Posts Tagged NIBS

[Abstract] The treatment of fatigue by non-invasive brain stimulation


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.

Source: The treatment of fatigue by non-invasive brain stimulation

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[ARTICLE] Cognitive and Neurophysiological Effects of Non-invasive Brain Stimulation in Stroke Patients after Motor Rehabilitation – Full Text

The primary aim of this study was to evaluate and compare the effectiveness of two specific Non-Invasive Brain Stimulation (NIBS) paradigms, the repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial Direct Current Stimulation (tDCS), in the upper limb rehabilitation of patients with stroke.

Short and long term outcomes (after 3 and 6 months, respectively) were evaluated. We measured, at multiple time points, the manual dexterity using a validated clinical scale (ARAT), electroencephalography auditory event related potentials, and neuropsychological performances in patients with chronic stroke of middle severity.

Thirty four patients were enrolled and randomized. The intervention group was treated with a NIBS protocol longer than usual, applying a second cycle of stimulation, after a washout period, using different techniques in the two cycles (rTMS/tDCS). We compared the results with a control group treated with sham stimulation. We split the data analysis into three studies. In this first study we examined if a cumulative effect was clinically visible. In the second study we compared the effects of the two techniques. In the third study we explored if patients with minor cognitive impairment have most benefit from the treatment and if cognitive and motor outcomes were correlated.

We found that the impairment in some cognitive domains cannot be considered an exclusion criterion for rehabilitation with NIBS. ERP improved, related to cognitive and attentional processes after stimulation on the motor cortex, but transitorily. This effect could be linked to the restoration of hemispheric balance or by the effects of distant connections. In our study the effects of the two NIBS were comparable, with some advantages using tDCS vs. rTMS in stroke rehabilitation. Finally we found that more than one cycle (2–4 weeks), spaced out by washout periods, should be used, only in responder patients, to obtain clinical relevant results.


Motor and cognitive impairment are frequent aftermaths of brain damage after a stroke. Many authors reports cognitive deficits in 12–56% of stroke patients and reduced performances in several cognitive domains in 32% (Ebrahim et al., 1985; Tatemichi et al., 1994; Patel et al., 2002). Moreover, dysfunctions in the use of upper limb and in functional walking are among the more common consequences for many stroke survivors. Of note, only 5% of adult stroke survivors regain full function of the upper limb and 20% do not recover any functional use.

The severity of cognitive impairment negatively correlates with motor and functional recovery achieved in stroke patients after rehabilitation. Indeed, a cognitive assessment should be used to select patients that could have the best benefits from rehabilitation (Patel et al., 2002; Mehta et al., 2003; Saxena et al., 2007; Rabadi et al., 2008).

Event Related Potentials (ERP) are a reproducible electrophysiological response to an external stimulus (visual or auditory), representing the brain activity associated with various cognitive processes such as selective attention, memory, or decision making. Interestingly, ERP can be valuable in the diagnosis of cognitive impairment and are able to track the cognitive changes during the follow-up in stroke patients (Trinka et al., 2000; Alonso-Prieto et al., 2002; Yamagata et al., 2004; Stahlhut et al., 2014).

Recently, Non-Invasive Brain Stimulation (NIBS) techniques have been proposed as support of standard cognitive and motor rehabilitation. The application of NIBS in stroke rehabilitation arises from the observation that cortical excitability can be modulated after electrical or magnetic brain stimulation. It can be reduced or enhanced (Miniussi et al., 2008; Sandrini and Cohen, 2013) depending on many factors (stimulation parameters, type of stimulation technique, timing of the stimulation, brain target region, and state of mind).

The physiological mechanisms underlying brain stimulation effects are still partially unknown, but several evidences explain these effects with Long Term Potentiation (LTP) and Long Term Depression (LTD) like mechanisms (Thickbroom, 2007; Fritsch et al., 2010; Bliss and Cooke, 2011).

Repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) are the most used NIBS techniques in rehabilitation (Hummel et al., 2005; Miniussi et al., 2008; Bolognini et al., 2009). Both can induce long lasting effect on cortical plasticity (30–90 min). Modification of cortical activity may improve the subject’s ability to relearn or acquire new strategies for carrying out motor or behavioral task, by facilitating perilesional activity or by suppressing maladaptive interfering activity from other brain areas (Miniussi et al., 2008). Even if most of the effects are transient, NIBS during or before a learning process may yield the behavioral improvements more robust and stable (Rossi and Rossini, 2004;Pascual-Leone, 2006). Indeed, during motor learning not only the fast (intra-sessions) and slow (inter-sessions) learning during training are relevant, but also the memory consolidation and the savings (Wessel et al., 2015). Plasticity induced by NIBS could thus have important effects not only in the online phase of motor rehabilitation, but also in the offline phases.

A growing number of studies indicates that NIBS could be useful in chronic stroke rehabilitation (Hummel and Cohen, 2006;Sandrini and Cohen, 2013; Liew et al., 2014; Wessel et al., 2015), but no one compared directly the two techniques or explored the link between cognitive and motor improvement. TMS is able to directly induce action potentials in the axons while the currents used in tDCS (1–2 mA) cannot. The first technique is, therefore, best suited to be used offline, while the second can be used online in conjunction with other rehabilitation techniques or tasks (Wessel et al., 2015). Simis et al. (2013) compared rTMS and tDCS in healthy subjects, observing that both techniques induced similar motor gains. The comparison of brain plasticity induced by NIBS in pathologic subjects could thus extend significantly the Simis’ results.

In this paper, the primary aim was to evaluate and compare the motor and cognitive changes induced by rTMS and tDCS in the upper limb rehabilitation in patients with stroke, both in short and in long term outcome. Secondarily we searched for a possible link between motor and cognitive measures.

We chose the most effective paradigm of rTMS in chronic stroke according to meta-analyses and consensus papers (Lefaucheur et al., 2014), a low-frequency protocol applied onto the controlesional motor cortex (M1). For tDCS, in the absence of a gold standard, we chose a paradigm with a dual sites montage validated in non-inferiority trials (Schlaug et al., 2008; Lüdemann-Podubecká et al., 2014). The tDCS was performed in conjunction with a cognitive training focused on the brain representation of the hands, the mirror-box therapy (MT), to direct the neuromodulation effect as wished. Our aim was to create a paradigm easy to apply in a clinical setting.

To compare the NIBS techniques in the same patients we created a treatment longer than usual applying a second cycle of stimulation, after a washout period, using different techniques in the two cycles (rTMS/tDCS).

A randomized clinical trial divided into three studies was designed to explore the following issues:

A longer NIBS stimulation could be beneficial in stroke rehabilitation?

What are the differences between rTMS and tDCS in stroke rehabilitation?

NIBS motor stimulation effects can modulate or be modulated by patients’ cognitive status?

In the first study we evaluated if a cumulative effect, mediated by an offline improvement (consolidation or savings), was clinically detectable. We also evaluated the differences between a first priming cycle with rTMS followed by tDCS and first priming with tDCS followed by rTMS.

In the second study we compared the effects of the two techniques to test if brain plasticity effects could depend on the type of NIBS. In the third study, we searched for a possible link between motor and cognition changes, evaluating if cognitive measures changed in patients with motor improvement differently from the patients without motor improvement.

Continue —> Frontiers | Cognitive and Neurophysiological Effects of Non-invasive Brain Stimulation in Stroke Patients after Motor Rehabilitation | Frontiers in Behavioral Neuroscience

Figure 1. Experimental design. After screening the patients were randomized into three groups with different interventions: MT, Mirror Therapy; tDCS, transcranial Direct Current Stimulation; rTMS, repetitive Transranial Magnetic Stimulation. In the scheme the outcome measures: ARAT, Action Research Arm Test; P300, cognitive auditory evoked response potentials; NPS, neuropsychological test where assessed in multiple time frames; w, week; mos, months.

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Stroke is a leading cause of long-term adult motor disability. While current rehabilitation strategies carry promise, gains in function are modest where approximately 60-80% of survivors continue to experience motor impairments of the upper-limb well into the chronic phase of recovery. One reason for the modest recovery of upper-limb function is the diminishing time available for rehabilitation, where therapists are required to administer best practice in a limited number of sessions. Therefore, current research emphasizes the need for maximizing and accelerating outcomes of rehabilitation within constraints of time permitted for outpatient clinical therapy.

One strategy to maximize rehabilitative outcomes emphasizes the importance of engaging the paretic upper-limb in intensive movements/activities, defined operationally here as ‘unilateral therapies.’ Examples include constraint-induced movement therapy (CIMT) that requires patients to use the paretic upper-limb in tasks of daily living while restraining use of the non-paretic upper-limb, or electrical stimulation that targets weaker muscles to elicit more movement of the paretic upper-limb. Unilateral therapies are emphasized because they are derived from a popular, standard neurophysiologic model of stroke recovery commonly referred to as the ‘interhemispheric competition model’ (figure 1). According to this model, paresis originates from loss of output to the paretic upper-limb, but it persists due to inter-hemispheric imbalances.

The contralesional hemisphere excessively inhibits the ipsilesional hemisphere that is too weak to counter. As patients rely on using the non-paretic upper-limb to compensate for failures in using the paretic upper-limb, inter-hemispheric ‘competition’ intensifies. Output from the ipsilesional hemisphere weakens further, while excitability and inhibition imposed from the contralesional hemisphere continues to rise.

To maximize output to the paretic upper-limb, the model recommends emphasizing use of the paretic upper-limb in unilateral therapies and disregarding or de-incentivizing use of the non-paretic upper-limb. …

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[ARTICLE] The effects of individually tailored rTMS on hand function in chronic stroke: a protocol for an adaptive, phase II, randomized, sham-controlled clinical trial – Full Text PDF


Stroke is a leading cause of disability among adults. Existing rehabilitation programs haven’t been able to accomplish full motor recovery partially due to the pathologic plasticity exerted from the unaffected hemisphere to the affected one.
This inhibition can be disrupted using non-invasive brain stimulation (NIBS). Transcranial magnetic stimulation (TMS) is a NIBS technique that has the capacity of depolarizing or hyperpolarizing neurons depending on the frequency of the pulses. Although several trials have been conducted to find the efficacy of low frequency rTMS for motor recovery after stroke, their results have been heterogeneous. One of the main variables that determine the response to rTMS is the dose, corresponding to the number of pulses delivered to the patients.
However, due to the localization and the extension of the stroke, each patient responds differently to certain dose. Therefore, using the SPIRIT statement, we designed a protocol for an adaptive, phase II, randomized, sham-controlled clinical trial. The study proposed will include 75 patients between 45 and 80 years old, with hand function impairment after 1 to 3 years of stroke; it will exclude patients with severe cognitive or neuropsychiatric comorbilities, any previous stroke episode, Fugl Meyer (Upper limb) < 20, inability to understand the task or contraindications for rTMS.
The study will have 3 arms: individually tailored (adaptive dosing) low frequency (1Hz) rTMS plus standard of care rehabilitation (physical therapy) compared to sham and fixed rTMS plus standard of care rehabilitation. The intervention will be applied during 6 weeks after which the main analysis will be performed. Subjects will be followed-up during 3 months and the results from this analysis will be exploratory. This protocol will use the results from the Pegboard test as a primary outcome and SF-36 questionnaire, hand strength, and responder´s rate as secondary outcomes.

Source: The effects of individually tailored rTMS on hand function in chronic stroke: a protocol for an adaptive, phase II, randomized, sham-controlled clinical trial | Jannati | Principles and Practice of Clinical Research

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[BLOG POST] A window into the brain networks: magnetoencephalography (MEG) and simultaneous Transcranial Current Stimulation (tCS). | Blog Neuroelectrics

A window into the brain networks: magnetoencephalography (MEG) and simultaneous Transcranial Current Stimulation (tCS).

Based on already published large evidence, non-invasive brain stimulation (NIBS) techniques like tdCS represent very important approach for the improvement of abnormal brain functions in various conditions (psychiatric and neurological). NIBS can induce temporary changes of neural oscillations and performance on various functional tasks. One of the key-points in understanding a mechanism of NIBS is the knowledge about the brains response to current stimulation and underlying brain network dynamics changes. Until recently, concurrent observation of the effect of NIBS on multiple brain networks interactions and most importantly, how current stimulation modifies these networks remained unknown because of difficulties in simultaneous recording and current stimulation. Recently, in Neuroelectrics wireless hybrid EEG/tCS 8-channel neurostimulator system has been developed that allows simultaneous EEG recording and current stimulation. Now, a relatively new imaging technique called magnetoencephalography (MEG) has emerged as a procedure that can bring new inside into brain dynamics. In this context, our group conducted a successfully proof of concept test to ensure the feasibility of concurrent MEG recording and current stimulation using Starstim and a set of non-ferrous electrodes (Figure 1). But first of all, what actually is MEG? Magnetoencephalography (MEG) is a noninvasive recording method of the magnetic flux from the head surface. Magnetic flux is associated with intracranial electrical currents produced by neural activity (the neural currents are caused by a flow of ions through postsynaptic dendritic membranes). From Maxwell equations, magnetic fields are found whenever there is a current flow, whether in a wire or a neuronal element. Hence, MEG detects these magnetic fields generated by spontaneous or evoked brain activity.

Continue —> A window into the brain networks: magnetoencephalography (MEG) and simultaneous Transcranial Current Stimulation (tCS). | Blog Neuroelectrics

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[ARTICLE] Anodal tDCS Combined With Radial Nerve Stimulation Promotes Hand Motor Recovery in the Acute Phase After Ischemic Stroke


Background and Objective: The question of the best therapeutic window in which noninvasive brain stimulation (NIBS) could potentiate the plastic changes for motor recovery after a stroke is still unresolved. Most of the previous NIBS studies included patients in the chronic phase of recovery and very few in the subacute or acute phase. We investigated the effect of transcranial direct current stimulation (tDCS) combined with repetitive peripheral nerve stimulation (rPNS) on the time course of motor recovery in the acute phase after a stroke.

Methods: Twenty patients enrolled within the first few days after a stroke were randomized in 2 parallel groups: one receiving 5 consecutive daily sessions of anodal tDCS over the ipsilesional motor cortex in association with rPNS and the other receiving the same rPNS combined with sham tDCS. Motor performance (primary endpoint: Jebsen and Taylor Hand Function Test [JHFT]) and transcranial magnetic stimulation cortical excitability measures were obtained at baseline (D1), at the end of the treatment (D5), and at 2 and 4 weeks’ follow-up (D15 and D30).

Results: The time course of motor recovery of the 2 groups of patients was different and positively influenced by the intervention (Group × Time interaction P = .01). The amount of improvement on the JHFT was greater at D15 and D30 in the anodal tDCS group than in the sham group.

Conclusion: These results show that early cortical neuromodulation with anodal tDCS combined with rPNS can promote motor hand recovery and that the benefit is still present 1 month after the stroke.

Source: Anodal tDCS Combined With Radial Nerve Stimulation Promotes Hand Motor Recovery in the Acute Phase After Ischemic Stroke

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[ARTICLE] Spaced Noninvasive Brain Stimulation


Neuroplasticity is critical for learning, memory, and recovery of lost function following neurological damage. Noninvasive brain stimulation (NIBS) techniques can induce neuroplastic changes in the human cortex that are behaviorally relevant, raising the exciting possibility that these techniques might be therapeutically beneficial for neurorehabilitation following brain injury. However, the short duration and instability of induced effects currently limits their usefulness.

To date, trials investigating the therapeutic value of neuroplasticity-inducing NIBS have used either single or multiple treatment sessions, typically repeated once-daily for 1 to 2 weeks.

Although multiple stimulation sessions are presumed to have cumulative effects on neuroplasticity induction, there is little direct scientific evidence to support this “once-daily” approach. In animal models, the repeated application of stimulation protocols spaced using relatively short intervals (typically of the order of minutes) induces long-lasting and stable changes in synaptic efficacy. Likewise, learning through spaced repetition facilitates the establishment of long-term memory. In both cases, the spacing interval is critical in determining the outcome.

Emerging evidence in healthy human populations suggests that the within-session spacing of NIBS protocols may be an effective approach for significantly prolonging the duration of induced neuroplastic changes. Similar to findings in the animal and learning literature, the interval at which spaced NIBS is applied seems to be a critical factor influencing the neuroplastic response.

In this Point of View article, we propose that to truly exploit the therapeutic opportunities provided by NIBS, future clinical trials should consider the optimal spacing interval for repeated applications.

Source: Spaced Noninvasive Brain Stimulation

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[ARTICLE] Non-invasive brain stimulation in early rehabilitation after stroke – Full Text HTML


The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed.

Continue —>  Non-invasive brain stimulation in early rehabilitation after stroke

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[ ARTICLE] Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation – Full Text PDF


Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques.


The American Heart Association estimates that approximately 795,000 individuals in the United States have a stroke each year (Go et al., 2014). A lack of mobility is the main obstacle for stroke survivors seeking to regain daily living independence and social integration. Thus, restoring impaired gait is one of the major goals of post-stroke rehabilitation. Recently, traditional rehabilitation techniques have been augmented by the use of a new methodology, noninvasive brain stimulation (NIBS), which facilitates neuroplasticity. To better understand the use of NIBS, this paper reviews literature regarding the neurophysiology of human gait, poststroke neuroplasticity in the motor control system underlying gait, and finally, approaches for using NIBS to enhance gait recovery.

Neurophysiology of Human Gait

Involvement of the cerebral cortices: In functional neuroimaging studies of human walking, the premotor cortex (PMC) and the supplementary motor cortex (SMC) are activated prior to step onset (Huppert et al., 2013). However, lesions in these two areas often lead to problems with gait initiation and the negotiation of narrow passages (Jahn et al., 2004), indicating their importance in the initiation and planning of walking. Furthermore, corticospinal inputs significantly facilitate muscular responses in the lower limbs, especially during the swing phase of the step cycle (Pijnappels et al., 1998). These observations suggest that cortical outputs play a critical role in the modulation of lower limb locomotion…

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[ARTICLE] Non Invasive Neuromodulation in Motor Recovery after Stroke: State of the Art, Open Questions and Future Perspectives – Open Access


Stroke is the leading cause of adult disability. Unfortunately, less than 40% of stroke survivors completely recover, despite intensive acute care and rehabilitation training.

Non invasive brain stimulation (NIBS) techniques have been recognized as a promising intervention to improve motor recovery after stroke. Repeated sessions of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) can, indeed, induce changes in cortical excitability and long term plasticity.

Several protocols of stimulation have been already tested and proven efficient in modulating the lesioned as well as the unlesioned hemisphere after stroke.

However, not all patients can be considered as responder to NIBS. We provide an overview of the rationale, open questions and future perspectives for NIBS after stroke.

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