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Using non-invasive transcranial direct current stimulation for neglect and associated attentional deficits following stroke
Abstract
Neglect is a disabling neuropsychological syndrome that is frequently observed following right-hemispheric stroke. Affected individuals often present with multiple attentional deficits, ranging from reduced orienting towards contralesional space to a generalized impairment in maintaining attention over time. Although a degree of spontaneous recovery occurs in most patients, in some individuals this condition can be treatment-resistant with prominent ongoing non-spatial deficits. Further, there is a large inter-individual variability in response to different therapeutic approaches. Given its potential to alter neuronal excitability and affect neuroplasticity, non-invasive brain stimulation is a promising tool that could potentially be utilized to facilitate recovery. However, there are many outstanding questions regarding its implementation in this heterogeneous patient group. Here we provide a critical overview of the available evidence on the use of non-invasive electrical brain stimulation, focussing on transcranial direct current stimulation (tDCS), to improve neglect and associated attentional deficits after right-hemispheric stroke. At present, there is insufficient robust evidence supporting the clinical use of tDCS to alleviate symptoms of neglect. Future research would benefit from careful study design, enhanced precision of electrical montages, multi-modal approaches exploring predictors of response, tailored dose-control applications and increased efforts to evaluate standalone tDCS versus its incorporation into combination therapy.
... Following right-hemisphere stroke, patients are frequently affected by the neglect syndrome, which includes lateralised and non-lateralised attentional deficits (Bartolomeo, Thiebaut De Schotten, & Chica, 2012;Corbetta & Shulman, 2011). Neglect is challenging to treat; lateralised deficits, whereby patients ignore targets located on the left hand side of space, most frequently represent the target of therapeutic studies (Harvey, Learmonth, Rossit, & Chen, 2022;Olgiati & Malhotra, 2020). However, non-lateralised attentional impairments such as deficits of vigilant attention, the ability to maintain goal-oriented behaviour over time, tend to persist and are strongly associated with greater functional disability (McDowd, Filion, Pohl, Richards, & Stiers, 2003;Van Vleet & DeGutis, 2013). ...
... This design does not allow us to directly link findings from the two studies. More research in the direct comparability of the effects of online and offline tDCS are needed (Olgiati & Malhotra, 2020). ...
... Despite the above mentioned limitations, our multimodal study adds to the emerging body of literature on prefrontal HD-tDCS being able to modulate non-lateralised attention (Luna et al., 2020). Although there is not yet robust evidence that tDCS is efficacious in neglect, preliminary evidence suggests that it can improve attentional deficits when applied as a stand-alone technique and in synergistic application with other therapies (for recent reviews, see Olgiati & Malhotra, 2020;Zebhauser, Vernet, Unterburger, & Brem, 2019). In the current work, patients could not distinguish stimulation from the sham condition, demonstrating that blinding was successful. ...
Right hemisphere stroke patients frequently present with a combination of lateralised and non-lateralised attentional deficits characteristic of the neglect syndrome. Attentional deficits are associated with poor functional outcome and are challenging to treat, with non-lateralised deficits often persisting into the chronic stage and representing a common complaint among patients and families.
In this study, we investigated the effects of non-invasive brain stimulation on non-lateralised attentional deficits in right-hemispheric stroke. In a randomised double-blind sham-controlled crossover study, twenty-two patients received real and sham transcranial Direct Current Stimulation (tDCS) whilst performing a non-lateralised attentional task. A high definition tDCS montage guided by stimulation modelling was employed to maximise current delivery over the right dorsolateral prefrontal cortex, a key node in the vigilance network. In a parallel study, we examined brain network response to this tDCS montage by carrying out concurrent fMRI during stimulation in healthy participants and patients.
At the group level, stimulation improved target detection in patients, reducing overall error rate when compared with sham stimulation. TDCS boosted performance throughout the duration of the task, with its effects briefly outlasting stimulation cessation. Exploratory lesion analysis indicated that response to stimulation was related to lesion location rather than volume. In particular, reduced stimulation response was associated with damage to the thalamus and postcentral gyrus. Concurrent stimulation-fMRI revealed that tDCS did not affect local connectivity but influenced functional connectivity within large-scale networks in the contralesional hemisphere.
This combined behavioural and functional imaging approach shows that brain stimulation targeted to surviving tissue in the ipsilesional hemisphere improves non-lateralised attentional deficits following stroke. This effect may be exerted via contralesional network effects.
... To date, there is no general agreement about the optimal stimulation site or mode in the treatment of VSN. The limited number of available studies and methodological heterogeneity of usually small-scale studies render definitive conclusions about the choice of intervention difficult [24,25]. Because of impairments in vigilance in severely affected post-stroke patients, neglect associated comorbidities, and safety criteria of tDCS a low recruiting rate can be anticipated in studies with subacute neglect patients [26,27]. ...
... In order to balance feasibility and after-effects a wash-out phase of at least 48 hours in-between (cross-over design) were chosen. The length of the intersession interval is comparable to other studies in subacute neglect patients [24,25]. Two visits before treatment (screening: v1, baseline: v2) and one visit after completion of all four treatment sessions (follow-up: v3) were performed. ...
... In fact, our results are consistent with other findings which showed that LBT is often the most sensitive test in neglect patients responding to parietal tDCS (cf. Olgiati and Malhotra [24]). Several reasons may account for this finding. ...
Different transcranial direct current stimulation (tDCS) protocols have been tested to improve visuospatial neglect (VSN). So far, methodological heterogenity limits reliable conclusions about optimal stimualtion set-up. With this proof-of-principle study behavioral effects of two promising (uni- vs. bilateral) stimulation protocols were directly compared to gain more data for an appropriate tDCS protocol in subacute neglect patients. Notably, each tDCS set-up was combined with an identical sham condition to improve comparability. In a double-blind sham-controlled cross-over study 11 subacute post-stroke neglect patients received 20 minutes or 30 seconds (sham) tDCS (2 mA, 0.8 A/m2) parallel to neglect therapy randomized in unilateral (anode-reference: P4-Fp2 10-20 electroencephalography [EEG] system) and bilateral manner (anode-cathode: P4-P3) and 48h wash-out in-between. Before and immediately after stimulation performance were measured in cancellation task (bell test), and line bisection (deviation error). Significant difference between active and assigned sham condition was found in line bisection but not cancellation task. Particularly, deviation error was reduced after bilateral tDCS (hedges g* = 0.6) compared to bilateral sham, no such advantage were obtained for unilateral stimulation (hedges g* = 0.2). Using a direct comparison approach findings add further evidence that stimulating both hemispheres (bilateral) is superior in alleviating VSN symptoms than unilateral stimulation in subacute neglect.
... To date, there is no general agreement about the optimal stimulation site or mode in the treatment of VSN. The limited number of available studies and methodological heterogeneity of usually small-scale studies render definitive conclusions about the choice of intervention difficult [24,25]. Because of impairments in vigilance in severely affected post-stroke patients, neglect associated comorbidities, and safety criteria of tDCS a low recruiting rate can be anticipated in studies with subacute neglect patients [26,27]. ...
... In order to balance feasibility and after-effects a wash-out phase of at least 48 hours in-between (cross-over design) were chosen. The length of the intersession interval is comparable to other studies in subacute neglect patients [24,25]. Two visits before treatment (screening: v1, baseline: v2) and one visit after completion of all four treatment sessions (follow-up: v3) were performed. ...
... In fact, our results are consistent with other findings which showed that LBT is often the most sensitive test in neglect patients responding to parietal tDCS (cf. Olgiati and Malhotra [24]). Several reasons may account for this finding. ...
Different transcranial direct current stimulation (tDCS) protocols have been tested to improve visuospatial neglect (VSN). So far, methodological heterogenity limits reliable conclusions about optimal stimualtion set-up. With this proof-of-principle study behavioral effects of two promising (uni- vs. bilateral) stimulation protocols were directly compared to gain more data for an appropriate tDCS protocol in subacute neglect patients. Notably, each tDCS set-up was combined with an identical sham condition to improve comparability. In a double-blind sham-controlled cross-over study 11 subacute post-stroke neglect patients received 20 minutes or 30 seconds (sham) tDCS (2 mA, 0.8 A/m2) parallel to neglect therapy randomized in unilateral (anode-reference: P4-Fp2 10-20 electroencephalography [EEG] system) and bilateral manner (anode-cathode: P4-P3) and 48h wash-out in-between. Before and immediately after stimulation performance were measured in cancellation task (bell test), and line bisection (deviation error). Significant difference between active and assigned sham condition was found in line bisection but not cancellation task. Particularly, deviation error was reduced after bilateral tDCS (hedges g* = 0.6) compared to bilateral sham, no such advantage were obtained for unilateral stimulation (hedges g* = 0.2). Using a direct comparison approach findings add further evidence that stimulating both hemispheres (bilateral) is superior in alleviating VSN symptoms than unilateral stimulation in subacute neglect.
... Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) techniques have been used in the past years to improve motor recovery in stroke patients, often jointly with standard physiotherapy practice. However, while at the single study level the administration of TMS and tDCS treatments appear beneficial to patients in motor and/or cognitive domain, meta-analysis results have shown that these effects are rather limited or, in some cases, even non-existent (e.g., [11][12][13][14][15]). It should be noticed that these stimulation protocols have been developed on the basis of the conviction that either the interhemispheric competition or the vicariation model might be the one that best predicts recovery [9]. ...
Stroke constitutes the main cause of adult disability worldwide. Even after application of standard rehabilitation protocols, the majority of patients still show relevant motor impairment. Outcomes of standard rehabilitation protocols have led to mixed results, suggesting that relevant factors for brain re-organization after stroke have not been considered in explanatory models. Therefore, finding a comprehensive model to optimally define patient-dependent rehabilitation protocols represents a crucial topic in clinical neuroscience. In this context, we first report on the rehabilitation models conceived thus far in the attempt of predicting stroke rehabilitation outcomes. Then, we propose a new framework to interpret results in stroke literature in the light of the latest evidence regarding: (1) the role of the callosum in inter-hemispheric communication, (2) the role of prefrontal cortices in exerting a control function, and (3) diaschisis mechanisms. These new pieces of evidence on the role of callosum can help to understand which compensatory mechanism may take place following a stroke. Moreover, depending on the individual impairment, the prefrontal control network will play different roles according to the need of high-level motor control. We believe that our new model, which includes crucial overlooked factors, will enable clinicians to better define individualized motor rehabilitation protocols.
Introduction:
Spatial neglect remains an underdiagnosed and undertreated consequence of stroke that imposes significant disability. A growing appreciation of brain networks involved in spatial cognition is helping us to develop a mechanistic understanding of different therapies under development.
Areas covered:
This review focuses on neuromodulation of brain networks for the treatment of spatial neglect after stroke, using evidence-based approaches including 1) Cognitive strategies that are more likely to impact frontal lobe executive function networks; 2) Visuomotor adaptation, which may depend on the integrity of parietal and parieto- and subcortical-frontal connections, and the presence of a particular subtype of neglect labeled Aiming neglect; 3) Non-invasive brain stimulation which may modulate relative levels of activity of the two hemispheres, and depend on corpus callosum connectivity; and 4) Pharmacological modulation which may exert its effect primarily via right-lateralized networks more closely involved in arousal.
Expert opinion:
Despite promising results from individual studies, significant methodological heterogeneity between trials weakened conclusions drawn from meta-analyses. Improved classification of spatial neglect subtypes will benefit research and clinical care. Understanding the brain network mechanisms of different treatments and different types of spatial neglect will make possible a precision medicine treatment approach.
A figyelem az életünk meghatározó része, a legapróbb cselekedeteinket is átszövi kora gyermekkortól egészen az időskorig. Mindenki tud példát mondani arra, amikor figyelt, amikor valamire direkt nem figyelt, amikor észrevett valami változást, amit mások nem, amikor elfáradt és nem tudott tovább figyelni, és arra is, amikor felfrissült és újra oda tudott figyelni. Persze ebben nagyok az egyéni különbségek, hiszen arra, hogy mire, mennyire és hogyan figyelünk, hat az, hogy milyen természetűek vagyunk. Az viszont mindenkire igaz, hogy figyelem nélkül sok szórakoztató tevékenységet nem tudnánk gyakorolni. A figyelmi képességünk alapvető, elválaszthatatlan része a kommunikációnak, a digitális eszközhasználatnak, a sportnak és a művészetnek. Ugyanakkor a figyelmi képességeink alapvetőségének akkor kerülünk igazán tudatába, amikor valamelyik „része” hiányzik. A figyelmi deficitek széles körben megjelennek a neuropszichológiától a különböző függőségeken át a figyelemhiányos hiperaktivitás-zavarig. Jelen kötet célja közérthetően bemutatni a figyelem (kognitív) pszichológiájának sokszínűségét és egyes aspektusainak gyakorlati relevanciáját olyan alkalmazott szemlélettel, amely érthető az érdeklődő laikusoknak és hasznára lehet számos diszciplínában tanuló (jövőbeli) szakembernek.
Unilateral spatial neglect declines when participants reach to grip the center of long metal rods compared with when they point to the perceived center, suggesting that visuomotor control systems are less affected by neglect than other representational systems (I. H. Robertson, D. Nico, & B. Hood, 1995). In this study, 16 participants with unilateral left neglect actually picked up rods, and we predicted short-term improvements in neglect because of induced conflict between a phenomenally symmetrical visual world on the one hand and a proprioceptively conveyed rightward-biased world on the other. With participants serving as their own controls, significant short-term improvements in neglect were found on 2 out of 4 neglect tasks after participants experienced proprioceptive feedback discrepant from the judgments they made on the basis of visual information alone.
Up to 80% of people who experience a right-hemisphere stroke suffer from hemispatial neglect. This syndrome is debilitating and impedes rehabilitation. We carried out a clinical feasibility trial of transcranial direct current stimulation (tDCS) and a behavioural rehabilitation programme, alone or in combination, in patients with neglect. Patients >4 weeks post right hemisphere stroke were randomized to 10 sessions of tDCS, 10 sessions of a behavioural intervention, combined intervention, or a control task. Primary outcomes were recruitment and retention rates, with secondary outcomes effect sizes on measures of neglect and quality of life, assessed directly after the interventions, and at 6 months follow up. Of 288 confirmed stroke cases referred (representing 7% of confirmed strokes), we randomized 8% (0.6% of stroke cases overall). The largest number of exclusions (91/288 (34%)) were due to medical comorbidities that prevented patients from undergoing 10 intervention sessions. We recruited 24 patients over 29 months, with 87% completing immediate post-intervention and 67% 6 month evaluations. We established poor feasibility of a clinical trial requiring repeated hospital-based tDCS within a UK hospital healthcare setting, either with or without behavioural training, over a sustained time period. Future trials should consider intensity, duration and location of tDCS neglect interventions.
Trial registration: ClinicalTrials.gov identifier: NCT02401724.
Visuospatial neglect constitutes a supramodal cognitive deficit characterized by reduction or loss of spatial awareness for the contralesional space. It occurs in over 40% of right- and 20% of left-brain-lesioned stroke patients with lesions located mostly in parietal, frontal and subcortical brain areas. Visuospatial neglect is a multifaceted syndrome - symptoms can be divided into sensory, motor and representational neglect - and therefore requires an individually adapted diagnostic and therapeutic approach. Several models try to explain the origins of visuospatial neglect, of which the “interhemispheric rivalry model” is strongly supported by animal and human research. This model proposes that allocation of spatial attention is balanced by transcallosal inhibition and both hemispheres compete to direct attention to the contralateral hemi-space. Accordingly, a brain lesion causes an interhemispheric imbalance, which may be re-installed by activation of lesioned, or deactivation of unlesioned (over-activated) brain areas through noninvasive brain stimulation. Research in larger patient samples is needed to confirm whether noninvasive brain stimulation can improve long-term outcomes and whether these also affect activities of daily living and discharge destination.
Non-invasive brain stimulation has been widely investigated as a potential treatment for a range of neurological and psychiatric conditions, including brain injury. However, the behavioural effects of brain stimulation are variable, for reasons that are poorly understood. This is a particular challenge for traumatic brain injury, where patterns of damage and their clinical effects are heterogeneous. Here we test the hypothesis that the response to transcranial direct current stimulation following traumatic brain injury is dependent on white matter damage within the stimulated network. We used a novel simultaneous stimulation-MRI protocol applying anodal, cathodal and sham stimulation to 24 healthy control subjects and 35 patients with moderate/severe traumatic brain injury. Stimulation was applied to the right inferior frontal gyrus/anterior insula node of the salience network, which was targeted because our previous work had shown its importance to executive function. Stimulation was applied during performance of the Stop Signal Task, which assesses response inhibition, a key component of executive function. Structural MRI was used to assess the extent of brain injury, including diffusion MRI assessment of post-traumatic axonal injury. Functional MRI, which was simultaneously acquired to delivery of stimulation, assessed the effects of stimulation on cognitive network function. Anodal stimulation improved response inhibition in control participants, an effect that was not observed in the patient group. The extent of traumatic axonal injury within the salience network strongly influenced the behavioural response to stimulation. Increasing damage to the tract connecting the stimulated right inferior frontal gyrus/anterior insula to the rest of the salience network was associated with reduced beneficial effects of stimulation. In addition, anodal stimulation normalized default mode network activation in patients with poor response inhibition, suggesting that stimulation modulates communication between the networks involved in supporting cognitive control. These results demonstrate an important principle: that white matter structure of the connections within a stimulated brain network influences the behavioural response to stimulation. This suggests that a personalized approach to non-invasive brain stimulation is likely to be necessary, with structural integrity of the targeted brain networks an important criterion for patient selection and an individualized approach to the selection of stimulation parameters.
Background:
Selecting optimal stimulation parameters from numerous possibilities is a major obstacle for assessing the efficacy of non-invasive brain stimulation.
Objective:
We demonstrate that Bayesian optimization can rapidly search through large parameter spaces and identify subject-level stimulation parameters in real-time.
Methods:
To validate the method, Bayesian optimization was employed using participants' binary judgements about the intensity of phosphenes elicited through tACS.
Results:
We demonstrate the efficiency of Bayesian optimization in identifying parameters that maximize phosphene intensity in a short timeframe (5 min for >190 possibilities). Our results replicate frequency-dependent effects across three montages and show phase-dependent effects of phosphene perception. Computational modelling explains that these phase effects result from constructive/destructive interference of the current reaching the retinas. Simulation analyses demonstrate the method's versatility for complex response functions, even when accounting for noisy observations.
Conclusion:
Alongside subjective ratings, this method can be used to optimize tACS parameters based on behavioral and neural measures and has the potential to be used for tailoring stimulation protocols to individuals.
Studies using transcranial direct current stimulation (tDCS) typically compare an active protocol relative to a shorter sham (placebo) protocol. Both protocols are presumed to be perceptually identical on the scalp, and thus represent an effective method of delivering double‐blinded experimental designs. However, participants often show above‐chance accuracy when asked which condition involved active/sham retrospectively. We assessed the time course of sham‐blinding during active and sham tDCS. We predicted that participants would be aware that the current is switched on for longer in the active versus sham protocol. 32 adults were tested in a pre‐registered, double‐blinded, within‐subjects design. A forced‐choice reaction time task was undertaken before, during and after active (10min 1mA) and sham (20s 1mA) tDCS. The anode was placed over the left primary motor cortex (C3) to target the right hand, and the cathode on the right forehead. Two probe questions were asked every 30s: “Is the stimulation on? “and “How sure are you?”. Distinct periods of non‐overlapping confidence intervals were identified between conditions, totalling 5min (57.1% of the total difference in stimulation time). These began immediately after sham ramp‐down and lasted until the active protocol had ended. We therefore show a failure of placebo control during 1mA tDCS. These results highlight the need to develop more effective methods of sham‐blinding during transcranial electrical stimulation protocols, even when delivered at low‐intensity current strengths. This article is protected by copyright. All rights reserved.
Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large‐scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within‐DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large‐scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.
Previous language production studies targeting the inferior frontal and superior temporal gyrus using anodal tDCS have provided mixed results. Part of this heterogeneity may be explained by limited target region focality of conventionally used electrode montages. We examined the focality of conventionally and alternative electrode montages. Electrical field distributions of anodal tDCS targeting IFG and pSTG were simulated in conventional setups (anodal electrode over left IFG/pSTG, reference electrode over right supraorbital region) and an alternative electrode montage in four different brains. Conventional montages showed maximum field strengths outside of the target regions. Results from alternative electrode montages showed that focality of tDCS could be improved by adjustments in electrode placement. Heterogeneity of findings of language production studies deploying conventional montages may in part be explained by diffuse electrical field distributions. Alternative montages may improve focality and provide more unequivocal results.
Objective
Unilateral neglect is a poststroke disorder that impacts negatively on functional outcome and lacks established, effective treatment. This multicomponent syndrome is characterised by a directional bias of attention away from contralesional space, together with impairments in several cognitive domains, including sustained attention and spatial working memory. This study aimed to test the effects of guanfacine, a noradrenergic alpha-2A agonist, on ameliorating aspects of neglect.
Methods
Thirteen right hemisphere stroke patients with leftward neglect were included in a randomised, double-blind, placebo-controlled proof-of-concept crossover study that examined the effects of a single dose of guanfacine. Patients were tested on a computerised, time-limited cancellation paradigm, as well as tasks that independently assessed sustained attention and spatial working memory.
Results
On guanfacine, there was a statistically significant improvement in the total number of targets found on the cancellation task when compared with placebo (mean improvement of 5, out of a possible 64). However, there was no evidence of a change in neglect patients’ directional attention bias. Furthermore, Bayesian statistical analysis revealed reliable evidence against any effects of guanfacine on search organisation and performance on our sustained attention and spatial working memory tasks.
Conclusions
Guanfacine improves search in neglect by boosting the number of targets found but had no effects on directional bias or search organisation, nor did it improve sustained attention or working memory on independent tasks. Further work is necessary to determine whether longer term treatment with guanfacine may be effective for some neglect patients and whether it affects functional outcome measures.
Trial registration number
NCT00955253.
Right brain injury causes visual neglect - lost awareness of left space. During prism adaptation therapy, patients adapt to a rightward optical shift by recalibrating right arm movements leftward. This can improve left neglect, but the benefit of a single session is transient (~1 day). Here we show that tonic disinhibition of left motor cortex during prism adaptation enhances consolidation, stabilizing both sensorimotor and cognitive prism after-effects. In three longitudinal patient case series, just 20 min of combined stimulation/adaptation caused persistent cognitive after-effects (neglect improvement) that lasted throughout follow-up (18–46 days). Moreover, adaptation without stimulation was ineffective. Thus stimulation reversed treatment resistance in chronic visual neglect. These findings challenge consensus that because the left hemisphere in neglect is pathologically over-excited it ought to be suppressed. Excitation of left sensorimotor circuits, during an adaptive cognitive state, can unmask latent plastic potential that durably improves resistant visual attention deficits after brain injury.
Background:
Stroke is associated with high rates of falling and severe impairment of lower limb in patients who survive.
Objective:
The aim of this study was to analyze the effectiveness of different montages of transcranial direct current stimulation (tDCS) on reducing falls and on lower limb function after acute stroke.
Methods:
Sixty participants with acute stroke were randomly allocated into four groups with different electrode's setups: anodal, cathodal, bilateral and sham tDCS. Each patient received 10 stimulation sessions (five consecutive days for two weeks). Four Square Step Test, Occurrence of Falling Index, Overall Stability Index, Falls Efficacy Scale - International, Berg Balance Scale, Six-minute walk test and Sit to Stand Test were measured at baseline, post-treatment, and at one- and three-month follow-up.
Results:
At baseline, no differences between the groups in terms of clinical and demographic characteristics were found. However, after treatment and during follow up, all the groups that received active stimulation showed greater reduction in the risk of falls and improved performance of the lower limb's motor skills when compared to the sham group. No significant differences were found between the three types of active montages in relation to the risk of falling. In relation to lower limb function, bilateral stimulation provided a higher improvement when compared to anodal and cathodal tDCS.
Conclusions:
This is the first trial with different setups of tDCS on acute stroke patients. tDCS presents as an effective treatment strategy in reducing the risk of falls and improving lower limb function after a stroke. ClinicalTrials.gov (NCT 02422173).
To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation.
Significance
Understanding the physiology of noninvasive brain stimulation requires precise knowledge of biophysical properties of brain tissue (e.g., conductivities). Numerous researchers have tried to measure these properties using in vitro, in vivo, and ex vivo preparations in nonhuman animals or human tissue, though findings have tended to vary across studies. We measured electric fields in the nonhuman primate brain during transcranial electric stimulation both in vivo and ex vivo. We found large changes in electric fields between in vivo and ex vivo measurements that increased with postmortem time, along with a significant effect of body temperature on electric field strength. Our findings underscore the necessity of nonhuman animal models for systematic study of brain stimulation effects under biophysically realistic conditions.
Transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (dlPFC) can modulate working memory (WM) performance. However, evidence regarding the enhancement of WM training, its sustainability and transferability is ambiguous. Since WM functioning appears to be lateralized in respect to stimulus characteristics, this study examined the difference between task-congruent (spatial-right, verbal-left), task-incongruent (spatial-left, verbal-right) and sham tDCS in regards to the efficacy of WM training. In a randomized, sham-controlled experiment, 71 healthy adults trained on a spatial or verbal adaptive n-back task. After a baseline session, anodal or sham tDCS (1 mA) to the right or left dlPFC was applied during the next three training sessions. Sustainability of training gains and near-transfer (verbal or spatial 3-back task) were tested in a fourth training and a follow-up session. Compared to sham stimulation, we found a steeper learning curve when WM training was combined with task-congruent tDCS. This advantage was also present compared to task-incongruent tDCS. Moreover, these effects lasted for up to nine months and transferred to the respective untrained task. These long-lasting, transferable, task-specific effects demonstrate a behaviorally relevant and sustainable facilitation of neuroplastic processes by tDCS that could be harnessed for the treatment of disorders associated with deficient WM.
Objectives:
The safety, painless, and tolerability features of transcranial Direct Current Stimulation (tDCS) have prompted the research on the therapeutic effects of this technique in stroke; however, an in-depth and unarguable examination of the adverse effects of tDCS in stroke patients is still lacking. This review analyzes the reported adverse effects in stroke, looking for factors that may induce side-effects.
Materials and methods:
A comprehensive search of articles published from 1998 to 2015 describing tDCS application in stroke patients performed through data extraction from MEDLINE/PubMed database.
Results:
Only 11.62% of published papers reported the occurrence of tDCS adverse effects in stroke patients. The most common was itching (70%), followed by burning sensation (40%), headache (40%), tingling (30%), sleepiness (20%), difficulty of concentration, mild fatigue, skin redness, and dizziness (10%). No significant difference was found between studies "Reporting" vs. "Non-reporting" adverse effects regarding tDCS parameters (intensity, current density, duration of stimulation, and number of sessions).
Conclusion:
In the majority of stroke patients, tDCS did not induce any severe adverse effect. Regrettably, many published papers did not provide a careful description of exclusion criteria, nor a systematic report of side effects. Our work emphasizes the need of a more meticulous description of the adopted exclusion criteria and of the induced adverse effects, in order to optimize the therapeutic use of tDCS and to better delineate its safety parameters in stroke.
Transcranial direct current stimulation (tDCS) is a common method to modulate cortical activity. Anodal tDCS is usually associated with an enhancement of the stimulated brain area, whereas cathodal tDCS is often described as inhibitory brain stimulation method. Our aim was to investigate whether this canonical assumption derived from the motor system could be transferred to the semantic system. Three groups with 20 healthy subjects each were stimulated at Wernicke's area with either anodal, cathodal or sham tDCS. Subsequently, they performed a simple lexical decision task for a duration of about 25 minutes. Subjects receiving anodal tDCS revealed faster reaction times compared to the sham group, although not reaching statistical significance. Surprisingly, in the cathodal group reaction times were decreased significantly. All subjects were faster in the second half of the task, but the tDCS-induced improvement lasted for the entire duration of the task. Error rates were not influenced by tDCS, neither were reaction times in a choice reaction time task. Thus, both anodal and cathodal tDCS applied to Wernicke's area improved semantic processing. Recently, a meta-analysis revealed that the canonical anodal excitation and cathodal inhibition assumption is observed rarely in cognitive studies. In particular, an inhibitory effect of cathodal tDCS on cognition is rare. Our findings thus support the speculation, that especially language functions could be somewhat 'immune' to cathodal inhibition.
Key points:
Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings. However, the need for longer-lasting effects, combined with marked inter-individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects. We systematically investigated the full DC intensity range (0.5-2.0 mA) for both anodal and cathodal tDCS in a sham-controlled repeated measures design, monitoring changes in motor-cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation. For both tDCS polarities, the excitability after-effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor-cortical excitability. Further, while intra-individual responses showed good reliability, inter-individual sensitivity to TMS accounted for a modest percentage of the variance in the early after-effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations.
Abstract:
Contemporary non-invasive neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), have shown promising potential in both restituting impairments in cortical physiology in clinical settings, as well as modulating cognitive abilities in the healthy population. However, neuroplastic after-effects of tDCS are highly dependent on stimulation parameters, relatively short lasting, and not expectedly uniform between individuals. The present study systematically investigates the full range of current intensity between 0.5 and 2.0 mA on left primary motor cortex (M1) plasticity, as well as the impact of individual-level covariates on explaining inter-individual variability. Thirty-eight healthy subjects were divided into groups of anodal and cathodal tDCS. Five DC intensities (sham, 0.5, 1.0, 1.5 and 2.0 mA) were investigated in separate sessions. Using transcranial magnetic stimulation (TMS), 25 motor-evoked potentials (MEPs) were recorded before, and 10 time points up to 2 h following 15 min of tDCS. Repeated-measures ANOVAs indicated a main effect of intensity for both anodal and cathodal tDCS. With anodal tDCS, all active intensities resulted in equivalent facilitatory effects relative to sham while for cathodal tDCS, only 1.0 mA resulted in sustained excitability diminution. An additional experiment conducted to assess intra-individual variability revealed generally good reliability of 1.0 mA anodal tDCS (ICC(2,1) = 0.74 over the first 30 min). A post hoc analysis to discern sources of inter-individual variability confirmed a previous finding in which individual TMS SI1mV(stimulus intensity for 1 mV MEP amplitude) sensitivity correlated negatively with 1.0 mA anodal tDCS effects on excitability. Our study thus provides further insights on the extent of non-linear intensity-dependent neuroplastic after-effects of anodal and cathodal tDCS.
A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints.
Objective:
Transcranial direct current stimulation (tDCS) aims to alter brain function non-invasively via electrodes placed on the scalp. Conventional tDCS uses two relatively large patch electrodes to deliver electrical current to the brain region of interest (ROI). Recent studies have shown that using dense arrays containing up to 512 smaller electrodes may increase the precision of targeting ROIs. However, this creates a need for methods to determine effective and safe stimulus patterns as the number of degrees of freedom is much higher with such arrays. Several approaches to this problem have appeared in the literature. In this paper, we describe a new method for calculating optimal electrode stimulus patterns for targeted and directional modulation in dense array tDCS which differs in some important aspects with methods reported to date.
Approach:
We optimize stimulus pattern of dense arrays with fixed electrode placement to maximize the current density in a particular direction in the ROI. We impose a flexible set of safety constraints on the current power in the brain, individual electrode currents, and total injected current, to protect subject safety. The proposed optimization problem is convex and thus efficiently solved using existing optimization software to find unique and globally optimal electrode stimulus patterns.
Main results:
Solutions for four anatomical ROIs based on a realistic head model are shown as exemplary results. To illustrate the differences between our approach and previously introduced methods, we compare our method with two of the other leading methods in the literature. We also report on extensive simulations that show the effect of the values chosen for each proposed safety constraint bound on the optimized stimulus patterns.
Significance:
The proposed optimization approach employs volume based ROIs, easily adapts to different sets of safety constraints, and takes negligible time to compute. An in-depth comparison study gives insight into the relationship between different objective criteria and optimized stimulus patterns. In addition, the analysis of the interaction between optimized stimulus patterns and safety constraint bounds suggests that more precise current localization in the ROI, with improved safety criterion, may be achieved by careful selection of the constraint bounds.
Objective:
To examine whether transcranial direct current stimulation (tDCS) applied over the posterior parietal cortex (PPC) improves visuospatial attention in stroke patients with left visuospatial neglect.
Methods:
Patients were randomly assigned to 1 of 3 treatment groups: anodal tDCS over the right PPC, cathodal tDCS over the left PPC, or sham tDCS. Each patient underwent 15 sessions of tDCS (5 sessions per week for 3 weeks; 2 mA for 30 minutes in each session). Outcome measures were assessed before treatment and 1 week after completing the treatment.
Results:
From pre- to post-treatment, there was an improvement in the motor-free visual perception test (MVPT), line bisection test (LBT), star cancellation test (SCT), Catherine Bergego Scale (CBS), Korean version of Modified Barthel Index (K-MBI), and Functional Ambulation Classification in all 3 groups. Improvements in the MVPT, SCT, and LBT were greater in the anodal and cathodal groups than in the sham group. However, improvements in other outcomes were not significantly different between the 3 groups, although there was a tendency for improved CBS or K-MBI scores in the anodal and cathodal groups, as compared with the sham group.
Conclusion:
The study results indicated that the facilitatory effect of anodal tDCS applied over the right PPC, and the inhibitory effect of cathodal tDCS applied over the left PPC, improved symptoms of visuospatial neglect. Thus, tDCS could be a successful adjuvant therapeutic modality to recover neglect symptom, but this recovery might not lead to improvements in activities of daily living function and gait function.
Non-invasive brain stimulation techniques, including transcranial direct current stimulation (t-DCS) have been used in the rehabilitation of cognitive function in a spectrum of neurological disorders. The present review outlines methodological communalities and differences of t-DCS procedures in neurocognitive rehabilitation. We consider the efficacy of tDCS for the management of specific cognitive deficits in four main neurological disorders by providing a critical analysis of recent studies that have used t-DCS to improve cognition in patients with Parkinson's Disease, Alzheimer's Disease, Hemi-spatial Neglect, and Aphasia. The evidence from this innovative approach to cognitive rehabilitation suggests that tDCS can influence cognition. However, the results show a high variability between studies both in terms of the methodological approach adopted and the cognitive functions targeted. The review also focuses both on methodological issues such as technical aspects of the stimulation (electrode position and dimension; current intensity; duration of protocol) and on the inclusion of appropriate assessment tools for cognition. A further aspect considered is the optimal timing for administration of tDCS: before, during or after cognitive rehabilitation. We conclude that more studies using common methodology are needed to gain a better understanding of the efficacy of tDCS as a new tool for rehabilitation of cognitive disorders in a range of neurological disorders.
Background:
tDCS studies typically find that: lowest levels of comfort occur at stimulation-onset; young adult participants experience less comfort than older participants; and participants' blinding seems effective at low current strengths. At 2 mA conflicting results have been reported, questioning the effectiveness of blinding in sham-controlled paradigms using higher current strengths. Investigator blinding is rarely reported.
Objective:
Using a protocol with 30 min of 2 mA stimulation we sought to: (a) investigate the level of perceived comfort in young and older adults, ranging in age from 19 to 29 years and 63 to 76 years, respectively; (b) test investigator and participant blinding; (c) assess comfort over a longer stimulation duration; (d) add to the literature on protocols using 2 mA current strength.
Methods:
A two-session experiment was conducted where sham and active stimulation were administered to the frontal cortex at the F8/FP1 sites in a within-subjects manner. Levels of perceived comfort were measured, using a visual analogue scale, at the start and end of stimulation in young and older adults. Post-stimulation, participants and investigators judged whether or not active stimulation was used.
Results:
Comfort scores were lower at stimulation onset in both age groups. Older adults reported: (i) more comfort than young participants overall; (ii) comparable levels of comfort in sham and active stimulation; (iii) significantly more comfort than the young participants during active stimulation. Stimulation mode was correctly identified above chance in the second of the two sessions; 65% of all participants correctly identified the stimulation mode, resulting in a statistical trend. Similarly, the experimenter correctly identified stimulation mode significantly above chance, with 62% of all investigator judgements correct across 120 judgements.
Conclusions:
Using 2 mA current strength over 30 minutes, tDCS stimulation comfort is lower at stimulation onset in young and older adults and, overall, lower for young participants. Investigators and participants may be able to identify active stimulation at above chance levels, although accuracy never exceeded 65% for either participants or the experimenter. Further research into blinding efficacy is recommended.
Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.
[Purpose] To investigate the effects of a combination of transcranial direct current stimulation (tDCS) and feedback training (FT) on subacute stroke patients with unilateral visuospatial neglect. [Subjects] The subjects were randomly assigned to a tDCS + FT group (n=6) and a FT group (n=6). [Methods] Patients in the tDCS + FT group received tDCS for 20 minutes and then received FT for 30 minutes a day, 5 days a week for 3 weeks. The control group received FT for 30 minutes a day, 5 days a week for 3 weeks. [Results] After the intervention, both groups showed significant improvements in the Motor-Free Visual Perception Test (MVPT), line bisection test (LBT), and modified Barthel index (MBI) over the baseline results. The comparison of the two groups after the intervention revealed that the rDCS + FT group showed more significant improvements in MVPT, LBT, and MBI. [Conclusion] The results of this study suggest that tDCS combined with FT has a positive effect on unilateral visuospatial neglect in patients with subacute stroke. © 2015 The Society of Physical Therapy Science. Published by IPEC Inc.
Background:
Transcranial Direct Current Stimulation has been increasing in popularity in the last few years. Despite vast amounts of articles on the use of tDCS on stroke patients, very little has been done during the acute phase.
Objectives:
Measure the effects of tDCS on functional and sensory outcomes throughout the first year post onset of stroke.
Methods:
50 acute stroke patients were randomized and placed into either the treatment or sham group. Anodal tDCS was applied (2 mA, 20 min) 5 times a week during the first month post stroke. Patients were evaluated with the Wolf Motor Function Test, the Semmes Weinstein Monofilament Test, the Upper Extremity section (UEFM), the Lower Extremity section (LEFM) and the Somatosensory section of the Fugl Meyer Test, the Tardieu Spasticity Scale, the Stroke Impact Scale (SIS), the Hospital Anxiety and Depression Scale (HADS) and the Barthel Index. Evaluations were held at 48 h post stroke, week 1, 2, 3, 4, 3 months, 6 months and 1 year.
Results:
There were statistically and clinically significant improvements after tDCS in all functional motor outcomes, and somatosensory functions. Differences between both groups for the main outcome (WMFT time) were 51% (p = 0.04) at one month, and 57% (p = 0.02) at one year.
Conclusion:
tDCS seems to be an effective adjuvant to conventional rehabilitation techniques. If applied in the acute stages of stroke, functional recovery is not only accelerated, but improved, and results are maintained up to one-year post stroke.
Transcranial electrical brain stimulation (tES) techniques have shown substantial promise in research and applied settings. However, over the last few years the technique has courted significant controversy, resulting in scepticism regarding its reported beneficial effects and future potential. In this opinion article, we examine the key points of criticism raised to date, including whether tES has any meaningful effect on the cortex, issues of replicability, and the variability in its efficacy across individuals. For each point, we assess the strength of the evidence for and against the argument and, where relevant, suggest how the field can improve. We conclude that while some of the highlighted shortcomings of research using electrical brain stimulation are justified, on balance the arguments against using such techniques in cognitive neuroscience are often overstated and elevate the risk of the field "throwing the baby out with the bath water".
Transcranial direct current stimulation (tDCS) is a non‐invasive brain stim‐ulation method that is frequently used to study cortical excitability changes and their impact on cognitive functions in humans. While most stimulators are capable of operating in double‐blind mode, the amount of discomfort ex‐perienced during tDCS may break blinding. Therefore, specifically designed sham stimulation protocols are being used. The “fade‐in, short‐stimulation, fade‐out” (FSF) protocol has been used in hundreds of studies and is com‐monly believed to be indistinguishable from real stimulation applied at 1 mA for 20 minutes. We analyzed subjective reports of 192 volunteers, who either received real tDCS (n=96) or FSF tDCS (n=96). Participants reported more discomfort for real tDCS and correctly guessed the condition above chance‐level. These findings indicate that FSF does not ensure complete blinding and that better active sham protocols are needed.
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This book provides a comprehensive overview on Transcranial Direct Current Stimulation (tDCS) and the clinical applications of this promising technique. Separated into three parts, the book begins with basic principles, mechanisms and approaches of tDCS. This is followed by a step-by-step practicum, methodological considerations and ethics and professional conduct pertaining to this novel technique. Chapters are authored by renowned experts who also direct and plan tDCS educational events worldwide. Bridging the existing gap in instructional materials for tDCS while addressing growing interest in education in this field, professionals within a broad range of medical disciplines will find this text to be an invaluable guide.
Neglect treatment with prismatic lenses (PL) has been demonstrated to be effective in improving hemispatial neglect. This study aimed to compare the effect of cathodal transcranial direct current stimulation (c-tDCS), anodal tDCS (a-tDCS) or sham stimulation in modulating the PL effect in stroke patients. Fifteen subacute stroke patients with pathological performance on the Behavioral Inattention Test (BIT) battery, indicative of neglect, were included in this study. Patients underwent to a-tDCS over the right posterior parietal cortex (PPC), c-tDCS over the left PPC and sham stimulation during three PL training sessions (with PL of 10? rightward shift), in random sequence and separated by at least 1 day. Thirty “invisible” pointing (visual target not visible) were performed before and after each session to evaluate the after-effect of the PL training. Leftward shift after PL training was significantly reduced by a-tDCS over the ipsilasional PPC in comparison with c-tDCS over the contralesional PPC (p = 0.019) and sham stimulation (p = 0.047). No difference in the after-effect was obtained comparing the c-tDCS and sham stimulation. Error correction during the PL training do not significantly differed among the three sessions. A-tDCS over the ipsilesional PPC reduced the leftward deviation possibly interfering with the network involved in visuo-motor adaptation to PL training.
Objectives:
To examine the occurrence of and recovery from visual neglect-related symptoms with the focus on neglect laterality, ipsilateral orienting bias, and slowed processing speed in right hemisphere (RH) infarct patients during a 1-year follow-up. Furthermore, to propose guidelines for assessing processing speed alongside the Behavioural Inattention Test (BIT).
Methods:
We studied three RH patient groups: neglect (N+), mild left inattention (MLI+), and non-neglect (N-) patients, and healthy controls. The BIT with some additional analyses was conducted at the acute phase and at 6 and 12 months.
Results:
The N+ group's BIT score increased and originally lateralized omissions became more evenly distributed during the follow-up. The N+ and MLI+ groups' starting points were more rightward located than the healthy group's at the acute phase and at 6, and partly at 12 months. Patient groups were slower than the controls in performing cancellation tests at the acute phase. The N+ and MLI+ groups remained slower than the controls throughout the follow-up.
Conclusions:
During the first year after RH infarct, originally left-sided manifestation of neglect shifted toward milder non-lateralized attentional deficit. Ipsilateral orienting bias and slowed processing speed appeared to be rather persistent neglect-related symptoms both in neglect patients and patients with initially milder inattention. We propose some effortless, tentative ways of examining processing speed and ipsilateral orienting bias alongside the BIT to better recognize these neglect-related symptoms, and highlight the need to assess and treat patients with initially milder inattention, who have been under-recognized and under-treated in clinical work. (JINS, 2018, 24, 1-12).
Schizophrenia is a severe and often detrimental psychiatric disorder. The individual patients’ level of functioning is essentially determined by cognitive, particularly working memory (WM), deficits that are critically linked to dysfunctional activity of the dorsolateral prefrontal cortex (dlPFC). Transcranial direct current stimulation (tDCS) can transiently modulate activity of the dlPFC and remote areas and has been shown to improve WM functions. It may therefore provide a new, targeted treatment option.
For this aim, the present study investigated the effect of anodal tDCS of different intensities on spatial WM in patients with schizophrenia. In two experiments, 32 patients performed a spatial n-back task with increasing WM load (1-, 2-, and 3-back) at baseline and in two sessions with anodal or sham tDCS (EXP I [n = 16]: 1 mA; EXP II [n = 16]: 2 mA) to the right dlPFC (cathode: left m. deltoideus). With 1 mA anodal tDCS, no effect on WM performance could be detected. However, 2 mA anodal tDCS increased accuracy (measured by d’) of the task with the highest WM load (3-back). This effect was larger in patients with a lower level of general neurocognitive functioning.
These results demonstrate a beneficial effect of 2 mA anodal tDCS on deficient WM accuracy in patients with schizophrenia particularly under challenging conditions and in subjects with higher cognitive impairments. This data will inform future clinical trials on tDCS-enhanced cognitive training to improve treatment of schizophrenia.
To reach a deep target in the brain with transcranial electric stimulation (TES), currents have to pass also through the cortical surface. Thus, it is generally thought that TES cannot achieve focal deep brain stimulation. Recent efforts with interfering waveforms and pulsed stimulation have argued that one can achieve deeper or more intense stimulation in the brain. Here we argue that conventional transcranial stimulation with multiple current sources is just as effective as these new approaches. The conventional multi-electrode approach can be numerically optimized to maximize intensity or focality at a desired target location. Using such optimal electrode configurations we find in a detailed and realistic head model that deep targets may in fact be strongly stimulated, with cerebro-spinal fluid guiding currents deep into the brain.
It has recently been revealed that spatial neglect can be modulated by motivational factors including anticipated monetary reward. A number of dopaminergic agents have been evaluated as treatments for neglect, but the results have been mixed, with no clear anatomical or cognitive predictors of dopaminergic responsiveness. Given that the effects of incentive motivation are mediated by dopaminergic pathways that are variably damaged in stroke, we tested the hypothesis that the modulatory influences of reward and dopaminergic drugs on neglect are themselves related. We employed a single-dose, double-blind, crossover design to compare the effects of Co-careldopa and placebo on a modified visual cancellation task in patients with neglect secondary to right hemisphere stroke. Whilst confirming that reward improved visual search in this group, we showed that dopaminergic stimulation only enhances visual search in the absence of reward. When patients were divided into REWARD-RESPONDERs and REWARD-NON-RESPONDERs, we found an interaction, such that only REWARD-NON-RESPONDERs showed a positive response to reward after receiving Co-careldopa, whereas REWARD-RESPONDERs were not influenced by drug. At a neuroanatomical level, responsiveness to incentive motivation was most associated with intact dorsal striatum. These findings suggest that dopaminergic modulation of neglect follows an ‘inverted U’ function, is dependent on integrity of the reward system, and can be measured as a behavioural response to anticipated reward.
Importance
Aphasia is a debilitating language disorder for which behavioral speech therapy is the most efficient treatment, but therapy outcomes are variable and full recovery is not always achieved. It remains unclear if adjunctive brain stimulation (anodal transcranial direct current stimulation [A-tDCS]) applied during aphasia therapy can improve outcomes.
Objective
To examine the futility of studying A-tDCS as an adjunctive intervention during speech therapy to improve speech production (naming) for individuals with long-term poststroke aphasia.
Design, Setting, and Participants
Double-blinded, prospective randomized clinical trial using a futility design to test adjunctive A-tDCS during speech therapy. The setting was an outpatient clinic. Enrollment of individuals began in August 2012 and was completed in March 2017, and the duration of follow-up was 6 months. Analyses began in April 2017. The study recruited from a volunteer sample, and 89 patients were screened. Patients with long-term (>6 months) aphasia due to 1 previous left hemisphere stroke were enrolled. In comparing A-tDCS and sham tDCS, patients were matched based on site (University of South Carolina or Medical University of South Carolina), baseline age, type of aphasia, and aphasia severity.
Interventions
Outpatient speech therapy for 3 weeks (15 sessions, 45 minutes each) combined with either A-tDCS vs sham tDCS applied to preserved left temporal lobe regions.
Main Outcomes and Measures
The primary outcome was the ability to name common objects, assessed twice before and after therapy.
Results
A total of 74 patients were enrolled. Participants had a mean (SD) age of 60 (10) years, had 15 (2) years of education, and were 44 (40) months from stroke onset. There were 52 men (70%) and 62 non-Hispanic white individuals (84%). Most were retired or not employed (59 [80%]). Broca aphasia was the most common aphasia type (39 [52.7%]). The adjusted mean (SE) change from pretreatment baseline in correct naming was 13.9 (2.4) words (95% CI, 9.0-18.7) for A-tDCS and 8.2 (2.2) words (95% CI, 3.8-12.6) for sham tDCS, with mean (SE) A-tDCS difference of 5.7 (3.3) words (95% CI, −0.9 to 12.3), indicating a relative 70% increase in correct naming for A-tDCS relative to sham. The futility hypothesis P value was .90, indicating failure to reject the null hypothesis and, therefore, providing no evidence that further study of A-tDCS is futile. No serious adverse events were associated with A-tDCS.
Conclusions and Relevance
Our findings provide motivation to proceed with another trial to study the effect of A-tDCS on the outcome of aphasia treatment in individuals poststroke. Anodal tDCS during speech therapy is feasible and potentially transformative for aphasia treatment and should be further studied.
Trial Registration
ClinicalTrials.gov Identifier: NCT01686373.
The ability to sustain attention is integral to healthy cognition in aging. The right PFC (rPFC) is critical for maintaining high levels of attentional focus. Whether plasticity of this region can be harnessed to support sustained attention in older adults is unknown. We used transcranial direct current stimulation to increase cortical excitability of the rPFC, while monitoring behavioral and electrophysiological markers of sustained attention in older adults with suboptimal sustained attention capacity. During rPFC transcranial direct current stimulation, fewer lapses of attention occurred and electroencephalography signals of frontal engagement and early visual attention were enhanced. To further verify these results, we repeated the experiment in an independent cohort of cognitively typical older adults using a different sustained attention paradigm. Again, prefrontal stimulation was associated with better sustained attention. These experiments suggest the rPFC can be manipulated in later years to increase top-down modulation over early sensory processing and improve sustained attention performance. This holds valuable information for the development of neurorehabilitation protocols to ameliorate age-related deficits in this capacity.
In the past three decades, our understanding of brain-behavior relationships has been significantly shaped by research using non-invasive brain stimulation (NIBS) techniques. These methods allow non-invasive and safe modulation of neural processes in the healthy brain, enabling researchers to directly study how experimentally altered neural activity causally affects behavior. This unique property of NIBS methods has, on the one hand, led to groundbreaking findings on the brain basis of various aspects of behavior and has raised interest in possible clinical and practical applications of these methods. On the other hand, it has also triggered increasingly critical debates about the properties and possible limitations of these methods. In this review, we discuss these issues, clarify the challenges associated with the use of currently available NIBS techniques for basic research and practical applications, and provide recommendations for studies using NIBS techniques to establish brain-behavior relationships.
Large-scale synchronization of neural oscillations is a key mechanism for functional information exchange among brain areas. Dual-site Transcranial Alternating Current Stimulation (ds-TACS) has been recently introduced as non-invasive technique to manipulate the temporal phase relationship of local oscillations in two connected cortical areas. While the frequency of ds-TACS is matched, the phase of stimulation is either identical (in-phase stimulation) or opposite (anti-phase stimulation) in the two cortical target areas. In-phase stimulation is thought to synchronize the endogenous oscillations and hereby to improve behavioral performance. Conversely, anti-phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in- and anti-phase ds-TACS should only differ with respect to temporal phase, while all other stimulation parameters such as focality and stimulation intensity should be matched to enable an unambiguous interpretation of the behavioral effects. Using electric field simulations based on a realistic head geometry, we tested how well this goal has been met in studies, which have employed ds-TACS up to now. Separating the induced electrical fields in their spatial and temporal components, we investigated how the chosen electrode montages determined the spatial field distribution and the generation of phase variations in the injected electric fields. Considering the basic physical mechanisms, we derived recommendations for an optimized stimulation montage. The latter allows for a principled design of in- and anti-phase ds-TACS conditions with matched spatial distributions of the electric field. This knowledge will help cognitive neuroscientists to design optimal ds-TACS configurations, which are suited to probe unambiguously the causal contribution of phase coupling to specific cognitive processes in the human brain.
Objective:
To evaluate the effectiveness of noninvasive brain stimulation (NIBS) - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - on hemispatial neglect and performance in activities of daily living (ADL) after stroke.
Data sources:
MEDLINE (Pubmed), Embase, Cochrane CENTRAL, SCOPUS, Scielo and Physiotherapy Evidence Database (PEDro) were searched from database inception to December 2016.
Data selection:
Randomized controlled trials or crossover trials focused on determining the effects of tDCS or rTMS combined or not combined with other therapies for hemispatial neglect after stroke.
Data extraction:
Methodological characteristics of the studies, number of participants, comparison groups, interventions and outcomes were extracted.
Data synthesis:
Ten trials comprising 226 participants had data that were suitable for the meta-analysis. Meta-analysis showed that NIBS combined with another therapy significantly improves hemispatial neglect [SMD -1.91 (95% CI, -2.57 to -1.25; I(2) 71%)]. A sensitivity analysis showed that rTMS [SMD -2.16 (95% CI, -3.00 to -1.33; I(2) 76%)] and tDCS [SMD -1.07 (95% CI, -1.76 to -0.37; I(2) 0%)] had positive effects on hemispatial neglect. Furthermore, both excitatory [SMD -2.34 (95% CI, -3.56 to -1.12; I(2) 65%)] and inhibitory [SMD -1.69 (95% CI, -2.49 to -0.88; I(2) 75%)] stimulations were effective.
Conclusions:
This meta-analysis revels a moderate-quality of evidence for the effectiveness of NIBS protocols combined with other therapies on hemispatial neglect and performance in ADL after stroke.
Hemispatial neglect is a severe cognitive condition frequently observed after a stroke, associated with unawareness of one side of space, disability and poor long-term outcome. Visuomotor feedback training (VFT) is a neglect rehabilitation technique that involves a simple, inexpensive and feasible training of grasping-to-lift rods at the centre. We compared the immediate and long-term effects of VFT vs. a control training when delivered in a home-based setting. 20 participants were randomly allocated to an intervention (who received VFT) or a control group (n = 10 each). Training was delivered for 2 sessions by an experimenter and then patients self-administered it for 10 sessions over 2 weeks. Outcome measures included the Behavioural Inattention Test (BIT), line bisection, Balloons Test, Landmark task, room description task, subjective straight-ahead pointing task and the Stroke Impact Scale. The measures were obtained before, immediately after the training sessions and after 4-months post-training. Significantly greater short and long-term improvements were obtained after VFT when compared to control training in line bisection, BIT and spatial bias in cancellation. VFT also produced improvements on activities of daily living. We conclude that VFT is a feasible, effective, home-based rehabilitation method for neglect patients that warrants further well-designed randomized controlled trials on a large sample of patients.
Visuospatial neglect is a disabling syndrome resulting in impaired activities of daily living and in longer durations of inpatient rehabilitation. Effective interventions to remediate neglect are still needed. The combination of tDCS and an optokinetic task might qualify as a treatment method. A total of 32 post-acute patients with left (n = 20) or right-sided neglect were allotted to an intervention or a control group (both groups n = 16). The intervention group received eight sessions of 1.5-2.0 mA parietal transcranial direct current stimulation (tDCS) during the performance of an optokinetic task distributed over two weeks. Additionally they received standard therapy for five hours per day. The control group received only the standard therapy. Patients were examined twice before (with 3-4 days between examinations) and twice after treatment (5-6 days between examinations). Compared to the control group and controlling for spontaneous remission, the intervention group improved on spontaneous body orientation and the Clock Drawing Test. Intragroup comparisons showed broad improvements on egocentric but not on allocentric symptoms only for the intervention group. A short additional application of tDCS during an optokinetic task led to improvements of severe neglect compared to a standard neurological early rehabilitation treatment. Improvements seem to concern primarily egocentric rather than allocentric neglect.
To explore the relationship between transcranial current stimulation (tCS) and the electroencephalography (EEG) forward problem, we investigate and compare accuracy and efficiency of a reciprocal and a direct EEG forward approach for dipolar primary current sources both based on the finite element method (FEM), namely the adjoint approach (AA) and the partial integration (PI) approach in conjunction with a transfer matrix concept. By analyzing numerical results, comparing to analytically derived EEG forward potentials and estimating computational complexity in spherical shell models, AA turns out to be essentially identical to PI. It is then proven that AA and PI are also algebraically identical even for general head models. This relation offers a direct link between the EEG forward problem and tCS. We then demonstrate how the quasi-analytical EEG forward solutions in sphere models can be used to validate the numerical accuracies of FEM-based tCS simulation approaches. These approaches differ with respect to the ease with which they can be employed for realistic head modeling based on MRI-derived segmentations. We show that while the accuracy of the most easy to realize approach based on regular hexahedral elements is already quite high, it can be significantly improved if a geometry-adaptation of the elements is employed in conjunction with an isoparametric FEM approach. While the latter approach does not involve any additional difficulties for the user, it reaches the high accuracies of surface-segmentation based tetrahedral FEM, which is considerably more difficult to implement and topologically less flexible in practice. Finally, in a highly realistic head volume conductor model and when compared to the regular alternative, the geometry-adapted hexahedral FEM is shown to result in significant changes in tCS current flow orientation and magnitude up to 45° and a factor of 1.66, respectively.
Neurological disorders are not only the direct result of an initial insult, but also represent the consequences of dynamic, plastic changes in distributed neural networks as the entire nervous system attempts to adapt. In such cases, cerebral plastic changes after brain insult may lead to additional neuropathic functional disability (maladaptive response). In this context, transcranial electrical stimulation (tES) aims to enhance adaptive patterns of activity and suppress maladaptive patterns of activity, restoring the equilibrium in imbalanced neural networks in the patient’s brain. Similarly, tES has the aim of enhancing intact human abilities. Although there are various methods of non-invasive delivery of electrical current to the brain, the most prominent of currently used methods include transcranial direct current stimulation (tDCS); transcranial alternating current stimulation (tACS); transcranial pulsed current stimulation (tPCS), which includes cranial electrotherapy stimulation (CES); and transcranial random noise stimulation (tRNS).
Hemi-spatial neglect syndrome is common and sometimes long-lasting. It is characterized by a deficit in the use and awareness of one side of space, most often consecutive to a right hemisphere injury, mainly in the parietal region. Acknowledging the different types and all clinical characteristics is essential for an appropriate evaluation and adapted rehabilitation care management, especially as it constitutes a predictive factor of a poor functional prognosis. Some new approaches have been developed in the last fifteen years in the field of hemi-spatial neglect rehabilitation, where non-invasive brain stimulation (TMS and tDCS) holds an important place. Today's approaches of unilateral spatial neglect modulation via non-invasive brain stimulation are essentially based on the concept of inter-hemispheric inhibition, suggesting an over-activation of the contralesional hemisphere due to a decrease of the inhibiting influences of the injured hemisphere. Several approaches may then be used: stimulation of the injured right hemisphere, inhibition of the hyperactive left hemisphere, or a combination of both. Results are promising, but the following complementary aspects must be refined before a more systematic application: optimal stimulation protocol, individual management according to the injured region, intensity, duration and frequency of care management, delay post-stroke before the beginning of treatment, combination of different approaches, as well as prognostic and efficacy criteria. An encouraging perspective for the future is the combination of several types of approaches, which would be largely facilitated by the improvement of fundamental knowledge on neglect mechanisms, which could in the future refine the choice for the most appropriate treatment(s) for a given patient.
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