Searching for the optimal tDCS target for motor rehabilitation

Transcranial direct current stimulation (tDCS) has been investigated over the years due to its short and also long-term effects on cortical excitability and neuroplasticity. Although its mechanisms to improve motor function are not fully understood, this technique has been suggested as an alternative therapeutic method for motor rehabilitation, especially those with motor function deficits. When applied to the primary motor cortex, tDCS has shown to improve motor function in healthy individuals, as well as in patients with neurological disorders. Based on its potential effects on motor recovery, identifying optimal targets for tDCS stimulation is essential to improve knowledge regarding neuromodulation as well as to advance the use of tDCS in clinical motor rehabilitation. Therefore, this review discusses the existing evidence on the application of four different tDCS montages to promote and enhance motor rehabilitation: (1) anodal ipsilesional and cathodal contralesional primary motor cortex tDCS, (2) combination of central tDCS and peripheral electrical stimulation, (3) prefrontal tDCS montage and (4) cerebellar tDCS stimulation. Although there is a significant amount of data testing primary motor cortex tDCS for motor recovery, other targets and strategies have not been sufficiently tested. This review then presents the potential mechanisms and available evidence of these other tDCS strategies to promote motor recovery. In spite of the large amount of data showing that tDCS is a promising adjuvant tool for motor rehabilitation, the diversity of parameters, associated with different characteristics of the clinical populations, has generated studies with heterogeneous methodologies and controversial results. The ideal montage for motor rehabilitation should be based on a patient-tailored approach that takes into account aspects related to the safety of the technique and the quality of the available evidence.

[1]  P. H. Peckham,et al.  Combined Brain and Peripheral Nerve Stimulation in Chronic Stroke Patients With Moderate to Severe Motor Impairment , 2018, Neuromodulation : journal of the International Neuromodulation Society.

[2]  Sergio P. Rigonatti,et al.  Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. , 2007, Restorative neurology and neuroscience.

[3]  Lumy Sawaki,et al.  Effects of Somatosensory Stimulation on Use-Dependent Plasticity in Chronic Stroke , 2006, Stroke.

[4]  L. Bindman,et al.  Long-lasting Changes in the Level of the Electrical Activity of the Cerebral Cortex produced by Polarizing Currents , 1962, Nature.

[5]  F. Fregni,et al.  Transcranial direct current stimulation: electrode montage in stroke , 2011, Disability and rehabilitation.

[6]  Abhishek Datta,et al.  tDCS‐Induced Analgesia and Electrical Fields in Pain‐Related Neural Networks in Chronic Migraine , 2012, Headache.

[7]  Dennis J. L. G. Schutter,et al.  Targeting the Human Cerebellum with Transcranial Direct Current Stimulation to Modulate Behavior: a Meta-Analysis , 2017, The Cerebellum.

[8]  Non-invasive Cerebellar Stimulation: a Promising Approach for Stroke Recovery? , 2018, The Cerebellum.

[9]  S. Jaberzadeh,et al.  How Does Anodal Transcranial Direct Current Stimulation of the Pain Neuromatrix Affect Brain Excitability and Pain Perception? A Randomised, Double-Blind, Sham-Control Study , 2015, PloS one.

[10]  Heidi M. Schambra,et al.  Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning , 2010, Neuron.

[11]  Elzbieta Jankowska,et al.  Evidence for long‐lasting subcortical facilitation by transcranial direct current stimulation in the cat , 2013, The Journal of physiology.

[12]  Walter Paulus,et al.  Introducing graph theory to track for neuroplastic alterations in the resting human brain: A transcranial direct current stimulation study , 2011, NeuroImage.

[13]  A. Bastian Moving, sensing and learning with cerebellar damage , 2011, Current Opinion in Neurobiology.

[14]  C. Gerloff,et al.  Enhancing Consolidation of a New Temporal Motor Skill by Cerebellar Noninvasive Stimulation. , 2016, Cerebral cortex.

[15]  S. Jaberzadeh,et al.  A Meta-Analysis of Site-Specific Effects of Cathodal Transcranial Direct Current Stimulation on Sensory Perception and Pain , 2015, PloS one.

[16]  Felipe Fregni,et al.  Effects of 8-week sensory electrical stimulation combined with motor training on EEG-EMG coherence and motor function in individuals with stroke , 2018, Scientific Reports.

[17]  Vincent P. Clark,et al.  Mechanisms and Effects of Transcranial Direct Current Stimulation , 2017, Dose-response : a publication of International Hormesis Society.

[18]  C. Normann,et al.  PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal transcranial direct current stimulation (tDCS) in major depressive disorder—study design and methodology of a multicenter double-blind randomized placebo-controlled trial , 2017, European Archives of Psychiatry and Clinical Neuroscience.

[19]  Xin Zheng,et al.  Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow , 2011, NeuroImage.

[20]  Á. Pascual-Leone,et al.  Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury. , 2010, Brain : a journal of neurology.

[21]  N. Smania,et al.  Combined effects of transcranial direct current stimulation (tDCS) and transcutaneous spinal direct current stimulation (tsDCS) on robot-assisted gait training in patients with chronic stroke: A pilot, double blind, randomized controlled trial. , 2015, Restorative neurology and neuroscience.

[22]  M. Nitsche,et al.  Modulating cortico‐striatal and thalamo‐cortical functional connectivity with transcranial direct current stimulation , 2012, Human brain mapping.

[23]  Yasuo Hori,et al.  Increase in the calcium level following anodal polarization in the rat brain , 1995, Brain Research.

[24]  Vimonwan Hiengkaew,et al.  Effect of single-session dual-tDCS before physical therapy on lower-limb performance in sub-acute stroke patients: A randomized sham-controlled crossover study. , 2018, Annals of physical and rehabilitation medicine.

[25]  S. Jaberzadeh,et al.  Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: A systematic review and meta-analysis , 2012, Clinical Neurophysiology.

[26]  Jeffrey M. Hausdorff,et al.  Multitarget transcranial direct current stimulation for freezing of gait in Parkinson's disease , 2018, Movement disorders : official journal of the Movement Disorder Society.

[27]  Giovanni Pellegrino,et al.  Immediate and Late Modulation of Interhemipheric Imbalance With Bilateral Transcranial Direct Current Stimulation in Acute Stroke , 2014, Brain Stimulation.

[28]  L. Cohen,et al.  Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke. , 2007, Archives of physical medicine and rehabilitation.

[29]  R. de Raedt,et al.  Neurocognitive mechanisms behind emotional attention: Inverse effects of anodal tDCS over the left and right DLPFC on gaze disengagement from emotional faces , 2018, Cognitive, Affective, & Behavioral Neuroscience.

[30]  Á. Pascual-Leone,et al.  Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus. , 2012, Journal of neurophysiology.

[31]  Julie M. Baker,et al.  Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient , 2011, Brain Stimulation.

[32]  M. Nitsche,et al.  Physiological Basis of Transcranial Direct Current Stimulation , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[33]  L. Cohen,et al.  Effects of somatosensory stimulation on motor function in chronic cortico-subcortical strokes , 2007, Journal of Neurology.

[34]  Shapour Jaberzadeh,et al.  The effects of anodal-tDCS on corticospinal excitability enhancement and its after-effects: conventional vs. unihemispheric concurrent dual-site stimulation , 2015, Front. Hum. Neurosci..

[35]  R. Buckner The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging , 2013, Neuron.

[36]  Pablo Celnik,et al.  Cerebellar tDCS: A Novel Approach to Augment Language Treatment Post-stroke , 2017, Front. Hum. Neurosci..

[37]  Alvaro Pascual-Leone,et al.  Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients , 2007, NeuroImage.

[38]  Á. Pascual-Leone,et al.  Effects of tDCS on executive function in Parkinson's disease , 2014, Neuroscience Letters.

[39]  Min-Kyun Oh,et al.  Effect of Transcranial Direct Current Stimulation on Motor Recovery in Patients with Subacute Stroke , 2010, American journal of physical medicine & rehabilitation.

[40]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[41]  V. Di Lazzaro,et al.  Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation. , 2012, Journal of neurophysiology.

[42]  Steven Laureys,et al.  Clinical Response to tDCS Depends on Residual Brain Metabolism and Grey Matter Integrity in Patients With Minimally Conscious State , 2015, Brain Stimulation.

[43]  Michael A. Nitsche,et al.  Putative physiological mechanisms underlying tDCS analgesic effects , 2013, Front. Hum. Neurosci..

[44]  M. Hallett,et al.  Modeling the current distribution during transcranial direct current stimulation , 2006, Clinical Neurophysiology.

[45]  Agnes Flöel,et al.  tDCS-enhanced motor and cognitive function in neurological diseases , 2014, NeuroImage.

[46]  M. Nitsche,et al.  P19.21 Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation , 2011, Clinical Neurophysiology.

[47]  L. Cohen,et al.  Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke. , 2009, Stroke.

[48]  François Chollet,et al.  Correlation between cerebral reorganization and motor recovery after subcortical infarcts , 2003, NeuroImage.

[49]  P. Celnik,et al.  Cerebellar direct current stimulation enhances motor learning in older adults , 2014, Neurobiology of Aging.

[50]  Artur Luczak,et al.  Transcranial Direct Current Stimulation in Stroke Rehabilitation: A Review of Recent Advancements , 2013, Stroke research and treatment.

[51]  S. Swinnen,et al.  Anodal tDCS increases corticospinal output and projection strength in multiple sclerosis , 2013, Neuroscience Letters.

[52]  R. Calabró,et al.  Effects of cerebellar transcranial alternating current stimulation on motor cortex excitability and motor function , 2017, Brain Structure and Function.

[53]  Paul A. Pope,et al.  Task-specific facilitation of cognition by cathodal transcranial direct current stimulation of the cerebellum , 2012, Brain Stimulation.

[54]  Richard S. J. Frackowiak,et al.  How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? , 2005, The European journal of neuroscience.

[55]  M. Parazzini,et al.  Modulating Human Procedural Learning by Cerebellar Transcranial Direct Current Stimulation , 2013, Cerebellum.

[56]  A. Priori,et al.  Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis. , 2014, NeuroRehabilitation.

[57]  P. F. Vasconcelos,et al.  In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus , 2018, Scientific Reports.

[58]  Andreas R. Luft,et al.  Lesion location alters brain activation in chronically impaired stroke survivors , 2004, NeuroImage.

[59]  P. Celnik,et al.  Modulation of Cerebellar Excitability by Polarity-Specific Noninvasive Direct Current Stimulation , 2009, The Journal of Neuroscience.

[60]  Heidi Johansen-Berg,et al.  Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke , 2011, Brain : a journal of neurology.

[61]  M. Nitsche,et al.  Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. , 2002, Brain : a journal of neurology.

[62]  J. Rothwell,et al.  Bi‐directional modulation of somatosensory mismatch negativity with transcranial direct current stimulation: an event related potential study , 2014, The Journal of physiology.

[63]  Mark Hallett,et al.  Cerebellum and processing of negative facial emotions: Cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness , 2012, Cognition & emotion.

[64]  F. Fregni,et al.  A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. , 2011, The international journal of neuropsychopharmacology.

[65]  L. Bindman,et al.  The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long‐lasting after‐effects , 1964, The Journal of physiology.

[66]  P. Tugwell,et al.  Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand. , 2003, The Cochrane database of systematic reviews.

[67]  S. Oveisgharan,et al.  Enhancement of Motor Recovery through Left Dorsolateral Prefrontal Cortex Stimulation after Acute Ischemic Stroke. , 2018, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[68]  D. Stegeman,et al.  Simulating Transcranial Direct Current Stimulation With a Detailed Anisotropic Human Head Model , 2014, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[69]  Reza Shadmehr,et al.  Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories , 2014, NeuroImage.

[70]  Mark Hallett,et al.  Transcranial direct current stimulation for the treatment of Parkinson's disease , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[71]  F. Fregni,et al.  A combined therapeutic approach in stroke rehabilitation: A review on non-invasive brain stimulation plus pharmacotherapy. , 2014, International journal of neurorehabilitation.

[72]  M. Steinhauser,et al.  Stimulation of Dorsolateral Prefrontal Cortex Enhances Adaptive Cognitive Control: A High-Definition Transcranial Direct Current Stimulation Study , 2016, The Journal of Neuroscience.

[73]  Pablo Celnik,et al.  Cerebellar Direct Current Stimulation Enhances On-Line Motor Skill Acquisition through an Effect on Accuracy , 2015, The Journal of Neuroscience.

[74]  L. Cohen,et al.  Improvement of Motor Function with Noninvasive Cortical Stimulation in a Patient with Chronic Stroke , 2005, Neurorehabilitation and neural repair.

[75]  G. Hammond,et al.  The Causal Role of the Dorsolateral Prefrontal Cortex in the Modification of Attentional Bias: Evidence from Transcranial Direct Current Stimulation , 2014, Biological Psychiatry.

[76]  P. Celnik,et al.  Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. , 2011, Cerebral cortex.

[77]  Markus Zahn,et al.  Transcranial direct current stimulation: A computer-based human model study , 2007, NeuroImage.

[78]  L. Cohen,et al.  Influence of electric somatosensory stimulation on paretic-hand function in chronic stroke. , 2006, Archives of physical medicine and rehabilitation.

[79]  Sergio P. Rigonatti,et al.  Transcranial direct current stimulation of the unaffected hemisphere in stroke patients , 2005, Neuroreport.

[80]  A. Antal,et al.  Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients , 2007, Brain Research Bulletin.

[81]  B. Clark,et al.  Preliminary Evidence That Anodal Transcranial Direct Current Stimulation Enhances Time to Task Failure of a Sustained Submaximal Contraction , 2013, PloS one.

[82]  V. Welch,et al.  Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand (Review) , 2022 .

[83]  G. Morone,et al.  The ABC of tDCS: Effects of Anodal, Bilateral and Cathodal Montages of Transcranial Direct Current Stimulation in Patients with Stroke—A Pilot Study , 2013, Stroke research and treatment.

[84]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[85]  Frank Padberg,et al.  Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex—correlation or causality in stimulation-mediated effects? , 2016, Neuroscience & Biobehavioral Reviews.

[86]  Yasuo Hori,et al.  Biphasic effects of polarizing current on adenosine-sensitive generation of cyclic AMP in rat cerebral cortex , 1990, Neuroscience Letters.

[87]  Cheryl Carrico,et al.  Effects of electrode configurations in transcranial direct current stimulation after stroke , 2014, 2014 IEEE 16th International Conference on e-Health Networking, Applications and Services (Healthcom).

[88]  M. Nitsche,et al.  Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016 , 2016, Brain Stimulation.

[89]  D. Timmann,et al.  Acquisition of Conditioned Eyeblink Responses is Modulated by Cerebellar tDCS , 2014, Brain Stimulation.

[90]  Matthew Garner,et al.  The Effect of Prefrontal Transcranial Direct Current Stimulation on Attention Network Function in Healthy Volunteers , 2018, Neuromodulation : journal of the International Neuromodulation Society.

[91]  Felipe Fregni,et al.  The potential dual role of transcallosal inhibition in post-stroke motor recovery. , 2018, Restorative neurology and neuroscience.

[92]  D Comar,et al.  Noninvasive tomographic study of cerebral blood flow and oxygen metabolism in vivo. Potentials, limitations, and clinical applications in cerebral ischemic disorders. , 1981, European neurology.

[93]  G. Kwakkel,et al.  Short-Term Effects of Cerebellar tDCS on Standing Balance Performance in Patients with Chronic Stroke and Healthy Age-Matched Elderly , 2018, The Cerebellum.

[94]  Gottfried Schlaug,et al.  Dual-hemisphere tDCS facilitates greater improvements for healthy subjects' non-dominant hand compared to uni-hemisphere stimulation , 2008, BMC Neuroscience.

[95]  L. Cohen,et al.  Increase in hand muscle strength of stroke patients after somatosensory stimulation , 2002, Annals of neurology.

[96]  P. Wall,et al.  Pain mechanisms: a new theory. , 1965, Science.

[97]  M. Banissy,et al.  Transcranial Direct Current Stimulation in Sports Training: Potential Approaches , 2013, Front. Hum. Neurosci..

[98]  S.M.A. João,et al.  Analgesic efficacy of cerebral and peripheral electrical stimulation in chronic nonspecific low back pain: a randomized, double-blind, factorial clinical trial , 2015, BMC Musculoskeletal Disorders.

[99]  Leslie G. Ungerleider,et al.  The prefrontal cortex and the executive control of attention , 2008, Experimental Brain Research.

[100]  Tetsunari Inamura,et al.  Development of VR platform for cloud-based neurorehabilitation and its application to research on sense of agency and ownership , 2017, Adv. Robotics.

[101]  Alvaro Pascual-Leone,et al.  Transcranial DC Stimulation Coupled With TENS for the Treatment of Chronic Pain: A Preliminary Study , 2009, The Clinical journal of pain.

[102]  Matteo Ciocca,et al.  Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists , 2014, The Journal of physiology.

[103]  Christian Gerloff,et al.  Modulation of Training by Single-Session Transcranial Direct Current Stimulation to the Intact Motor Cortex Enhances Motor Skill Acquisition of the Paretic Hand , 2012, Stroke.

[104]  S. Page,et al.  Moving Forward by Stimulating the Brain: Transcranial Direct Current Stimulation in Post-Stroke Hemiparesis , 2016, Front. Hum. Neurosci..

[105]  Yan Fu,et al.  An Automatic Classification Method on Chronic Venous Insufficiency Images , 2018, Scientific Reports.

[106]  Gottfried Schlaug,et al.  Transcranial direct current stimulation in stroke recovery. , 2008, Archives of neurology.

[107]  A. Brunoni,et al.  A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters , 2016, Brain Stimulation.

[108]  Robert Lindenberg,et al.  Combined Central and Peripheral Stimulation to Facilitate Motor Recovery After Stroke , 2012, Neurorehabilitation and neural repair.

[109]  J. Rothwell,et al.  Driving Plasticity in Human Adult Motor Cortex Is Associated with Improved Motor Function after Brain Injury , 2002, Neuron.

[110]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[111]  Martin Lauritzen,et al.  Neuronal deactivation explains decreased cerebellar blood flow in response to focal cerebral ischemia or suppressed neocortical function , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[112]  H. Möller,et al.  Prefrontal Transcranial Direct Current Stimulation Changes Connectivity of Resting-State Networks during fMRI , 2011, The Journal of Neuroscience.