Clinical Neurophysiology 125 (2014) 217–219
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
Transcranial pulsed current stimulation: A new way forward? See Article, pages 344–351
There has been interest for more than 200 years in the potential use of low intensity electrical currents to try to modulate and modify brain activity. Various forms of electrical stimulation were developed in the 18th century, for example when galvanic (direct current) stimulation was applied by Giovanni Aldini to his own head (Zaghi et al., 2010). By the 1870s German psychiatrists were investigating the use of electrical stimulation to treat patients with what appear to have been a variety of mood and psychotic disorders. Notably, some of the publications from this time differentiated between the use of galvanic stimulation: the equivalent of modern day transcranial direct current stimulation (tDCS), and faradic stimulation: an approach utilising an alternating current (Steinberg, 2013) with different clinical indications suggested for differing types of stimulation. Interestingly, they also described a method where the stimulating electrode was removed from the skin surface intermittently and reapplied (intermittent galvanisation) (Steinberg, 2013). These approaches to brain stimulation faded from use particularly with the interest developed in the 20th century in the use of convulsive forms of electrical stimulation. However, the last decade has seen an unprecedented explosion in research on techniques of this sort, their effects on brain activity and their potential therapeutic utility. Somewhat mirroring these early historical developments, there are two commonly utilised forms of electrical stimulation that are currently being actively investigated as potential therapeutic tools. tDCS involves the application of a low intensity constant current between an anode and cathode (Nitsche et al., 2008). In typical applications, tDCS stimuli are applied for between 10 and 20 min at a time. Transcranial alternating current stimulation (tACS) on the other hand, involves the application of an alternating current, such that the electrical current flow cycles backwards and forwards across time at a fixed stimulation frequency (Antal and Paulus, 2013). tDCS, and to a somewhat lesser degree tACS, have been subject to a considerable body of research. This research has established their capacity to modulate cortical excitability in motor cortex and other brain regions and is suggesting that these methodologies have therapeutic potential in the treatment of a number of conditions (Brunoni et al., 2012; Herrmann et al., 2013). For example, research has suggested that tDCS may improve cognition in disorders such as Parkinson’s disease and schizophrenia, it may modulate the experience of pain or improve mood in patients with depression (Nitsche and Paulus, 2011; Brasil-Neto, 2012; Berlim et al., 2013). In spite of this research and the historical interest in electrical stimulation methods, we are still at a relatively early stage in
understanding how to optimise these non-invasive forms of brain stimulation. It is notable that one characteristic of both tDCS and tACS differs significantly from other forms of neural stimulation: in particular the constant nature of the current applied in both of these techniques. Other forms of neural stimulation, including electroconvulsive therapy, vagal nerve stimulation, spinal cord stimulation, transcutaneous nerve stimulation and deep brain stimulation all differ significantly from these two techniques in this way (Zaghi et al., 2010). When current is applied to stimulate nervous tissue in these applications, the current is interrupted rather than constant. This raises a significant question as to whether non-constant current stimulation can be effectively applied to noninvasively modulate brain activity, and whether there may be advantages in non-constant current stimulation when applied to modify traditional methods of tDCS or tACS. Jaberzadeh et al. (2014) have started to explore this possibility. In this study, they applied the use of a technique which they describe as transcranial pulsed current stimulation (tPCS), something that might be considered the modern equivalent of 18th century intermittent galvanisation. tPCS is essentially a non-constant current form of direct current stimulation where a current is applied through an anode and cathode with a fixed stimulation amplitude. However, instead of applying stimulation constantly as with tDCS, the stimulation is interrupted at regular intervals, defining the pulse duration, frequency and inter-pulse intervals of stimulation: a format much more comparable to other forms of neural stimulation. In this study, they compared two forms of tPCS: one with a short and one with a long inter-pulse interval (50 and 650 ms) but where the pulse width was kept constant. They compared these to a standard form of tDCS and a sham condition. Importantly, the total charge applied to the brain was kept constant across all three active stimulation conditions. With this design they clearly found that anodal tPCS with a short interstimulus interval appears to produce greater effects on corticospinal excitability (CSE) than tDCS or a tPCS condition with a significantly longer inter-stimulus interval. This research raises a series of interesting and important questions that hopefully the authors and others will go on to explore. The first of these concerns the method in which the investigators controlled for differences in stimulation type across treatment conditions. As mentioned above, across both the tPCS and the tDCS conditions the total charge was kept constant across conditions. This seems a reasonable and logical element to keep constant across intervention conditions. However, we don’t know whether total charge is directly related to the efficacy of these forms of
1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.10.009
218
Editorial / Clinical Neurophysiology 125 (2014) 217–219
non-invasive electrical stimulation. This is implied by early tDCS studies where a longer duration of stimulation was related to greater stimulation effects (Nitsche and Paulus, 2001). However, it is possible that charge isn’t the feature most closely linked to the effects of stimulation, but, for example that time of persistent stimulation or maximal amplitude are ultimately more important independently of overall charge. In this context, an additional experiment would be useful to compare whether the same effects on CSE are achieved with similar stimulation conditions but where the amplitude of the current is kept constant rather than the total charge. Second, this is clearly just the first step in exploring the potential use of tPCS. Further studies are required to explore the optimal conditions for inducing changes in CSE with this modality. This study suggests that shorter interstimulus intervals are likely to be more effective than longer intervals but whether the 50 ms interval utilised here is optimal is clearly unknown. In addition to the interstimulus interval, research is required to explore whether variations in pulse duration are important and combining these factors to explore the actual effect of differing frequencies of stimulation. In regards to frequency, a relevant but as yet unexplored question relates to whether the most effective frequency of pulsed stimulation is likely to relate to the underlying baseline oscillatory frequency of brain activity prior to exposure to, or during exposure to, this form of stimulation. Presumably, there may be benefits from the use of this type of pulsed stimulation in entraining oscillatory activity in some manner. A third and highly critical question, that is applicable across all types of non-invasive brain stimulation, is concerned with whether findings such as these achieved in the motor cortex can be extrapolated to stimulation of non-motor regions. Studies such as those conducted by Jaberzadeh et al. (2014) are typically performed in the motor cortex as this may have relevance to the use of non-invasive brain stimulation in the treatment of neuro-motor disorders, but also because of the ease of experimental design and implementation. In the application of electrical stimulation to the motor cortex there are reliable and easily recorded dependent variables that may be rapidly assessed (transcranial magnetic stimulation (TMS) measures of CSE). However, many clinical applications of non-invasive brain stimulation techniques require application to non-motor regions where it is far harder to establish optimal stimulation parameters. It is increasingly possible to assess the effects of non-invasive brain stimulation in non-motor regions by assessing local cortical excitability using TMS–EEG methods although this form of assessment is significantly more complicated than assessing activity in motor cortex (Fitzgerald, 2010; Rogasch and Fitzgerald, 2013). First, the equipment required for optimal TMS–EEG data collection is more expensive, time-consuming and complicated to use than simple electromyography (EMG) (Rogasch and Fitzgerald, 2013). Second, a significantly greater number of data points needs to be collected to reliably assess excitability using EEG as compared to EMG: in many experiments between 50 and 75 stimuli are applied for each measurement of excitability with EEG compared to between 10 and 20 with EMG. Finally, the processing and analysis of TMS–EEG data and particularly addressing various stimulation artefacts, is markedly more complex than the process for analysing EMG data (Mutanen et al., 2013; Rogasch et al., 2013). Therefore, it is highly desirable if stimulation in motor cortex can be used as a model that can be potentially applied to develop non-invasive brain stimulation methods that can be subsequently utilised in non-motor brain regions. For example, studies could be relatively easily done to define optimal tPCS pulse width, frequency and other characteristics in motor cortex prior to their application in non-motor indications, such as mood disorders or to enhance cognitive functioning. However, perhaps more limited but careful
studies are going to be required to validate the degree to which findings in motor cortex can be translated to non-motor regions, and these may need to be repeated for each potential different site of stimulation application. It is also possible that an improved understanding of the mechanism of action of tPCS and other forms of non-invasive brain stimulation will be able to be used to fast track the development of optimal clinically applicable protocols. Although a significant body of work has investigated the mechanism of action of tDCS (Zaghi et al., 2010; Nitsche and Paulus, 2011), the degree to which the effects of this technique on CSE are mediated by changes in transmembrane potentials and/or synaptic alterations remains unclear. It is possible that tDCS effects the quantitative characteristics of membrane excitability (how likely neurons are to fire) as well as the characteristics of transmembrane or synaptic proteins (Stagg and Nitsche, 2011). Regardless, given that the magnitude of effects produced with tDCS are directly related to the duration of stimulation (Nitsche and Paulus, 2001), these changes are presumably produced through the cumulative effects of the small currents applied. The mechanism of action of tACS, remains even less well established (Zaghi et al., 2010). tACS does not appear to have the same strong effects that tDCS has on local cortical excitability (Antal et al., 2008) and its effects on broader electrical activity as studied with EEG are inconsistent or at least very specifically dependent on stimulation parameters including location (Zaghi et al., 2010). Jaberzadeh et al. (2014) propose that the greater effects seen with tPCS compared to tDCS in their experiment relates to the phasic effects of this form of stimulation. Given the fixed charge density applied between tPCS and tDCS and the greater effects seen with the former, this seems a reasonable assumption. If this is the case, the frequency of stimulation may well be a much more critical factor than pulse length and the total charge applied across time. Certainly, the rationale for the application of tACS has been based around the interaction with endogenous oscillatory activity and this may well apply to tPCS, although some research suggests tACS may not work via the modulation of brain oscillations (Brignani et al., 2013). If frequency is relevant, consideration should be given towards the development of protocols that individualise stimulation parameters, especially frequency, based upon individual subject’s oscillatory characteristics. It is important to note that if the mechanisms of action of tPCS (and tACS) are very much related to underlying oscillatory activity, optimal parameters for these techniques may translate more poorly from motor cortex to other brain regions where intrinsic brain rhythms are likely to significantly differ. If tPCS does prove to be a more effective method of enhancing CSE compared to other non-invasive brain stimulation methods, this will have significant implications for the development of non-invasive brain therapies for both motor disorders, and disorders where the pathophysiology is primarily localised in nonmotor brain regions. Small studies have suggested potential therapeutic benefits of tDCS approaches to a series of clinical conditions such as depression (Berlim et al., 2013) but in none of these conditions have large multi-site studies been conducted. Unfortunately, it was many years from the conduct of the first TMS studies until this technique was able to be utilised in clinical practice and this has only happened for limited conditions to date. This delay in part related to the conduct of a large series of small investigatorinitiated, rather than larger multi-site studies. There is certainly the real possibility that the development of direct current and related electrical therapies will be drawn out in a similar manner, especially given limitations in the degree to which intellectual property in this domain can be protected and the impact that this has on pathways to commercialisation. On the other hand, as tPCS develops over coming years, hopefully the science establishing its utility can precede any hype and the spread of its use into the
Editorial / Clinical Neurophysiology 125 (2014) 217–219
general community in the manner seen recently with tDCS, especially in the area of cognitive enhancement. Acknowledgements P.B.F. was supported by a Practitioner Fellowship grant from the National Health and Medical Research Council (NHMRC). He has received equipment for research from Medtronic, MagVenture A/S and Brainsway Ltd. and research funding from Cervel Neurotech. References Antal A, Boros K, Poreisz C, Chaieb L, Terney D, Paulus W. Comparatively weak aftereffects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimul 2008;1:97–105. Antal A, Paulus W. Transcranial alternating current stimulation (tACS). Front Hum Neurosci 2013;7:317. Berlim MT, Van den Eynde F, Daskalakis ZJ. Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. J Psychiatr Res 2013;47:1–7. Brasil-Neto JP. Learning, memory, and transcranial direct current stimulation. Front Psychiatry 2012;3:80. Brignani D, Ruzzoli M, Mauri P, Miniussi C. Is transcranial alternating current stimulation effective in modulating brain oscillations? PLoS One 2013;8:e56589. Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, et al. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul 2012;5:175–95. Fitzgerald PB. TMS–EEG: a technique that has come of age? Clin Neurophysiol 2010;121:265–7. Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci 2013;7:279.
219
Jaberzadeh S, Bastani A, Zoghi M. Anodal transcranial pulsed current stimulation: a novel technique to enhance corticospinal excitability. Clin Neurophysiol 2014;125:344–51. Mutanen T, Maki H, Ilmoniemi RJ. The effect of stimulus parameters on TMS–EEG muscle artifacts. Brain Stimul 2013;6:371–6. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: state of the art 2008. Brain Stimul 2008;1:206–23. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 2001;57:1899–901. Nitsche MA, Paulus W. Transcranial direct current stimulation–update 2011. Restor Neurol Neurosci 2011;29:463–92. Rogasch NC, Fitzgerald PB. Assessing cortical network properties using TMS–EEG. Hum Brain Mapp 2013;34:1652–69. Rogasch NC, Thomson RH, Daskalakis ZJ, Fitzgerald PB. Short-latency artifacts associated with concurrent TMS–EEG. Brain Stimul 2013 [in press]. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist 2011;17:37–53. Steinberg H. Letter to the editor: transcranial direct current stimulation (tDCS) has a history reaching back to the 19th century. Psychol Med 2013;43:669–71. Zaghi S, Acar M, Hultgren B, Boggio PS, Fregni F. Noninvasive brain stimulation with low-intensity electrical currents: putative mechanisms of action for direct and alternating current stimulation. Neuroscientist 2010;16:285–307.
⇑
Paul B. Fitzgerald Monash Alfred Psychiatry Research Centre (MAPrc), The Alfred and Monash University Central Clinical School, Melbourne, Victoria 3004, Australia ⇑ Address: MAPrc, Level 4, 607 St. Kilda Road, Melbourne, Victoria 3004, Australia. Tel.: +61 3 9076 6552; fax: +61 3 9076 6588 E-mail address: paul.fi[email protected] Available online 7 November 2013
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
Transcranial pulsed current stimulation: A new way forward? See Article, pages 344–351
There has been interest for more than 200 years in the potential use of low intensity electrical currents to try to modulate and modify brain activity. Various forms of electrical stimulation were developed in the 18th century, for example when galvanic (direct current) stimulation was applied by Giovanni Aldini to his own head (Zaghi et al., 2010). By the 1870s German psychiatrists were investigating the use of electrical stimulation to treat patients with what appear to have been a variety of mood and psychotic disorders. Notably, some of the publications from this time differentiated between the use of galvanic stimulation: the equivalent of modern day transcranial direct current stimulation (tDCS), and faradic stimulation: an approach utilising an alternating current (Steinberg, 2013) with different clinical indications suggested for differing types of stimulation. Interestingly, they also described a method where the stimulating electrode was removed from the skin surface intermittently and reapplied (intermittent galvanisation) (Steinberg, 2013). These approaches to brain stimulation faded from use particularly with the interest developed in the 20th century in the use of convulsive forms of electrical stimulation. However, the last decade has seen an unprecedented explosion in research on techniques of this sort, their effects on brain activity and their potential therapeutic utility. Somewhat mirroring these early historical developments, there are two commonly utilised forms of electrical stimulation that are currently being actively investigated as potential therapeutic tools. tDCS involves the application of a low intensity constant current between an anode and cathode (Nitsche et al., 2008). In typical applications, tDCS stimuli are applied for between 10 and 20 min at a time. Transcranial alternating current stimulation (tACS) on the other hand, involves the application of an alternating current, such that the electrical current flow cycles backwards and forwards across time at a fixed stimulation frequency (Antal and Paulus, 2013). tDCS, and to a somewhat lesser degree tACS, have been subject to a considerable body of research. This research has established their capacity to modulate cortical excitability in motor cortex and other brain regions and is suggesting that these methodologies have therapeutic potential in the treatment of a number of conditions (Brunoni et al., 2012; Herrmann et al., 2013). For example, research has suggested that tDCS may improve cognition in disorders such as Parkinson’s disease and schizophrenia, it may modulate the experience of pain or improve mood in patients with depression (Nitsche and Paulus, 2011; Brasil-Neto, 2012; Berlim et al., 2013). In spite of this research and the historical interest in electrical stimulation methods, we are still at a relatively early stage in
understanding how to optimise these non-invasive forms of brain stimulation. It is notable that one characteristic of both tDCS and tACS differs significantly from other forms of neural stimulation: in particular the constant nature of the current applied in both of these techniques. Other forms of neural stimulation, including electroconvulsive therapy, vagal nerve stimulation, spinal cord stimulation, transcutaneous nerve stimulation and deep brain stimulation all differ significantly from these two techniques in this way (Zaghi et al., 2010). When current is applied to stimulate nervous tissue in these applications, the current is interrupted rather than constant. This raises a significant question as to whether non-constant current stimulation can be effectively applied to noninvasively modulate brain activity, and whether there may be advantages in non-constant current stimulation when applied to modify traditional methods of tDCS or tACS. Jaberzadeh et al. (2014) have started to explore this possibility. In this study, they applied the use of a technique which they describe as transcranial pulsed current stimulation (tPCS), something that might be considered the modern equivalent of 18th century intermittent galvanisation. tPCS is essentially a non-constant current form of direct current stimulation where a current is applied through an anode and cathode with a fixed stimulation amplitude. However, instead of applying stimulation constantly as with tDCS, the stimulation is interrupted at regular intervals, defining the pulse duration, frequency and inter-pulse intervals of stimulation: a format much more comparable to other forms of neural stimulation. In this study, they compared two forms of tPCS: one with a short and one with a long inter-pulse interval (50 and 650 ms) but where the pulse width was kept constant. They compared these to a standard form of tDCS and a sham condition. Importantly, the total charge applied to the brain was kept constant across all three active stimulation conditions. With this design they clearly found that anodal tPCS with a short interstimulus interval appears to produce greater effects on corticospinal excitability (CSE) than tDCS or a tPCS condition with a significantly longer inter-stimulus interval. This research raises a series of interesting and important questions that hopefully the authors and others will go on to explore. The first of these concerns the method in which the investigators controlled for differences in stimulation type across treatment conditions. As mentioned above, across both the tPCS and the tDCS conditions the total charge was kept constant across conditions. This seems a reasonable and logical element to keep constant across intervention conditions. However, we don’t know whether total charge is directly related to the efficacy of these forms of
1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.10.009
218
Editorial / Clinical Neurophysiology 125 (2014) 217–219
non-invasive electrical stimulation. This is implied by early tDCS studies where a longer duration of stimulation was related to greater stimulation effects (Nitsche and Paulus, 2001). However, it is possible that charge isn’t the feature most closely linked to the effects of stimulation, but, for example that time of persistent stimulation or maximal amplitude are ultimately more important independently of overall charge. In this context, an additional experiment would be useful to compare whether the same effects on CSE are achieved with similar stimulation conditions but where the amplitude of the current is kept constant rather than the total charge. Second, this is clearly just the first step in exploring the potential use of tPCS. Further studies are required to explore the optimal conditions for inducing changes in CSE with this modality. This study suggests that shorter interstimulus intervals are likely to be more effective than longer intervals but whether the 50 ms interval utilised here is optimal is clearly unknown. In addition to the interstimulus interval, research is required to explore whether variations in pulse duration are important and combining these factors to explore the actual effect of differing frequencies of stimulation. In regards to frequency, a relevant but as yet unexplored question relates to whether the most effective frequency of pulsed stimulation is likely to relate to the underlying baseline oscillatory frequency of brain activity prior to exposure to, or during exposure to, this form of stimulation. Presumably, there may be benefits from the use of this type of pulsed stimulation in entraining oscillatory activity in some manner. A third and highly critical question, that is applicable across all types of non-invasive brain stimulation, is concerned with whether findings such as these achieved in the motor cortex can be extrapolated to stimulation of non-motor regions. Studies such as those conducted by Jaberzadeh et al. (2014) are typically performed in the motor cortex as this may have relevance to the use of non-invasive brain stimulation in the treatment of neuro-motor disorders, but also because of the ease of experimental design and implementation. In the application of electrical stimulation to the motor cortex there are reliable and easily recorded dependent variables that may be rapidly assessed (transcranial magnetic stimulation (TMS) measures of CSE). However, many clinical applications of non-invasive brain stimulation techniques require application to non-motor regions where it is far harder to establish optimal stimulation parameters. It is increasingly possible to assess the effects of non-invasive brain stimulation in non-motor regions by assessing local cortical excitability using TMS–EEG methods although this form of assessment is significantly more complicated than assessing activity in motor cortex (Fitzgerald, 2010; Rogasch and Fitzgerald, 2013). First, the equipment required for optimal TMS–EEG data collection is more expensive, time-consuming and complicated to use than simple electromyography (EMG) (Rogasch and Fitzgerald, 2013). Second, a significantly greater number of data points needs to be collected to reliably assess excitability using EEG as compared to EMG: in many experiments between 50 and 75 stimuli are applied for each measurement of excitability with EEG compared to between 10 and 20 with EMG. Finally, the processing and analysis of TMS–EEG data and particularly addressing various stimulation artefacts, is markedly more complex than the process for analysing EMG data (Mutanen et al., 2013; Rogasch et al., 2013). Therefore, it is highly desirable if stimulation in motor cortex can be used as a model that can be potentially applied to develop non-invasive brain stimulation methods that can be subsequently utilised in non-motor brain regions. For example, studies could be relatively easily done to define optimal tPCS pulse width, frequency and other characteristics in motor cortex prior to their application in non-motor indications, such as mood disorders or to enhance cognitive functioning. However, perhaps more limited but careful
studies are going to be required to validate the degree to which findings in motor cortex can be translated to non-motor regions, and these may need to be repeated for each potential different site of stimulation application. It is also possible that an improved understanding of the mechanism of action of tPCS and other forms of non-invasive brain stimulation will be able to be used to fast track the development of optimal clinically applicable protocols. Although a significant body of work has investigated the mechanism of action of tDCS (Zaghi et al., 2010; Nitsche and Paulus, 2011), the degree to which the effects of this technique on CSE are mediated by changes in transmembrane potentials and/or synaptic alterations remains unclear. It is possible that tDCS effects the quantitative characteristics of membrane excitability (how likely neurons are to fire) as well as the characteristics of transmembrane or synaptic proteins (Stagg and Nitsche, 2011). Regardless, given that the magnitude of effects produced with tDCS are directly related to the duration of stimulation (Nitsche and Paulus, 2001), these changes are presumably produced through the cumulative effects of the small currents applied. The mechanism of action of tACS, remains even less well established (Zaghi et al., 2010). tACS does not appear to have the same strong effects that tDCS has on local cortical excitability (Antal et al., 2008) and its effects on broader electrical activity as studied with EEG are inconsistent or at least very specifically dependent on stimulation parameters including location (Zaghi et al., 2010). Jaberzadeh et al. (2014) propose that the greater effects seen with tPCS compared to tDCS in their experiment relates to the phasic effects of this form of stimulation. Given the fixed charge density applied between tPCS and tDCS and the greater effects seen with the former, this seems a reasonable assumption. If this is the case, the frequency of stimulation may well be a much more critical factor than pulse length and the total charge applied across time. Certainly, the rationale for the application of tACS has been based around the interaction with endogenous oscillatory activity and this may well apply to tPCS, although some research suggests tACS may not work via the modulation of brain oscillations (Brignani et al., 2013). If frequency is relevant, consideration should be given towards the development of protocols that individualise stimulation parameters, especially frequency, based upon individual subject’s oscillatory characteristics. It is important to note that if the mechanisms of action of tPCS (and tACS) are very much related to underlying oscillatory activity, optimal parameters for these techniques may translate more poorly from motor cortex to other brain regions where intrinsic brain rhythms are likely to significantly differ. If tPCS does prove to be a more effective method of enhancing CSE compared to other non-invasive brain stimulation methods, this will have significant implications for the development of non-invasive brain therapies for both motor disorders, and disorders where the pathophysiology is primarily localised in nonmotor brain regions. Small studies have suggested potential therapeutic benefits of tDCS approaches to a series of clinical conditions such as depression (Berlim et al., 2013) but in none of these conditions have large multi-site studies been conducted. Unfortunately, it was many years from the conduct of the first TMS studies until this technique was able to be utilised in clinical practice and this has only happened for limited conditions to date. This delay in part related to the conduct of a large series of small investigatorinitiated, rather than larger multi-site studies. There is certainly the real possibility that the development of direct current and related electrical therapies will be drawn out in a similar manner, especially given limitations in the degree to which intellectual property in this domain can be protected and the impact that this has on pathways to commercialisation. On the other hand, as tPCS develops over coming years, hopefully the science establishing its utility can precede any hype and the spread of its use into the
Editorial / Clinical Neurophysiology 125 (2014) 217–219
general community in the manner seen recently with tDCS, especially in the area of cognitive enhancement. Acknowledgements P.B.F. was supported by a Practitioner Fellowship grant from the National Health and Medical Research Council (NHMRC). He has received equipment for research from Medtronic, MagVenture A/S and Brainsway Ltd. and research funding from Cervel Neurotech. References Antal A, Boros K, Poreisz C, Chaieb L, Terney D, Paulus W. Comparatively weak aftereffects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimul 2008;1:97–105. Antal A, Paulus W. Transcranial alternating current stimulation (tACS). Front Hum Neurosci 2013;7:317. Berlim MT, Van den Eynde F, Daskalakis ZJ. Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. J Psychiatr Res 2013;47:1–7. Brasil-Neto JP. Learning, memory, and transcranial direct current stimulation. Front Psychiatry 2012;3:80. Brignani D, Ruzzoli M, Mauri P, Miniussi C. Is transcranial alternating current stimulation effective in modulating brain oscillations? PLoS One 2013;8:e56589. Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, et al. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul 2012;5:175–95. Fitzgerald PB. TMS–EEG: a technique that has come of age? Clin Neurophysiol 2010;121:265–7. Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci 2013;7:279.
219
Jaberzadeh S, Bastani A, Zoghi M. Anodal transcranial pulsed current stimulation: a novel technique to enhance corticospinal excitability. Clin Neurophysiol 2014;125:344–51. Mutanen T, Maki H, Ilmoniemi RJ. The effect of stimulus parameters on TMS–EEG muscle artifacts. Brain Stimul 2013;6:371–6. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: state of the art 2008. Brain Stimul 2008;1:206–23. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 2001;57:1899–901. Nitsche MA, Paulus W. Transcranial direct current stimulation–update 2011. Restor Neurol Neurosci 2011;29:463–92. Rogasch NC, Fitzgerald PB. Assessing cortical network properties using TMS–EEG. Hum Brain Mapp 2013;34:1652–69. Rogasch NC, Thomson RH, Daskalakis ZJ, Fitzgerald PB. Short-latency artifacts associated with concurrent TMS–EEG. Brain Stimul 2013 [in press]. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist 2011;17:37–53. Steinberg H. Letter to the editor: transcranial direct current stimulation (tDCS) has a history reaching back to the 19th century. Psychol Med 2013;43:669–71. Zaghi S, Acar M, Hultgren B, Boggio PS, Fregni F. Noninvasive brain stimulation with low-intensity electrical currents: putative mechanisms of action for direct and alternating current stimulation. Neuroscientist 2010;16:285–307.
⇑
Paul B. Fitzgerald Monash Alfred Psychiatry Research Centre (MAPrc), The Alfred and Monash University Central Clinical School, Melbourne, Victoria 3004, Australia ⇑ Address: MAPrc, Level 4, 607 St. Kilda Road, Melbourne, Victoria 3004, Australia. Tel.: +61 3 9076 6552; fax: +61 3 9076 6588 E-mail address: paul.fi[email protected] Available online 7 November 2013
