By Faddi G. Saleh Velez, MD, participant of the Young Stroke Physicians and Researchers Research Design Workshop for Studies in Development – ESOC 2019 Department of Neurology, University of Chicago Medical Center, United States of America

Although the neuropsychiatric field continues to rapidly evolve, and newer and more accurate treatments continue emerging hastily, there is still a vast amount of disorders and pathologies that remain not well understood and without accurate therapies. The field of non-invasive brain stimulation (NIBS) arose, contrary to the believe of many people, several thousand years ago. The use of electricity for therapeutic purposes seems to date even to the 3000 before Christ (B.C.) as historical drawings describe that ancient Egyptians discovered the electrical properties of the Nile catfish1,2. However, it was around 1780s when Luigi Galvan and Alexandro Volta were capable of inducing muscle twitching in animals utilizing the first electrical stimulation device developed1,2. From their design is that a large amount of electrical stimulator devices were created.

Nowadays, the main goal of the field of NIBS is to study and evaluate the effects of small electrical currents applied directly to the brain or peripheral nerves as to understand the underlying mechanism of a disease and as well to develop new therapeutic approaches to treat them3,4,5. The most common and investigated techniques in the past decades are transcranial magnetic stimulation (TMS) which has been approved by the Food and Drug administration (FDA) for the management of treatment-resistant Major depressive disorder and migraine; and transcranial direct current stimulation (tDCS) which has not been approved by the FDA for the treatment of any specific disorder, nonetheless the device was approved for research purposes and can be currently applied as “off label” treatment4,5.

The latest technique is in fact the technological tool that is currently most investigated in clinical trials all over the world, having over 700 clinical studies under development in several neuropsychiatric disorders and an approximate of more than 800 peer-reviewed scientific manuscripts are published yearly related to tDCS. In this regard, we are currently developing a clinical trial recently presented at the ESOC 2019 young stroke physician and researcher workshop in Milan. The trial evaluates the safety and feasibility of tDCS in patients with paroxysmal sympathetic hyperactivity after acute stroke or traumatic brain injury in an acute setting. In particular in stroke patients, we believe that the presence of either ischemic or hemorrhagic lesions disrupts network connections between central centers of autonomic system control that can be safely modulated with the effects of mild direct electrical currents that tDCS exerts.

TDCS as implied by its name is a non-invasive modulatory technique in which two electrodes soaked in saline solution are applied directly over the scalp. The device is powered by a 9 millivolt (mv) battery that delivers small direct currents (1 to 2 milliamperes) with the goal of modulating either facilitating or difficulting neuronal network connections6. Even though its mechanisms of action are not completely well described; tDCS seems to modulate neuronal activity by increasing (anodal) or decreasing (cathodal) action potential threshold, therefore promoting changes in brain excitability6,7. As a modulatory technique, the effects of tDCS vary depending on the type of stimulation applied and the current “brain state” of the subject of intervention. Being most of the times: anodal an excitatory type and cathodal an inhibitory tool6,7. tDCS is now widely investigated in combination with other therapies (i.e, medications, behavioral therapies) as it is believed that tDCS effects are higher in networks that are activated or primed at either prior, after or at the moment of stimulation, and changes in the patients neuronal activity can affect the stimulation3,6,7.

TDCS is a “flexible technique” that can be used in several disorders (i.e, stroke, neuropathic pain, etc.) in which an imbalance in excitation and inhibition networks seems to play a role4,8. The capability to easily adjust and modify the montage (electrode positioning over the scalp) in the brain4 allows us to target determined pathways and networks that are presumably involved in the pathophysiology of a specific disease4.

TDCS is a safe technique; several studies have been performed as to evaluate safety, showing few transitory side effects, being itching, tingling and transient headache the most frequently described by patients9,10. Additionally, few moderate adverse effects have been reported (i.e, acute mood changes)9,10. However, although the application of tDCS seems quite simple, the underlying mechanism of its application involves short- and long-term effects as it has been shown that a single stimulation is able to generate long-term potentiation changes through the modulation of neuronal channels and receptors causing endogenous plasticity changes in brain networks. Therefore its application requires of dedicated and specific training and it should only be performed by certified providers and researchers11.

Although all the current literature and published research has shown extremely promising results with the use of tDCS in the field of NIBS, there is still a large need of more and larger studies as to understand in its totality the underlying mechanisms of its effects and potential clinical applications in different clinical disorders.

 

References

  1. C.I. Sarmiento, D. San-Juan, V.B. Prasath. Letter to the Editor: Brief history of transcranial direct current stimulation (tDCS): from electric fishes to microcontrollers. Psychol Med. 2016 Nov;46(15):3259-3261. Epub 2016 Aug 30.
  2. A. Heidland, G. Fazeli, A. Klassen, K. Sebekova, H. Hennemann, U. Bahner , B. Di Iorio. Neuromuscular electrostimulation techniques: historical aspects and current possibilities in treatment of pain and muscle waisting. Clin Nephrol. 2013 Jan;79 Suppl 1:S12-23.
  3. N. Rochea, M. Geigera, B. Busselb. Mechanisms underlying transcranial direct current stimulation in rehabilitation. Annals of Physical and Rehabilitation Medicine. Volume 58, Issue 4, September 2015, Pages 214-219
  4. M.F.G. Lucena, P.E.P. Teixeira, C. Bonin Pinto, F. Fregni. Top 100 cited noninvasive neuromodulation clinical trials. Expert Rev Med Devices. 2019 May 26:1-16
  5. F. Fregni, M.A. Nitsche, C.K. Loo, A.R. Brunoni,P. Marangolo, J. Leite, S. Carvalho, N. Bolognini, W. Caumo, N.J. Paik, M. Simis, K. Ueda, H. Ekhitari, P. Luu, D.M. Tucker, W.J Tyler, J. Brunelin, A. Datta, C.H. Juan, G. Venkatasubramanian, P.S. Boggio, M. Bikson. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin Res Regul Aff. 2015 Mar 1; 32(1): 22–35.
  6. A. F. DaSilva, M. S. Volz, M. Bikson, F. Fregni. Electrode Positioning and Montage in Transcranial Direct Current Stimulation. J Vis Exp. 2011; (51): 2744.
  7. C.B. Pinto, B. Teixeira Costa, D. Duarte, F. Fregni. Transcranial Direct Current Stimulation as a Therapeutic Tool for Chronic Pain. J ECT. 2018 Sep;34(3):e36-e50
  8. C.B. Pinto, F.G. Saleh Velez, N. Bolognini, D. Crandell, L.B. Merabet, F. Fregni. Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol. JMIR Res Protoc. 2016 Jul 6;5(3):e138
  9. A.R. Brunoni, J. Amadera, B. Berbel, M.S. Volz, B.G. Rizzerio, F. Fregni. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int. J. Neuropsychopharmacol., 14 (2011), pp. 1133-114
  10. H. Matsumotoa, Y. Ugawa. Adverse events of tDCS and tACS: A review. Clinical Neurophysiology Practice. Volume 2, 2017, Pages 19-25
  11. G. Kronberg, M. Bridi, T. Abel, M. Bikson, L.C. Parra. Direct Current Stimulation Modulates LTP and LTD: Activity Dependence and Dendritic Effects. Brain Stimul. 2017 Jan – Feb;10(1):51-58