Non-invasive brain stimulation (rTMS and tDCS) in patients with aphasia: Mode of action at the cellular level

A high proportion of patients who have suffered a stroke also suffer from aphasia. Approximately half of those affected will remain in this state despite intensive language therapy. Non-invasive brain stimulation allows us to directly and focally stimulate areas of the brain. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), methods used in the treatment of aphasia, are based on an imbalance of mutual interhemispheric inhibition. In open and sham-controlled studies, a low-frequency, 1 Hz stimulation of the non-lesioned hemisphere (the homologue of Broca's area) for a week or more significantly improved spontaneous speech and anomia in patients with non-fluent aphasia. These positive outcomes from rTMS stimulation developed slowly, often over months following treatment, and persisted. Effects of intermittent theta burst stimulation (iTBS) developed faster than the low-frequency stimulation, and high-activity enhancement was detected in the left hemisphere after the stimulation of Broca's region. Both types of tDCS stimulation resulted in improved comprehension and reduced anomia, their primary modes of action are distinct, however, both share a common site of action with regard to the balance that occurs between inhibitory and excitatory neurotransmitters (synaptic and non-synaptic). Both types of non-invasive stimulation prepare the lesioned brain for better outcome.     

Treatment of depression with transcranial direct current stimulation (tDCS): A Review

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.     

Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice

BackgroundTranscranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home.ObjectiveTo provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use.MethodsProviding treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities.ResultsTo date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time.ConclusionThese guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.     

Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial

BackgroundDepression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy.ObjectiveTo conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression.MethodsIn this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum.ResultsOf 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04).ConclusionsResults support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).     

Alternate sessions of transcranial direct current stimulation (tDCS) reduce chronic pain in women affected by chikungunya. A randomized clinical trial

ContextThousands of people worldwide have been infected by the chikungunya virus (CHIKV), and the persistence of joint pain symptoms has been considered the main problem. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) act on brain areas involved in the processing of chronic pain. It was previously demonstrated that tDCS for five consecutive days significantly reduced pain in the chronic phase of chikungunya (CHIK).ObjectiveTo analyze the effect of alternate tDCS sessions on pain and functional capacity in individuals affected by CHIK.MethodsIn a randomized clinical trial, 58 women in the chronic phase of CHIK were divided into two groups: active-tDCS (M1-S0, 2 mA, 20 min) and sham-tDCS. The Visual Analogue Scale (VAS) and the Brief Pain Inventory (BPI) were used to assess pain, while the Health Assessment Questionnaire (HAQ) assessed functional capacity. These scales were used before and after six sessions of tDCS in nonconsecutive days on the primary motor cortex, and at follow-up consultation 7 and 15 days after the last session. A repeated measures mixed-model ANOVA was used for comparison between groups (significant p-values < 0.05).ResultsA significant pain reduction (Z [3, 171] = 14.303; p < 0.0001) was observed in the tDCS group compared to the sham group; no significant difference in functional capacity was observed (Z [1.57] = 2.797; p = 0.1).ConclusionOur results suggest that six nonconsecutive sessions of active tDCS on M1 reduce pain in chronic CHIKV arthralgia.     

Repetitive transcranial magnetic stimulation in treatment of post polio syndrome

Background

Post polio syndrome is a rare disease that occurs decades after polio virus infection. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness in drug resistant depression. Possibly it can be helpful in therapy of other neurological diseases including post polio syndrome.

A randomized,double blind,sham-controlled trial of repetitive transcranial magnetic stimulation (rTMS) in the treatment of negative symptoms in schizophrenia

BackgroundResearch has implicated hypofrontality in the pathogenesis of Negative symptoms of schizophrenia.These symptoms are often resistant to treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to reverse this hypofrontality. Higher frequency rTMS has shown better promise, but so far there has been very little research in this area.ObjectiveWe aimed to evaluate the efficacy of high-frequency (20 Hz) unilateral rTMS over the left Dorso-Lateral Pre-frontal Cortex (DLPFC) in the improvement of Negative symptoms in Schizophrenia. Methods:100 patients of schizophrenia with predominantly negative symptoms, were enrolled for this randomized, sham-controlled, double-blind trial.Each participant received 20 sessions of rTMS at 20 Hz frequency and 100% motor threshold, via either the active or the sham coil, over 4 weeks. A total of 2000 pulses were imparted in 10 trains per session. Negative symptoms were assessed with the SANS and PANSS. CDSS was used to rule out depressive symptoms. Assessments were carried out at baseline, post-intervention, and 1-month, 2-months, 3-months and 4-months follow ups.ResultsThe improvement in the negative symptoms (Anhedonia, Alogia, Avolition, Attention impairment) in active group was statistically significant at 0.01 and 0.05 (p-value) as compared to sham group.ConclusionsThese results suggest that high-frequency rTMS may lead to improvement in negative symptoms of schizophrenia. It may be worth considering its use as an adjunct to pharmacological treatment of negative symptoms.     

Recovery of motor disability and spasticity in post-stroke after repetitive transcranial magnetic stimulation (rTMS)

Lately it has been indicated that the stimulation of both sides of the motor cortices with different frequencies of rTMS can improve the behaviour of a paretic arm. We studied the effect of rTMS in severe cases of post-stroke after nearly 10 years. They had wide hemispheric lesion and their paresis had not changed for more than 5 years. The majority of patients could not move their fingers on the affected side. In our study we examined whether the active movement could be induced by rTMS even several years after stroke and which hemisphere (affected or unaffected) stimulated by rTMS would be the best location for attenuating the spasticity and for developing movement in the paretic arm.Sixty-four patients (more than 5 years after stroke in a stable state) were followed for 3 months. They were treated with rTMS with 1 Hz at 30% of 2.3 T 100 stimuli per session twice a day for a week. The area to be stimulated was chosen according to the evoked movement by TMS in the paretic arm. That way, four groups were created and compared. In group A, where both hemispheres were stimulated (because of the single stimulation of TMS could induce movement from both sides of hemispheres) the spasticity decreased but the movement could not be influenced. A highly significant improvement in spasticity, in movement induction and in the behaviour of paresis was observed in group B, where before treatment, there was no evoked movement in the paretic arm from stimulating either hemispheres of the brain. For treatment we stimulated the unaffected hemisphere from where the intact arm is moved (ipsilateral to the paretic side). In both groups C (contralateral hemisphere to the paretic arm) and D (ipsilaterally evoked movement in the paretic arm), the spasticity decreased during the first week, but the movement of the paretic arm improved only in group C.It seems that spasticity can be modified by the stimulation either the affected or the unaffected hemisphere, but the induction of movement can be achieved only by the stimulation of an intact motor pathway and its surrounding area (groups B and C). The improvement in paretic extremities can be achieved with rTMS even after years of stroke when the traditional rehabilitation has failed.     

Plasticity induced by non-invasive transcranial brain stimulation: A position paper

Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. Non-invasive transcranial brain stimulation may modulate cortical excitability outlasting the period of non-invasive transcranial brain stimulation itself from several minutes to more than one hour. Quite a few lines of evidence, including pharmacological, physiological and behavioral studies in humans and animals, suggest that the effects of non-invasive transcranial brain stimulation are produced through effects on synaptic plasticity. However, there is still a need for more direct and conclusive evidence. The fragility and variability of the effects are the major challenges that non-invasive transcranial brain stimulation currently faces. A variety of factors, including biological variation, measurement reproducibility and the neuronal state of the stimulated area, which can be affected by factors such as past and present physical activity, may influence the response to non-invasive transcranial brain stimulation. Work is ongoing to test whether the reliability and consistency of non-invasive transcranial brain stimulation can be improved by controlling or monitoring neuronal state and by optimizing the protocol and timing of stimulation.     

Concurrent conventional & high-definition transcranial direct current stimulation for treatment of schizophrenia with co-morbid obsessive-compulsive disorder: A case report

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.     

Effects of high-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex on motor recovery in severe hemiplegic stroke: A randomized clinical trial

BackgroundThe contralesional hemisphere compensation may play a critical role in the recovery of stroke when there is extensive damage to one hemisphere. There is little research on the treatment of hemiplegia by high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the contralesional cortex.ObjectiveWe conducted a 2-week randomized, sham-controlled, single-blind trial to determine whether high-frequency rTMS (HF-rTMS) over the contralesional motor cortex can improve motor function in severe stroke patients.MethodsForty-five patients with ischemic or hemorrhagic stroke in the middle cerebral artery territory were randomly assigned to treatment with 10 Hz rTMS (HF group), 1 Hz rTMS (LF group) or sham rTMS (sham group) applied over the contralesional motor cortex (M1) before physiotherapy daily for two weeks. The primary outcome was the change in the Fugl-Meyer Motor Assessment (FMA) Scale score from baseline to 2 weeks. The secondary endpoints included root mean square of surface electromyography (RMS-SEMG), Barthel Index (BI), and contralesional hemisphere cortical excitability.ResultsThe HF group showed a more significant improvement in FMA score (p < 0.05), BI (p < 0.005), contralesional hemisphere cortical excitability and conductivity (p < 0.05), and RMS-SEMG of the key muscles (p < 0.05) compared with the LF group and sham group. There were no significant differences between the LF group and sham group. There was a positive correlation between cortical conductivity of the uninjured hemisphere and recovery of motor impairment (p = 0.039).ConclusionsHF-rTMS over the contralesional cortex was superior to low-frequency rTMS and sham stimulation in promoting motor recovery in patients with severe hemiplegic stroke by acting on contralesional cortex plasticity.Trial registrationClinical trial registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn/showproj.aspx?proj=23264 (ChiCTR-IPR-17013580).     

A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique, which can be used to selectively disrupt patterns of neural activity that are associated with symptoms of mental illness. tDCS has been implemented in numerous therapeutic trials across a range of patient populations, with a rapidly increasing number of studies being published each year. This systematic review aimed to evaluate the efficacy of tDCS in the treatment of psychiatric disorders. Four electronic databases were searched from inception until December 2015 by two independent reviewers, and 66 eligible studies were identified. Depression was the most extensively researched condition, followed by schizophrenia and substance use disorders. Data on obsessive compulsive disorder, generalised anxiety disorder, and anorexia nervosa were also obtained. The quality of included studies was appraised using a standardised assessment framework, which yielded a median score corresponding to “weak” on the three-point scale. This improved to “moderate” when case reports/series were excluded from the analysis. Overall, data suggested that tDCS interventions comprising multiple sessions can ameliorate symptoms of several major psychiatric disorders, both acutely and in the long-term. Nevertheless, the tDCS field is still in its infancy, and several methodological and ethical issues must be addressed before clinical efficacy can truly be determined. Studies probing the mechanisms of action of tDCS and those facilitating the definition of optimised stimulation protocols are warranted. Furthermore, evidence from large-scale, multi-centre randomised controlled trials is required if the transition of this therapy from the laboratory to the clinic is to be considered.     

Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humans

Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (PM) modifies the excitability of the ipsilateral primary motor cortex (M1). Transcranial direct current stimulation (tDCS) is a new method to induce neuroplasticity in humans non-invasively. tDCS generates neuroplasticity directly in the cortical area under the electrode, but might also induce effects in distant brain areas, caused by activity modulation of interconnected areas. However, this has not yet been tested electrophysiologically. We aimed to study whether premotor tDCS can modify the excitability of the ipsilateral M1 via cortico-cortical connectivity. Sixteen subjects received cathodal and anodal tDCS of the PM and eight subjects of the dorsolateral prefrontal cortex. Premotor anodal, but not premotor cathodal or prefrontal tDCS, modified selectively short intracortical inhibition/intracortical facilitation (SICI/ICF), while motor thresholds, single test-pulse motor-evoked potential and input–output curves were stable throughout the experiments. Specifically, anodal tDCS decreased intracortical inhibition and increased paired-pulse excitability. The selective influence of premotor tDCS on intracortical excitability of the ipsilateral M1 suggests a connectivity-driven effect of tDCS on remote cortical areas. Moreover, this finding indirectly substantiates the efficacy of tDCS to modulate premotor excitability, which might be of interest for applications in diseases accompanied by pathological premotor activity.     

The effects of repetitive transcranial magnetic stimulation on eating behaviors and body weight in obesity: A randomized controlled study

Background

Although some studies have reported significant reductions in food cravings following repetitive transcranial magnetic stimulation (rTMS), none have examined changes in body weight.

Repetitive transcranial magnetic stimulation (rTMS) for depression: outcomes in a United Kingdom (UK) clinical practice

Objective: The aim of this paper is to present the outcomes data from the largest United Kingdom’s (UK) National Health Service (NHS) clinical rTMS service treating treatment resistant depression (TRD).

Methods: The study was a retrospective investigation of routinely collected data on patients receiving rTMS between 2015 and 2017. Measures used were the clinician-rated Clinical Global Impression (CGI) and Hamilton Depression Rating Scale (HAM-D), and patient rated Beck Depression Inventory (BDI). The outcome data of 73 patients with TRD were analysed. The sample included patients with co-morbid psychiatric diagnosis.

Results: Response and remission rates, respectively, were 40.4% and 25.5% for the HAM-D; 35.6% and 20.8% for the BDI; and 51.1% and 52.1% for the CGI. Effect sizes were medium (0.54, 0.52 and 0.56, respectively).

Conclusions: The results show that a UK-based clinical service achieves similar results to those published internationally and that clinical rTMS can have significant impact on symptoms of depression in many patients with TRD. Health services are under pressure to make financial savings, investment in rTMS could reduce the long-term treatment costs associated with TRD.     

The effects of repetitive transcranial magnetic stimulation on body weight and food consumption in obese adults: A randomized controlled study

BackgroundAlthough some studies have reported significant reductions in food cravings following the single-session of repetitive transcranial magnetic stimulation (rTMS), there is little research on the effects of multi-session of rTMS on food consumption and body weight in obese subjects.ObjectiveWe conducted 4-week randomized, sham-controlled, single-blind, parallel-group trial to examine the effect of rTMS on body weight in obese adults.MethodsForty-three obese patients (body mass index [BMI] ≥25 kg/m²) aged between 18 and 70 years were randomized to the sham or real treatment group (21 in the TMS group and 22 in the sham treatment group). A total of 8 sessions of rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) was provided over a period of 4 weeks. The primary outcome measure was weight change in kilograms from baseline to 4 weeks. Secondary endpoints included changes in anthropometric measures, cardiovascular risk factors, food intake, and appetite.ResultsParticipants in the rTMS group showed significantly greater weight loss from baseline following the 8 session of rTMS (−2.75 ± 2.37 kg vs. 0.38 ± 1.0 kg, p < 0.01). Consistent with weight loss, there was a significant reduction in fat mass and visceral adipose tissue at week 4 in the rTMS group compared with the control group (p < 0.01). After the 8 sessions of rTMS, the TMS group consumed fewer total kilocalories and carbohydrates per day than the control group (p < 0.05).Conclusions8 sessions of HF rTMS delivered to the left DLPFC were effective in inducing weight loss and decreasing food intake in obese patients.Trial registrationClinical trial registered with the Clinical Trials Registry at http://cris.cdc.go.kr (KCT0002548).     

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.

BACKGROUND: Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). METHODS: Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. RESULTS: The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. CONCLUSIONS: Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.     

Target specific effects of direct current stimulation in schizo-obsessive disorder: A case report

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation technique that is explored as an add-on treatment for the alleviation of symptoms across the diverse symptom domains in neuropsychiatric disorders. In psychiatry, data is emerging on the effects of tDCS as an add-on treatment in schizophrenia as well as obsessive-compulsive disorder (OCD). But despite high prevalence, the effectiveness of tDCS in co-morbid schizophrenia and OCD is lacking. This case report for the first time examines the clinical utility with target-specific effects of the add-on tDCS in a patient diagnosed with schizo-obsessive disorder.