Asia.</a> Basic Clin Neurosci. 4 (3), 188-189 (2013).</li><li>Boggio, P. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeated+sessions+of+noninvasive+brain+DC+stimulation+is+associated+with+motor+function+improvement+in+stroke+patients.">Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients.</a> Restor Neurol Neurosci. 25 (2), 123-129 (2007).</li><li>Brunoni, A. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+research+with+transcranial+direct+current+stimulation+(tDCS):+challenges+and+future+directions.">Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions.</a> Brain Stimul. 5 (3), 175-195 (2012).</li><li>Kalu, U. G., Sexton, C. E., Loo, C. K., Ebmeier, K. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+in+the+treatment+of+major+depression:+a+meta-analysis.">Transcranial direct current stimulation in the treatment of major depression: a meta-analysis.</a> Psychol Med. 42 (9), 1791-1800 (2012).</li><li>Kasschau, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Protocol+for+the+Use+of+Remotely-Supervised+Transcranial+Direct+Current+Stimulation+(tDCS)+in+Multiple+Sclerosis+(MS).">A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS).</a> J Vis Exp. (106), e53542 (2015).</li><li>Ferrucci, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+(tDCS)+for+fatigue+in+multiple+sclerosis.">Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis.</a> NeuroRehabilitation. 34 (1), 121-127 (2014).</li><li>Charvet, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remotely+Supervised+Transcranial+Direct+Current+Stimulation+Increases+the+Benefit+of+At-Home+Cognitive+Training+in+Multiple+Sclerosis.">Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis.</a> Neuromodulation. , (2017).</li><li>Mattioli, F., Bellomi, F., Stampatori, C., Capra, R., Miniussi, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroenhancement+through+cognitive+training+and+anodal+tDCS+in+multiple+sclerosis.">Neuroenhancement through cognitive training and anodal tDCS in multiple sclerosis.</a> Mult Scler. , (2015).</li><li>Manenti, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mild+cognitive+impairment+in+Parkinson's+disease+is+improved+by+transcranial+direct+current+stimulation+combined+with+physical+therapy.">Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.</a> Mov Disord. 31 (5), 715-724 (2016).</li><li>Benninger, D. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+for+the+treatment+of+Parkinson's+disease.">Transcranial direct current stimulation for the treatment of Parkinson's disease.</a> J Neurol Neurosurg Psychiatry. 81 (10), 1105-1111 (2010).</li><li>Fregni, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+cortical+stimulation+with+transcranial+direct+current+stimulation+in+Parkinson's+disease.">Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson's disease.</a> Mov Disord. 21 (10), 1693-1702 (2006).</li><li>Larocca, N. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+walking+impairment+in+multiple+sclerosis:+perspectives+of+patients+and+care+partners.">Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners.</a> Patient. 4 (3), 189-201 (2011).</li><li>Smith, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Symbol Digit Modalities Test (SDMT) Symbol Digit Modalities Test: Manual. , (1982).</li><li>Kurtzke, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rating+neurologic+impairment+in+multiple+sclerosis:+an+expanded+disability+status+scale+(EDSS).">Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).</a> Neurology. 33 (11), 1444-1452 (1983).</li><li>Suresh, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+overview+of+randomization+techniques:+An+unbiased+assessment+of+outcome+in+clinical+research.">An overview of randomization techniques: An unbiased assessment of outcome in clinical research.</a> J Hum Reprod Sci. 4 (1), 8-11 (2011).</li><li>Langdon, D. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+a+Brief+International+Cognitive+Assessment+for+Multiple+Sclerosis+(BICAMS).">Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).</a> Mult Scler. 18 (6), 891-898 (2012).</li><li>Martinez-Martin, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Unified+Parkinson's+Disease+Rating+Scale+characteristics+and+structure.+The+Cooperative+Multicentric+Group.">Unified Parkinson's Disease Rating Scale characteristics and structure. The Cooperative Multicentric Group.</a> Mov Disord. 9 (1), 76-83 (1994).</li><li>Krupp, L. B., LaRocca, N. G., Muir-Nash, J., Steinberg, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+fatigue+severity+scale.+Application+to+patients+with+multiple+sclerosis+and+systemic+lupus+erythematosus.">The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.</a> Arch Neurol. 46 (10), 1121-1123 (1989).</li><li>O'Brien, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+of+the+Multiple+Sclerosis+Neuropsychological+Questionnaire+(MSNQ)+to+functional,+emotional,+and+neuropsychological+outcomes.">Relationship of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to functional, emotional, and neuropsychological outcomes.</a> Arch Clin Neuropsychol. 22 (8), 933-948 (2007).</li><li>Christodoulou, C., Junghaenel, D. U., DeWalt, D. A., Rothrock, N., Stone, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+interviewing+in+the+evaluation+of+fatigue+items:+results+from+the+patient-reported+outcomes+measurement+information+system+(PROMIS).">Cognitive interviewing in the evaluation of fatigue items: results from the patient-reported outcomes measurement information system (PROMIS).</a> Qual Life Res. 17 (10), 1239-1246 (2008).</li><li>Watson, D., Clark, L. A., Tellegen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+validation+of+brief+measures+of+positive+and+negative+affect:+the+PANAS+scales.">Development and validation of brief measures of positive and negative affect: the PANAS scales.</a> J Pers Soc Psychol. 54 (6), 1063-1070 (1988).</li><li>Forogh, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeated+sessions+of+transcranial+direct+current+stimulation+evaluation+on+fatigue+and+daytime+sleepiness+in+Parkinson's+disease.">Repeated sessions of transcranial direct current stimulation evaluation on fatigue and daytime sleepiness in Parkinson's disease.</a> Neurol Sci. 38 (2), 249-254 (2017).</li><li>Seibt, O., Brunoni, A. R., Huang, Y., Bikson, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Pursuit+of+DLPFC:+Non-neuronavigated+Methods+to+Target+the+Left+Dorsolateral+Pre-frontal+Cortex+With+Symmetric+Bicephalic+Transcranial+Direct+Current+Stimulation+(tDCS).">The Pursuit of DLPFC: Non-neuronavigated Methods to Target the Left Dorsolateral Pre-frontal Cortex With Symmetric Bicephalic Transcranial Direct Current Stimulation (tDCS).</a> Brain Stimul. , (2015).</li><li>Nord, C. L., Lally, N., Charpentier, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Harnessing+electric+potential:+DLPFC+tDCS+induces+widespread+brain+perfusion+changes.">Harnessing electric potential: DLPFC tDCS induces widespread brain perfusion changes.</a> Front Syst Neurosci. 7, 99 (2013).</li><li>Eddy, C. M., Shapiro, K., Clouter, A., Hansen, P. C., Rickards, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+can+enhance+working+memory+in+Huntington's+disease.">Transcranial direct current stimulation can enhance working memory in Huntington's disease.</a> Prog Neuropsychopharmacol Biol Psychiatry. 77, 75-82 (2017).</li><li>Lefaucheur, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+treatment+of+fatigue+by+non-invasive+brain+stimulation.">The treatment of fatigue by non-invasive brain stimulation.</a> Neurophysiol Clin. , (2017).</li><li>. TeamViewer-the All-In-One Software for Remote Support and Online Meetings Available from: <a target="_blank" href="https://www.teamviewer.com/en/index.aspx">https://www.teamviewer.com/en/index.aspx</a> (2015)</li><li>Flachenecker, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+implications+of+neuroplasticity+-+the+role+of+rehabilitation+in+multiple+sclerosis.">Clinical implications of neuroplasticity - the role of rehabilitation in multiple sclerosis.</a> Front Neurol. 6, 36 (2015).</li><li>Mattioli, F., Bellomi, F., Stampatori, C., Capra, R., Miniussi, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroenhancement+through+cognitive+training+and+anodal+tDCS+in+multiple+sclerosis.">Neuroenhancement through cognitive training and anodal tDCS in multiple sclerosis.</a> Mult Scler. 22 (2), 222-230 (2016).</li><li>Borckardt, J. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+pilot+study+of+the+tolerability+and+effects+of+high-definition+transcranial+direct+current+stimulation+(HD-tDCS)+on+pain+perception.">A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception.</a> J Pain. 13 (2), 112-120 (2012).</li><li>Kasschau, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+Direct+Current+Stimulation+Is+Feasible+for+Remotely+Supervised+Home+Delivery+in+Multiple+Sclerosis.">Transcranial Direct Current Stimulation Is Feasible for Remotely Supervised Home Delivery in Multiple Sclerosis.</a> Neuromodulation. , (2016).</li></ol>

The authors have nothing to disclose.

This study employed the DLPFC left anodal montage24, but this could easily be interchanged for another montage and the effects of stimulation may change accordingly. Depending on the location of stimulation, the brain effects and side effects experienced may change1. Stimulation type, such as intended inhibition instead of excitement may influence effects as well. Similarly, the form of remediation paired with stimulation may influence the results of the study31. Future experiments need to be conducted with different remediation strategies paired with RS-tDCS to identify its specific affects.
While the RS-tDCS protocol focuses on providing tDCS to patients in their homes, there may still be a place for stimulation provided in a clinical setting. For example, more complex montages, such as those used by HD-tDCS, may not be feasible at home even with proper training32. The RS-tDCS protocol provides a detailed procedure to ensure clinical trial standards of treatment sessions and dosing control while delivering the stimulation at home using a tele-rehabilitation protocol. Uniform electrode preparation and placement as well as simplified procedures, including the incorporation of simpler sponge electrode techniques, ensure consistency across participants. The RS-tDCS protocol allows for the completion of stimulation sessions by cognitively and physically impaired individuals who otherwise would have great difficulty reaching the clinic daily.
All troubleshooting can be immediately addressed by the study personnel who are live video-conferencing with participants during at-home stimulation sessions. In the case that the study laptop is malfunctioning, a simple restart of the computer can resolve technical issues. In the case that study equipment malfunctions from a laptop or the tDCS device are not resolved following technical support, then study personnel should arrange for the delivery of new, properly functioning equipment.
The protocol is inherently reliant upon internet access, which is the method&#39;s greatest limitation. Currently, those without internet cannot be enrolled in any trial using RS-tDCS. The internet utilized in conjunction with our protocol enables the remote supervision in our RS-tDCS protocol.
RS-tDCS remains one of the few recognized and feasible protocols for at-home delivery of tDCS33. The large volume of sessions completed with the protocol (748 in little over a year), speaks to the effectiveness of the protocol, as other centers have reported smaller and underpowered studies. The RS-tDCS protocol has been effective in providing tDCS directly to patients with a wide range of disabilities. By enabling clinical trials with the RS-tDCS protocol, rapid recruitment and swift trial completion are possible.
The RS-tDCS protocol is generalizable to other neurologic conditions. As demonstrated here, we have already generalized our protocol to PD and plan to demonstrate the applicability of the protocol to other conditions. Both the parameters of stimulation and the remediation strategy can be adjusted to target specific treatment outcomes.

Transcranial direct current stimulation (tDCS) is a type of noninvasive brain stimulation with a wide range of potential therapeutic uses. A mild electrical current (typically &#8804;2.5 mA) is directed through electrodes placed on the scalp to influence brain activity by altering neuronal polarization1. tDCS is typically paired with a rehabilitation strategy in efforts to increase training outcomes. Other popular forms of neuromodulation, such as repetitive transcranial magnetic stimulation, are used to similar ends, but lack key advantages of tDCS such as its portability, simple applicability, and relative inexpensiveness1,2.
Multiple tDCS sessions are required for cumulative clinical benefit1,3. Behavioral effects, such as reductions in fatigue or depressive symptoms, rely upon repeated, consecutive sessions. For instance, studies have only observed such treatment effects after twenty or more sessions4,5.
Typically, tDCS is administered in clinic by a trained clinician or study personnel familiar with the facets and operations of the device and stimulation method. This is costly to both the patient and clinician as significant time, clinic space, and travel are required. As a solution to the need for daily, in-clinic tDCS, we have developed remotely supervised tDCS (RS-tDCS)6. This protocol enables at-home tDCS sessions to be completed through controlled supervision and guidance as provided by study personnel via a study laptop and has the benefit of only requiring two in-clinic visits (baseline and study-end visits) by the participant.
The patient populations chosen to pilot the methodology of this protocol include patients with multiple sclerosis (MS) and Parkinson&#39;s disease (PD). Both diseases impose distinct deficits on the patient, such as symptoms of fatigue in patients with MS and dyskinesia in patients with PD. tDCS presents a unique opportunity to improve symptoms of fatigue7 and cognitive dysfunction8,9,10 as well as to promote motor learning and control11,12. Participants representing a spectrum of disease severity were included in this study with steps taken, as permitted by RS-tDCS, to accommodate their respective disability.
Among these populations, people with MS or PD may have distinct obstacles that prevent them from conveniently reaching the clinic. Motor impairments such as confinement to a wheelchair or cognitive deficits that result in loss of autonomy can limit their inclusion in clinical trials or other cognitive studies. Additionally, familial and professional obligations reduce the time available to attend clinic, limiting availability for cognitive remediation trials confined to the clinic13. These patient populations, due to their diverse range of impairment, serve as model populations to test the limits and feasibility of RS-tDCS.
The RS-tDCS protocol marks a major step in the tDCS field, since it studies the use of stimulation, as it will be administered in a patient&#39;s care at home. The protocol strengthens the rate of recruitment, trial completion rate, relieves patient burden, and minimizes clinical costs. Herein we report the specific details of the protocol as well as preliminary findings regarding the feasibility, safety, and tolerability of the device when remotely administered.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr >
			<td >tDCS Mini-CT device</td>
			<td >Soterix</td>
			<td ></td>
			<td >Provides direct current stimulation</td>
		</tr>
		<tr >
			<td >EASYstrap with conducting cables</td>
			<td>Soterix</td>
			<td></td>
			<td >Sponges attach to the strap and the strap lays on the head</td>
		</tr>
		<tr >
			<td >EASYpad sponges</td>
			<td>Soterix</td>
			<td></td>
			<td >Premoistened sponges with 5mL of saline. Snaps into electodes.</td>
		</tr>
		<tr >
			<td >Stream laptop</td>
			<td>Hewlett Packard</td>
			<td></td>
			<td >Used for videoconferencing and cognitive remediation.</td>
		</tr>
		<tr >
			<td >Device Charger</td>
			<td>Soterix</td>
			<td></td>
			<td >Recharges the Mini-CT.</td>
		</tr>
		<tr >
			<td >TeamViewer Software</td>
			<td>Teamviewer</td>
			<td></td>
			<td >Remote desktop software that enable remote control of participant&#39;s computers.</td>
		</tr>
		<tr >
			<td >Vsee Software</td>
			<td>VSee Lab, Inc.</td>
			<td></td>
			<td >Enables HIPAA compliant video-conferencing</td>
		</tr>
		<tr >
			<td >Lumosity</td>
			<td>Lumos Labs</td>
			<td></td>
			<td >Online platform used for cognitive remediation</td>
		</tr>
	</tbody>
</table>

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.

One pilot study has been completed using the RS-tDCS protocol at Stony Brook University and a second is currently ongoing at NYULMC. Respective institutional review boards approved all study procedures at both sites.
Since the presented studies were both intended to pilot the RS-tDCS methodology, participants were not selected on the basis on symptoms but instead using broad eligibility criteria for both patients with MS and PD. Similarly, patients who could not tolerate the target amperage of the stimulation were given an option of lower amperage (detailed further below).
Study 1: 
MS participants were recruited through the Lourie Center for Pediatric MS at Stony Brook between the dates of March 2015 and February 2016. This trial was an open-label RS-tDCS study to pilot the feasibility of the protocol in MS. All participants knowingly received 20 minutes x 1.5 mA (or 1.0 mA if 1.5 mA was not initially tolerated) open-label tDCS applied to the DLPFC (left anodal)23,24,25,26,27. During the stimulation, cognitive training games30 targeting attention, information speed, and working memory were completed. The first session was completed at the end of the baseline visit in clinic and the remaining sessions were completed at-home, daily, five days per week (M-F) over the course of two weeks, for a total of nine sessions at home. In total, 26 participants were recruited for this study.
Study 2: 
MS Arm - Participants with MS were recruited through the NYULMC&#39;s MS Comprehensive Care Center between the dates of January 2016 and October 2016. This arm of the study was a randomized, double-blinded, sham-controlled trial using 2.0 mA (or 1.5 mA if 2.0 mA was not initially tolerated) of RS-tDCS applied to the DLPFC (left anodal) for twenty minutes daily. The first stimulation session was completed at the end of the baseline visit in clinic while the remaining nineteen at-home sessions were completed over the following four weeks (M-F). This study is ongoing and we report the findings of 20 MS participants that have been recruited and completed the study.
PD Arm - Participants with PD were recruited through the NYULMC&#39;s Fresco Institute for Parkinson&#39;s and Movement Disorders between the dates of June 2016 and December 2016. This arm&#39;s focus was to pilot the RS-tDCS protocol in patients with PD, similar to the pilot study conducted with MS. The study was open-label, and all participants knowingly received 2.0 or 1.5 milliamps of tDCS applied to the DLPFC (left anodal). Similar to Study 1, the first session was completed at the end of the baseline clinic visit and the remaining nine sessions were completed at the participant&#39;s home remotely (M-F). This study is ongoing and we report the completed findings from 6 PD participants that have been recruited.
To assess the feasibility and tolerability of the RS-tDCS protocol, we measured the percentage of completed sessions, adverse event rates, and the average intensity of the most common adverse events.
A total of 748 RS-tDCS sessions have been successfully completed across 46 participants in approximately a year. This supports the feasibility of the RS-tDCS protocol. In Study 1, 2 participants discontinued tDCS: one participant discontinued due to personal obligations and the other participant discontinued due to study stop criteria of uncomfortable sensations of skin burning greater than a score of 7 (albeit without physical burns). In Study 2, 2 participants were discontinued: one was discontinued due to an abnormal adverse event of &#34;tongue tingling&#34; and the other was discontinued due to a pain rating of 7 (on the 1-10 analog scale) from headaches. From the PD cohort, no patients have been discontinued. In total, 4 patients were discontinued from the study and none of them were discontinued due to an inability to complete the RS-tDCS sessions.
The numbers of adverse events per stimulation type were tallied and their rates of occurrence were calculated. The stimulation types have been placed into four different categories: 1.5 mA open-label, 2.0 mA blinded, 2.0 mA open-label, and the sham condition. The rationale for division into these categories is that participants may have differing interpretations of their sensations depending on what they expected during stimulation. As seen in Figure 1, the three most common adverse events were sensations of skin tingling, itching, and burning (no participants received physical burns).
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56211/56211fig2.jpg" /> 
Figure 2: Rates of adverse events experienced with tDCS.&#160;1.5 mA OL refers to sessions in which participants knowingly received 1.5 mA of open-label tDCS. 2.0 mA BL refers to sessions in which participants were blinded to the stimulation they were receiving which was 2.0 mA tDCS. 2.0 mA OL refers to sessions in which participants knowingly received 2.0 mA of open-label tDCS. Sham refers to sessions in which participants were blinded to the stimulation they were receiving but only received 60 s of stimulation at the beginning and end of the 20 min session in order to simulate active tDCS.&#160;<a href="https://cloudflare.jove.com/files/ftp_upload/56211/56211fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
The average intensity of the most common adverse events has been calculated. As shown in Table 1, the average intensity of the most common adverse events did not exceed a score of 3 (on a 1-10 visual analog scale, 1 being mild and 10 being extreme) for any of the adverse events in any of the stimulation conditions.
<table>
	<tbody>
		<tr>
			<td>Session Condition</td>
			<td>Total Sessions</td>
			<td>Tingling (SD, n)</td>
			<td>Itching (SD, n)</td>
			<td>Burning Sens. (SD, n)</td>
		</tr>
		<tr>
			<td>2.0 mA Blinded</td>
			<td>201</td>
			<td>1.6 (0.8, 75)</td>
			<td>2.2 (0.9, 36)</td>
			<td>2.5 (1.3, 59)</td>
		</tr>
		<tr>
			<td>2.0 mA Open-Label</td>
			<td>104</td>
			<td>1.9 (1.2, 43)</td>
			<td>1.8 (1.1, 8)</td>
			<td>2.0 (1.4, 32)</td>
		</tr>
		<tr>
			<td>1.5 mA Open-Label</td>
			<td>268</td>
			<td>2.4 (2.2, 161)</td>
			<td>2.0 (1.6, 65)</td>
			<td>2.9 (2.0, 79)</td>
		</tr>
		<tr>
			<td>Sham</td>
			<td>175</td>
			<td>1.9 (1.2, 72)</td>
			<td>1.7 (0.9, 17)</td>
			<td>1.6 (1.2, 46)</td>
		</tr>
	</tbody>
</table>
Table 1: Average intensity of commonly experienced adverse events on a visual analog scale (1-10, mild-intense).
The stimulation also shows promise for symptom management as can be seen in Figure 3. Cohen&#39;s d values were calculated for change in mood, fatigue, and pain from baseline to study end for MS patients in studies 1 and 2. PD patients were not included in this analysis due to the small cohort completed to date (n=6). An effect size analysis was employed due to the small sample sizes in each study to identify signals suggesting efficacy. The active sessions in Studies 1 and 2 showed far greater average effect sizes for improvement. On average, participants who received active tDCS reported greater positive effects, and had less negative effects, fatigue, and pain by study end compared to the sham tDCS group.
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56211/56211fig3.jpg" /> 
Figure 3: Cohen&#39;s d for symptomatic outcome measures. Positive effects were shown by the participants receiving 20 active sessions of rtDCS while the participants in sham group had negligible effects. <a href="https://cloudflare.jove.com/files/ftp_upload/56211/56211fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability at JoVE.com

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

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 ...

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8.0K Views.  Langone Medical Center. 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.

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

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 ...

Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the stimulation parameters (e.g., orientation, field strength, and stimulation duration) need to be examined in mice brain slice preparations. Testing and arranging the orientation of the electrode relative to the position of the mice brain slice are feasible. The present method preserves the thalamocingulate pathway to evaluate the effect of DCS on anterior cingulate cortex seizure-like activities. The results of the multichannel array recordings indicated that cathodal DCS significantly decreased the amplitude of the stimulation-evoked responses and duration of 4-aminopyridine and bicuculline-induced seizure-like activity. This study also found that cathodal DCS applications at 15 min caused long-term depression in the thalamocingulate pathway. The present study investigates the effects of DCS on thalamocingulate synaptic plasticity and acute seizure-like activities. The current procedure can test the optimal stimulation parameters including orientation, field strength, and stimulation duration in an in vitro mouse model. Also, the method can evaluate the effects of DCS on cortical seizure-like activities at both the cellular and network levels.

Studies have shown that cathodal transcranial direct-current stimulation can produce suppressive effects on drug-resistant seizures. In this study, an in vitro experimental setup was devised in which the direct-current stimulation and multielectrode array recording of seizure-like activity were evaluated in mice brain slice preparation. The direct-current stimulation parameters were evaluated.

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the ...

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 ...

Transcranial Electrical Brain Stimulation in Alert Rodents

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

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, ...

In Vivo Intracellular Recording of Type-Identified Rat Spinal Motoneurons During Trans-Spinal Direct Current Stimulation

Intracellular recording of spinal motoneurons in vivo provides a &#8220;gold standard&#8221; for determining the cells&#8217; electrophysiological characteristics in the intact spinal network and holds significant advantages relative to classical in vitro or extracellular recording techniques. An advantage of in vivo intracellular recordings is that this method can be performed on adult animals with a fully mature nervous system, and therefore many observed physiological mechanisms can be translated to practical applications. In this methodological paper, we describe this procedure combined with externally applied constant current stimulation, which mimics polarization processes occurring within spinal neuronal networks. Trans-spinal direct current stimulation (tsDCS) is an innovative method increasingly used as a neuromodulatory intervention in rehabilitation after various neurological injuries as well as in sports. The influence of tsDCS on the nervous system remains poorly understood and the physiological mechanisms behind its actions are largely unknown. The application of the tsDCS simultaneously with intracellular recordings enables us to directly observe changes of motoneuron membrane properties and characteristics of rhythmic firing in response to the polarization of the spinal neuronal network, which is crucial for the understanding of tsDCS actions. Moreover, when the presented protocol includes the identification of the motoneuron with respect to an innervated muscle and its function (flexor versus extensor) as well as the physiological type (fast versus slow) it provides an opportunity to selectively investigate the influence of tsDCS on identified components of spinal circuitry, which seem to be differently affected by polarization. The presented procedure focuses on surgical preparation for intracellular recordings and stimulation with an emphasis on the steps which are necessary to achieve preparation stability and reproducibility of results. The details of the methodology of the anodal or cathodal tsDCS application are discussed while paying attention to practical and safety issues.

This protocol describes in vivo intracellular recording of rat lumbar motoneurons with simultaneous trans-spinal direct current stimulation. The method enables us to measure membrane properties and to record rhythmic firing of motoneurons before, during and after anodal or cathodal polarization of the spinal cord.