Basic and Clinical August 2013, Volume 4, Number 3 Review Paper: Methodological Dimensions of Transcranial Brain Stimulation with the Electrical Current in Human Maryam Rostami1, 4, Mehrshad Golesorkhi1, 2, 5, Hamed Ekhtiari1, 2, 3* 1. Translational Neuroscience Program, Institute for Cognitive Science Studies, Tehran, Iran. 2. Neuroimaging and Analysis Group, Research Center for Molecular and Cellular Imaging, Tehran University for Medical Sciences, Tehran, Iran. 3. Iranian National Center for Addiction Studies, Tehran University for Medical Sciences, Tehran, Iran. 4. Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran. 5. Department of Computer Science, School of Mathematics, Statistics and Computer Science, University of Tehran, Tehran, Iran. Article info: A B S T R A C T Received: 16 October 2012 Transcranial current stimulation (TCS) is a neuromodulation method in which the patient is First Revision: 10 February 2013 exposed to a mild electric current (direct or alternating) at 1-2 mA, resulting in an increase Accepted: 20 May 2013 or a decrease in the brain excitability. This modification in neural activities can be used as a method for functional human brain mapping with causal inferences. This method might Key Words: also facilitate the treatments of many neuropsychiatric disorders based on its inexpensive, Transcranial Electrical Stimulation (tES), simple, safe, noninvasive, painless, semi-focal excitatory and inhibitory effects. Given this, Transcranial Direct Current a comparison amongst different brain stimulation modalities has been made to determine Stimulation (tDCS), the potential advantages of the TCS method. In addition, considerable methodological Transcranial Alternating Current details on using TCS in basic and clinical neuroscience studies in human subjects have Stimulation (tACS), been introduced. Technical characteristics of TCS devices and their related accessories with Non Invasive Brain Stimulation regard to safety concerns have also been well articulated. Finally, some TCS application (NIBS). opportunities have been emphasized, including its potential use in the near future. 1. Introduction its discovery while it has been taken into consideration over the previous years. Hence, plenty of studies, pilot or hroughout the previous decades, thera- proof-of-principle, have been carried out to investigate peutic stimulation modalities have made a whether it can eventually result in a clinically approved great influence on paving the way towards application or not. Actually, a brilliant progress has been treating a number of neuropsychiatric dis- made and is still moving towards accomplishment in or- T orders. In the competitive field of achiev- der to have its efficacy depicted as a beneficial method in ing different ways to modulate the brain activity in a both basic and clinical neuroscience. The present article certain direction, there have been some other types of provides a technical comparison among the recent mo- brain stimulation techniques including TMS (Transcra- dalities of brain stimulation and presents an introduction nial Magnetic Stimulation), ECS (Electro Convulsive to the currently commercially available TCS devices il- Stimulation) and DBS (Deep Brain Stimulation) in par- lustrating some of their technical characteristics. More- allel with the presently focused technology, TCS (Tran- over, a brief discussion on TCS electrodes in addition to scranial Current Stimulation). TCS, the re-emerged way applications in basic studies where this method reveals of brain stimulation, had been forgotten for a while after as a potential method of choice will be made. * Corresponding Author: Hamed Ekhtiari, MD, Translational Neuroscience Program, Institute for Cognitive Science Studies. Address:No. 18, Pezeshkpour Alley, Vali-e-asr Avenue, Tehran, 1594834111,, Iran. Tel: +98 21 88802065, ext:119 E-mail: [email protected]/ [email protected] 190 Basic and Clinical August 2013, Volume 4, Number 3 2. Historical Overview & Hopkins, 1970; Lifshitz & Harper, 1968) until the 1990s (indeed from 2000s)that TCS came back to both The rudimentary idea of ‘therapeutic electricity’ is therapeutic and cognitive studies, specifically in human relatively old if we consider the application of some subjects. This approach started to offer new hopes after animals, fish for instance, to treat some neurological disappointing results came from pharmacological stud- disorders(Priori, 2003). Luigi Galvani and Alessandra ies where psychotropic drugs failed to control refractory Volta were two of such researchers who benefited from an patients’ symptoms. animal source of electricity to do tDCS-based researches. As such, many fundamental studies were made until the 3. Mechanism of Action 19th century by which TCS was developed as a technical method of brain stimulation. Eduard Hitzig (1867) who Based on recent neuroimaging studies, serving as was one of the pioneers in utilizing the constant current a helpful tool for improving the efficacy of stimula- to treat depression happened to notice involuntary move- tion according to determination of targeted area, some ment of the subjects’ eyes when doing his experiments. main effects have been discovered to better understand In collaborationwith an expert anatomist, Gustav Fritsch, the mechanism of tDCS. The imaging modalities such Hitzig conducted other studies to verify such phenome- as positron emission tomography (PET)(Lang et al., non. He ultimately demonstrated the correlation between 2005), functional magnetic resonance imaging (fMRI) stimulating different cortical areas and distinct responses (Baudewig, Nitsche, Paulus, & Frahm, 2001)and mag- in the contralateral limb (Gross, 2007; Pauly, 1983). netic resonance spectroscopy(Arul-Anandam & Loo, 2009; Rango et al., 2008)can be considered in this cat- Later, Bishop and Erlanger (1926) conducted a related egory. These methods have proven some changes in the study on the effect of polarity on motor neurons, which regional blood flow, glutamatergic neurotransmission led to the fact that the anodal stimulation would cause and membrane function after stimulating the brain re- an increase in the membrane potential difference, while gions distal to the sites involved. the cathodal one would result in a decrease of the same (Bishop & O'Leary, 1950). In the1960s, Bindman dis- Noteworthy is that, the tDCS potentially changes covered that a 0.1–0.5 μA of electrical current would suf- the spontaneous firing rates without influencing the ficiently produce a neural excitability shift in rat’s cortex action potentials (Arul-Anandam, Loo, & Sachdev, which remained for some hours after the stimulation 2009) and this is mainly due to the current densities be- was terminated(Bindman, Lippold, & Redfearn, 1962, ing less than the action potential threshold of cortical 1964). Such an incidence evoked a considerable enthu- neurons(Tehovnik, 1996; Wagner et al., 2007).Some siasm to modulate the brain excitability through brain studies have indicated that tDCS works successfully in polarization, which would cause a long-lasting result at stimulation since it changes the resting membrane poten- the expense of a relatively short duration of stimulation. tial while blocking the sodium ion channels through spe- cial drugs in order to decompose the changes in motor- Consequently, Lippold and Redfearn found many evoked from the resting potential(Liebetanz, Nitsche, benefits of brain polarization to treat depressive disor- Tergau, & Paulus, 2002; Nitsche et al., 2003). ders in patients, especially in those who had failed to respond to prior methods, including ECT (Electrocon- 4. Different Brain Stimulation Modalities vulsive Therapy). This became more evident following the experiments on rats’ cortex in collaboration with Currently, there are a variety of brain modulation meth- Bindman(Bindman, et al., 1964; Lippold & Redfearn, ods utilizing the electric and magnetic fields in order to al- 1964; Redfearn, Lippold, & Costain, 1964). Taken in ter the brain’s activity. Some of these include, ECT (Elec- to account that all subjects were healthy , these inves- troconvulsive Therapy), VNS (Vagus Nerve Stimulation), tigators found that the anodal stimulation increases the TMS (Transcranial Magnetic Stimulation), DBS (Deep alertness, mood and motor activity, while the cathodal Brain Stimulation), Ultrasonic and Photonic stimulation. one results in apathy and quietness(Lippold & Redfearn, 1964; Redfearn, et al., 1964). Costain continued to carry In table 1, some of these modalities are being compared out some controlled experiments to further prove the based on the interface, waveform and their general char- efficacy of such a method(Costain, Redfearn, & Lip- acteristics, stimulating machine and the approximate dura- pold, 1964). However, the desire to hold on the studies tion of stimulation. This is to provide an insight into techni- disappeared while trying to reach the analogous results cal properties of such methods. These descriptions partly (Arfai, Theano, Montagu, & Robin, 1970; Hall, Hicks, prove the privileges of TCS over the other modalities. 191 August 2013, Volume 4, Number 3 For TCS in particular, the interface is defined as a saline of the TCS device here describes the threshold of stimu- soaked cotton pad containing rubber electrodes for con- lation in which the device is turned off in order not to ex- ventional stimulation while some tiny set of electrodes ceed the outcome current.