Y P O C Methodological considerations T for tDCS O N O D - PowerPoint PPT Presentation

Y P O C Methodological considerations T for tDCS O N O D MA Nitsche E S Leibniz Research Centre for Working Environment and A Human Resources, Dortmund, Germany E Department of Neurology, University Medical Hospital L Bergmannsheil, Bochum, Germany P

Y P O C T O N O D E S A E L P

Y P O Motivation C T • tDCS is O increasingly applied N • Seemingly simple O tool D • Inappropriate use E can lead to S frustrating results A E • Not all practically L relevant information P readily available

Y P O Overview C T • Devices and application O N • Protocols O D E • Physiological effects S A E • Functional effects in healthy humans and L patients P

Y P O Devices I C T O N O D E S A E L P

Y P O Devices II C  Numerous CE-certified devices available T O  Different characteristics (MRI-suited, multiple channel, N wireless, simultaneous EEG, home-use units, range of stimulation modes) O  test for appropriate current flow! D E S A E L P Salimpour et al. 2016

Y P O Electrodes - Types C T O N O D E S A E L P

Y P O Electrodes – Contact Medium C T O • Saline and cream N are suitable O • Saline: not too wet D and not too dry... E • Cream: sufficiently S thick film A E • Electrode shape L and distance are P relevant Miranda et al. 2009, Palm et al. 2014

Y P O Electrodes – Placement I C T O N O D E S A E L P Nitsche & Paulus 2000 Moliadze et al. 2010 Datta et al. 2012

Y P O Electrodes – Placement II C T O • Standard systems N (e.g. 10 20 EEG) O D • Neuronavigation E (MRI-based) S A E • Physiology-based L P

Y P O Electrodes – Placement III C T O • Not too tight N • Not too loose O • Not too wet D • Not too dry E S • Constant position A • Not too close E L P

Y P O Conclusions - Devices C T • Different devices for different needs O available N • Make sure that stimulators deliver current O as expected! D • Electrodes come in different shapes and E S designs A • Saline solution and cream/gel suited E L • Take care for constant and correct P positioning!

Y P O Stimulation protocols C T • Stimulation duration and intensity O N • Focality of stimulation O D E • Blinding S A E • Safety L P

Y P O Stimulation duration C T O N O D E S A E L P 5-13 min 4 seconds Nitsche & Paulus 2000, 2001, Nitsche et al. 2003

Y P O Stimulation duration and intensity C T O N O D E S A 13 vs 26 min anodal tDCS 1 vs 2 mA cathodal tDCS E L Longer and stronger is not always better P Batsikadze et al. 2013, Monte-Silva et al. 2013

Y P Transferability to other cortices? O C T Visual cortex Somatosensory cortex O N O D E S A E L P Antal et al. 2004, Matsunaga et al. 2004

Y Shaping effects of tDCS by P O systematic protocol adaptation C T O N O D E S A E L P Cuypers et al. 2013, Boggio et al. 2006

Y P Conclusion Protocols I O C T • Protocols inducing acute and after-effects O available N • Longer and stronger stimulation does not O always increase efficacy D • Repetition can result in bidirectional E S interference effects A • Not identical effects in all areas E L • Titration of effects preferable for new P areas

Y P O Focalizing by reducing the size of C the stimulation electrode T O N O D E S A E L P

Y P Focalizing by use of an extracephalic return O electrode? C T O N O D E S A E L P Moliadze et al. 2010

Y P Focalizing by modification of O electrode shape? C T O N O D E S A E L P Kuo et al., 2013

Y P O Enhanced focality (?) C T O N O D E S A E L P Nikolin et al., 2015

Y P O New multi-electrode approach C „monopolar “ „bipolar “ T O N O D E S A E L P Ruffini et al. 2015

Y P Increasing the efficacy of tDCS by O network stimulation C T O N O D E S A E L P Fischer et al., 2017

Y P O Conclusion Protocols II C T • Focality of tDCS can be increased O • ...by altering electrode size N • ...by altering electrode configuration O D • ...by altering electrode position E • Application-dependent usefulness S • Physiological alterations induced by A E these alternative protocols not L sufficiently explored so far in each case P

Y P Blinding of stimulation O C T O N O D • Ramping of stimulation • Specific stimulators with coded stimulation • Reliable blinding at 1 mA E • Might be not reliable for • One experimenter only S stronger stimulation conducts stimulation A • Might be not reliable for • Reduction of repetitive sessions E stimulation-generated • Reduction of tingling L erythema with sensation by local P ketoprofen anesthetics • Active control

Y P Safety vs tolerability O C T O N Safety: induction of structural or functional damage O Tolerability: unintended or uncomfortable effects without D damage E S A E L P

Y P Safety and tolerability of tDCS I O C  No NSE enhancement T  No brain edema O  No structural damage N O D E S A E L P Nitsche et al. 2003, 2004, Poreisz et al. 2007

Y P Safety and tolerability of tDCS II O C This review updates and consolidates evidence on the safety T of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of O evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence- N based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation O with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are D avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose–response curves and dose metrics (e.g. current, E duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given S to the- oretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, A stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current E Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of L conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports P of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.

Y P Conclusion - Safety and tolerability of O tDCS C T O • Well tolerated, no serious adverse N effects O • Applies to conventional protocols D • Side effects can be monitored by tDCS E questionnaires (e.g. Poreisz et al. 2007) S A • Side effects like skin burns reported E caused by inappropriate application L P

Y P Monitoring physiological effects of tDCS - O preconditions C T O • Participants in relaxed, stable state N • Test session might help O D • Avoid unintended interference effects in case of multiple sessions E S • Avoid interference effects between A stimulation and monitoring method E L P

Y P Monitoring physiological effects of tDCS - O methods C T O N O D •Cortical excitability •Cortical activity •Cortical activity •Motor evoked potentials •Resting EEG •Functional MRI E S •Visual phosphenes •EP •BOLD A •TMS-EEG •ERP •ASL E •MRS L •Structural MRI P

Y P Monitoring physiological effects of tDCS - O TMS C T O •Reliable hot spot and coil position N •Reliable baseline O •Constant state throughout experiment D •Sufficient number of stimuli (20 or more) E S •No muscle activity before TMS A •TMS EEG over regions which do not E induce relevant muscle contraction L P

Y P Monitoring physiological effects of tDCS - O EEG C T O •Online or offline N •Online: cave artifacts, no EEG O electrodes under stimulation electrodes D •Offline: cave conductivity alterations E at former tDCS electrode positions S •Solution: integrated approaches with A recording/stimulation electrodes E L P Polania et al. 2011, Antal et al. 2004

Y P Monitoring physiological effects of tDCS - O MRI C T •Online or offline O •Online: cave artifacts, MRI-suited N tDCS system required O •Offline: tDCS outside scanner will D cause delay, and enhance „noise“ due to altered head position E •No saline-moisted sponges (will get S dry) A •Mark electrode positions with oil E capsules L •Cables parallel to magnet bore P •Sufficient sample size Polania et al. 2011, Jamil et al. submitted