To investigate the effect of cathodal transcranial direct-current stimulation (c-tDCS) on seizure frequency in patients with drug-resistant temporal lobe epilepsy (TLE).
The use of non-invasive brain neurostimulation (NIBS) techniques to treat neurological or psychiatric diseases is currently under development. Fatigue is a commonly observed symptom in the field of potentially treatable pathologies by NIBS, yet very little data has been published regarding its treatment. We conducted a review of the literature until the end of February 2017 to analyze all the studies that reported a clinical assessment of the effects of NIBS techniques on fatigue. We have limited our analysis to repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). We found only 15 studies on this subject, including 8 tDCS studies and 7 rTMS studies. Of the tDCS studies, 6 concerned patients with multiple sclerosis while 6 rTMS studies concerned fibromyalgia or chronic fatigue syndrome. The remaining 3 studies included patients with post-polio syndrome, Parkinson’s disease and amyotrophic lateral sclerosis. Three cortical regions were targeted: the primary sensorimotor cortex, the dorsolateral prefrontal cortex and the posterior parietal cortex. In all cases, tDCS protocols were performed according to a bipolar montage with the anode over the cortical target. On the other hand, rTMS protocols consisted of either high-frequency phasic stimulation or low-frequency tonic stimulation. The results available to date are still too few, partial and heterogeneous as to the methods applied, the clinical profile of the patients and the variables studied (different fatigue scores) in order to draw any conclusion. However, the effects obtained, especially in multiple sclerosis and fibromyalgia, are really carriers of therapeutic hope.
Visual field defects after posterior cerebral artery stroke can be improved by vision restoration training (VRT), but when combined with transcranial direct current stimulation (tDCS), which alters brain excitability, vision recovery can be potentiated in the chronic stage. To date, the combination of VRT and tDCS has not been evaluated in postacute stroke rehabilitation.
To determine whether combined tDCS and VRT can be effectively implemented in the early recovery phase following stroke, and to explore the feasibility, safety and efficacy of an early intervention.
Patients with homonymous visual field defects following a posterior cerebral artery stroke.
Seven homonymous hemianopia patients were prospectively treated with 10 sessions of combined tDCS (2.mA, 10 daily sessions of 20 minutes) and VRT at 66 (±50) days on average poststroke. Visual field recovery was compared with the retrospective data of 7 controls, whose defect sizes and age of lesions were matched to those of the experimental subjects and who had received standard rehabilitation with compensatory eye movement and exploration training.
All 7 patients in the treatment group completed the treatment protocol. The safety and acceptance were excellent, and patients reported occasional skin itching beneath the electrodes as the only minor side effect. Irrespective of their treatment, both groups (treatment and control) showed improved visual fields as documented by an increased mean sensitivity threshold in decibels in standard static perimetry. Recovery was significantly greater (P < .05) in the tDCS/VRT patients (36.73% ± 37.0%) than in the controls (10.74% ± 8.86%).
In this open-label pilot study, tDCS/VRT in subacute stroke was demonstrated to be safe, with excellent applicability and acceptance of the treatment. Preliminary effectiveness calculations show that tDCS/VRT may be superior to standard vision training procedures. A confirmatory, larger-sample, controlled, randomized, and double-blind trial is now underway to compare real-tDCS− versus sham-tDCS−supported visual field training in the early vision rehabilitation phase.
Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998.
Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment.
Methods: Articles were identified through a search in PubMed and through the reference list from its selected articles. We included only non-invasive human studies that provided controlled direct current and were written in English, French, Spanish or Portuguese before the year of 1998, the date in which modern stimulation paradigms were implemented.
Results: Fifteen articles met our criteria. The majority were small-randomized controlled clinical trials that enrolled a mean of approximately 26 subjects (Phase II studies). Most of the studies (around 83%) assessed the role of tDCS in the treatment of psychiatric conditions, in which the main outcomes were measured by means of behavioral scales and clinical observation, but the diagnostic precision and the quality of outcome monitoring, including adverse events, were deficient by modern standards. Compared to modern tDCS dose, the stimulation intensities used (0.1–1 mA) were lower, however as the electrodes were typically smaller (e.g., 1.26 cm2), the average electrode current density (0.2 mA/cm2) was approximately 4× higher. The number of sessions ranged from one to 120 (median 14). Notably, the stimulation session durations of several minutes to 11 h (median 4.5 h) could markedly exceed modern tDCS protocols. Twelve studies out of 15 showed positive results. Only mild side effects were reported, with headache and skin alterations the most common.
Conclusion: Most of the studies identified were for psychiatric indications, especially in patients with depression and/or schizophrenia and majority indicated some positive results. Variability in outcome is noted across trials and within trials across subjects, but overall results were reported as encouraging, and consistent with modern efforts, given some responders and mild side effects. The significant difference with modern dose, low current with smaller electrode size and interestingly much longer stimulation duration may worth considering.
Transcranial direct current stimulation (tDCS) consists of applying a weak direct current on the scalp, a portion of which crosses the skull (Datta et al., 2009) and induces cortical changes (Fregni and Pascual-Leone, 2007; Nitsche et al., 2008). The investigation of the application of electricity over the brain dates back to at least 200 years, when Giovanni Aldini (Zaghi et al., 2010) recommended galvanism for patients with deafness, amaurosis and “insanity”, reporting good results with this technique especially when used in patients with “melancholia”. Aldini also used tDCS in patients with symptoms of personality disorders and supposedly reported complete rehabilitation following transcranial administration of electric current (Parent, 2004).
These earliest studies used rudimentary batteries and so were constant voltage, where the resulting current depends on a variable body resistance. Over the 20th century, direct voltage continued to be used but most testing involved pulsed stimulation, starting with basic devices where a mechanical circuit that intermittently connected and broke the circuit between the battery and the subject and evolving to modern current control circuits including Cranial Electrotherapy Stimulation and its variants (Guleyupoglu et al., 2013). Interest in direct current stimulation (or tDCS) resurged with the studies of Priori et al. (1998) and Nitsche and Paulus (2000) that demonstrated weak direct current could change cortical response to Transcranial Magnetic Stimulation, thereby indicating that tDCS could change cortical “excitability”. Testing for clinical and cognitive modification soon followed (Fregni et al., 2005, 2006). Developments and challenges in tDCS research, including applications in the treatment of neuro-psychiatrics disease since 1998 have been reviewed in detailed elsewhere (Brunoni et al., 2012).
This historical note aims to explore earlier data on human trial using current controlled stimulation (tDCS) before 1998 with the goal of informing ongoing understanding and development of tDCS protocols. As expected, we found variability in the quality of trial design, data collection and reporting in these earlier studies. Nonetheless, many clinical findings are broadly consistent with modern efforts, including some encouraging results but also variability across subjects. We also describe a significant difference in dose with lower current, smaller electrodes and much longer durations (up to 11 h) than used in modern tDCS.
Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation technique with the potential to improve upper limb function after stroke. Ipsilesional primary motor cortex (M1) excitability can be increased with anodal tDCS, contralesional M1 excitability can be decreased with cathodal tDCS or both anodal and cathodal tDCS can be used simultaneously on both cortices (bihemispheric). The impact of these different electrode arrangements on the efficacy of tDCS, and whether any of the changes are due to callosal connections between cortices, is unclear.
This study aimed to investigate the effect of tDCS electrode arrangement on motor sequence learning and upper limb function in chronic stroke survivors.
21 stroke survivors (range 3–124 months post-stroke, 34–81 years of age) with upper limb impairment received 20 min of 1 mA tDCS (0.04 mA·cm−2) during performance of a motor sequence learning task which involved movement of a computer mouse with the paretic arm to circular targets on a monitor in a repeating pattern. Four tDCS conditions were studied in a repeated-measures design; (i) anodal to the ipsilesional M1, (ii) cathodal to the contralesional M1, (iii) bihemispheric and (iv) sham. Upper limb function was assessed before and after tDCS, using the Jebsen–Taylor hand function test (JTT). Changes in transcallosal inhibition (TCI) were assessed using transcranial magnetic stimulation (ipsilateral silent period duration).
There was no effect of tDCS condition on performance of the motor sequence learning task. Performance on the JTT improved significantly after unilateral tDCS (anodal or cathodal) compared to sham (p < 0.05), but not after bihemispheric (Fig. 1). There was no effect on TCI (p > 0.5), and no relationship between changes in TCI and upper limb function.
Unilateral, but not bihemispheric, tDCS improves upper limb function. The response to tDCS does not appear to be driven by changes in TCI. These results have implications for the use of tDCS for upper limb rehabilitation.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain-behavior connections have rapidly increased in the last ten years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understanding the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement (e.g., neural target(s) and montages employed) may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system.
Stroke is a neurological deficit induced by the interruption of the blood flow to the brain due to either a vessel occlusion or less frequently an intracerebral hemorrhage (1). Both may induce direct damage of brain tissue at the site of the lesion, along with potential for additional damage in the surrounding tissue, and long-range dysfunction through the interruption of structural and functional pathways in the brain. This also leads to a deregulation of cortical excitability (2–4) and abnormal interhemispheric interactions. Stroke may thus induce many neurological deficits and could result in death. According to the World Stroke Organization, one out of six people will suffer from a stroke, making stroke a leading cause of adult long-term disability worldwide (5–7). Importantly, one of the main challenges after stroke is the loss of one’s functional motor abilities. Research suggests that only 12% of stroke survivors achieve complete motor recovery by 6 months after the stroke (8). In addition, older individuals are more vulnerable to stroke and thus the incidence of stroke is expected to continue rising over the next few decades (9, 10). Accordingly, there is a need to find new potential therapeutic tools to enhance post-stroke motor recovery. Rebalancing interhemispheric interactions and/or restoring excitability in the ipsilesional hemisphere is thought to be beneficial for post-stroke motor recovery (11–17). Thus, techniques aimed at restoring functional brain activity are a promising way to enhance neural recovery after injury. Most of the literature on stroke recovery focuses on the recovery of upper limb motor function. Since the neural mechanisms involved in motor recovery of upper versus lower limbs may differ, in this review, we focus only on upper limb motor recovery after stroke.
Non-invasive brain stimulation (NIBS) techniques show strong therapeutic potential for post-stroke motor rehabilitation due to their ability to modulate cortical excitability (18–21). In particular, transcranial direct current stimulation (tDCS) has emerged as a viable neurorehabilitation tool due to its limited side-effects (22, 23) and safety [e.g., no known risk of neural damage or induction of seizures, as can be found in other NIBS methods like repetitive transcranial magnetic stimulation (rTMS) (24, 25)]. In addition, tDCS stimulators are commercially available and relatively affordable, on the order of several hundred dollars, and application of tDCS is considered relatively simple. By delivering a low-intensity direct current (between 0.5 and 2 mA) to the scalp via two saline-soaked electrodes—an anode and a cathode—tDCS can modulate the transmembrane potential of neurons, modifying cortical excitability and inducing changes in neural plasticity (see Figure 1) (26–30). In addition, recent work has attempted to enhance the spatial resolution of tDCS stimulation, using a new technique called high-definition tDCS (HD-tDCS) (31–34). With this technique, brain regions are more focally targeted using arrays of smaller electrodes arranged on the scalp (Figure 2), using multiple anodes and cathodes (see section on Focal versus Broad Stimulation for a more detailed description). Recently, there has also been increased interest in combining tDCS with imaging methods, such as fMRI or EEG, in order to better understand the local and global effects of tDCS on neural plasticity throughout the brain (35). These methods have all contributed to the growth and interest of tDCS as a viable neuromodulatory method for stroke.
Stroke is a leading cause of worldwide disability, and up to 75% of survivors suffer from some degree of arm paresis. Recently, rehabilitation of stroke patients has focused on recovering motor skills by taking advantage of use-dependent neuroplasticity, where high-repetition of goal-oriented movement is at times combined with non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS). Merging the two approaches is thought to provide outlasting clinical gains, by enhancing synaptic plasticity and motor relearning in the motor cortex primary area. However, this general approach has shown mixed results across the stroke population. In particular, stroke location has been found to correlate with the likelihood of success, which suggests that different patients might require different protocols. Understanding how motor rehabilitation and stimulation interact with ongoing neural dynamics is crucial to optimize rehabilitation strategies, but it requires theoretical and computational models to consider the multiple levels at which this complex phenomenon operate. In this work, we argue that biophysical models of cortical dynamics are uniquely suited to address this problem. Specifically, biophysical models can predict treatment efficacy by introducing explicit variables and dynamics for damaged connections, changes in neural excitability, neurotransmitters, neuromodulators, plasticity mechanisms and repetitive movement, which together can represent brain state, effect of incoming stimulus and movement-induced activity. In this work, we hypothesize that effects of tDCS depend on ongoing neural activity, and that tDCS effects on plasticity may be also related to enhancing inhibitory processes. We propose a model design for each step of this complex system, and highlight strengths and limitations of the different modeling choices within our approach. Our theoretical framework proposes a change in paradigm, where biophysical models can contribute to the future design of novel protocols, in which combined tDCS and motor rehabilitation strategies are tailored to the ongoing dynamics that they interact with, by considering the known biophysical factors recruited by such protocols and their interaction.
This literature review is aimed to explore the main technical characteristics of both transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) using the latest research on both healthy and impaired subjects. These techniques have no oﬃcial standards developed yet. Our intent is to underline the main properties and problems linked with the application of those techniques which show diverse, and sometimes even opposite, results depending mainly on electrode positioning and underlying brain activity.
Among diﬀerent impairments that can aﬀect standard brain functions, we choose to focus primarily on stroke, because it is one of the most prevalent and severe disability worldwide . It is known that after a cerebrovascular accident, reorganization of neural tissues takes place . If the ischemic event occurs on the motor area and it is severe enough to block the spontaneous neural reorganization, it could lead to paresis or even paralysis of one or more body parts .
In order to ameliorate stroke rehabilitation, diﬀerent approaches have been carried out. Over the last decade, within the ﬁeld of functional rehabilitation, transcranial current stimulation (tCS) has garnered considerable attention. It is assumed to improve, above other, motor functions in both healthy and stroke individuals , , .
There are three diﬀerent types of tCS: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS) and random noise stimulation (tRNS). All of them are non-invasive and involve low intensity current induction into the brain. Some studies have investi
gated the physiological basis of tDCS and tACS in order to get the picture of standard pattern that can be used for future research , .
This paper is oriented towards a broad audience who wants to understand the basic mechanisms of tDCS and tACS techniques. The main parameters of each type of stimulation and the implications related to its application on healthy subjects, stroke patients and individuals with unusual brain oscillations are discussed.
Transcranial direct current stimulation (tDCS) has been proposed as a tool to enhance stroke rehabilitation; however, evidence to support its use is lacking. The aim of this study was to investigate the effects of anodal and cathodal tDCS on upper limb function in chronic stroke patients. Twenty five participants were allocated to receive 20 min of 1 mA of anodal, cathodal or sham cortical stimulation in a random, counterbalanced order. Patients and assessors were blinded to the intervention at each time point. The primary outcome was upper limb performance as measured by the Jebsen Taylor Test of Hand Function (total score, fine motor subtest score and gross motor subtest score) as well as grip strength. Each outcome was assessed at baseline and at the conclusion of each intervention in both upper limbs. Neither anodal nor cathodal stimulation resulted in statistically significantly improved upper limb performance on any of the measured tasks compared with sham stimulation (P>0.05). When the data were analysed according to disability, participants with moderate/severe disability showed significantly improved gross motor function following cathodal stimulation compared with sham (P=0.014). However, this was accompanied by decreased key grip strength in the unaffected hand (P=0.003). We are unable to endorse the use of anodal and cathodal tDCS in the management of upper limb dysfunction in chronic stroke patients. Although there appears to be more potential for the use of cathodal stimulation in patients with severe disability, the effects were small and must be considered with caution as they were accompanied by unanticipated effects in the unaffected upper limb.
Motor skills are required for activities of daily living. Transcranial direct current stimulation (tDCS) applied in association with motor skill learning has been investigated as a tool for enhancing training effects in health and disease. Here, we review the published literature investigating whether tDCS can facilitate the acquisition, retention or adaptation of motor skills. Work in multiple laboratories is underway to develop a mechanistic understanding of tDCS effects on different forms of learning and to optimize stimulation protocols. Efforts are required to improve reproducibility and standardization. Overall, reproducibility remains to be fully tested, effect sizes with present techniques vary over a wide range, and the basis of observed inter-individual variability in tDCS effects is incompletely understood. It is recommended that future studies explicitly state in the Methods the exploratory (hypothesis-generating) or hypothesis-driven (confirmatory) nature of the experimental designs. General research practices could be improved with prospective pre-registration of hypothesis-based investigations, more emphasis on the detailed description of methods (including all pertinent details to enable future modeling of induced current and experimental replication), and use of post-publication open data repositories. A checklist is proposed for reporting tDCS investigations in a way that can improve efforts to assess reproducibility.
To investigate the effect of cathodal transcranial direct-current stimulation (c-tDCS) on seizure frequency in patients with drug-resistant temporal lobe epilepsy (TLE).
Twenty-nine patients with drug-resistant TLE participated in this study. They were randomized to experimental or sham group. Twenty participants (experimental group) received within-session repeated c-tDCS intervention over the affected temporal lobe, and nine (sham group) received sham tDCS. Paired-pulse transcranial magnetic stimulation was used to assess short interval intracortical inhibition (SICI) in primary motor cortex ipsilateral to the affected temporal lobe. SICI was measured from motor evoked potentials recorded from the contralateral first dorsal interosseous muscle. Adverse effects were monitored during and after each intervention in both groups. A seizure diary was given to each participant to complete for 4 weeks following the tDCS intervention. The mean response ratio was calculated from their seizure rates before and after the tDCS intervention.
The experimental group showed a significant increase in SICI compared to the sham group (F = 10.3, p = 0.005). None of the participants reported side effects of moderate or severe degree. The mean response ratio in seizure frequency was −42.14% (standard deviation [SD] 35.93) for the experimental group and −16.98% (SD 52.41) for the sham group.
Results from this pilot study suggest that tDCS may be a safe and efficacious nonpharmacologic intervention for patients with drug-resistant TLE. Further evaluation in larger double-blind randomized controlled trials is warranted.
The excitability of the γ-aminobutyric acid (GABA)ergic intracortical inhibitory circuits in primary motor cortex (M1) can be assessed noninvasively in humans by paired-pulse transcranial magnetic stimulation (TMS). In this technique, two stimuli are delivered 1–5 msec apart through the same coil. The first stimulus is subthreshold for a motor response; however, it activates intracortical inhibition (ICI) circuits and reduces the size of the motor evoked potentials (MEPs) elicited by the second stimulus, which is supra-threshold for a motor response. It has been shown that ICI measured using this method reflects the cortical activity of GABAergic interneurons in the M1 area. This inhibition is termed short-interval intracortical inhibition or SICI.
ICI circuits have been assessed extensively with a paired-pulse paradigm in patients with epilepsy.[6-8] Several studies on drug-naive patients with focal epilepsy showed a decrease in SICI in the ipsilateral hemisphere.[9-15] Badawy et al. showed increased M1 excitability and decreased SICI in 35 patients with focal epilepsy 24 h before and after a seizure.
Transcranial direct current stimulation (tDCS) is a well-established cortical stimulation method that can be used noninvasively to modulate neuronal excitability in humans. In this technique, a low intensity current (1–2 mA) is used that can affect the membrane potentials in two ways. Cathodal tDCS (c-tDCS) hyperpolarizes the resting membrane potentials, whereas anodal tDCS acts toward depolarization. Modification of seizure network excitability by tDCS is a potentially valuable noninvasive alternative for reducing the excitability of this abnormal network in patients with epilepsy and thereby reducing the seizure rates in this population.
The aim of this study was to examine the effects of this noninvasive therapeutic approach on seizure frequency in this group of patients. We hypothesized that compared to sham tDCS, application of c-tDCS over the temporal lobe in patients with drug-resistant TLE, decreases seizure frequency and increases intracortical inhibition in the ipsilateral M1 area.
Continue —> Cathodal transcranial direct-current stimulation for treatment of drug-resistant temporal lobe epilepsy: A pilot randomized controlled trial – Zoghi – 2016 – Epilepsia Open – Wiley Online Library