Non-invasive Brain Stimulation Therapy Research Articles

Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice.

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

FC24: Transcranial Magnetic Stimulation (TMS) as a Treatment for Dementia due to non-Alzheimer’s disease (non-AD): What is the Evidence?

Objective:There is no cure for dementia due to non-Alzheimer’s disease (non-AD), and current treatments are symptomatic. Noninvasive brain stimulation therapies such as transcranial magnetic stimulation (TMS) are increasingly being investigated to improve cognitive function in dementia. We conducted a systematic review to investigate the effectiveness of TMS on cognition in non-AD dementia.Methods:Comprehensive search of databases (Medline, Embase, Cochrane, APA PsycINFO, Web of Science, and Scopus) from 2000 to February 2023 using keywords related to TMS and dementia (PROSPERO, CRD42022326423). Here we report outcomes from randomized controlled trials (RCTs) of TMS on non-AD dementia populations.Results:In total, 20 RCTs comprised of 660 patients, mean age 62 years (range 46-71). Diagnostic groups include stroke (n=8), Parkinson’s disease (n=6), Frontotemporal dementia (n=3), Huntington’s disease (n=2) and Progressive non-fluent aphasia (n=1). The most common site of stimulation was left (L) dorsolateral prefrontal cortex (DLPFC, n=13); other sites were primary motor cortex (n=2); Right (R) Broca's area, Brodmann area, Contralesional pars triangularis, R Inferior Frontal Gyrus (IFG) (all n=1); and multiple sites in 1 RCT (L and R IFG, L superior frontal gyrus, L DLPFC, L and R right anterior temporal lobe, supplementary motor area, anterior cingulate, and vertex). Studies used both low (1Hz, n=5) and high (50Hz, n=5) frequencies, or other high (5Hz, 10Hz, 20Hz) or combination low/high frequencies. Frequent duration of treatment was 10 days (n=7), range 1-40. Of 20 studies, 19 (95%) demonstrated improvement of global cognition (on MoCA, MMSE) and specific cognitive domains (learning and memory, language, executive function, problem-solving, attention, reaction time). The only RCT with no effect utilized a single session intermittent theta burst stimulation on the LDLPFC on PD patients. Adverse events in 7 studies included headaches (most common), dull skull pain, dizziness, insomnia, fatigue, anxiety, temporary decrease in hearing, and temporary decreased mental clarity.Conclusion:There is favorable evidence that rTMS improves global and specific cognitive domains in non-AD dementia. Left DLPFC is the most common stimulation site, both low- and high-frequency are utilized, and 10 sessions is frequently used. Further studies are needed to determine optimal TMS treatments in cognitively impaired populations

Effectiveness of Low Frequency Noninvasive Brain Stimulation Therapy for Improving Neuropsychological and Neurophysiological Functions: A Systematic Review

Effectiveness of Low Frequency Noninvasive Brain Stimulation Therapy for Improving Neuropsychological and Neurophysiological Functions: A Systematic Review

Direct changes of neurometabolic concentrations in the pregenual anterior cingulate cortex among obsessive-compulsive patients after repetitive transcranial magnetic stimulation treatment

Background and aimAlthough Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising new noninvasive brain stimulation therapy, its underlying mechanisms of action remain unknown. OCD patients exhibit impaired response control and attention shifting, which is linked to some brain areas such as anterior cingulate cortex and basal ganglia. OCD patients also display altered neurometabolic concentrations in cortical cortical-striatal-thalamic-cortical (CSTC). In this study, we aimed to elucidate efficacy of rTMS treatment in alleviating related symptoms and pregenual anterior cingulate cortex (pACC) neurometabolites. MethodsOCD patients were randomly divided into either drug (n = 23) or drug + rTMS (n = 29) groups, and those in the latter group subjected to 4-week rTMS treatment. All participants were visited twice, at baseline and follow-up after four weeks. During both visits, all patients were subjected to 1H-MRS, then Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Global Assessment Function (GAF) used to assess severity of obsessive-compulsive symptoms. We also evaluated synchronous anxiety and depression by Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Scale (HAM-D). ResultsAfter 4 weeks of treatment, patients in the Drug + rTMS group displayed significantly lower Y-BOCS (p = 0.038), BDI (p = 0.009), HAM-D (p = 0.013), HAM-A (p = 0.012) scores than their counterparts in the Drug group. Conversely, patients in the Drug + rTMS group had significantly higher tNAA concentrations (p = 0.030) than those in the Drug group. Notably, the Drug + rTMS group exhibited higher, but insignificant Glu (p = 0.055) and Glx (p = 0.068) concentrations compared to the Drug group. Partial correlation analysis revealed a significant negative correlation between post HAM-A scores and 4-week change of pACC glutamate levels in the Drug + rTMS group (r = −0.434, p = 0.02). ConclusionrTMS treatment is an efficacious treatment therapy for OCD, mainly by inducing changes in neurometabolites.

Comparative efficacy of different noninvasive brain stimulation therapies for recovery of global cognitive function, attention, memory, and executive function after stroke: a network meta-analysis of randomized controlled trials.

Which noninvasive brain stimulation (NIBS) treatment - transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) - is more beneficial for stroke patients' cognitive rehabilitation is still up for debate. Our goal is to provide an overview of the research on the effectiveness and safety of various NIBS protocols. Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs). This NMA compared any active NIBS versus sham stimulation in adult stroke survivors to enhance cognitive function, with a focus on global cognitive function (GCF), attention, memory, and executive function (EF) using the databases MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. The NMA statistical approach was built on a frequency framework. The effect size was estimated by the standardized mean difference (SMD) and a 95% confidence interval (CI). We compiled a relative ranking of the competing interventions based on their surface under the cumulative ranking curve (SUCRA). NMA showed that high-frequency repeated TMS (HF-rTMS) improved GCF compared with sham stimulation (SMD = 1.95; 95% CI: 0.47-3.43), while dual-tDCS improved memory performance versus sham stimulation significantly (SMD = 6.38; 95% CI: 3.51-9.25). However, various NIBS stimulation protocols revealed no significant impact on enhancing attention, executive function, or activities of daily living. There was no significant difference between the active stimulation protocols for TMS and tDCS and sham stimulation in terms of safety. Subgroup analysis demonstrated an effect favoring activation site of the left dorsolateral prefrontal cortex (DLPFC) (SUCRA = 89.1) for enhancing GCF and bilateral DLPFC (SUCRA = 99.9) stimulation for enhancing memory performance. The HF-rTMS over the left DLPFC appears to be the most promising NIBS therapeutic option for improving global cognitive performance after stroke, according to a comparison of numerous NIBS protocols. Furthermore, for patients with post-stroke memory impairment, dual-tDCS over bilateral DLPFC may be more advantageous than other NIBS protocols. Both tDCS and TMS are reasonably safe. PROSPERO ID: CRD42022304865.

Non-invasive brain stimulation therapy on neurological symptoms in patients with multiple sclerosis: A network meta analysis

The aim of the study was to evaluate non-invasive brain stimulation (NIBS) [including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES)] on neurological symptoms in patients with multiple sclerosis (PwMS). We searched PubMed, Embase, Cochrane Library, Web of Science and Ovid MEDLINE until February 2022. And we evaluated the included studies for methodological quality by the Cochrane bias risk assessment tool and assessed the studies' certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We performed network meta analysis (NMA) by using Stata 15 and ranked the results of the NMA by using the surface under the cumulative ranking curve (SUCRA) ranking chart. Twenty seven clinical trials were finally included (N = 596, 66.4% women). For the immediate effects, rTMS over M1 yielded the most optimal scheme for fatigue reduction among all the interventions compared to the sham stimulation groups [MD = -0.85, 95% CI (-1.57, -0.14)] (SUCRA = 82.6%). iTBS over M1 yielded the most signifcant reduced pain level than the sham groups did [MD = -1.26, 95% CI (-2.40, -0.11)] (SUCRA = 98.4%). tDCS over F3 was the best protocol of NIBS to improve quality of life (QOL) [MD = 1.41, 95% CI = (0.45,2.36)] (SUCRA = 76.7%), and iTBS over M1 may significantly reduce spasticity compared to sham stimulation [MD = -1.20, 95% CI = (-1.99, -0.41)] (SUCRA = 90.3%). Furthermore, rTMS, tRNS, and tDCS on certain areas may improve PwMS accuracy, response time, manual dexterity, pain relief and QOL, but does not show statistically significant differences. The evidence assessed using GRADE is very low. Based on the NMA and SUCRA ranking, we can conclude that symptoms including fatigue, pain, spasticity, and QOL can be improved by following NIBS protocol after treatment. Nonetheless, most of the included studies lack a good methodology, and more high-quality randomized clinical trials are needed.

Potential Targets for Noninvasive Brain Stimulation on Depersonalization-Derealization Disorder.

Introduction: Non-invasive brain stimulation seems to be beneficial for DPD patients. However, the sites used in previous studies were empirical. Exploring new stimulation locations via functional magnetic resonance imaging may improve the efficacy. Objectives: The objective was to find potential locations for non-invasive brain stimulation on the depersonalization-derealization disorder. Methods: We explored the potential brain surface regions from three pipelines: pipeline 1: activation likelihood estimation meta-analysis (five studies with 36 foci included); pipeline 2: functional connectivity analysis based on DPD-network (76 subjects included); and pipeline 3: functional connectivity analysis based on DPD regions of interest from the meta-analysis. Potential targets were the 10–20 system coordinates for brain surface regions. Results: We identified several potential brain surface regions, including the bilateral medial prefrontal cortex, dorsal lateral prefrontal cortex, superior parietal gyrus, superior temporal gyrus, and right ventrolateral prefrontal cortex as potential sites. Conclusion: Our findings of the potential stimulation targets might help clinicians optimize the application of non-invasive brain stimulation therapy in individuals with DPD.

Noninvasive Brain Stimulation Therapies to Promote Recovery of Consciousness: Where We Are and Where We Should Go.

Therapeutic options for patients with disorders of consciousness (DoC) are still underexplored. Noninvasive brain stimulation (NIBS) techniques modulate neural activity of targeted brain areas and hold promise for the treatment of patients with DoC. In this review, we provide a summary of published research using NIBS as therapeutic intervention for DoC patients, with a focus on (but not limited to) randomized controlled trials (RCT). We aim to identify current challenges and knowledge gaps specific to NIBS research in DoC. Furthermore, we propose possible solutions and perspectives for this field. Thus far, the most studied technique remains transcranial electrical stimulation; however, its effect remains moderate. The identified key points that NIBS researchers should focus on in future studies are (1) the lack of large-scale RCTs; (2) the importance of identifying the endotypes of responders; and (3) the optimization of stimulation parameters to maximize the benefits of NIBS.

Potential Locations for Non-Invasive Brain Stimulation in Treating Schizophrenia: A Resting-State Functional Connectivity Analysis.

Introduction: Non-invasive brain stimulation (NIBS) techniques have been widely used for the purpose of improving clinical symptoms of schizophrenia. However, the ambiguous stimulation targets may limit the efficacy of NIBS for schizophrenia. Exploring effective stimulation targets may improve the clinical efficacy of NIBS in schizophrenia.Methods: We first conducted a neurosynth-based meta-analysis of 715 functional magnetic resonance imaging studies to identify schizophrenia-related brain regions as regions of interest. Then, we performed the resting-state functional connectivity analysis in 32 patients with first-episode schizophrenia to find brain surface regions correlated with the regions of interest in three pipelines. Finally, the 10–20 system coordinates corresponding to the brain surface regions were considered as potential targets for NIBS.Results: We identified several potential targets of NIBS, including the bilateral dorsal lateral prefrontal cortex, supplementary motor area, bilateral inferior parietal lobule, temporal pole, medial prefrontal cortex, precuneus, superior and middle temporal gyrus, and superior and middle occipital gyrus. Notably, the 10-20 system location of the bilateral dorsal lateral prefrontal cortex was posterior to F3 (F4), not F3 (F4).Conclusion: Conclusively, our findings suggested that the stimulation locations corresponding to these potential targets might help clinicians optimize the application of NIBS therapy in individuals with schizophrenia.

Repetitive Transcranial Magnetic Stimulation for Patients with Fibromyalgia: A Systematic Review with Meta-Analysis.

Fibromyalgia is a poorly understood pain syndrome. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy and is commonly applied for the management of fibromyalgia. However, controversy about its efficacy remains. Therefore, a meta-analysis was conducted to evaluate the effectiveness of rTMS for fibromyalgia syndrome. Four medical databases and one physiotherapy database were screened for randomized controlled trials. A systematic review and meta-analysis was performed. Numerical Pain Rating Scale (NPRS) score, Beck Depression Inventory (BDI) score, Hospital Anxiety and Depression Scale (HADS) anxiety score, Pain Catastrophizing Scale (PCS) score, Fatigue Severity Scale (FSS) score, Short Form-36 General Health Survey mental score, and Fibromyalgia Impact Questionnaire (FIQ) score were set as outcome measures. Analysis of 14 studies and 433 participants indicated that rTMS exerted more favorable effects than did sham rTMS after treatment on the NPRS (standardized mean difference = -0.49, 95% confidence interval = -0.86 to -0.13, P = 0.008, I2 = 68%) and the FIQ (standardized mean difference = -0.50, 95% confidence interval = -0.75 to -0.25, P = 0.0001, I2 = 28%). However, the BDI, FSS, PCS, mood index, and HADS scores showed no significant difference compared with sham rTMS after treatment. The mean methodological quality of the included studies was an acceptable score of 8.5 based on the PEDro scale, suggesting the validity of our conclusions. This study demonstrated that rTMS relieved pain and enhanced the quality of life of patients with fibromyalgia; however, on the basis of current reports, it did not improve anxiety, depression, or other symptoms.

How non-invasive brain stimulation therapy may influence the fatigue of patients with multiple sclerosis

How non-invasive brain stimulation therapy may influence the fatigue of patients with multiple sclerosis

How non-invasive brain stimulation therapy may influence the fatigue of patients with multiple sclerosis

How non-invasive brain stimulation therapy may influence the fatigue of patients with multiple sclerosis

Effect of non-invasive brain stimulation on behavior and serum brain-derived neurotrophic factor and insulin-like growth factor-1 levels in autistic patients.

Aberrant neural connectivity and intra-cortical inhibitory dysfunction are key features of autism. Non-invasive brain stimulation (NIBS) protocols have been proposed that modulate this aberrant plasticity. However, additional investigations are needed to evaluate the impact of this intervention on biological biomarkers of the disease. We recently demonstrated alterations in serum insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) immunoreactivity in subjects with autism compared to controls. The aim of this pilot study was to explore the change in serum levels of the neurotrophic factors BDNF and IGF-1 in patients undergoing NIBS therapy. Sixteen subjects with autism spectrum disorder (ASD) were tested 1 week before and 1 week after NIBS to determine the short-term outcome on behavior using the total score on the autism behavior checklist, autism treatment evaluation checklist, clinical global impression severity and the autism diagnostic interview. ASD subjects younger than 11 years old (n=11) were treated with transcranial direct current stimulation (tDCS), and those 11 years and older (n=5) were treated with repetitive transcranial magnetic stimulation (rTMS). Serum levels of BDNF and IGF-1 were evaluated by Enzyme-Linked Immuno-Sorbent Assay before and after the intervention with NIBS. A significant reduction in scores on the clinical behavioral scales was observed in patients treated with NIBS (ABC-T p=.002, CGI-S p=.008, ADI-T and ATEC-T p < .0001). There was a trend towards reduced serum BDNF levels after NIBS (p=.061), while there was no change in IGF-1 levels. These data support further studies on the potential of BDNF as a biomarker to measure the effectiveness of NIBS in autism.

From adults to pediatrics: A review noninvasive brain stimulation (NIBS) to facilitate recovery from brain injury.

Stroke is a major problem worldwide that impacts over 100 million adults and children annually. Rehabilitation therapy is the current standard of care to restore functional impairments post-stroke, however its effects are limited and many patients suffer persisting functional impairments and life-long disability. Noninvasive Brain Stimulation (NIBS) has emerged as a potential rehabilitation treatment option in both adults and children with brain injury. In the last decade, Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCS) and Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) have been investigated to improve motor recovery in adults post-stroke. These promising adult findings using NIBS, however, have yet to be widely translated to the area of pediatrics. The limited studies exploring NIBS in children have demonstrated safety, feasibility, and utility of stimulation-augmented rehabilitation. This chapter will describe the mechanism of NIBS therapy (cortical excitability, neuroplasticity) that underlies its use in stroke and motor function and how TMS, tDCS, and taVNS are applied in adult stroke treatment paradigms. We will then discuss the current state of NIBS in early pediatric brain injury and will provide insight regarding practical considerations and future applications of NIBS in pediatrics to make this promising treatment option a viable therapy in children.

Burst Motor Cortex Stimulation Evokes Sustained Suppression of Thalamic Stroke Pain: A Narrative Review and Single-Case Overview.

Chronic refractory central post-stroke pain (CPSP), one of the most disabling consequences of cerebral stroke, occurs in up to 10% of patients with CPSP. Because a considerable proportion of these patients with chronic pain remain resistant to pharmacological and behavioral therapies, adjunctive invasive and non-invasive brain stimulation therapies are needed. We performed a review of human studies applying burst and conventional motor cortex stimulation (burstMCS and cMCS, respectively) for chronic pain states, on the basis of data sources identified through searches of PubMed, MEDLINE/OVID, and SCOPUS, as well as manual searches of the bibliographies of known primary and review articles. Our aim was to review and discuss clinical data on the indications of burstMCS for various chronic pain states originating from central stroke (excluding trigeminal facial pain). In addition, we assessed the efficacy and safety of burst versus cMCS for central post-stroke pain with an extended follow-up of 5 years in a 60-year-old man. According to our review, uncontrolled observational human cohort studies and one RCT using cMCS waveforms have revealed a meaningful clinical response; however, these studies lacked placebo groups and extended observation periods. In our case report, we found that 3 months of adjunctive cMCS reduced pain levels [visual analog scale (VAS) pre: 9/10 versus VAS post 7/10], whereas the pain decreased further under burstMCS (VAS pre: 7/10 versus VAS post: 2/10); the study involved a follow-up of 5 years and the following parameters: burst rate 40 Hz (500 Hz), 1–1.75 mA, 1 ms, bipolar configuration. To date, only limited evidence exists for the efficacy and safety of burst motor cortex stimulation for the treatment of refractory chronic pain. BurstMCS resulted in significantly decreased post-stroke pain observed after 5 years of cMCS. The available literature suggests similar efficacy as that of conventional (tonic) motor cortex stimulation, although the results are preliminary. Mechanistically, the precise mechanism of action is not fully understood. However, burstMCS may interact with the nociceptive thalamic-cingulate and descending spinal pain networks. To determine the potential utility of this treatment, large-scale sham-controlled trials comparing cMCS and burstMCS are highly recommended.Supplementary InformationThe online version of this article (10.1007/s40122-020-00221-0) contains supplementary material, which is available to authorized users.

Association of Central Noninvasive Brain Stimulation Interventions With Efficacy and Safety in Tinnitus Management

Tinnitus has a prevalence of 10% to 25% and is frequently associated with numerous complications, such as neuropsychiatric disease. Traditional treatments have failed to meet the needs of patients with tinnitus. Noninvasive brain stimulation (NIBS) can focally modify cortical functioning and has been proposed as a strategy for reducing tinnitus severity. However, the results have been inconclusive. To evaluate the association between different central NIBS therapies and efficacy and acceptability for treatment of tinnitus. ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, and Web of Science databases were searched from inception to August 4, 2019. No language restriction was applied. Manual searches were performed for potentially eligible articles selected from the reference lists of review articles and pairwise meta-analyses. Randomized clinical trials (RCTs) examining the central NIBS method used in patients with unilateral or bilateral tinnitus were included in the current network meta-analysis. The central NIBS method was compared with sham, waiting list, or active controls. Studies that were not clinical trials or RCTs and did not report the outcome of interest were excluded. Two authors independently screened the studies, extracted the relevant information, and evaluated the risk of bias in the included studies. In cases of discrepancy, a third author became involved. If manuscript data were not available, the corresponding authors or coauthors were approached to obtain the original data. This network meta-analysis was based on the frequentist model. The primary outcome was change in the severity of tinnitus. Secondary outcomes were changes in quality of life and the response rate related to the NIBS method in patients with tinnitus. Overall, 32 unique RCTs were included with 1458 unique participants (mean female proportion, 34.4% [range, 0%-81.2%]; mean age, 49.6 [range, 40.0-62.8] years; median age, 49.8 [interquartile range, 48.1-52.4] years). The results of the network meta-analysis revealed that cathodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex combined with transcranial random noise stimulation over the bilateral auditory cortex was associated with the greatest improvement in tinnitus severity (standardized mean difference [SMD], -1.89; 95% CI, -3.00 to -0.78) and quality of life (SMD, -1.24; 95% CI, -2.02 to -0.45) compared with the controls. Improvement in tinnitus severity ranked more favorably for continuous theta-burst stimulation (cTBS) over both auditory cortices (SMD, -0.79; 95% CI = -1.57 to -0.01) than cTBS over only the left auditory cortex (SMD, -0.30; 95% CI, -0.87 to 0.28), compared with controls. Repetitive transcranial magnetic stimulation with priming had a superior beneficial association with tinnitus severity compared with the strategies without priming. None of the investigated NIBS types had a significantly different dropout rate compared with that of the control group. This network meta-analysis suggests a potential role of NIBS interventions in tinnitus management. Future large-scale RCTs focusing on longer follow-up and different priming procedure NIBS are warranted to confirm these findings.

Non-invasive brain stimulation therapies

Noninvasive brain stimulation therapies are a promising field for the development of new protocols for the treatment of neuropsychiatric disorders. They are based on the stimulation of neural networks with the intent of modeling their synaptic activity to adequate levels. For this, it is necessary to precisely determine which networks are related to which brain functions, and the normal activation level of each of these networks, so that it is possible to direct the stimulation to the affected networks in order to induce the desired effects. These relationships are under intense investigation by the scientific community, and will contribute to the advancement of treatments by neurostimulation, with the emergence of increasingly accurate and effective protocols for different disorders. Currently, the most used techniques are Transcranial Direct Current Stimulation and Transcranial Magnetic Stimulation, with the most common applications being for treating Major Depressive Disorder. The advancement of research in this field may determine new target networks for stimulation in the treatment of other disorders, extending the application of these techniques and also our knowledge about brain functioning.

The Effects of Transcranial Direct Current Stimulation on Chronic Ankle Instability.

Given maladaptive neuroplasticity after musculoskeletal injury, interventions capable of restoring corticospinal excitability should be considered. We therefore aimed to determine if a 4-wk intervention of anodal transcranial direct current stimulation (aTDCS) with eccentric exercise would improve neural excitability, functional performance, and patient-reported function in individuals with chronic ankle instability (CAI). Twenty-six individuals with CAI were recruited to undergo 4 wk of eccentric evertor strengthening. Subjects were randomized into aTDCS (n = 13) and sham (n = 13) groups, where the aTDCS group received 18 min of aTDCS (1.5 mA) over the primary motor cortex. Participants were assessed for cortical excitability, dynamic balance, muscle activation, functional performance, strength, and patient-reported function at baseline, week 2, week 4, and week 6. Twenty-two subjects completed the training and test sessions. Cortical excitability (resting motor threshold) to peroneus longus in aTDCS increased from baseline (36.92 ± 11.53) to week 6 (32.91 ± 12.33, P = 0.024), whereas sham increased excitability from baseline (36.67 ± 12.74) to week 2 (27.86 ± 14.69, P = 0.007), but decreased at week 4 (35.63 ± 13.10, P = 0.022) and week 6 (35.99 ± 13.52, P = 0.006). Dynamic balance and muscle activation also improved in the aTDCS group from baseline to week 6 (P = 0.034). Functional performance on a side-hop test increased in all participants from baseline to week 2 (P = 0.003). The aTDCS group had decreased perceived disablement from week 2 (18.09 ± 6.41) to week 4 (15.55 ± 4.82, P = 0.046), whereas the sham group reported increased disablement from baseline (17.91 ± 4.59) to week 2 (21.00 ± 8.52, P = 0.047). Our results provide preliminary evidence that 4 wk of eccentric training with aTDCS improves cortical excitability, functional performance, and patient-reported function in individuals with CAI. These data are the first to show the efficacy of noninvasive brain stimulation therapies in patients with musculoskeletal injury, and demonstrate the link between improved neural excitability and functional outcomes.

Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals

Substance use disorders (SUDs) impose severe negative impacts upon individuals, their families, and society. Clinical studies demonstrate that some chronic stimulant users are able to curtail their drug use when faced with adverse consequences while others continue to compulsively use drugs. The mechanisms underlying this dichotomy are poorly understood, which hampers the development of effective individualized treatments of a disorder that currently has no Food and Drug Administration-approved pharmacological treatments. In the present study, using a rat model of methamphetamine self-administration (SA) in the presence of concomitant foot shocks, thought to parallel compulsive drug taking by humans, we found that SA behavior correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal "go" circuit and a decreased prelimbic cortex-ventrolateral striatal "stop" circuit. Critically, this correlation was seen only in rats who continued to self-administer at a relatively high rate despite receiving foot shocks of increasing intensity. While the stop circuit functional connectivity became negative after repeated SA in all rats, "shock-resistant" rats showed strengthening of this negative connectivity after shock exposure. In contrast, "shock-sensitive" rats showed a return toward their baseline levels after shock exposure. These results may help guide novel noninvasive brain stimulation therapies aimed at restoring the physiological balance between stop and go circuits in SUDs.

Therapeutic Intervention for Visuo-Spatial Neglect after Stroke: A Meta-Analysis of Randomized Controlled Trials.

ObjectivesThe aims of this meta-analysis were to examine intervention methods of qualitatively, well-designed studies from the past 10 years for treating visuo-spatial neglect (VSN) in patients who had suffered a stroke, and to evaluate the combined effects of intervention.MethodsStudies published between 2008 and 2017 on the theme of VSN were collected from PubMed, CINAHL, and MEDLINE, representative academic databases and search engines. The PEDro scale was used for evaluating the quality of methodology. The sample size, mean, and standard deviation of identified studies were used for meta-analysis.ResultsEight studies were selected for analysis. The PEDro scores of the selected studies were ≥ 7, with 237 subjects analyzed. The results of intervention were classified into “mental function” and “activity and participation” based on the International Classification of Functioning, Disability and Health. The analyzed effect sizes for combined outcomes, mental function and, activity and participation, were 0.728 (medium effect size), 0.850 (large effect size), and 0.536 (medium effect size), respectively.ConclusionIntervention methods for treating VSN had a short-term effect on cognitive function (visual perception). In particular, non-invasive brain stimulation therapy showed a large effect size for VSN treatment.