Posts Tagged Transcranial Direct Current Stimulation

[ARTICLE] Timing-dependent effects of transcranial direct current stimulation with mirror therapy on daily function and motor control in chronic stroke: a randomized controlled pilot study – Full Text



The timing of transcranial direct current stimulation (tDCS) with neurorehabilitation interventions may affect its modulatory effects. Motor function has been reported to be modulated by the timing of tDCS; however, whether the timing of tDCS would also affect restoration of daily function and upper extremity motor control with neurorehabilitation in stroke patients remains largely unexplored. Mirror therapy (MT) is a potentially effective neurorehabilitation approach for improving paretic arm function in stroke patients. This study aimed to determine whether the timing of tDCS with MT would influence treatment effects on daily function, motor function and motor control in individuals with chronic stroke.


This study was a double-blinded randomized controlled trial. Twenty-eight individuals with chronic stroke received one of the following three interventions: (1) sequentially combined tDCS with MT (SEQ), (2) concurrently combined tDCS with MT (CON), and (3) sham tDCS with MT (SHAM). Participants received interventions for 90 min/day, 5 days/week for 4 weeks. Daily function was assessed using the Nottingham Extended Activities of Daily Living Scale. Upper extremity motor function was assessed using the Fugl-Meyer Assessment Scale. Upper extremity motor control was evaluated using movement kinematic assessments.


There were significant differences in daily function between the three groups. The SEQ group had greater improvement in daily function than the CON and SHAM groups. Kinematic analyses showed that movement time of the paretic hand significantly reduced in the SEQ group after interventions. All three groups had significant improvement in motor function from pre-intervention to post-intervention.


The timing of tDCS with MT may influence restoration of daily function and movement efficiency of the paretic hand in chronic stroke patients. Sequentially applying tDCS prior to MT seems to be advantageous for enhancing daily function and hand movement control, and may be considered as a potentially useful strategy in future clinical application.


Stroke remains one of the leading causes of long-term disability [1]. Most stroke patients have difficulties performing every day activities due to paresis of upper limbs, which results in impaired activities of daily living (ADL) and reduced quality of life [23]. Identifying strategies that can facilitate functional recovery is thus an important goal for stroke rehabilitation. In recent years, several neurorehabilitation approaches have been developed to augment functional recovery, for example repetitive, task-oriented training and non-invasive brain stimulation (NIBS) [45]. Repetitive, task-oriented training emphasizes repetitive practice of task-related arm movements to facilitate motor relearning and restore correct movement patterns [6]. On the other hand, non-invasive brain simulation aims to maximize brain plasticity by externally applying electrical stimulation to modulate cortical excitability [7]. Since these two types of approaches individually have been shown to improve stroke recovery, it has been proposed that a synergistic approach that combines both of them may further augment overall treatment effects [89].

Mirror therapy (MT) is one type of repetitive task-oriented training that has been widely used in clinical and research settings [10]. During MT training, a mirror is positioned in between the paretic and non-paretic arm. The paretic arm is behind the mirror and participants can only see the non-paretic arm and its mirror reflection. Participants are required to focus their attention on the mirror reflection and imagine it is the paretic arm while performing bilateral movements as simultaneously as possible. This mirrored visual feedback is hypothesized to restore the efferent-afferent loop that is damaged after stroke and facilitate re-learning of correct movement patterns [11]. MT has been demonstrated to reduce arm impairment and improve sensorimotor function and quality of life in individuals with stroke [10,11,12,13].

Transcranial direct current stimulation (tDCS) is a commonly used NIBS technique in stroke rehabilitation. tDCS applies weak direct current to the scalp to modulate brain excitability [14]. This weak direct current gradually changes neural membrane potentials to facilitate depolarization (excitation) or hyper-polarization (inhibition) of the neurons to enhance plasticity of the brain [15]. tDCS has been demonstrated to modulate neural networks and enhance motor learning in stroke patients [716,17,18]. Although tDCS can be used alone, it is often combined with other rehabilitation approaches to boost responses of the brain to therapies [81920]. A recent meta-analysis further showed that combining tDCS with rehabilitation interventions could produce greater treatment effects on recovery of motor function than tDCS alone in stroke patients [21].

Combining tDCS with MT is a potentially promising approach to not only augment neural responses of the brain but also increase treatment benefits of MT. Nevertheless, one crucial factor that needs to be considered when combining tDCS with MT is the timing of tDCS [22]. tDCS can be applied prior to MT (i.e., offline tDCS) or concurrently with MT (i.e., online tDCS). To our knowledge, only two studies have examined the synergistic effects of combined tDCS with MT in chronic stroke patients [2324]. Cho et al. (2015) applied tDCS prior to MT or motor training without mirror reflection. They found significant improvements in manual dexterity and grip strength in the combined tDCS with MT group, suggesting that sequentially applying tDCS prior to MT could improve motor function. By contrast, Jin et al. (2019) delivered tDCS prior to or concurrently with MT and found advantageous effects on hand function in the concurrent tDCS with MT group. The conflicting results between these two studies indicated further needs to explore the interaction effects of the timing of tDCS with MT to determine the optimal combination strategy.

The important factor to consider when examining the effects of combined tDCS with MT is the treatment outcomes, especially for outcomes that are related to daily activities. ADL such as the basic ADL and complex instrumental ADL (IADL) are essential for independent living and well-being of stroke patients. Therefore, restoring daily function should be one of the priority goals of stroke rehabilitation. However, the previous two studies only examined the effects of combined tDCS with MT on motor function [2324]. No studies to date have examined the timing-dependent effects of tDCS with MT on daily function in chronic stroke patients. Whether the timing of tDCS can affect restoration of daily function with MT remains uncertain.

In addition to daily function, investigating arm movement kinematics changes with respect to the timing of tDCS with MT is also critical for determining the optimal combination strategy. Movement kinematics of the arms can provide information of whether true behavioral changes or compensation strategies occur during training [2526]. However, the two previous studies included only clinical motor function measurements [2324]. While these clinical measurements can inform clinicians/researchers of motor function changes, they may not necessarily capture spatial and temporal characteristics of movement as well as motor control strategies changes after the combined interventions [2627]. Assessing movement kinematics changes with respect to the timing of tDCS with MT would help to unravel the benefits of combined approach on motor control of the paretic arm.

The purpose of this study was to examine the timing-dependent effects of tDCS with MT on daily function, upper extremity motor function and motor control in chronic stroke patients. The tDCS was applied sequentially prior to MT (i.e., sequentially combined tDCS with MT group, SEQ) or concurrently with MT (i.e., concurrently combined tDCS with MT, CON). The sham tDCS with MT was used as the control condition. In addition to motor function outcomes, we further included the ADL/IADL measurement and movement kinematics assessments. We hypothesized that the SEQ and COM groups would demonstrate differential improvements in daily function, motor function and motor control.[…]

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[ARTICLE] Enhancing cognitive control training with transcranial direct current stimulation: a systematic parameter study – Full Text



Cognitive control (CC) is an important prerequisite for goal-directed behaviour and efficient information processing. Impaired CC is associated with reduced prefrontal cortex activity and various mental disorders, but may be effectively tackled by transcranial direct current stimulation (tDCS)-enhanced training. However, study data are inconsistent as efficacy depends on stimulation parameters whose implementations vary widely between studies.


We systematically tested various tDCS parameter effects (anodal/cathodal polarity, 1/2 mA stimulation intensity, left/right prefrontal cortex hemisphere) on a six-session CC training combined with tDCS.


Nine groups of healthy humans (male/female) received either anodal/cathodal tDCS of 1/2 mA over the left/right PFC or sham stimulation, simultaneously with a CC training (modified adaptive Paced Auditory Serial Addition Task [PASAT]). Subjects trained thrice per week (19 min each) for two weeks. We assessed performance progress in the PASAT before, during, and after training. Using a hierarchical approach, we incrementally narrowed down on optimal stimulation parameters supporting CC. Long-term CC effects as well as transfer effects in a flanker task were assessed after the training period as well as three months later.


Compared to sham stimulation, anodal but not cathodal tDCS improved performance gains. This was only valid for 1 mA stimulation intensity and particularly detected when applied to the left PFC.


Our results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions.



Continuously changing environments require dynamic adaptation by means of filtering and evaluating internal and external stimuli to orchestrate goal-directed behaviour. This is especially important for situations in which distractions might influence efficient responses. Important information is maintained, while non-relevant stimuli must be suppressed or ignored. Dysfunctions of cognitive control (CC) processes are at the core of many psychopathological conditions [1,2], comprise the intentional selection of thoughts, emotions, and behaviours based on current task demands [3] involving functions of attention, memory, and emotional control [4], and are associated with altered patterns of brain activation [5,6]. The prefrontal cortex (PFC), particularly the dorsolateral prefrontal cortex (dlPFC), is known to be highly involved in CC processes [7] by means of processes related to working memory [8], encoding of task relevant rules and responses [9], and emotion regulation [10].

Transcranial direct current stimulation (tDCS) has been put forward as a means to influence these processes by modulating the likelihood of neuronal firing in response to a stimulus [11]. At the macroscopic level, within the common and safe range of stimulation parameters (1–2 mA, up to 30 min of stimulation [12]), it is supposed that anodal tDCS predominantly enhances, while cathodal tDCS mainly reduces the excitability and spontaneous activity of the targeted and connected areas [13]. This polarity-dependent modulation of brain activity by tDCS has a remarkable potential to influence corresponding cognition and behaviour [[14][15][16]]. However, tDCS does not induce cortical activity per se. It develops its effects particularly in interaction with spontaneous neuronal activity [17,18]. This activity-dependent influence on brain networks allows for a ‘functional targeting’ of stimulation when tDCS is directly coupled with the respective cognitive or behavioural process [19], where the target regions are activated (i.e. by a task) and further specifically modulated by the stimulation [20]. Correspondingly, tDCS effects have been found especially in neuronal correlates of task features that were active during stimulation [21]. Therefore, the combination of tDCS with task training is suggested to have a synergistic ‘neuroenhancing’ effect that is currently subject of extensive research [[22][23][24][25]]. However, available data are still inconsistent as efficacy depends on stimulation parameters that vary widely between studies. For a meaningful clinical application, a sustainable enhancement of adaptive plasticity would be most desirable [26]. Based on this notion, a specific activation of the CC network and concomitant tDCS holds promise to provide new treatment strategies for cognitive and behavioural disorders [[27][28][29]]. In a plethora of studies, stimulation has already shown to enhance CC by changing emotion regulation processes [30], improving frustration tolerance [31], modulating emotional vulnerability [32], dissolving attentional biases [33], augmenting working memory training [16], and increasing multitasking capacity [34]. However, reliability of results and the plausibility of approaches leaves room for improvement, not at least because studies often yield varying results even for similar tasks [[35][36][37][38]]. Therefore, reliable knowledge about the efficacy of parameter settings is mandatory for further advancements [39].

To this aim, we systematically tested different standard stimulation parameters (anodal/cathodal tDCS with 1/2 mA to the left/right dlPFC) in 162 healthy subjects, combining repeated CC training (6 sessions within 2 weeks) with tDCS, and additionally analysed pre- and post-training assessments. We applied a modified adaptive paced auditory serial addition task (PASAT) to challenge and train CC [40]. This task requires continuous updating of working memory with parallel distracting performance feedback; it is known to activate CC [31], critically involves resources within the PFC [41], and adapts task difficulty to individual performance [42]. We hypothesized that adding anodal but not cathodal tDCS to PASAT-induced neuronal activity of the dlPFC [43,44] can enhance cognitive training effects [45,46], improve performance of the PASAT or similar, even more challenging tasks [16,31,[46][47][48][49][50]], and that higher stimulation intensity does not increase efficacy [51]. Furthermore, we wanted to test if the laterality of stimulation matters. Therefore, PASAT performance under eight different tDCS conditions (combined N = 119) was compared to a sham intervention group (N = 43). Analyses were conducted hierarchically, allowing us to narrow down the responsible factors for the most efficient combination of CC training and tDCS.[…]

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[ARTICLE] Feasibility of single and combined with other treatments using transcranial direct current stimulation for chronic stroke: A pilot study – Full Text

This pilot study aimed to investigate the safety and efficacy of transcranial direct current stimulation (tDCS) for chronic stroke in adult and pediatric patients. We also aimed to verify the efficacy of botulinum toxin A and peripheral neuromuscular electrical stimulation combined therapy involving bilateral tDCS in adult patients with chronic stroke.

We conducted a pilot study applying an unblinded, non-randomized design. Eleven patients were recruited, and classified into three groups. Group I-a involved bilateral transcranial direct current stimulation and intensive occupational therapy for chronic stroke in adult patients. Group I-b involved bilateral tDCS and intensive occupational therapy for chronic stroke in pediatric patients. Group II involved bilateral tDCS, peripheral neuromuscular electrical stimulation, and intensive occupational therapy after botulinum toxin A injection for chronic stroke in adult patients. Clinical evaluations to assess motor function and spasticity were performed at baseline as well as in 2-week and 4-month follow-up visits. The questionnaire included questions regarding the presence of tDCS side effects, such as headache, redness, pain, itching, and fever.

There were clinically meaningful changes in total Fugl–Meyer Assessment Upper Extremity (FMA-UE) scores at the 2-week follow-up and in the Action Research Arm Test (ARAT) scores at 4-month follow-up in Group I-b. In addition, Group II showed significant improvement in total FMA-UE scores in the 2-week follow-up (p < 0.05) but not on the ARAT scores (p > 0.05). However, Group II showed improvements in total Motor Activity Log scores at both follow-up visits (p < 0.05). No serious adverse events were reported.

The results of this study indicate that tDCS therapy is a potential treatment in pediatric patients with chronic stroke. Furthermore, our data indicate that botulinum toxin A and peripheral neuromuscular electrical stimulation combined therapy may enhance the efficacy of tDCS on motor function.

Previous longitudinal studies have reported that between 30% and 66% of patients experience upper limb paralysis 6 months after suffering from a stroke.13 Recent studies have demonstrated the efficacy of various treatments for patients with chronic stroke, who experience upper limb paralysis, including botulinum toxin A (BTX-A) treatment, functional electrical stimulation therapy, and robotic therapy for functional motor recovery.46 In addition, repetitive transcranial magnetic stimulation and transcranial direct current stimulation (tDCS), have been reported to induce long-term effects on cortical excitability, lasting for months after the intervention.7,8

tDCS modulates cortical excitability which influences neural plasticity.9 Anodal tDCS (anodal electrode placed over standard scalp coordinates for motor ipsilesional M1, the cathodal electrode over the contralesional supraorbital ridge) also modulates cortical excitability in motor areas within affected hemisphere.9,10 Furthermore, bilateral tDCS, which stimulates both hemispheres simultaneously, could affect excitatory and inhibitory synaptic transmission in the bilateral motor cortex in patients with chronic stroke.9,1113 By modulating cortical excitability, tDCS may alter maladaptive neural plasticity after stroke.9 Moreover, peripheral neuromuscular electrical stimulation (PNMES) enhances the effects of tDCS on cortical excitability, relative to tDCS alone.14,15 Furthermore, rehabilitation therapy using PNMES combined with BTX-A has been shown to be an effective treatment in chronic stroke or spinal cord injury.16

However, no studies have examined the efficacy of the use of bilateral tDCS with PNMES and BTX-A therapy in patients with stroke and upper limb paralysis. Therefore, based on the results of each combination therapy effect from previous studies, we predicted that a new multiple combination of adding BTX-A to existing tDCS and PNMES combination therapy would result in more effective results. In addition, tDCS may help improve upper limb paralysis in pediatric patients with chronic stroke. Since tDCS alone has been rarely used in pediatrics, our pilot study aimed to investigate the safety and efficacy of tDCS in adult and pediatric patients with chronic stroke. We also aimed to verify the efficacy of BTX-A and PNMES combined therapy involving bilateral tDCS in adult patients with chronic stroke.

Study design

We conducted a pilot study applying an unblinded, non-randomized design. This study included patients with chronic stroke (>6 months from stroke onset) experiencing paralysis in an upper limb. Patients between 6 and 85 years old were included. We also excluded patients with epilepsy, complete paralysis, and/or severe pain, as well as those who were unable to follow directions due to cognitive impairment and/or aphasia. All participants provided written informed consent. Our institutional review board approved the study. Patient characteristics are summarized in Table 1.


Table 1. Demographics and clinical characteristics.

We included 11 patients (four males and seven females; mean age 43.5 ± 5.1 years) including 7 cases of hemorrhagic stroke and 4 cases of ischemic stroke. All study participants were right handed. There were six cases of right upper limb paralysis and five cases of left upper limb paralysis. All of four ischemic stroke cases had a lesion in the middle cerebral arterial territtory, and three hemorrhagic stroke patients had a lesion in the putamen, two stroke patients had a lesion in the subcortical, and other two patients had lesions were in the thalamus and pontine. These treatment programs were initiated on 54.9 ± 23.2 days from stroke onset. Of the included cases, data from 1 patient (Case 1) was published previously.13

Five patients, included in Group I, underwent bilateral tDCS therapy alongside intensive occupational therapy (OT) (Group I-a: two adults; Group I-b: three children). Group II included six adult patients in chronic stroke who underwent BTX-A and PNMES combined therapy involving bilateral tDCS.

Each rehabilitation session lasted 60 min. Sessions were performed twice daily for 10 days so that all patients completed 20 sessions for the 2-week intervention period in the hospital. In Group I, tDCS started at the same time as the intensive OT for 25 min; and a 45-min only intensive OT was performed after the tDCS. In Group II, patients were given a BTX-A injection. Following this, patients simultaneously underwent intensive OT for 25 min using tDCS, and PNMES (25 min). Meanwhile, intensive OT was continued as well, and finally alone intensive OT (10 minutes) was performed (Figure 1). Intensive OT involved task-oriented training. The content of the task-oriented training mainly consisted of the task on the desk. The difficulty of the task was adjusted for each patient depending on the extent of their upper limb paralysis and their rehabilitation goals. Examples of activities included gripping or picking up blocks or pegs, varying in size; as well as using a keyboard and playing cards. The activities performed by each patient were recorded. In addition, patients were instructed to increase their use of upper limb paralysis. After the 2-week intervention period, patients presented as outpatients and were given exercises to complete at home. Patients were encouraged to use their paralyzed upper limbs depending on their individual rehabilitation needs. Daily activities involved tasks related to their own rehabilitation goals from the activities of daily living (ADL) and instrumental activities of daily living (IADL) tasks.


Figure 1. Study protocol in Groups I, bilateral tDCS started at the same time as the intensive occupational therapy for 25 min; and a 45-min-only intensive occupational therapy was performed after bilateral tDCS. Study protocol for combined therapy involving bilateral tDCS. Patients in Group II received BTX-A therapy 25 min prior to bilateral tDCS, which was immediately followed by a 25-min PNMES. Intensive occupational therapy was also provided simultaneously and performed alone for 10 min.

BTX-A: botulinum toxin A; tDCS: transcranial direct current stimulation; PNMES: peripheral neuromuscular electrical stimulation.

Clinical evaluations were performed at baseline and in 2-week and 4-month follow-up visits conducted after the intervention. We used the following clinical outcome measures to evaluate upper limb function, including the Fugl–Meyer Assessment Upper Extremity (FMA-UE; range: 0–66) and the Action Research Arm Test (ARAT; range: 0–57).17,18 Limb functioning used during daily activities were assessed using the Motor Activity Log (MAL; range: 0–5).19 The severity of spasticity symptoms were evaluated using the Disability Assessment Scale (DAS; range: 0–12).20 DAS evaluations were conducted with patients who had received BTX-A injections. The questionnaire included questions regarding the presence of tDCS side effects, such as headache, redness, pain, itching, and fever.

The effective change in this pilot study was defined as the minimal clinically important difference (MCID) for endpoints with established values, and the MCID for FMA-UE, ARAT and MAL were 4.25, 5.7 and 0.5 points, respectively.21,22 Furthermore, the statistically significant difference in the amount of change from the baseline within the group and the presence or absence of serious adverse events were used as reference indicators of feasibility.

Statistical analysis

Within-group comparisons were conducted to investigate changes in clinical symptoms (FMA-UE, ARAT, and MAL) before and after treatment using the Wilcoxon signed-rank test. All analyses were performed using SPSS, version 21.0 (IBM Corp., Armonk, NY, USA). The significance threshold was set to p < 0.05.

tDCS-supported rehabilitation

We used the DC-STIMULATOR PLUS system (neuroConn GmbH, Germany) to perform tDCS. The anodal electrode was placed over standard scalp coordinates for the ipsilesional M1; whereas the cathodal electrode was placed over standard scalp coordinates for the contralesional M1 (C3 or C4 points according to the 10–20 system). Bilateral tDCS using electrodes (size of 5 × 7 cm; 35 cm2) using a constant current intensity of 2.5 mA for 25 min (Figure 2). Our protocol used current densities below 25 mA/cm2 which should not induce damage even when high-frequency stimulation is applied for several hours.23,24 The tDCS protocol that we used has been described previously (Figure 3).13,25


Figure 2. Bilateral tDCS with intensive occupational therapy: (1) DC-STIMULATOR PLUS system (neuroConn GmbH, Germany) for transcranial direct current stimulation.

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[Abstract] Evaluating the effects of tDCS in stroke patients using functional outcomes: a systematic review

Background and purpose: Transcranial direct current stimulation (tDCS) has been extensively studied over the past 20 years to promote functional motor recovery after stroke. However, tDCS clinical relevance still needs to be determined. The present systematic review aims to determine whether tDCS applied to the primary motor cortex (M1) in stroke patients can have a positive effect on functional motor outcomes.

Materials and methods: Two databases (Medline & Scopus) were searched for randomized, double-blinded, sham-controlled trials pertaining to the use of M1 tDCS on cerebral stroke patients, and its effects on validated functional motor outcomes. When data were provided, effect sizes were calculated. PROSPERO registration number: CRD42018108157

Results: 46 studies (n = 1291 patients) met inclusion criteria. Overall study quality was good (7.69/10 on the PEDro scale). Over half (56.5%) the studies were on chronic stroke patients. There seemed to be a certain pattern of recurring parameters, but tDCS protocols still remain heterogeneous. Overall results were positive (71.7% of studies found that tDCS has positive results on functional motor outcomes). Effect-sizes ranged from 0 to 1.33. No severe adverse events were reported.

Conclusion: Despite heterogeneous stimulation parameters, outcomes and patient demographics, tDCS seems to be complementary to classical and novel rehabilitation approaches. With minimal adverse effects (if screening parameters are respected), none of which were serious, and a high potential to improve recovery when using optimal parameters (i.e.: 20 min of stimulation, at 2 mA with 25 or 35cm2 electrodes that are regularly humidified), tDCS could potentially be ready for clinical applications.

  • Implications for Rehabilitation
  • tDCS could potentially be ready for clinical application.

  • Evidence of very low to very high quality is available on the effectiveness of tDCS to improve motor control following stroke.

  • This should with caution be focused on the primary motor cortex.

via Evaluating the effects of tDCS in stroke patients using functional outcomes: a systematic review: Disability and Rehabilitation: Vol 0, No 0

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[ARTICLE] Transcranial Direct Current Stimulation to Facilitate Lower Limb Recovery Following Stroke: Current Evidence and Future Directions – Full Text HTML


Stroke remains a global leading cause of disability. Novel treatment approaches are required to alleviate impairment and promote greater functional recovery. One potential candidate is transcranial direct current stimulation (tDCS), which is thought to non-invasively promote neuroplasticity within the human cortex by transiently altering the resting membrane potential of cortical neurons. To date, much work involving tDCS has focused on upper limb recovery following stroke. However, lower limb rehabilitation is important for regaining mobility, balance, and independence and could equally benefit from tDCS. The purpose of this review is to discuss tDCS as a technique to modulate brain activity and promote recovery of lower limb function following stroke. Preliminary evidence from both healthy adults and stroke survivors indicates that tDCS is a promising intervention to support recovery of lower limb function. Studies provide some indication of both behavioral and physiological changes in brain activity following tDCS. However, much work still remains to be performed to demonstrate the clinical potential of this neuromodulatory intervention. Future studies should consider treatment targets based on individual lesion characteristics, stage of recovery (acute vs. chronic), and residual white matter integrity while accounting for known determinants and biomarkers of tDCS response.

1. Introduction

Stroke is the second leading cause of death and third leading cause of adult disability globally [1]. With advancement in acute medical care, more people now survive stroke, but frequently require extensive rehabilitative therapy to reduce impairment and improve quality of life. For those that survive stroke, the damaging effects not only impact the individual and their family, but there is also increased burden on health unit resources and community services as the person leaves hospital, potentially requiring assistance to live in the community. Novel treatments that can enable restoration and enhance potential for stroke recovery are desperately needed and will have significant value for many aspects of stroke care.
True recovery from stroke impairment is underpinned by neuroplasticity. Neuroplasticity describes the brain’s ability to change in structure or function in order to help restore behavior following neural damage. Mechanisms of neuroplasticity are available throughout life but appear enhanced during critical periods of learning [2]. Across several animal studies, it has been shown that there is a period of heightened neuroplasticity that appears to open within several days following stroke [2,3,4] and correlates with rapid recovery [5]. In humans, the timing and duration of a similar critical period of heightened neuroplasticity are not clear, but it likely emerges early after stroke. Understanding the characteristics of a potential critical period of heightened neuroplasticity in humans is important for optimizing stroke rehabilitation and is the subject of current trials [6]. However, the importance of neuroplasticity for stroke recovery in humans is unequivocal, with imaging and physiological studies providing extensive evidence of brain changes correlating with improved behavior [7,8,9,10,11,12,13].
Transcranial direct current stimulation (tDCS) is a promising, non-invasive, method to induce neuroplasticity within the cerebral cortex and augment stroke recovery. Importantly, tDCS has potential to bidirectionally and selectively alter corticospinal excitability for up to one hour after stimulation [14,15]. Animal models indicate that tDCS modulates resting membrane potential, with anodal stimulation leading to neuronal depolarization and cathodal stimulation leading to neuronal hyperpolarization over large cortical populations [16]. Stimulation-induced changes may be potentiated by changes in intracellular calcium concentrations. For example, anodal tDCS applied to the surface of the rat sensorimotor cortex led to a rise in the intracellular calcium concentrations [17]. Local increases in calcium can result in short- and long-term changes in synaptic function [18]. In humans, pharmacological studies have also provided indirect evidence to suggest that tDCS after effects are mediated by changes in synaptic plasticity through mechanisms that resemble long-term potentiation (LTP) and long-term depression-like effects [19]. Oral administration of the NMDA-receptor antagonist dextromethorphan was found to suppress the post-tDCS effects of both anodal and cathodal stimulation, suggesting that tDCS after effects involve NMDA receptors [19]. Importantly, modulation of cortical activity with tDCS changes human behavior [20]. For example, in randomized sham-controlled trials, anodal stimulation of the motor cortex (M1) in the lesioned hemisphere was found to improve upper limb outcomes in chronic [21,22,23] and subacute stroke survivors [24,25,26], with behavior changes underpinned by increased cortical activity within the M1 [27]. Although much work remains to be performed regarding optimal stimulation doses, cortical targets and electrode montages, these studies provide some indication that tDCS may be beneficial in stroke recovery.
While there is indication that tDCS has potential to improve stroke recovery of the upper limb [28], there are comparatively fewer studies that have investigated tDCS for lower limb recovery after stroke. Lower limb rehabilitation is especially important, as the simple act of regaining the ability to walk has subsequent effects on the ability to engage in activities of daily living [29,30]. Furthermore, those receiving therapy targeting mobility have been shown to have reduced levels of depression and anxiety [31], which are important determinants of stroke recovery [32,33,34]. Therefore, novel interventions capable of enhancing lower limb recovery might improve not only lower limb motor performance but could have added benefit for stroke rehabilitation in general. The purpose of this review is to discuss tDCS as a technique to modulate brain activity and promote recovery of walking following stroke. Within this review, we will outline current studies that have investigated tDCS to improve lower limb motor performance in both healthy adults and people with stroke. Additionally, we propose a best-practice model of experimental design for lower limb tDCS to guide future application for lower limb stroke recovery.

2. Is it Possible to Modify Lower Limb Motor Networks with Transcranial Direct Current Stimulation?

One approach to modify activity of the lower limb motor network with tDCS is to target the M1, similar to studies involving the upper limb. However, targeted application with tDCS is challenging as, compared with upper limb representations, the lower limb M1 representations are more medial and deeper within the interhemispheric fissure (Figure 1). This presents two notable difficulties. First, the ability of targeted stimulation to the lower limb M1 within one hemisphere (e.g., the lesioned hemisphere in stroke) is challenging, as tDCS electrodes can be relatively large compared to the size of cortical representations, resulting in current spread that may inadvertently lead to stimulation within the opposite hemisphere. Second, the depth of the lower limb M1 representations may present a challenge to current penetration and depth with traditional tDCS applications. However, there is evidence to indicate that it is possible to modulate activity of the lower limb M1 with tDCS. Computational modelling has revealed that traditional anodal tDCS electrode montages (anode overlying the lower limb M1 and cathode overlying the contralateral orbit; Figure 1) can lead to the expected cortical excitability enhancement in the target cortex [35]. Indeed, reducing the size of the anode (3.5 cm × 1 cm) was found to improve the specificity of the current delivered to the cortex, while positioning the return electrode (cathode) to a more lateral position (T7/8 on the 10–10 EEG system) further improved current specificity, leading to greater changes in cortical excitability [35]. Experimental evidence also suggests that tDCS targeting the lower limb M1 can modify excitability. Jeffrey and colleagues [36] utilized an anodal-tDCS montage (2 mA, 10 min) over the lower limb M1 and found that motor-evoked potentials (MEPs) of the tibialis anterior muscle increased by as much as 59% compared to sham conditions. Along similar lines, 10 sessions of anodal tDCS (2 mA, 10 min) targeting the lower limb M1 was found to increase the amplitude of MEPs recorded from the paretic tibialis anterior compared to sham stimulation [37]. This empirical evidence provides some support to the computational modelling to suggest that the use of tDCS targeting the lower limb M1 can modify corticospinal excitability.
Although M1 has received attention as a stimulation target to modify excitability of the lower limb M1, there is potential for cerebellar tDCS to induce similar, or possibly more prominent, behavioral and neurophysiological changes. It is noteworthy that a computational modelling study that compared electrode montages targeting M1 and the cerebellum found that cerebellar stimulation produced substantially higher electric field strengths in the target area compared to M1 stimulation, suggesting the cerebellum may indeed be a suitable target for tDCS [38]. Behaviorally, the cerebellum contributes to motor planning, learning, and control; this influence is in part mediated by connections to M1 via the cerebellothalamocortical tracts, previously reported to play a key role in motor skill learning in mice [39]. Although this stimulation technique has received comparatively little attention compared to M1 stimulation, there is some indication that it is possible to modify cerebellar excitability in a focal and polarity specific manner [40]. Whether cerebellar tDCS is required to modify excitability of M1 for behavioral change is unclear. However, if a desired outcome was to modify M1 excitability with cerebellar stimulation, a pertinent challenge would be whether cerebellar tDCS can achieve the specificity required to precisely target the lower limb M1 in one hemisphere. Although speculative, one approach could be to pre-activate M1 through a contralateral lower limb motor task in order to bias the effects of tDCS towards those networks activated to perform the task. In support, there is some evidence in the upper limb that performance of a task during cerebellar tDCS does interact with the change in M1 excitability [41].[…]

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[Review] Immediate and long-term effects of BCIbased rehabilitation of the upper extremity after stroke: a systematic review and metaanalysis – Full Text PDF


Background: A substantial number of clinical studies have demonstrated the functional recovery induced by the use of brain-computer interface (BCI) technology in patients after stroke. The objective of this review is to evaluate the effect sizes of clinical studies investigating the use of BCIs in restoring upper extremity function after stroke and
the potentiating effect of transcranial direct current stimulation (tDCS) on BCI training for motor recovery.

Methods: The databases (PubMed, Medline, EMBASE, CINAHL, CENTRAL, PsycINFO, and PEDro) were systematically searched for eligible single-group or clinical controlled studies regarding the effects of BCIs in hemiparetic upper extremity recovery after stroke. Single-group studies were qualitatively described, but only controlled-trial studies were included in the meta-analysis. The PEDro scale was used to assess the methodological quality of the controlled studies. A meta-analysis of upper extremity function was performed by pooling the standardized mean difference (SMD). Subgroup meta-analyses regarding the use of external devices in combination with the application of BCIs were also carried out. We summarized the neural mechanism of the use of BCIs on stroke.

Results: A total of 1015 records were screened. Eighteen single-group studies and 15 controlled studies were included. The studies showed that BCIs seem to be safe for patients with stroke. The single-group studies consistently showed a
trend that suggested BCIs were effective in improving upper extremity function. The meta-analysis (of 12 studies) showed a medium effect size favoring BCIs for improving upper extremity function after intervention (SMD = 0.42; 95% CI = 0.18–0.66; I2 = 48%; P < 0.001; fixed-effects model), while the long-term effect (five studies) was not significant (SMD = 0.12; 95% CI = − 0.28 – 0.52; I2 = 0%; P = 0.540; fixed-effects model). A subgroup meta-analysis indicated that using functional electrical stimulation as the external device in BCI training was more effective than using other devices (P = 0.010). Using movement attempts as the trigger task in BCI training appears to be more effective than using motor
imagery (P = 0.070). The use of tDCS (two studies) could not further facilitate the effects of BCI training to restore upper extremity motor function (SMD = − 0.30; 95% CI = − 0.96 – 0.36; I2 = 0%; P = 0.370; fixed-effects model).

Conclusion: The use of BCIs has significant immediate effects on the improvement of hemiparetic upper extremity function in patients after stroke, but the limited number of studies does not support its long-term effects. BCIs combined with functional electrical stimulation may be a better combination for functional recovery than other kinds
of neural feedback. The mechanism for functional recovery may be attributed to the activation of the ipsilesional premotor and sensorimotor cortical network.

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[Abstract] Timing-dependent interaction effects of tDCS with mirror therapy on upper extremity motor recovery in patients with chronic stroke: A randomized controlled pilot study


  • The priming effect of dual tDCS was important to facilitate motor recovery in combination with mirror therapy in stroke.


This study was a randomized, controlled pilot trial to investigate the timing-dependent interaction effects of dual transcranial direct current stimulation (tDCS) in mirror therapy (MT) for hemiplegic upper extremity in patients with chronic stroke. Thirty patients with chronic stroke were randomly assigned to three groups: tDCS applied before MT (prior-tDCS group), tDCS applied during MT (concurrent-tDCS group), and sham tDCS applied randomly prior to or concurrent with MT (sham-tDCS group). Dual tDCS at 1 mA was applied bilaterally over the ipsilesional M1 (anodal electrode) and the contralesional M1 (cathodal electrode) for 30 min. The intervention was delivered five days per week for two weeks. Upper extremity motor performance was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT), and the Box and Block Test (BBT). Assessments were administered at baseline, post-intervention, and two weeks follow-up. The results indicated that concurrent-tDCS group showed significant improvements in the ARAT in relation to the prior-tDCS group and sham-tDCS group at post-intervention. Besides, a trend toward greater improvement was also found in the FMA-UE for the concurrent-tDCS group. However, no statistically significant difference in the FMA-UE and BBT was identified among the three groups at either post-intervention or follow-up. The concurrent-tDCS seems to be more advantageous and time-efficient in the context of clinical trials combining with MT. The timing-dependent interaction factor of tDCS to facilitate motor recovery should be considered in future clinical application.

via Timing-dependent interaction effects of tDCS with mirror therapy on upper extremity motor recovery in patients with chronic stroke: A randomized controlled pilot study – Journal of the Neurological Sciences

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[Abstract] Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation


Background: Early rehabilitation after stroke is essential to help reduce disability.
Purpose: To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke.
Data Sources: English-language searches of multiple electronic databases from April 2009 through July 2018; targeted searches to December 2018 for studies of selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors.
Study Selection: 19 systematic reviews and 37 randomized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke.
Data Extraction: One investigator abstracted the data, and quality and GRADE assessment were checked by a second investigator.
Data Synthesis: Most interventions (for example, SSRIs, mental practice, mirror therapy) did not improve motor function. High-quality evidence did not support use of fluoxetine to improve motor function. Moderate-quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living (ADLs). Low-quality evidence supported use of robotic arm training to improve ADLs. Low-quality evidence indicated that antidepressants may reduce depression, whereas the frequency and severity of antidepressant-related adverse effects was unclear. Low-quality evidence suggested that cognitive behavioral therapy and exercise, including mind–body exercise, may reduce symptoms of depression and anxiety.
Limitation: Studies were of poor quality, interventions and comparators were heterogeneous, and evidence on harms was scarce.
Conclusion: Cardiorespiratory training, repetitive task training, and transcranial direct current stimulation may improve ADLs in adults with stroke. Cognitive behavioral therapy, exercise, and SSRIs may reduce symptoms of poststroke depression, but use of SSRIs to prevent depression or improve motor function was not supported.
Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.

via Treatments for Poststroke Motor Deficits and Mood Disorders | Annals of Internal Medicine | American College of Physicians

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[ARTICLE] A Novel tDCS Sham Approach Based on Model-Driven Controlled Shunting – Full Text



Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single- and double-blinding, especially in non-naïve subjects.


/hypothesis: To ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an “active” sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation, while preventing currents from reaching the cortex and cause changes in brain excitability.


A novel model-based multielectrode technique —optimizing the location and currents of a set of small electrodes placed on the scalp— was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects’ ability to discriminate across conditions for both traditional (Bifocal-tDCS and -Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG).


Subjects perceived Multifocal-tDCS and ActiSham similarly in terms of both scalp sensations and their localization on the scalp, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F(1,13)= 6.67, p=.023), with higher MEPs amplitudes after the application of Bifocal-Sham.


Compared to traditional Bifocal-tDCS, ActiSham offers better participants’ blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.


Non-invasive Brain Stimulation (NIBS) techniques are used to modulate brain activity in a safe and well-tolerated way [1]. In particular, Transcranial direct current stimulation (tDCS), uses low-intensity electrical currents to modulate cortical excitability in a polarity-specific manner [1]. Classical tDCS montages consist of two rectangular sponge electrodes with a contact area of ∼25-35 cm2, where electrical current between 0.5mA and 4mA flows from a positively charged electrode (anode) to a negative one (cathode)[2] passing through various tissue compartments including skin, muscle, bone, cerebrospinal fluid and brain. Due to its safety and relatively low-cost, tDCS experiments have been widely carried out to investigate human neurophysiology and to test its application as a new potential therapeutic solution for neurological and psychiatric conditions. To ensure adequate understanding of the observed effects, however, researchers need to rely on valid and approved control placebo conditions, a fundamental requirement in randomized controlled trials. Traditional standard sham protocols consist on an initial ramp up of the current, followed by a short stimulation period (usually for 5-60 seconds) and a final ramp down [[3][4][5]], (i.e., Fade In of current, brief real Stimulation, Fade-Out; commonly known as “FISSFO” protocol), an approach thought to cause sensory stimulation similar to real tDCS without affecting cortico-spinal excitability [6]. However, both these assumptions (i.e., adequate blinding and absence of effects on the brain) are still under examination. FISSFO sham has been considered effective in providing a proper blinding when compared with real tDCS at 1mA for 20 minutes [6], becoming the standard for sham tDCS [7]. The rationale stems from participants’ reports in which the cutaneous perceptions that generally cue subjects on tDCS being effectively delivered (i.e., tingling or itching sensation), have been mostly reported during the first 30-60 seconds of stimulation to then gradually decrease, possibly due to habituation [4]. However, a recent investigation has revealed that even naïve subjects (N=192) are capable of distinguishing classic sham stimulation (FISSFO) from active tDCS when delivered at 1 mA for 20 minutes over the left dorsolateral prefrontal cortex (DLPFC) [8]. Prior experiments had already suggested blinding inefficacy when real tDCS is applied at 1.5-2 mA, even for only 10 minutes [9,10]. Accordingly, non-naïve subjects seem more capable of distinguishing real from sham tDCS [11] and extreme individual variability has been reported with regard to sensibility to stimulation intensity and duration, with subjects being able to perceive tDCS even at very low intensity (i.e., 400 μA) [11].

On the other hand, additional sham protocols have been developed with modified durations of ramp up/down, or even delivering constant low intensity currents (0.016 or 0.034 mA) [7,12,13]. However, these approaches have not been properly tested on large sample of patients/subjects, with no data on the effects of such alternative sham protocols on the brain, while inconsistent results on many neurophysiological parameters have been documented when adopting such modified approaches [13].

Beyond the single or double blinding efficacy of FISSFO and related approaches [14], an element of interest is the question of whether tDCS effects are due to cortical interaction of the generated electric fields or from peripheral nervous system (PNS) stimulation. Since the ramp-up/ramp-down method for blinding decreases both cortical and peripheral stimulation, they cannot help disentangling cortical and peripheral effects. In addition, cortical effects of the brief period of real stimulation during sham protocols may not completely be excluded [15].

An additional challenge is the fact that the induced tDCS electric field is conditioned by the heterogeneity of cortical and non-cortical tissues, as well as by the complexity of cortical geometry [16]. In recent years, this has been addressed by the use of multichannel tDCS systems in combination with realistic finite element modeling of current propagation in the head derived from subject neuroimaging data (e.g. MRI, fMRI) [17,18]. The rationale for multifocal stimulation resides on both the need for more targeted stimulation of the cortex, as well as the notion that brain regions operate in networks and communicate with each other’s through modulatory interactions [[19][20][21]]. Realistic physical models provide a crucial element for better experimental understanding and control of the electric fields generated by tDCS.

In the present study, we investigate a novel approach to sham stimulation based on controlled shunting of currents via a model-based quantification of transcutaneous and transcranial effects. Specifically, the novel sham tDCS solution benefits from the use of an optimization algorithm allowing tDCS montages to be tailored in such a way that zero or very low magnitude electric fields are delivered on the brain, while medium to high intensity currents are maintained in at least some scalp electrodes, thus eliciting scalp sensations necessary for blinding. Notably, this allows to maintain the stimulation ON for the entire duration of sham tDCS, therefore inducing scalp sensations similar to real tDCS, while avoiding known limitations of the FISSFO protocol. We hypothesize that such montage (Active Sham, ActiSham hereafter) (i) will generate scalp sensations similar to a Multifocal (real) tDCS montage based on the same electrodes’ location and identical stimulation intensity/duration; and that (ii) ActiSham will not induce changes in cortico-spinal excitability (CSE), as assessed through Motor Evoked Potentials (MEPs) induced by Transcranial Magnetic Stimulation (TMS) as an index of corticospinal excitability. If successful, this and similar other approaches for improved sham stimulation could contribute to more efficient design of future tDCS research studies and clinical trials.


Study design

Fourteen subjects participated in 4 randomized tDCS stimulation visits, spaced 7±3 days to ensure no carryover effects. The tDCS conditions were: real Bifocal-tDCS, Bifocal-Sham, real Multifocal-tDCS and ActiSham. Each session lasted approximately 90 minutes during which participants seated in a comfortable chair with their eyes open. To measure changes in corticospinal excitability, single pulse TMS was applied over the left primary motor cortex (M1) at the beginning and the end of each stimulation session. Somatosensory sensations elicited by tDCS were addressed by means of ad-hoc questionnaires. See dedicated sections below for further details about tools and procedures.


Fourteen healthy right-handed naïve subjects (25.4 years ± 2.1; 5 males) were recruited at the University Campus of Siena, School of Medicine (Siena, Italy). Possible contraindications to either TMS or tDCS were assessed by means of a screening questionnaire [22]. Exclusion criteria included: history of seizures, head injury, pacemakers or other implanted medical devices, metallic objects in the head, hearing impairments, medications altering cortical excitability or other significant medical concerns. All participants gave written informed consent prior to participating to the study. The research proposal and associated methodologies were approved by the local ethical committee in accordance with the principles of the Declaration of Helsinki.


tDCS sessions lasted 15 minutes, with electrode types, scalp montages and stimulation intensities customized for each tDCS protocol (Figure 1). Transcranial stimulation was delivered using a “Starstim 8” brain stimulator controlled via Bluetooth using a laptop computer (Neuroelectrics, Barcelona, Spain). For canonical Bifocal-tDCS (active or sham), stimulation was delivered through traditional 5×7 cm rectangular sponge electrodes, with a contact area of 35 cm2 (SPONSTIM, Neuroelectrics, Barcelona, Spain). Before current delivery, electrodes were soaked with 15 ml of sterile sodium chloride solution (0.9%). For Multichannel stimulation conditions (real and ActiSham), current was instead delivered using circular Ø 20 mm PISTIM electrodes (Neuroelectrics, Barcelona, Spain) with an Ag/AgCl core and a gel/skin contact area of 3.14 cm2. Electrodes were filled with a conductive gel before the tDCS intervention. To further improve current conductivity, the scalp was gently rubbed with an alcohol solution at the beginning of each session. Electrodes were inserted in a neoprene cap with available positions following the 10/20 EEG system.

Figure 1

Figure 1Study design. (A) Active stimulation was delivered for 15 minutes, (30 seconds of ramp up and down). Corticospinal excitability was measured via TMS three times prior to stimulation (Pre-10, Pre-5 and Pre-0) and compared with post measurements collected up to 15 minutes after stimulation (Post-0, Post-5, Post-10, Post-15). Halfway through the protocol (i.e., at minute 7), subjects were asked to rate stimulation-related annoyance and pain levels. tDCS montages for Multifocal-tDCS (B), ActiSham (C), Bifocal-tDCS and Bifocal-Sham (D) are shown.


Continue —-> A Novel tDCS Sham Approach Based on Model-Driven Controlled Shunting – ScienceDirect

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[Abstract] Effects of Bihemispheric Transcranial Direct Current Stimulation on Upper Extremity Function in Stroke Patients: A randomized Double-Blind Sham-Controlled Study


Background and Purpose

Transcranial direct current stimulation (tDCS) is a treatment used in the rehabilitation of stroke patients aiming to improve functionality of the plegic upper extremity. Currently, tDCS is not routinely used in post stroke rehabilitation. The aim of this study was to establish the effects of bihemspheric tDCS combined with physical therapy (PT) and occupational therapy (OT) on upper extremity motor function.


Thirty-two stroke inpatients were randomised into 2 groups. All patients received 15 sessions of conventional upper extremity PT and OT over 3 weeks. The tDCS group (n = 16) also received 30 minutes of bihemispheric tDCS and the sham group (n = 16) 30 minutes of sham bihemispheric tDCS simultaneously to OT. Patients were evaluated before and after treatment using the Fugl Meyer upper extremity (FMUE), functional independence measure (FIM), and Brunnstrom stages of stroke recovery (BSSR) by a physiatrist blind to the treatment group


The improvement in FIM was higher in the tDCS group compared to the sham group (P = .001). There was a significant within group improvement in FMUE, FIM and BSSR in those receiving tDCS (P = .001). There was a significant improvement in FIM in the chronic (> 6months) stroke sufferers who received tDCS when compared to those who received sham tDCS and when compared to subacute stroke (3-6 months) sufferers who received tDCS/sham.


Upper extremity motor function in hemiplegic stroke patients improves when bihemispheric tDCS is used alongside conventional PT and OT. The improvement in functionality is greater in chronic stroke patients.

via Effects of Bihemispheric Transcranial Direct Current Stimulation on Upper Extremity Function in Stroke Patients: A randomized Double-Blind Sham-Controlled Study – ScienceDirect

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