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[REVIEW] Repetitive transcranial magnetic stimulation in stroke rehabilitation: review of the current evidence and pitfalls – Full Text

Acute brain ischemia causes changes in several neural networks and related cortico-subcortical excitability, both in the affected area and in the apparently spared contralateral hemisphere. The modulation of these processes through modern techniques of noninvasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), has been proposed as a viable intervention that could promote post-stroke clinical recovery and functional independence. This review provides a comprehensive summary of the current evidence from the literature on the efficacy of rTMS applied to different clinical and rehabilitative aspects of stroke patients. A total of 32 meta-analyses published until July 2019 were selected, focusing on the effects on motor function, manual dexterity, walking and balance, spasticity, dysphagia, aphasia, unilateral neglect, depression, and cognitive function after a stroke. Only conventional rTMS protocols were considered in this review, and meta-analyses focusing on theta burst stimulation only were excluded. Overall, both HF-rTMS and LF-rTMS have been shown to be safe and well-tolerated. In addition, the current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and cognitive impairment, where definitive evidence of efficacy cannot be drawn. However, routine use of a specific paradigm of stimulation cannot be recommended yet due to a significant level of heterogeneity of the studies in terms of protocols to be set and outcome measures that have to be used. Future studies need to preliminarily evaluate the most promising protocols before going on to multicenter studies with large cohorts of patients in order to achieve a definitive translation into daily clinical practice.

Background

Stroke is a common acute neurovascular disorder that causes disabling long-term limitations to daily living activities. The most common consequence of a stroke is motor deficit of variable degree,1 although nonmotor symptoms are also relevant and often equally disabling.2 To date, to the best of the authors’ knowledge, there is no validated treatment that is able to restore the impaired functions by a complete recovery of the damaged tissue. Indeed, stroke management basically consists of reducing the initial ischemia in the penumbra, preventing future complications, and promoting a functional recovery using physiotherapy, speech therapy, occupational therapy, and other conventional treatments.3,4

Ischemic damage is associated with significant metabolic and electrophysiological changes in cells and neural networks involved in the affected area. From a pure electrophysiological perspective, however, beyond the affected area, there is a local shift in the balance between the inhibition and excitation of both the affected and contralateral hemisphere, consisting of increased excitability and disinhibition (reduced activity of the inhibitory circuits).3,5 In addition, subcortical areas and spinal regions may be altered.3,5 In particular, the role of the uninjured hemisphere seems to be of utmost significance in post-stroke clinical and functional recovery.

Different theoretical models have been proposed to explain the adaptive response of the brain to acute vascular damage. According to the vicariation model, the activity of the unaffected hemisphere contributes to the functional recovery after a stroke through the replacement of the lost functions of the affected areas. The interhemispheric competition model considers the presence of mutual inhibition between the hemispheres, and the damage caused by a stroke disrupts this balance, thus producing a reduced inhibition of the unaffected hemisphere by the affected side. This results in increased inhibition of the affected hemisphere by the unaffected side. More recently, a new model, called bimodal balance recovery, has been proposed.3,5 It introduces the concept of a structural reserve, which describes the extent to which the nondamaged neural pathways contribute to the clinical recovery. The structural reserve determines the prevalence of the interhemispheric imbalance over vicariation. When the structural reserve is high, the interhemispheric competition model can predict the recovery better than the vicariation model, and vice versa.3

Repetitive transcranial magnetic stimulation

One of the proposed interventions to improve stroke recovery, by the induction of neuromodulation phenomena, is based on methods of noninvasive brain stimulation. Among them, transcranial magnetic stimulation (TMS) is a feasible and painless neurophysiological technique widely used for diagnostic, prognostic, research, and, when applied repetitively, therapeutic purposes.69 By electromagnetic induction, TMS generates sub or suprathreshold currents in the human cortex in vivo and in real time.10,11

The most common stimulation site is the primary motor cortex (M1), that generates motor evoked potentials (MEPs) recorded from the contralateral muscles through surface electromyography electrodes.11 The intensity of TMS, measured as a percentage of the maximal output of the stimulator, is tailored to each patient based on the motor threshold (MT) of excitability. Resting MT (rMT) is found when the target muscle is at rest, it is defined as the minimal intensity of M1 stimulation required to elicit an electromyography response with a peak-to-peak amplitude > 50 µV in at least 5 out of 10 consecutive trials.11 Alternatively TMS MTAT 2.0 software (http://www.clinicalresearcher.org/software.htm) is a free tool for TMS researchers and practitioners. It provides four adaptive methods based on threshold-tracking algorithms with the parameter estimation by sequential testing, using the maximum-likelihood strategy for estimating MTs. Active MT (aMT) is obtained during a tonic contraction of the target muscle at approximately 20% of the maximal muscular strength.11

The rMT is considered a basic parameter in providing the global excitation state of a central core of M1 neurons.11 Accordingly, rMT is increased by drugs blocking the voltage-gated sodium channels, where the same drugs may not have an effect on the gamma-aminobutyric acid (GABA)-ergic functions. In contrast, rMT is reduced by drugs increasing glutamatergic transmission not mediated by the N-methyl-D-aspartate (NMDA) receptors, suggesting that rMT reflects both neuronal membrane excitability and non-NMDA receptor glutamatergic neurotransmission.12 Finally, the MT increases, being often undetectable, when a substantial portion of M1 or the cortico-spinal tract is damaged (i.e. by stroke or motor neuron disease), and decreases when the motor pathway is hyperexcitable (such as epilepsy).13

Repetitive (rTMS) is a specific stimulation paradigm characterized by the administration of a sequence of consecutive stimuli on the same cortical region, at different frequencies and inter sequence intervals. As known, rTMS can transiently modulate the excitability of the stimulated cortex, with both local and remote effects outlasting the stimulation period. Conventional rTMS modalities include high-frequency (HF-rTMS) stimulation (>1 Hz) and low-frequency (LF-rTMS) stimulation (⩽1 Hz).11 High-frequency stimulation typically increases motor cortex excitability of the stimulated area, whereas low-frequency stimulation usually produces a decrease in excitability.14 The mechanisms by which rTMS modulates the brain are rather complex, although they seem to be related to the phenomena of long-term potentiation (LTP) and long-term depression (LTD).15

When applied after a stroke, rTMS should ideally be able to suppress the so called ‘maladaptive plasticity’16,17 or to enhance the adaptive plasticity during rehabilitation. These goals can be achieved by modulating the local cortical excitability or modifying connectivity within the neuronal networks.10

rTMS in stroke rehabilitation: an overview

According to the latest International Federation of Clinical Neurophysiology (IFCN) guidelines on the therapeutic use of rTMS,10 there is a possible effect of LF-rTMS of the contralesional motor cortex in post-acute motor stroke, and a probable effect in chronic motor stroke. An effect of HF-rTMS on the ipsilesional motor cortex in post-acute and chronic motor stroke is also possible.

The potential role of rTMS in gross motor function recovery after a stroke has been assessed in a recent comprehensive systematic review of 70 studies by Dionisio and colleagues.18 The majority of the publications reviewed report a role of rTMS in improving motor function, although some randomized controlled trials (RCTs) were not able to confirm this result,1923 as shown by a recent large randomized, sham-controlled, clinical trial of navigated LF-rTMS.24 It has also been suggested that rTMS can specifically improve manual dexterity,10 which is defined as the ability to coordinate the fingers and efficiently manipulate objects, and is of crucial importance for daily living activities.25 Notably, most of the studies focused on motor impairment in the upper limbs, whereas limited data is available on the lower limbs.18 Walking and balance are frequently impaired in stroke patients and significantly affect the quality of life (QoL),26,27 and rTMS might represent a valid aid in the recovery of these functions.28,29 Spasticity is another common complication after a stroke, consisting of a velocity-dependent increase of muscular tone,30 and for which rTMS has been proposed as a rehabilitation tool.31

Dysphagia is highly common in stroke patients, it impairs the global clinical recovery, and predisposes to complications.32 It has been pointed out that rTMS targeting the M1 area representing the muscles involved in swallowing may contribute to the treatment of post-stroke dysphagia.33

Nonmotor deficit is also a relevant post-stroke disability that negatively impacts the QoL. Aphasia is a very common consequence of stroke, affecting approximately 30% of stroke survivors and significantly limiting rehabilitation.34 According to the IFCN guidelines, to date, there is no recommendation for LF-rTMS of the contralesional right inferior frontal gyrus (IFG). Similarly, no recommendation for HF-rTMS or intermittent theta burst stimulation (TBS) of the ipsilesional left IFG or dorsolateral prefrontal cortex (DLPFC) in Broca’s aphasia has been currently approved.10 The same is true for LF-rTMS of the right superior temporal gyrus in Wernicke’s aphasia.10

Neglect is the incapacity to respond to tactile or visual contralateral stimuli that are not caused by a sensory-motor deficit.35 Although hard to treat, rTMS has been proposed as a tool for neglect rehabilitation.36 However, the IFCN guidelines state that currently there is no recommendation for LF-rTMS of the contralesional left posterior parietal cortex, or for HF-rTMS of the ipsilesional right posterior parietal cortex.10 In a recent systematic review, most of the included studies supported the use of TMS for the rehabilitation of aphasia, dysphagia, and neglect, although the heterogeneity of stimulation protocols did not allow definitive conclusions to be drawn.37

Post-stroke depression is a relevant complication of cerebrovascular diseases.38 The role of rTMS in the management of major depressive disorders is well documented,39,40 and currently, rTMS is internationally approved and indicated for the treatment of major depression in adults with antidepressant medication resistance, and in those with a recurrent course of illness, or in cases of moderate-to-severe disease severity.39 In major depression disorders, according to the IFCN guidelines, there is a clear antidepressant effect of HF-rTMS over the left DLPFC, a probable antidepressant effect of LF-rTMS on the right DLPFC, and probably no differential antidepressant effect between right LF-rTMS and left HF-rTMS. Moreover, there is currently no recommendation for bilateral stimulation combining HF-rTMS of the left DLPFC and LF-rTMS of the right DLPFC. The mentioned guidelines also state that the antidepressant effect when stimulating DLPFC is probably additive, and possibly potentiating, to the efficacy of antidepressant drugs.10 However, no specific recommendation currently addresses the use of rTMS in post-stroke depression. Recently, rTMS has been proposed as a treatment option for the late-life depression associated with chronic subcortical ischemic vascular disease, the so called ‘vascular depression’.4144 Three studies tested rTMS efficacy in vascular depression (one was a follow-up study with citalopram). Although presenting positive findings, further trials should refine clinical and diagnostic criteria to assess its impact on antidepressant efficacy.45

Approximately 25–30% of stroke patients develop an immediate or delayed cognitive impairment or an overt picture of vascular dementia.46 There is evidence of an overall positive effect on cognitive function for both LF-rTMS47 and HF-rTMS,48 supported by studies on experimental models of vascular dementia.4952 Nonetheless, the few trials examining the effect on stroke-related cognitive deficit produced mixed results.5356 In particular, two studies found no effect on cognition when stimulating the left DLPFC at 1 Hz and 10 Hz,53,54 whereas a pilot study found a positive effect on the Stroop interference test with HF-rTMS over the left DLPFC in patients with vascular cognitive impairment without dementia.55 However, this finding was not replicated in a follow-up study.56 To summarize, rTMS can induce beneficial effects on specific cognitive domains, although data are limited and their clinical significance needs to be further validated. Major challenges exist in terms of appropriate patient selection and optimization of the stimulation protocols.57

Central post-stroke pain (CPSP) is the pain resulting from an ischemic lesion of the central nervous system.58 It represents a relatively common complication after a stroke, although it is often under-recognized and, therefore, undertreated.59 According to the IFCN guidelines for the use of rTMS in the treatment of neuropathic pain, there is a definite analgesic effect of HF-rTMS of contralateral M1 to the pain side, and LF-rTMS of contralateral M1 to the pain side is probably ineffective. In addition, there is currently no recommendation for cortical targets other than contralateral M1 to the pain side.10 Notably, rTMS might be effective in drug-resistant CPSP patients.58 A recent systematic review that included nine HF-rTMS studies suggested an effect on CPSP relief, but also underlined the insufficient quality of the studies considered.60

Study objective

In this article, we aim to provide an up-to-date overview of the most recent evidence on the efficacy of rTMS in the rehabilitation of stroke patients. Although several studies have been published, a conclusive statement supporting a systematic use of rTMS in the multifaceted clinical aspects of stroke rehabilitation is still lacking.

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Continue —> Repetitive transcranial magnetic stimulation in stroke rehabilitation: review of the current evidence and pitfalls – Francesco Fisicaro, Giuseppe Lanza, Alfio Antonio Grasso, Giovanni Pennisi, Rita Bella, Walter Paulus, Manuela Pennisi, 2019

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[Abstract + References] Motor stroke recovery after tDCS: a systematic review

Abstract

The purpose of the present study was to investigate the effects of transcranial direct current stimulation (tDCS) on motor recovery in adult patients with stroke, taking into account the parameters that could influence the motor recovery responses. The second aim was to identify the best tDCS parameters and recommendations available based on the enhanced motor recovery demonstrated by the analyzed studies. Our systematic review was performed by searching full-text articles published before February 18, 2019 in the PubMed database. Different methods of applying tDCS in association with several complementary therapies were identified. Studies investigating the motor recovery effects of tDCS in adult patients with stroke were considered. Studies investigating different neurologic conditions and psychiatric disorders or those not meeting our methodologic criteria were excluded. The main parameters and outcomes of tDCS treatments are reported. There is not a robust concordance among the study outcomes with regard to the enhancement of motor recovery associated with the clinical application of tDCS. This is mainly due to the heterogeneity of clinical data, tDCS approaches, combined interventions, and outcome measurements. tDCS could be an effective approach to promote adaptive plasticity in the stroke population with significant positive premotor and postmotor rehabilitation effects. Future studies with larger sample sizes and high-quality studies with a better standardization of stimulation protocols are needed to improve the study quality, further corroborate our results, and identify the optimal tDCS protocols.

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via Motor stroke recovery after tDCS: a systematic review : Reviews in the Neurosciences

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[Abstract] Learning a Bimanual Cooperative Skill in Chronic Stroke Under Noninvasive Brain Stimulation: A Randomized Controlled Trial

Abstract

Background. Transcranial direct current stimulation (tDCS) has been suggested to improve poststroke recovery. However, its effects on bimanual motor learning after stroke have not previously been explored.

Objective. We investigated whether dual-tDCS of the primary motor cortex (M1), with cathodal and anodal tDCS applied over undamaged and damaged hemispheres, respectively, improves learning and retention of a new bimanual cooperative motor skill in stroke patients.

Method. Twenty-one chronic hemiparetic patients were recruited for a randomized, double-blinded, cross-over, sham-controlled trial. While receiving real or sham dual-tDCS, they trained on a bimanual cooperative task called CIRCUIT. Changes in performance were quantified via bimanual speed/accuracy trade-off (Bi-SAT) and bimanual coordination factor (Bi-Co) before, during, and 0, 30, and 60 minutes after dual-tDCS, as well as one week later to measure retention. A generalization test then followed, where patients were asked to complete a new CIRCUIT layout.

Results. The patients were able to learn and retain the bimanual cooperative skill. However, a general linear mixed model did not detect a significant difference in retention between the real and sham dual-tDCS conditions for either Bi-SAT or Bi-Co. Similarly, no difference in generalization was detected for Bi-SAT or Bi-Co.

Conclusion. The chronic hemiparetic stroke patients learned and retained the complex bimanual cooperative task and generalized the newly acquired skills to other tasks, indicating that bimanual CIRCUIT training is promising as a neurorehabilitation approach. However, bimanual motor skill learning was not enhanced by dual-tDCS in these patients.

via Learning a Bimanual Cooperative Skill in Chronic Stroke Under Noninvasive Brain Stimulation: A Randomized Controlled Trial – Maral Yeganeh Doost, Jean-Jacques Orban de Xivry, Benoît Herman, Léna Vanthournhout, Audrey Riga, Benoît Bihin, Jacques Jamart, Patrice Laloux, Jean-Marc Raymackers, Yves Vandermeeren, 2019

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[Abstract] The Effect of Noninvasive Brain Stimulation on Poststroke Cognitive Function: A Systematic Review

Abstract

Introduction. Cognitive impairment after stroke has been associated with lower quality of life and independence in the long run, stressing the need for methods that target impairment for cognitive rehabilitation. The use of noninvasive brain stimulation (NIBS) on recovery of language functions is well documented, yet the effects of NIBS on other cognitive domains remain largely unknown. Therefore, we conducted a systematic review that evaluates the effects of different stimulation techniques on domain-specific (long-term) cognitive recovery after stroke. 

Methods. Three databases (PubMed, EMBASE, and PsycINFO) were searched for articles (in English) on the effects of NIBS on cognitive domains, published up to January 2018. 

Results. A total of 40 articles were included: randomized controlled trials (n = 21), studies with a crossover design (n = 9), case studies (n = 6), and studies with a mixed design (n = 4). Most studies tested effects on neglect (n = 25). The majority of the studies revealed treatment effects on at least 1 time point poststroke, in at least 1 cognitive domain. Studies varied highly on the factors time poststroke, number of treatment sessions, and stimulation protocols. Outcome measures were generally limited to a few cognitive tests. 

Conclusion. Our review suggests that NIBS is able to alleviate neglect after stroke. However, the results are still inconclusive and preliminary for the effect of NIBS on other cognitive domains. A standardized core set of outcome measures of cognition, also at the level of daily life activities and participation, and international agreement on treatment protocols, could lead to better evaluation of the efficacy of NIBS and comparisons between studies.

https://journals.sagepub.com/doi/abs/10.1177/1545968319834900

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[ARTICLE] Noninvasive Brain Stimulation to Enhance Functional Recovery After Stroke: Studies in Animal Models – Full Text

Background. Stroke is the leading cause of adult disability, but treatment options remain limited, leaving most patients with incomplete recovery. Patient and animal studies have shown potential of noninvasive brain stimulation (NIBS) strategies to improve function after stroke. However, mechanisms underlying therapeutic effects of NIBS are unclear and there is no consensus on which NIBS protocols are most effective.

Objective. Provide a review of articles that assessed effects and mechanisms of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in animal stroke models.

Methods. Articles were searched in PubMed, including cross-references.

Results. Nineteen eligible studies reporting effects of rTMS or tDCS after stroke in small rodents were identified. Seventeen of those described improved functional recovery or neuroprotection compared with untreated control or sham-stimulated groups. The effects of rTMS could be related to molecular mechanisms associated with ischemic tolerance, neuroprotection, anti-apoptosis, neurogenesis, angiogenesis, or neuroplasticity. Favorable outcome appeared most effectively when using high-frequency (>5 Hz) rTMS or intermittent theta burst stimulation of the ipsilesional hemisphere. tDCS effects were strongly dependent on stimulation polarity and onset time. Although these findings are promising, most studies did not meet Good Laboratory Practice assessment criteria.

Conclusions. Despite limited data availability, animal stroke model studies demonstrate potential of NIBS to promote stroke recovery through different working mechanisms. Future studies in animal stroke models should adhere to Good Laboratory Practice guidelines and aim to further develop clinically applicable treatment protocols by identifying most favorable stimulation parameters, treatment onset, adjuvant therapies, and underlying modes of action.

Globally, stroke is a devastating neurological disorder and a leading cause of death and acquired disability.1 The majority of stroke patients experience motor impairment, which affects movement of the face, leg, and/or arm on one side of the body.2 Upper limb motor deficiencies are often persistent and disabling, affecting independent functional activities of daily living.3 Unfortunately, most stroke patients recover incompletely after stroke, despite intensive rehabilitation strategies.3,4 Although there is a diverse range of interventions (for overview, see review by Pollock and colleagues4) aimed at improving motor outcome after stoke, there is still a pressing need for novel treatment therapies and continued research to reduce disability and improve functional recovery after stroke.

Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have shown promising therapeutic potential in stroke patient studies.5,6 The rationale behind rTMS or tDCS therapy is to modulate cortical excitability, increase neural plasticity, and improve functional motor outcome. For many studies, this approach has been based on the interhemispheric competition model.7 The interhemispheric competition model suggests that functional recovery in stroke patients is hindered due to reduced output from the affected hemisphere and excessive transcallosal inhibition from the unaffected hemisphere.8 Therefore, improvement in motor deficits may be obtained with NIBS strategies that facilitate excitability in the affected hemisphere or suppress inhibitory activity from the unaffected hemisphere.9,10 Depending on the type and duration of the stimulation protocol, both rTMS and tDCS can be used to increase (>5 Hz rTMS; intermittent theta burst stimulation; anodal tDCS) or decrease (⩽1 Hz rTMS; continuous theta burst stimulation; cathodal tDCS) cortical excitability, with potentially lasting effects beyond the stimulation period, promoting mechanisms of synaptic plasticity.11 Evidence suggests that rTMS and tDCS techniques are able to induce changes in cortical excitability associated with facilitation or long-term potentiation like plasticity via glutamatergic neurotransmission, or inhibition and long-term depression via GABAergic neurotransmission.12,13 Furthermore, effects of rTMS and tDCS are not restricted to the target region of stimulation, but also affect distantly connected cortical areas, allowing for the modulation of large-scale neural networks.14

However, despite accumulating evidence of the potential of NIBS, the precise therapeutic mechanisms of action of rTMS and tDCS are largely unidentified and there is no consensus about standardized treatment protocols. Moreover, when deciding on treatment after stroke with either rTMS or tDCS, the poststroke time and lesion status should be considered, and stimulation intensity and duration must be fine-tuned to prevent further tissue damage or the interruption of beneficial plastic changes.15,16 These uncertainties emphasize the critical need for basic understanding of the (patho)physiological processes that are influenced by rTMS and tDCS paradigms after stroke, which may ideally be explored in well-controllable and reproducible experimental animal models.

In animal models of stroke, similar to the human condition, there is a variable degree of spontaneous functional improvement after stroke, associated with a complex cascade of cellular and molecular processes that are activated within minutes after the insult, both in perilesional tissue and remote brain regions.17,18 These events include changes in genetic transcriptional and translational processes, alterations in neurotransmitter interactions, altered secretion of growth factors, gliosis, vascular remodeling, and structural changes in axons, dendrites, and synapses.19,20 Therefore, assessment of the effects of NIBS on endogenous recovery processes in animal stroke models offer excellent opportunities for the exploration of neuroplastic and neuromodulatory mechanisms, which could aid in the optimization of treatment protocols for clinical applications.

Our goal was to provide an overview of studies that assessed functional outcomes and potential mechanisms of action of rTMS and tDCS in animal models of stroke, which may guide future studies that aim to improve mechanistic insights and therapeutic utilization of NIBS effects after stroke.[…]

 

Continue —->  Noninvasive Brain Stimulation to Enhance Functional Recovery After Stroke: Studies in Animal Models – Julia Boonzaier, Geralda A. F. van Tilborg, Sebastiaan F. W. Neggers, Rick M. Dijkhuizen, 2018

 

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[Abstract] Effects of Electrical Stimulation in Tinnitus Patients: Conventional Versus High-Definition tDCS

Abstract

Background. Contradictory results have been reported for transcranial direct current stimulation (tDCS) as treatment for tinnitus. The recently developed high-definition tDCS (HD tDCS) uses smaller electrodes to limit the excitation to the desired brain areas.

Objective. The current study consisted of a retrospective part and a prospective part, aiming to compare 2 tDCS electrode placements and to explore effects of HD tDCS by matched pairs analyses.

Methods. Two groups of 39 patients received tDCS of the dorsolateral prefrontal cortex (DLPFC) or tDCS of the right supraorbital–left temporal area (RSO-LTA). Therapeutic effects were assessed with the tinnitus functional index (TFI), a visual analogue scale (VAS) for tinnitus loudness, and the hyperacusis questionnaire (HQ) filled out at 3 visits: pretherapy, posttherapy, and follow-up. With a new group of patients and in a similar way, the effects of HD tDCS of the right DLPFC were assessed, with the tinnitus questionnaire (TQ) and the hospital anxiety and depression scale (HADS) added.

Results. TFI total scores improved significantly after both tDCS and HD tDCS (DLPFC: P < .01; RSO-LTA: P < .01; HD tDCS: P = .05). In 32% of the patients, we observed a clinically significant improvement in TFI. The 2 tDCS groups and the HD tDCS group showed no differences on the evolution of outcomes over time (TFI: P = .16; HQ: P = .85; VAS: P = .20).

Conclusions. TDCS and HD tDCS resulted in a clinically significant improvement in TFI in 32% of the patients, with the 3 stimulation positions having similar results. Future research should focus on long-term effects of electrical stimulation.

via Effects of Electrical Stimulation in Tinnitus Patients: Conventional Versus High-Definition tDCS – Laure Jacquemin, Giriraj Singh Shekhawat, Paul Van de Heyning, Griet Mertens, Erik Fransen, Vincent Van Rompaey, Vedat Topsakal, Julie Moyaert, Jolien Beyers, Annick Gilles, 2018

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[Abstract] Transcranial Direct Current Stimulation Enhances Motor Skill Learning but Not Generalization in Chronic Stroke

Background. Motor training alone or combined with transcranial direct current stimulation (tDCS) positioned over the motor cortex (M1) improves motor function in chronic stroke. Currently, understanding of how tDCS influences the process of motor skill learning after stroke is lacking.

Objective. To assess the effects of tDCS on the stages of motor skill learning and on generalization to untrained motor function.

Methods. In this randomized, sham-controlled, blinded study of 56 mildly impaired chronic stroke patients, tDCS (anode over the ipsilesional M1 and cathode on the contralesional forehead) was applied during 5 days of training on an unfamiliar, challenging fine motor skill task (sequential visual isometric pinch force task). We assessed online and offline learning during the training period and retention over the following 4 months. We additionally assessed the generalization to untrained tasks.

Results. With training alone (sham tDCS group), patients acquired a novel motor skill. This skill improved online, remained stable during the offline periods and was largely retained at follow-up. When tDCS was added to training (real tDCS group), motor skill significantly increased relative to sham, mostly in the online stage. Long-term retention was not affected by tDCS. Training effects generalized to untrained tasks, but those performance gains were not enhanced further by tDCS.

Conclusions. Training of an unfamiliar skill task represents a strategy to improve fine motor function in chronic stroke. tDCS augments motor skill learning, but its additive effect is restricted to the trained skill.

 

via Transcranial Direct Current Stimulation Enhances Motor Skill Learning but Not Generalization in Chronic Stroke – Manuela Hamoudi, Heidi M. Schambra, Brita Fritsch, Annika Schoechlin-Marx, Cornelius Weiller, Leonardo G. Cohen, Janine Reis, 2018

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[Review] Transcranial Electrical Brain Stimulation – Full Text

Abstract

Transcranial electrical brain stimulation using weak direct current (tDCS) or alternating current (tACS) is being increasingly used in clinical and experimental settings to improve cognitive and motor functions in healthy subjects as well as neurological patients. This review focuses on the therapeutic value of transcranial direct current stimulation for neurorehabilitation and provides an overview of studies addressing motor and non-motor symptoms after stroke, disorders of attention and consciousness as well as Parkinson’s disease.

 

Background

The past 10 years have seen an increased clinical and experimental focus on noninvasive electrical brain stimulation as an innovative therapeutic approach to support neurorehabilitation. This entails the application of either transcranial direct current stimulation (tDCS), or less commonly, transcranial alternating current stimulation (tACS). Typically, up to 0.8 A/m² is used for up to 40 min per single stimulation session [1]. The electrical current partially penetrates the underlying structures and affects nerve cells, glia and vessels in the stimulated brain area [1] [2]. Early animal experiments during the 1960s and 1970s on the effects of weak DC stimulation demonstrated an excitement-induced change of neurons lasting several hours after the end of the stimulation [3] [4]. Therapeutic studies of the 1970s, at that time mainly concerning the treatment of depression, did not yield any success, which in retrospect could be attributed to the stimulation parameters used. In 2 000 key experiments by Nitsche and Paulus on polarity-related excitability changes in the human motor system after transcranial application of tDCS led to a renewed interest in the approach [5]. The authors documented increased cortical excitability measured by the amplitude of motor-evoked potentials in healthy volunteers after anodal stimulation above the motor cortex lasting at least 9 min [6]. Reversing the direction of stimulation (cathodal tDCS) resulted in a decrease in motor-evoked potential. In addition to the concept of pure excitability modulation, a large number of studies demonstrate modulation of neuroplasticity by tDCS in various ways, including basic scientific and mechanistic findings regarding improvement of synaptic transmission strength [7] [8] [9], long-term influence on learning processes and behavior [10] [11], as well as a therapeutic approach to improve function in neurological and psychiatric disorders associated with altered or disturbed neuroplasticity (overview in [12]). In particular, simultaneous application of tDCS together with different learning paradigms, such as motor or cognitive training, appears to produce favorable effects in healthy subjects and in various patient groups [11] [13].

The following review presents the effects of tDCS on the improvement in the function of some neurological disease patterns which are regularly the focus of neurorehabilitative treatment. This especially includes stroke. In addition, we shall refer to a current database of clinical studies containing a comprehensive list of scientific and clinical studies of tDCS in the treatment of neurological and psychiatric disorders [14].

Post-stroke Motor Impairment

Stroke is one of the primary causes worldwide of permanent limitations of motor function and speech. Despite intensive rehabilitation efforts, approx. 50% of stroke patients remain limited in their motor and speech capabilities [15] [16] [17]. Current understanding of the mechanisms of tDCS is largely based on data documented for the human motor system. The reasons for this include the presence of direct and easily objectifiable measurement criteria (for example, motor-evoked potential, fine motor function), as well as anatomical accessibility of brain motor regions for non-invasive stimulation. Therefore, it is not surprising that the clinical syndrome of stroke with the frequent symptom of hemiparesis as a “lesion model of the pyramidal tract” received significant scientific interest with respect to researching the effects of tDCS, as evidenced by the numerous scientific publications since 2005 ([Fig. 1]). In contrast to earlier largely mechanistic studies, in the past 5 years there has been a trend toward studies addressing clinically-oriented therapeutic issues. […]

Continue —> Thieme E-Journals – Neurology International Open / Full Text

Fig. 2 Illustration of the 3 typical brain stimulation montages exemplified by tDCS above the motor cortex. In example a, the anode (red) is placed above the ipsilesional motor cortex, and the cathode (blue) is located on the contralateral forehead. Example b shows the cathode placed above the motor cortex of the non-lesioned hemisphere, and the anode is placed on the contralateral forehead. Example c illustrates bihemispheric montage, with the anode located above the ipsilesional motor cortex, and the cathode placed above the motor cortex of the non-lesioned hemisphere. The white arrow shows the intracerebral current flow. The goal of these 3 arrangements is to modulate the interaction between both motor cortices by changing the activity of one or both hemispheres c.

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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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[Abstract] Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) – Clinical Neurophysiology

Highlights

  • A group of European experts reviewed current evidence for therapeutic efficacy of tDCS.
  • Level B evidence (probable efficacy) was found for fibromyalgia, depression and craving.
  • The therapeutic relevance of tDCS needs to be further explored in these and other indications.

Abstract

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson’s disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer’s disease, tinnitus, depression, schizophrenia, and craving/addiction.

The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10–24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode.

It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.

Source: Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) – Clinical Neurophysiology

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