- •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.
Posts Tagged Noninvasive brain stimulation
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.
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 . The electrical current partially penetrates the underlying structures and affects nerve cells, glia and vessels in the stimulated brain area  . 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  . 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 . 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 . 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   , long-term influence on learning processes and behavior  , as well as a therapeutic approach to improve function in neurological and psychiatric disorders associated with altered or disturbed neuroplasticity (overview in ). 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  .
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 .
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   . 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. […]
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.
[Abstract] Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) – Clinical Neurophysiology
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.
For acute, subacute, or chronic stroke, and neurotrauma, a range of rehabilitation strategies will be essential to optimize possible benefits of molecular, cellular, and novel pharmacological restorative approaches. The neurorehabilitation strategies must be chosen to engage the targeted networks of these novel approaches, drawing upon studies of motor and cognitive learning-related neural adaptations that accompany progressive practice. Regulatory agencies and the pharma/biotech industry will need to keep an open mind about the likely synergy that will come from interleaving repair strategies and rehabilitation interventions.
For clinical trials aimed at motor restoration, outcome measurement tools should be relevant to the anticipated targets of repair-enhanced rehabilitation. Most outcomes to date have been drawn from disease-specific and rehabilitation toolboxes. In studies that include participants who are more than a few weeks beyond acquiring profound impairments and disabilities, outcome measures will likely have to go beyond off-the-shelf tools that were not designed to detect modest clinical evidence of sensorimotor system repair. This chapter describes specific rehabilitation strategies and outcome assessments in the context of interfacing them with neurorestoration approaches.
[ ARTICLE] Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation – Full Text PDF
Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques.
The American Heart Association estimates that approximately 795,000 individuals in the United States have a stroke each year (Go et al., 2014). A lack of mobility is the main obstacle for stroke survivors seeking to regain daily living independence and social integration. Thus, restoring impaired gait is one of the major goals of post-stroke rehabilitation. Recently, traditional rehabilitation techniques have been augmented by the use of a new methodology, noninvasive brain stimulation (NIBS), which facilitates neuroplasticity. To better understand the use of NIBS, this paper reviews literature regarding the neurophysiology of human gait, poststroke neuroplasticity in the motor control system underlying gait, and finally, approaches for using NIBS to enhance gait recovery.
Neurophysiology of Human Gait
Involvement of the cerebral cortices: In functional neuroimaging studies of human walking, the premotor cortex (PMC) and the supplementary motor cortex (SMC) are activated prior to step onset (Huppert et al., 2013). However, lesions in these two areas often lead to problems with gait initiation and the negotiation of narrow passages (Jahn et al., 2004), indicating their importance in the initiation and planning of walking. Furthermore, corticospinal inputs significantly facilitate muscular responses in the lower limbs, especially during the swing phase of the step cycle (Pijnappels et al., 1998). These observations suggest that cortical outputs play a critical role in the modulation of lower limb locomotion…
[ARTICLE] Rehabilitation with Poststroke Motor Recovery: A Review with a Focus on Neural Plasticity – Full Text HTML
Motor recovery after stroke is related to neural plasticity, which involves developing new neuronal interconnections, acquiring new functions, and compensating for impairment. However, neural plasticity is impaired in the stroke-affected hemisphere. Therefore, it is important that motor recovery therapies facilitate neural plasticity to compensate for functional loss. Stroke rehabilitation programs should include meaningful, repetitive, intensive, and task-specific movement training in an enriched environment to promote neural plasticity and motor recovery. Various novel stroke rehabilitation techniques for motor recovery have been developed based on basic science and clinical studies of neural plasticity. However, the effectiveness of rehabilitative interventions among patients with stroke varies widely because the mechanisms underlying motor recovery are heterogeneous. Neurophysiological and neuroimaging studies have been developed to evaluate the heterogeneity of mechanisms underlying motor recovery for effective rehabilitation interventions after stroke. Here, we review novel stroke rehabilitation techniques associated with neural plasticity and discuss individualized strategies to identify appropriate therapeutic goals, prevent maladaptive plasticity, and maximize functional gain in patients with stroke.
Walking rehabilitation is one of the primary goals in stroke survivors because of its great potential for recovery and its functional relevance in daily living activities. Although 70% to 80% of people in the chronic poststroke phases are able to walk, impairment of gait often persists, involving speed, endurance, and stability.
Walking involves several brain regions, such as the sensorimotor cortex, supplementary motor area, cerebellum, and brainstem, which are approachable by the application of noninvasive brain stimulation (NIBS). NIBS techniques, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have been reported to modulate neural activity beyond the period of stimulation, facilitating neuroplasticity. NIBS methods have been largely applied for improving paretic hand motor function and stroke-associated cognitive deficits. Recent studies suggest a possible effectiveness of these techniques also in the recovery of poststroke gait disturbance. This article is a selective review about functional investigations addressing the mechanisms of lower-limb motor system reorganization after stroke and the application of NIBS for neurorehabilitation.
[Supplement] It Takes Two: Noninvasive Brain Stimulation Combined With Neurorehabilitation- Full Text
The goal of postacute neurorehabilitation is to maximize patient function, ideally by using surviving brain and central nervous system tissue when possible. However, the structures incorporated into neurorehabilitative approaches often differ from this target, which may explain why the efficacy of conventional clinical treatments targeting neurologic impairment varies widely.
Noninvasive brain stimulation (eg, transcranial magnetic stimulation [TMS], transcranial direct current stimulation [tDCS]) offers the possibility of directly targeting brain structures to facilitate or inhibit their activity to steer neural plasticity in recovery and measure neuronal output and interactions for evaluating progress. The latest advances as stereotactic navigation and electric field modeling are enabling more precise targeting of patient’s residual structures in diagnosis and therapy.
Given its promise, this supplement illustrates the wide-ranging significance of TMS and tDCS in neurorehabilitation, including in stroke, pediatrics, traumatic brain injury, focal hand dystonia, neuropathic pain, and spinal cord injury. TMS and tDCS are still not widely used and remain poorly understood in neurorehabilitation. Therefore, the present supplement includes articles that highlight ready clinical application of these technologies, including their comparative diagnostic capabilities relative to neuroimaging, their therapeutic benefit, their optimal delivery, the stratification of likely responders, and the variable benefits associated with their clinical use because of interactions between pathophysiology and the innate reorganization of the patient’s brain. Overall, the supplement concludes that whether provided in isolation or in combination, noninvasive brain stimulation and neurorehabilitation are synergistic in the potential to transform clinical practice.
The incidence of many neurologic diseases is rising partly because of an increasingly aged population and improved delivery and timing of acute care for neurologic disorders. As a result, more survivors are emerging from acute care, with most exhibiting life-altering impairments that require neurorehabilitation. One prominent example of this trend is stroke; taking into account both the years of potential life lost from premature death and long-term disability, stroke is also one of the most costly diseases, with 36% of this growing population exhibiting a discernable disability 5 years poststroke,1 and almost half of survivors remaining dependent on others 6 years poststroke because of the severity of their disability.2
The focus of medical teams during hyperacute and acute neurologic care is usually 3-fold: ensure survival/reduce mortality; manage and prevent medical complications; and when possible, salvage existing central nervous system tissue (eg, through the use of thrombolytics in stroke).3 In contrast, the goal of postacute neurorehabilitation is to maximize patient function, ideally by using surviving brain and central nervous system tissue when possible. However, despite their widely appreciated importance, the efficacy of conventional clinical treatments targeting specific neurologic impairments and sequelae vary widely. Again in the case of stroke, conventional rehabilitative strategies targeting upper extremity hemiparesis in adults offer negligible or no efficacy.4, 5
Recently developed neurorehabilitative strategies offer slightly more promise but remain limited because of the considerable time and resources that they require to administer. Perhaps the most notable example is constraint-induced movement therapy (CIMT), which has been applied to the affected upper extremity after stroke and other neurologic disorders (eg, multiple sclerosis, aphasia, traumatic brain injury [TBI]). One of the hallmarks of CIMT is long-duration training using an affected body part (eg, paretic upper extremity) or capacity (eg, speaking) that lasts up to 6 hours per day and is administered over multiple days (usually 10 consecutive weekdays). Although results have been promising,6 several studies7, 8 have found that most patients with stroke do not wish to participate in CIMT because of these long-duration treatment parameters, have reported high attrition rates,9 have reported poor compliance with the CIMT restrictive device wear,10, 11 and have reported on patient inability to participate in the entire 6-hour regimen as a result of fatigue.12 As a result of the required time, financial resources, and human resources, CIMT has not realized widespread clinical application.13, 14
Other new neurorehabilitative approaches being taught by training programs and/or adopted by clinics worldwide (eg, partial weight-supported treadmill training, certain automated and splinting approaches) offer negligible efficacy when compared with more conventional strategies15, 16, 17 and/or only work on patients displaying a particular level of impairment. As a result, there remains a gap centering on the need for techniques that extend the efficacy, duration of treatment effect, and/or number of patients who may benefit from promising neurorehabilitative therapies. Noninvasive brain stimulation offers the ability to meet all of these needs and offers efficacy as a stand-alone treatment approach for many neurologic impairments.
Low-intensity transcranial electrical stimulation (tES) methods are a group of noninvasive brain stimulation techniques, whereby currents are applied with intensities typically ranging between 1 and 2 mA, through the human scalp. These techniques have been shown to induce changes in cortical excitability and activity during and after the stimulation in a reversible manner. They include transcranial direct current simulation (tDCS), transcranial alternating current simulation (tACS), and transcranial random noise stimulation (tRNS).
Currently, an increasing number of studies have been published regarding the effects of tES on cognitive performance and behavior. Processes of learning and increases in cognitive performance are accompanied by changes in cortical plasticity. tES can impact upon these processes and is able to affect task execution. Many studies have been based on the accepted idea that by increasing cortical excitability (e.g., by applying anodal tDCS) or coherence of oscillatory activity (e.g., by applying tACS) an increase in performance should be detected; however, a number of studies now suggest that the basic knowledge of the mechanisms of action is insufficient to predict the outcome of applied stimulation on the execution of a cognitive or behavioral task, and so far no standard paradigms for increasing cortical plasticity changes during learning or cognitive tasks have been established.
The aim of this review is to summarize recent findings with regard to the effects of tES on behavior concentrating on the motor and visual areas…
Neuroplasticity is critical for learning, memory, and recovery of lost function following neurological damage. Noninvasive brain stimulation (NIBS) techniques can induce neuroplastic changes in the human cortex that are behaviorally relevant, raising the exciting possibility that these techniques might be therapeutically beneficial for neurorehabilitation following brain injury. However, the short duration and instability of induced effects currently limits their usefulness.
To date, trials investigating the therapeutic value of neuroplasticity-inducing NIBS have used either single or multiple treatment sessions, typically repeated once-daily for 1 to 2 weeks. Although multiple stimulation sessions are presumed to have cumulative effects on neuroplasticity induction, there is little direct scientific evidence to support this “once-daily” approach. In animal models, the repeated application of stimulation protocols spaced using relatively short intervals (typically of the order of minutes) induces long-lasting and stable changes in synaptic efficacy. Likewise, learning through spaced repetition facilitates the establishment of long-term memory. In both cases, the spacing interval is critical in determining the outcome.
Emerging evidence in healthy human populations suggests that the within-session spacing of NIBS protocols may be an effective approach for significantly prolonging the duration of induced neuroplastic changes. Similar to findings in the animal and learning literature, the interval at which spaced NIBS is applied seems to be a critical factor influencing the neuroplastic response. In this Point of View article, we propose that to truly exploit the therapeutic opportunities provided by NIBS, future clinical trials should consider the optimal spacing interval for repeated applications.