Posts Tagged rTMS

[Abstract] Low-frequency rTMS of the unaffected hemisphere in stroke patients: A systematic review

Abstract

The aim of this review was to summarize the evidence for the effectiveness of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere in promoting functional recovery after stroke. We performed a systematic search of the studies using LF-rTMS over the contralesional hemisphere in stroke patients and reviewed the 67 identified articles. The studies have been gathered together according to the time interval that had elapsed between the stroke onset and the beginning of the rTMS treatment. Inhibitory rTMS of the contralesional hemisphere can induce beneficial effects on stroke patients with motor impairment, spasticity, aphasia, hemispatial neglect and dysphagia, but the therapeutic clinical significance is unclear. We observed considerable heterogeneity across studies in the stimulation protocols. The use of different patient populations, regardless of lesion site and stroke aetiology, different stimulation parameters and outcome measures means that the studies are not readily comparable, and estimating real effectiveness or reproducibility is very difficult. It seems that careful experimental design is needed and it should consider patient selection aspects, rTMS parameters and clinical assessment tools. Consecutive sessions of rTMS, as well as the combination with conventional rehabilitation therapy, may increase the magnitude and duration of the beneficial effects. In an increasing number of studies, the patients have been enrolled early after stroke. The prolonged follow-up in these patients suggests that the effects of contralesional LF-rTMS can be long-lasting. However, physiological evidence indicating increased synaptic plasticity, and thus, a more favourable outcome, in the early enrolled patients, is still lacking. Carefully designed clinical trials designed are required to address this question. LF rTMS over unaffected hemisphere may have therapeutic utility, but the evidence is still preliminary and the findings need to be confirmed in further randomized controlled trials.

Source: Low-frequency rTMS of the unaffected hemisphere in stroke patients: A systematic review – Sebastianelli – 2017 – Acta Neurologica Scandinavica – Wiley Online Library

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[ARTICLE] The Effects of Navigated Repetitive Transcranial Magnetic Simulation and Brunnstrom Movement Therapy on Upper Extremity Proprioceptive Sense and Spasticity in Stroke Patients: A Double-Blind Randomized Trial – Full Text PDF

Abstract

Purpose: The purpose of this study is to investigate the effects of various treatments (repetitive transcranial magnetic stimulation and Brunnstrom movement therapy) on upper extremity proprioceptive sense and spasticity.

Methods: Twenty-one stroke patients were included in the study. The treatment group (Group 1; n=10) was administered navigated real repetitive transcranial magnetic stimulation (rTMS), and the control group (Group 2; n=11) was administered sham rTMS by the first researcher. The patients in both groups had upper extremity exercises according to Brunnstrom movement therapy (BMT). The patients were assessed using the Brunnstrom recovery stages (BRS), proprioceptive sense assessment, and the modified Ashworth scale (MAS).

Results: Between the treatment group and control group patients, there were no significant statistical differences obtained from pre-treatment and postreatment tenth day, first month, and third month by BRS wrist, hand, and upper extremity stages. The intragroup comparison of the treatment group patients revealed a statistically significant difference between the pre-treatment and post-treatment third month BRS-hand and BRS-upper extremity stages.The pretreatment and postreatment tenth day and first month evaluations of the wrist proprioceptive sense of the groups presented a significant difference. There was no statistically significant difference between the groups in terms of MAS scores before and after treatment evaluations.

Conclusion: The rTMS and BMT approaches that were implemented in the study affected the proprioceptive sense of the wrist after the treatment and in the early period but did not change spasticity.

Keywords: Repetitive transcranial magnetic stimulation, stroke, Brunnstrom recovery stages, proprioceptive sense, spasticity

INTRODUCTION

Proprioceptive sense is the individual’s ability to perceive the position and the motion of his/her body segments in the space via somatosensorial impulses sent by the receptors in the skin, muscles, and joints (1). Researchers have stated that the proprioceptive sense, which is the awareness sense of the body, consists of three fundamental senses: kinesthesia, joint position sense, and neuromuscular control (2). The proprioceptive sense plays a crucial role in carrying out and controlling daily activities, maintaining posture and balance, joint stability, and motor learning (3, 4). Neuromuscular control is affected by proprioceptive inefficiencies apart from motor dysfunctions. It has been shown that proprioceptive knowledge is of extreme importance for the neural control of motion and that the upper extremity proprioceptive sense is commonly decreased or evanished following stroke (5). It has been explained that the proprioceptive deficit incidence rate is 50-65% in stroke patients, which affects daily activities and quality of life negatively (6, 7). It has been stated that proprioceptive and motor deficits have different recovery rates in the first six months following stroke (8). In stroke patients, sensorimotor learning calls for a sound somatosensorial impulse, which is possible through sensorimotor rehabilitation (9). The Bobath, Brunnstrom, Johnstone, and Rood proprioceptive neuromuscular facilitation techniques and the motor learning method, commonly utilized by physiotherapists, are based upon treating sensorimotor functions (10). There exist several recent studies that report that the pain-free, non-invasive transcranial magnetic stimulation (rTMS) application decreases spasticity or that it has no effect (11-13). Stroke rehabilitation is provided by decreasing the transcallosal inhibition from the unaffected motor cortex to the affected motor cortex via 1 Hz rTMS applied on the motor cortex (14, 15). Whereas there is a limited number of studies in the literature with various results on the effects of rTMS and physiotherapy combination on spasticity, a study dealing with the effect of rTMS and physiotherapy combination on proprioceptive sense has not been found. This study was planned to investigate the effect of rTMS and Brunnstrom movement therapy (BMT) on upper extremity proprioceptive sense and spasticity (11, 12).

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[Abstract] Spasticity Management: The Current State of Transcranial Neuromodulation

Abstract

This narrative review aims to provide an objective view of the non-invasive neuromodulation (NINM) protocols available for treating spasticity, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). On the basis of the relevant randomized controlled trials, we infer that NINM is more effective in reducing spasticity when combined with the conventional therapies than used as a stand-alone treatment. However, the magnitude of NINM aftereffects depends significantly on the applied hemisphere and the underlying pathology. Being in line with these arguments, low-frequency rTMS and cathodal-tDCS over the unaffected hemisphere are more effective in reducing spasticity than high-frequency rTMS and anodal-tDCS over the affected hemisphere in chronic post-stroke. However, most of the studies are heterogeneous in the stimulation setup, patient selection, follow-up duration, and the availability of the sham operation. Therefore, the available data on the usefulness of NINM in reducing spasticity need to be confirmed by further larger and multicentric randomized controlled trials to gather evidence on the efficiency of NINM regimens in reducing spasticity in various neurologic conditions.

Source: Spasticity Management: The Current State of Transcranial Neuromodulation

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

Summary

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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[Abstract] Importance and Difficulties of Pursuing rTMS Research in Acute Stroke

Abstract

Although much research has been done on repetitive transcranial magnetic stimulation (rTMS) in chronic stroke, only sparse research has been done in acute stroke despite the particularly rich potential for neuroplasticity in this stage.

We attempted a preliminary clinical trial in one active, high-quality inpatient rehabilitation facility (IRF) in the U.S. But after enrolling only four patients in the grant period, the study was stopped because of low enrollment.

The purpose of this paper is to offer a perspective describing the important physiologic rationale for including rTMS in the early phase of stroke, the reasons for our poor patient enrollment in our attempted study, and recommendations to help future studies succeed.

We conclude that, if scientists and clinicians hope to enhance stroke outcomes, more attention must be directed to leveraging conventional rehabilitation with neuromodulation in the acute phase of stroke when the capacity for neuroplasticity is optimal. Difficulties with patient enrollment must be addressed by reassessing traditional inclusion and exclusion criteria. Factors that shorten patients’ length of stay in the IRF must also be reassessed at all policy-making levels to make ethical decisions that promote higher functional outcomes while retaining cost consciousness.

Source: Importance and Difficulties of Pursuing rTMS Research in Acute Stroke | Physical Therapy | Oxford Academic

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[ARTICLE] Short- and Long-term Effects of Repetitive Transcranial Magnetic Stimulation on Upper Limb Motor Function after Stroke: a Systematic Review and Meta-Analysis – Full Text

The aim of this study was to evaluate the short- and long-term effects as well as other parameters of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor functional recovery after stroke.

The databases of PubMed, Medline, Science Direct, Cochrane, and Embase were searched for randomized controlled studies reporting effects of rTMS on upper limb motor recovery published before October 30, 2016.

The short- and long-term mean effect sizes as well as the effect size of rTMS frequency of pulse, post-stroke onset, and theta burst stimulation patterns were summarized by calculating the standardized mean difference (SMD) and the 95% confidence interval using fixed/random effect models as appropriate.

Thirty-four studies with 904 participants were included in this systematic review. Pooled estimates show that rTMS significantly improved short-term (SMD, 0.43; P < 0.001) and long-term (SMD, 0.49; P < 0.001) manual dexterity. More pronounced effects were found for rTMS administered in the acute phase of stroke (SMD, 0.69), subcortical stroke (SMD, 0.66), 5-session rTMS treatment (SMD, 0.67) and intermittent theta burst stimulation (SMD, 0.60). Only three studies reported mild adverse events such as headache and increased anxiety .

Five-session rTMS treatment could best improve stroke-induced upper limb dyskinesia acutely and in a long-lasting manner. Intermittent theta burst stimulation is more beneficial than continuous theta burst stimulation. rTMS applied in the acute phase of stroke is more effective than rTMS applied in the chronic phase. Subcortical lesion benefit more from rTMS than other lesion site.

Continue —> Short- and Long-term Effects of Repetitive Transcranial Magnetic Stimulation on Upper Limb Motor Function after Stroke: a Systematic Review and Meta-Analysis – Feb 17, 2017

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Figure 1. The flow diagram of the selection process.

 

 

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[ARTICLE] Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis? – Full Text HTML

 

Abstract

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) to the contralesional hemisphere and intensive occupational therapy (iOT) have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-rTMS and iOT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient’s Trail-Making Test part B (TMT-B) performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-rTMS to the contralesional hemisphere and 2 sessions of iOT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-rTMS to the contralesional hemisphere combined with iOT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

 

Introduction
Upper limb hemiparesis is reported to be observed in 55–75% of post-stroke patients, and affects the patient’s activities of daily living and quality of life (Nichols-Larsen et al., 2005; Wolf et al., 2006). Duncan et al. (1992) reported that dramatic recovery of motor function was completed by 1month post-stroke, and that recovery often plateaued by 6 months. In recent years, repetitive transcranial magnetic stimulation (rTMS) has attracted attention as a treatment technique for the sequelae of stroke. It is a non-invasive, painless method to stimulate regions of the cerebral cortex, in which a figure-8 or a round coil converts electrical current into a rapidly variable magnetic field that is orthogonal to the current. Eddy currents generated by the changes of the magnetic field directly affect neurons (Barker, 1999). In addition, it has been known that different stimulation frequencies have different effects on the activities of the cerebral cortex, with high-frequency (> 5 Hz) stimulation facilitating local neuronal excitability and low-frequency (< 1 Hz) stimulation showing inhibitory effects (Lefaucheur, 2006; Butler and Wolf, 2007). Low-frequency rTMS (LF-rTMS) aims at increasing the excitability of the ipsilesional hemisphere by exerting its effects on the disrupted interhemispheric inhibition following stroke and thereby providing inhibitory stimulation to the contralesional hemisphere. Meta-analyses of rTMS in patients with stroke indicate that LF-rTMS is recommended for stroke patients in the chronic phase (> 6 months post-stroke), showing a strong possibility of a significant improvement of their upper limb function (Hsu et al., 2012; Le et al., 2014). In the past, our research group implemented a 15-day treatment protocol consisting of LF-rTMS and an intensive individualized rehabilitation program for patients with upper limb hemiparesis following stroke, and demonstrated a significant improvement of upper limb hemiparesis (Kakuda et al., 2011, 2012, 2016). Furthermore, we investigated the effects of our treatment protocol on brain activity and demonstrated a significant increase in the fMRI laterality index, indicating increased neuronal activity in the ipsilesional hemisphere (Yamada et al., 2013). Our single photon emission computed tomography (SPECT) study also demonstrated a significant decrease in perfusion in the middle frontal gyrus (Brodmann area; BA6), precentralgyrus (BA4), and post central gyrus (BA3) of the contralesional hemisphere, as well as an increased perfusion in the insula (BA13) and precentral gyrus (BA44) of the ipsilesional hemisphere (Hara et al., 2013). Thus, we demonstrated changes in brain activity between pre- and post-treatment that combined LF-rTMS and an intensive occupational therapy (iOT) program.

In recent studies, rTMS was used not only in treating upper limb hemiparesis after stroke, but also for other conditions, including neurological and psychiatric disorders, pain, and Parkinson’s disease (Lefaucheur et al., 2014). Furthermore, some studies conducted neuropsychological examinations at the time of rTMS to evaluate its effect on cognitive function (Nardone et al., 2014; Drumond Marra et al., 2015). One study reported an improvement in cognitive function following rTMS in patients with mild cognitive impairment (Nardone et al., 2014). Drumond Marra et al. (2015) reported an improved performance on the Rivermead Behavioral Memory Test following high-frequency rTMS (HF-rTMS) to the left dorsolateral prefrontal cortex (DLPFC).

Furthermore, the effects of rTMS on cognitive function in addition to motor disorders, aphasia, and affective disorders have been attracting attention (Lefaucheur et al., 2014; Nardone et al., 2014; Drumond Marra et al., 2015). One study reported an improvement in Trail-Making Test part B (TMT-B) performance by HF-rTMS, while another study reported a lack of significant improvement relative to a control group (Moser et al., 2002; Mittrach et al., 2010). However, few studies have investigated the effects of LF-rTMS on cognitive function. As described earlier, LF-rTMS exerts an inhibitory stimulation to the side of administration and is considered to affect the contralateral cerebral cortices via a modulation of interhemispheric inhibition. Therefore, LF-rTMS possibly affects a broader region than that affected by HF-rTMS. Meta-analyses of rTMS in patients with stroke indicate that LF-rTMS is recommended for stroke patients in the chronic phase (> 6 months post-stroke).

Although previous studies indicate a possibility of positive effects of rTMS on cognitive function; however, to the best of our knowledge, there has been no report describing the effect of a combined intervention program of LF-rTMS and intensive occupational therapy (iOT) on cognitive function in post-stroke patients. Therefore, the present study aimed to explore the therapeutic effect of the combined intervention program on patients with post-stroke upper limb hemiparesis.

Continue —> Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis? Hara T, Abo M, Kakita K, Masuda T, Yamazaki R – Neural Regen Res

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[ARTICLE] The Effect of rTMS with Rehabilitation on Hand Function and Corticomotor Excitability in Sub-Acute Stroke – Full Text PDF

Abstract:

Objectives: Stroke is the leading cause of long-term disability. Hand motor impairment resulting from chronic stroke may have extensive physical, psychological, financial, and social implications despite available rehabilitative treatments. The best time to start treatment for stroke, is in sub-acute period. Repetitive transcranial magnetic stimulation (rTMS) is a method of stimulating and augmenting the neurophysiology of the motor cortex in order to promote the neuroplastic changes that are associated with motor recovery. The purpose of this study was to compare the effects of repetitive transcranial magnetic stimulation protocols plus routine rehabilitation on hand motor functions and hand corticomotor excitability in stroke patients with hemiplegia with pure routine rehabilitation programs.

Methods: This study was a randomized clinical trial which was performed on 24 patients with hemiplegia who were randomly divided in to three groups. One group (n=7), received high frequency repetitive transcranial magnetic stimulation (Hf rTMS) on lesioned M1 with routine rehabilitation program, and the other group (n=7), received rehabilitation program with low frequency repetitive transcranial magnetic stimulation stimulation (Lf rTMS) on nonlesined M1, and a control group (n=10), who were given only routine rehabilitation programs. The treatment was performed for 10 sessions, three times peri-test, Post and follow-up about neurophysiological contralesional hemisphere evaluations using record of MEP wave indices by single pulse TMS, and assessing functional wolf test and hand grip power of disabled hand by dynamometer.

Results: The results demonstrated that the rest MEP threshold reduction in experimental group which received high frequency magnetic stimulation was statistically significant (P<0.05). There was similar finding for active MEP threshold in the both high and low frequency but not in control group (P<0.05). Also there were more significant relation between obtained results from WOLF test and grip power with MEP mentioned parameters, in high frequency group, but not in low frequency and control group.

Discussion: According to the results, However it seems that Hf rTMS combined with routin physiotherapy can significantly improve hand functions and brain neurophysiology via specifically increase of contralesional corticomotor excitability in sever stroke patients that is representative of the role of neuroplasticity in nonlesioned hemisphere but the hypothesis of movement improvement related cognitive balance can’t be eliminated by exploring powerful approved effect of Hf rTMS on mood regulation.

Source: The Effect of rTMS with Rehabilitation on Hand Function and Corticomotor Excitability in Sub-Acute Stroke – Iranian Rehabilitation Journal

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[ARTICLE] Systems Biology of Immunomodulation for Post-Stroke Neuroplasticity: Multimodal Implications of Pharmacotherapy and Neurorehabilitation – Full Text

AIMS: Recent studies indicate that anti-inflammatory drugs, act as a double-edged sword, not only exacerbating secondary brain injury but also contributing to neurological recovery after stroke. Our aim is to explore whether there is a beneficial role for neuroprotection and functional recovery using antiinflammatory drug along with neurorehabilitation therapy using transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), so as to improve functional recovery after ischemic stroke. METHODS: We develop a computational systems biology approach from preclinical data using ordinary differential equations, to study the behavior of both phenotypes of microglia such as M1 type (pro-inflammatory) vis-à-vis M2 type (anti-inflammatory) under anti-inflammatory drug action (minocycline). We explore whether pharmacological treatment along with cerebral stimulation using tDCS and rTMS is beneficial or not. We utilize the systems pathway analysis of minocycline in NF-κB (nuclear factor kappa beta) signaling and neurorehabilitation therapy using tDCS and rTMS which act through brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) signaling pathways. RESULTS: We demarcate the role of neuroinflammation and immunomodulation in post-stroke recovery, under minocycline activated microglia and neuroprotection together with improved neurogenesis, synaptogenesis and functional recovery under the action of rTMS or tDCS. We elucidate the feasibility of utilizing rTMS/tDCS to increase neuroprotection across the reperfusion stage during minocycline administration. We delineate that the signaling pathways of minocycline by modulation of inflammatory genes in NF-κB and proteins activated by tDCS and rTMS through BDNF, Trk-B and Calmodulin kinase (CaMK) signaling. Utilizing systems biology approach, we show the activation pathways for pharmacotherapy (minocycline) and neurorehabilitation (rTMS applied to ipsilesional cortex and tDCS) results into increased neuronal and synaptic activity that commonly occur through activation of N-methyl-D-aspartate (NMDA) receptors. We construe that considerable additive neuroprotection effect would be obtained and delayed reperfusion injury can be remedied, if one uses multimodal intervention of minocycline together with tDCS and rTMS. CONCLUSION: Additive beneficial effect is thus noticed for pharmacotherapy along with neurorehabilitation therapy, by maneuvering the dynamics of immunomodulation using anti-inflammatory drug and cerebral stimulation for augmenting the functional recovery after stroke, which may engender clinical applicability for enhancing plasticity, rehabilitation and neurorestoration.

Continue —> Frontiers | Systems Biology of Immunomodulation for Post-Stroke Neuroplasticity: Multimodal Implications of Pharmacotherapy and Neurorehabilitation | Stroke

Figure 3. BDNF and TrkB signaling pathway.

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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.

Introduction

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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