Sham Stimulation Group Research Articles

Repetitive transcranial magnetic stimulation for prophylactive treatment of chronic migraine: A randomised, single-blind, parallel-group, sham-controlled trial

Background: Pilot studies suggest that repetitive transcranial magnetic stimulation could be effective in migraine. We studied its efficacy for prophylaxis of chronic migraine. Methods: We undertook a randomised, single-blind, sham-controlled study in patients with chronic migraine. Subjects were randomly allocated to sham, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) or low-frequency repetitive transcranial magnetic stimulation (LF-rTMS). The primary outcome was the reduction of attacks at four weeks. In addition, reduction of severity of headache based on the Visual Analogue Scale score at two & four weeks and a functional disability score at four weeks was recorded. Results: One hundred and eight patients were allocated to sham stimulation (n=36), HF-rTMS (n=36) and LF-rTMS (n=36) groups. The number of attacks per month decreased to 7.05+/-1.45 at four weeks post-rTMS in the HF-rTMS (p<0.001) as compared to the LF-rTMS (10.61+/-1.69) and sham (10.83+/-3.37) groups. The VAS score in the HF-rTMS group was significantly lowered (p < 0.001) from 8.61+/-1.15 at baseline to 6.63+/-0.96, and 7.19+/-0.98 at two and four weeks respectively. The duration of headache in hours over 4 weeks reduced from 32.4+/-14.9 to 11.6+/-6.14 in the HF-rTMS group (p<0.001), but did not change significantly in the LF-rTMS (30.4+/-11.9 to 27.8+/-14, p>0.05) and sham (26.8+/-11.06 to 37+/-15, p>0.05) in sham groups. There was no significant difference in functional disability between all the study groups at four weeks. Conclusion: High-frequency, but not low-frequency, repetitive transcranial magnetic stimulation may be useful in management of chronic migraine.

Investigating the Optimal Initiation Time of Ultrasound Therapy for Peripheral Nerve Regeneration after Axonotmesis in Rats.

This study was aimed at identifying the optimal initiation time of ultrasound (US) therapy for peripheral nerve regeneration after axonotmesis. Thirty-six rats with sciatic nerve crush injury were divided into four groups that received US irradiation initiated 1, 7 or 14 d after injury, or sham stimulation for 4 wk. Motor function analysis was conducted weekly; however, there was no significant improvement attributed to US treatment. Four weeks after injury, compound muscle action potential amplitude values of the group in which US irradiation was initiated 1 d after the injury exhibited significant improvement compared with the sham stimulation group. In addition, myelin sheath thickness was significantly greater in the 1-d group than in other groups. These results indicate that US treatment initiated 1 d after peripheral nerve injury promotes maximum regeneration.

Metaboreflex Activity is Attenuated by Transcutaneous Electrical Nerve Stimulation and Interferential Electrical Stimulation in Healthy Individuals

Background: Transcutaneous electrical nervous stimulation (TENS) and interferential electrical stimulation (IES) attenuates muscle metaboreflex by sympathetic nervous modulation. Objective: We tested the hypothesis that IES may be more effective than TENS to improves blood flow which may be linked to greater of deep tissue. Methods: Eleven health subjects were randomized to TENS (80 Hz, 150μs), IES (4000 Hz, ΔAMF=25 Hz) or sham stimulation group, during 30 minutes. The acute intervention was applied on stellate ganglion region (C7-T4). Results: Were measured metaboreflex activity by calf vascular resistance (CVR) and calf blood flow (CBF) and HRV during three times: rest, exercise (static handgrip) and postexercise circulatory occlusion (PECO+ and PECO-). At the exercise peak, compared with TENS and Sham, the IES group reduced CVR (36 ± 3 vs 43 ± 3; p<0.05) and increased CBF (p<0.01). Also, IES was associated with a greater reduction on the MMA (IES: 9 ± 2, TENS: 14 ± 4, Sham: 26 ± 5 units; p<0.01). Furthermore, the IES group had a higher reduction of LF/HF ratio during PECO- and PECO+ (p<0.05). Conclusion: The IES over the stellate ganglion region seems to have superior efficacy compared with TENS to attenuate metaboreflex activation and vasodilatory responses during exercise in healthy subjects.

Low-Frequency Repetitive Transcranial Magnetic Stimulation Restores Dynamic Functional Connectivity in Subcortical Stroke.

Background and Purpose: Strokes consistently result in brain network dysfunction. Previous studies have focused on the resting-state characteristics over the study period, while dynamic recombination remains largely unknown. Thus, we explored differences in dynamics between brain networks in patients who experienced subcortical stroke and the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on dynamic functional connectivity (dFC).Methods: A total of 41 patients with subcortical stroke were randomly divided into the LF-rTMS (n = 23) and the sham stimulation groups (n = 18). Resting-state functional MRI data were collected before (1 month after stroke) and after (3 months after stroke) treatment; a total of 20 age- and sex-matched healthy controls were also included. An independent component analysis, sliding window approach, and k-means clustering were used to identify different functional networks, estimate dFC matrices, and analyze dFC states before treatment. We further assessed the effect of LF-rTMS on dFCs in patients with subcortical stroke.Results: Compared to healthy controls, patients with stroke spent significantly more time in state I [p = 0.043, effect size (ES) = 0.64] and exhibited shortened stay in state II (p = 0.015, ES = 0.78); the dwell time gradually returned to normal after LF-rTMS treatment (p = 0.015, ES = 0.55). Changes in dwell time before and after LF-rTMS treatment were positively correlated with changes in the Fugl–Meyer Assessment for Upper Extremity (pr = 0.48, p = 0.028). Moreover, patients with stroke had decreased dFCs between the sensorimotor and cognitive control domains, yet connectivity within the cognitive control network increased. These abnormalities were partially improved after LF-rTMS treatment.Conclusion: Abnormal changes were noted in temporal and spatial characteristics of sensorimotor domains and cognitive control domains of patients who experience subcortical stroke; LF-rTMS can promote the partial recovery of dFC. These findings offer new insight into the dynamic neural mechanisms underlying effect of functional recombination and rTMS in subcortical stroke.Registration: http://www.chictr.org.cn/index.aspx, Unique.identifier: ChiCTR1800019452.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment.Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls.Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively.Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment.Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Robotic Kinematic measures of the arm in chronic Stroke: part 1 \u2013 Motor Recovery patterns from tDCS preceding intensive training

BackgroundEffectiveness of robotic therapy and transcranial direct current stimulation is conventionally assessed with clinical measures. Robotic metrics may be more objective and sensitive for measuring the efficacy of interventions on stroke survivor’s motor recovery. This study investigated if robotic metrics detect a difference in outcomes, not seen in clinical measures, in a study of transcranial direct current stimulation (tDCS) preceding robotic therapy. Impact of impairment severity on intervention response was also analyzed to explore optimization of outcomes by targeting patient sub-groups.MethodsThis 2020 study analyzed data from a double-blind, sham-controlled, randomized multi-center trial conducted from 2012 to 2016, including a six-month follow-up. 82 volunteers with single chronic ischemic stroke and right hemiparesis received anodal tDCS or sham stimulation, prior to robotic therapy. Robotic therapy involved 1024 repetitions, alternating shoulder-elbow and wrist robots, for a total of 36 sessions. Shoulder-elbow and wrist kinematic and kinetic metrics were collected at admission, discharge, and follow-up.ResultsNo difference was detected between the tDCS or sham stimulation groups in the analysis of robotic shoulder-elbow or wrist metrics. Significant improvements in all metrics were found for the combined group analysis. Novel wrist data showed smoothness significantly improved (P < ·001) while submovement number trended down, overlap increased, and interpeak interval decreased. Post-hoc analysis showed only patients with severe impairment demonstrated a significant difference in kinematics, greater for patients receiving sham stimulation.ConclusionsRobotic data confirmed results of clinical measures, showing intensive robotic therapy is beneficial, but no additional gain from tDCS. Patients with severe impairment did not benefit from the combined intervention. Wrist submovement characteristics showed a delayed pattern of motor recovery compared to the shoulder-elbow, relevant to intensive intervention-related recovery of upper extremity function in chronic stroke.Trial registrationhttp://www.clinicaltrials.gov. Actual study start date September 2012. First registered on 15 November 2012. Retrospectively registered. Unique identifiers: NCT01726673 and NCT03562663.

Improved Executive Functions and Reduced Craving in Youths with Methamphetamine Addiction: Evidence from Combined Transcranial Direct Current Stimulation with Mindfulness Treatment.

ObjectiveTranscranial direct current stimulation (tDCS) and mindfulness practices have been proposed as a potential approach to improve executive functions (EFs) and reduce craving in persons with substance use disorders. Based on the neural mechanisms of action of each of these interventions, the combination of both non-pharmacological interventions might have additive effects. In the current study, the effects of tDCS combined with mindfulness-based substance abuse treatment (MBSAT) to improve EFs and reduce craving were investigated in early abstinent methamphetamine abuse.MethodsEighty (youths aged between 18 and 21) early-abstinent methamphetamine users were randomly assigned to the research groups (tDCS group [n = 20], mindfulness group [n = 20], combined mindfulness-tDCS group [n = 20], and sham group [n = 20]). Active tDCS (1.5 mA,20 min, 12 sessions) or sham tDCS was appliedover the left dorsolateral prefrontal cortex and the MBSAT protocol was used over twelve 50-min sessions.ResultsBoth in the post-test phase (immediately after the intervention) and follow-up phase (one month after the intervention), performance in most EFs tasks significantly improved in the combination group which received real tDCS ＋ MBSAT, as compared to baseline values and sham stimulation group. Similarly, a significant reduction in craving was observed after intervention inall treatment groups, but not the sham stimulation group. Interestingly, the increase in EFs and the reduction in craving post versus pre tDCS ＋ MBSAT intervention were correlated.ConclusionFindings from the current study provide initial support for the clinical effectiveness of combination tDCS ＋ MBSAT, possibly influencing cognitive/affective processes.

Mindfulness augmentation for anxiety through concurrent use of transcranial direct current stimulation: a randomized double-blind study

Transcranial direct current stimulation (tDCS) have revealed the capability to augment various types of behavioural interventions. We aimed to augment the effects of mindfulness, suggested for reducing anxiety, with concurrent use of tDCS. We conducted a double-blind randomized study with 58 healthy individuals. We introduced treadmill walking for focused meditation and active or sham tDCS on the left dorsolateral prefrontal cortex for 20 min. We evaluated outcomes using State-Trait Anxiety Inventory-State Anxiety (STAI) before the intervention as well as immediately, 60 min, and 1 week after the intervention, and current density from electroencephalograms (EEG) before and after the intervention. The linear mixed-effect models demonstrated that STAI-state anxiety showed a significant interaction effect between 1 week after the intervention and tDCS groups. As for alpha-band EEG activity, the current density in the rostral anterior cingulate cortex (rACC) was significantly reduced in the active compared with the sham stimulation group, and a significant correlation was seen between changes in STAI-trait anxiety and the current density of the rACC in the active stimulation group. Our study provided that despite this being a one-shot and short intervention, the reduction in anxiety lasts for one week, and EEG could potentially help predict its anxiolytic effect.

Effects of High-Frequency (HF) Repetitive Transcranial Magnetic Stimulation (rTMS) on Upper Extremity Motor Function in Stroke Patients: A Systematic Review.

Background and Objectives: Repetitive transcranial magnetic stimulation (rTMS) is being widely used for treating upper extremity paresis after stroke, however, evidence of applying high-frequency rTMS (HF-rTMS) on the ipsilesional hemisphere for upper extremity motor recovery remains limited. This systematic review aimed to investigate the effect of high-frequency repetitive transcranial magnetic stimulation for upper extremity motor function recovery after a first-time ischaemic stroke. Materials and Methods: This systematic review was prepared according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify all studies published before 12 February 2021. The search was performed on the following databases: PubMed, Ovid, The Cochrane Library. Results: A total of 6440 studies were found in the databases and four trials were included in the review. Three of the studies were randomized control trials (RCT), and one was a pseudo-RCT. Three of the studies showed good methodological quality and one study was rated as excellent. Fugl-Meyer Assessment (FMA) was performed in three out of four studies and the score significantly increased in the HF-rTMS treatment group compared with sham stimulation in all trials. Other measures used in the studies were handgrip strength, shoulder abduction, Motricity Index, Wolf Motor Function Test (WMFT), and Box and Block, although these tests did not show unanimous results. Overall, all four studies conveyed significantly better results in at least one test that was performed for hand motor function evaluation in a 10 Hz stimulation group while none of the tests showed any advantage for sham stimulation groups. Two studies reported headache as an adverse event (six patients in total). Conclusion: The overall results showed that HF-rTMS may increase impaired upper extremity motor function better than sham stimulation in stroke patients.

Protocol of Non-invasive Current Stimulation in Acute Posterior-circulation Stroke with High Risk for Falling (NAPS trial): A Randomized Double-blind Sham-controlled Study

Abstract Background: Posterior-circulation stroke accounts for approximately 20∼30% of all ischemic stroke. It can manifest as symptoms with a variety of headache, nausea, diplopia, ataxia and gait disturbance. Among them, imbalance and gait problem are main symptoms that can induce a difficulty for living daily life and a high risk for falling in these patients. In many neurological diseases including stroke and cerebellar ataxia, a therapeutic approach to imbalance and gait problem through brain stimulation has received much attention at neurorehabilitation field. However, there has been no such effort focusing on acute posterior-circulation stroke patients with imbalance and/or gait problem. Our study’s aim is to investigate the effect of non-invasive repetitive transcranial direct current stimulation (tDCS) of cerebellum on improving balance/gait control in acute posterior-circulation stroke patients with imbalance or gait problem. Methods: Acute posterior-circulation stroke patients who were admitted within 5 days of symptom onset and at high risk for falling due to imbalance and/or gait problem, were recruited and randomized into two groups: intervention (tDCS stimulation) and control (sham stimulation) groups. Intervention group will receive 10 daily sessions of tDCS for 2 weeks (2 mA for 20 min). Outcome measurement was performed at baseline, after 2 weeks (the end of stimulation), and 4 weeks. Primary outcome was mean difference of Performance-oriented assessment of mobility (POMA) total score (baseline - 4 weeks) between the two groups. Secondary outcomes were difference of the balance and gait score of POMA, Dizziness Handicap Inventory (DHI), Falls Self-Efficiency Scale (FES-I), Beck Depression Invention (BDI), Beck Anxiety Inventory (BAI) and gait analysis. Conclusion: Our study focuses on the acute-stage (<1 week of symptom onset) and more specific symptoms in posterior-circulation stroke patients to improve the clinical outcome and quality of life in those and prove the effect of early tDCS intervention. Keywords: Transcranial direct current stimulation, Acute stroke, Posterior-circulation, Outcome

Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial.

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients.Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention.Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group.Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).

A New Approach to Assess Blinding for Transcranial Direct Current Stimulation Treatment in Patients with Fibromyalgia. A Randomized Clinical Trial.

Correct blinding is essential for preventing potential biases. The aim of this study was to assess the blinding of participants and a therapist following treatment with transcranial direct current stimulation in subjects with fibromyalgia using James’ and Bang’s blinding indexes. Eighty subjects were randomly allocated either active or sham stimulation groups in an intervention of five sessions lasting 20 min each. A questionnaire was delivered to both the therapist and patients after the last session to record their guess of which treatment had been applied. No differences between the groups were noted at baseline in terms of demographic or clinical data. James’ BI was 0.83 (CI 95%: 0.76–0.90) for the patients and 0.55 (CI 95%: 0.45–0.64) for the therapist. Bang’s BI for subjects was −0.08 (CI 95%: −0.24–0.09) and −0.8 (CI 95%: −0.26–0.1) for the active and sham transcranial direct current stimulation groups, respectively. Bang’s BI for the therapist was 0.21 (CI 95%: −0.02–0.43) and 0.13 (CI 95%: −0.09–0.35) for the active and sham transcranial direct current stimulation groups, respectively. Protocols of active and sham transcranial direct current stimulation applied in this study have shown satisfactory blinding of the therapist and subjects with fibromyalgia.

Research on enhancement of mental rotation ability based on transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a non-invasive low-current brain stimulation technique, which is mainly based on the different polarity of electrode stimulation to make the activation threshold of neurons different, thereby regulating the excitability of the cerebral cortex. In this paper, healthy subjects were randomly divided into three groups: anodal stimulation group, cathodal stimulation group and sham stimulation group, with 5 subjects in each group. Then, the performance data of the three groups of subjects were recorded before and after stimulation to test their mental rotation ability, and resting state and task state electroencephalogram (EEG) data were collected. Finally, through comparative analysis of the behavioral data and EEG data of the three groups of subjects, the effect of electrical stimulation of different polarities on the three-dimensional mental rotation ability was explored. The results of the study found that the correct response time/accuracy rate and the accuracy rate performance of the anodal stimulation group were higher than those of the cathodal stimulation and sham stimulation groups, and there was a significant difference ( P < 0.05). The alpha wave power analysis found that the mental rotation mainly activates the frontal lobe, central area, parietal lobe and occipital lobe. In the anodal stimulation group, the alpha wave power changed significantly in the frontal lobe and occipital lobe ( P < 0.05). The results of this paper show that anodal stimulation group can improve the mental rotation ability of the subjects to a certain extent. The results of this paper can provide important theoretical support for further research on the mechanism of tDCS on mental rotation ability.

Long-Term Application of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Learning in Parkinson's Disease.

Cerebellar transcranial direct current stimulation (c-tDCS) enhances motor skill acquisition and motor learning in young and old adults. Since the cerebellum is involved in the pathophysiology of Parkinson’s disease (PD), c-tDCS may represent an intervention with potential to improve motor learning in PD. The primary purpose was to determine the influence of long-term application of c-tDCS on motor learning in PD. The secondary purpose was to examine the influence of long-term application of c-tDCS on transfer of motor learning in PD. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-one participants with PD were allocated to either a tDCS group or a SHAM stimulation group. Participants completed 9 practice sessions over a 2-week period that involved extensive practice of an isometric pinch grip task (PGT) and a rapid arm movement task (AMT). These practice tasks were performed over a 25-min period concurrent with either anodal c-tDCS or SHAM stimulation. A set of transfer tasks that included clinical rating scales, manual dexterity tests, and lower extremity assessments were quantified in Test sessions at Baseline, 1, 14, and 28 days after the end of practice (EOP). There were no significant differences between the c-tDCS and SHAM groups as indicated by performance changes in the practice and transfer tasks from Baseline to the 3 EOP Tests. The findings indicate that long-term application of c-tDCS does not improve motor learning or transfer of motor learning to a greater extent than practice alone in PD.

Improved Pre-attentive Processing With Occipital rTMS Treatment in Major Depressive Disorder Patients Revealed by MMN.

ObjectivesTo investigate the improvement effect of occipital repetitive transcranial magnetic stimulation (rTMS) combined with escitalopram oxalate tablets on pre-attentive processing in patients with first-episode, medication-naive depression.MethodsPatients who were hospitalized between January and December 2019 were selected. They were randomly allocated to real occipital rTMS stimulation group with 27 cases receiving intermittent theta-burst (iTBS) and sham stimulation group with 24 cases over 20 days. The rTMS treatment target is located at the Oz point of the occipital region. Both groups took escitalopram oxalate tablets, and the average daily drug dose was 15.294 ± 5.041 mg. Hamilton Depression Rating Scale (HAMD) was used to assess the symptoms of depression before and after treatment, and mismatch negativity (MMN) was used to assess the improvement of pre-attentive processing before and after treatment.ResultsAfter 20 days of treatment, the total score of HAMD (13.495 ± 3.700) in both groups was significantly lower than that before treatment [21.910 ± 3.841, F(1, 49) = 46, 3.690, p < 0.001]. After treatment, the latency of MMN in the real stimulation group (182.204 ± 31.878 ms) was significantly lower than that in the sham stimulation group (219.896 ± 42.634 ms, p < 0.001), and the amplitude of MMN in the real stimulation group (−7.107 ± 3.374 ms) was significantly higher than that in the sham stimulation group (−2.773 ± 3.7 32 ms, p < 0.001).ConclusionOccipital rTMS treatment can enhance the early therapeutic effect and effectively improve the pre-attentive processing of patients with depression and provide a scientific basis for the new target of rTMS therapy in clinical patients with depression.

Non-invasive brain stimulation for speech in Parkinson’s disease: A randomized controlled trial

BackgroundHypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson’s disease (PD). ObjectivesWe evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. MethodsA randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. ResultsAltogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. ConclusionsThis is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.

The Effects of Combined Transcranial Direct Current Stimulation (tDCS) with Mindfulness on Negative Emotions and Craving in Adolescents with Methamphetamine Dependence

Background: Mindfulness-based substance abuse treatment and transcranial direct current stimulation (tDCS) have been proposed as a potential approach to improve negative emotions and reduce craving in persons with substance use disorders. Recent studies suggest that tDCS may enhance psychological interventions. Objectives: The current study, hence, investigated the effects of combined tDCS with mindfulness-based substance abuse treatment (MBSAT) to improve negative emotions and reduce craving in adolescents with methamphetamine dependence. Patients and Methods: Eighty early-abstinent methamphetamine users aged between 18 and 21 were randomly assigned to the research groups (tDCS group (n = 20), mindfulness group (n = 20), combined mindfulness-tDCS group (n = 20), and sham group (n = 20). Active tDCS (intensity of 1.5 mA, with 20 min duration) or sham tDCS (intensity of 0.0 mA, with 20 min duration) was used over the left dorsolateral prefrontal cortex (DLPFC), and the MBSAT protocol was used over twelve 50-min sessions. Results: Negative emotions significantly improved in the combination group receiving real tDCS + MBSAT (PIN-CODES), as compared to baseline values and sham stimulation group. Similarly, a significant reduction in craving was observed after intervention in the tDCS + MBSAT group but not in the sham stimulation group. Also, a significant correlation was shown between the enhancement of negative emotions and the decrease of craving in the combination group (tDCS + MBSAT) compared to the other groups. Conclusions: The findings of the present study confirm the effectiveness of the combined approach of mindfulness therapy with electrical stimulation in substance use groups

Noninvasive vagus nerve stimulation to reduce ileus after major colorectal surgery: early development study.

Vagus nerve stimulation has emerged as a plausible intervention to reduce ileus after surgery. An early development study was undertaken with the aim of exploring the feasibility of self-administered, noninvasive vagus nerve stimulation (nVNS) after major colorectal surgery. A parallel-group, randomized controlled trial was undertaken between 1 January 2018 and 31 August 2019. Forty patients undergoing colorectal surgery for malignancy were allocated equally to Sham and Active stimulation groups. Electrical vagus nerve stimulation was self-administered bilaterally over the cervical surface landmarks for 5days before and after surgery. Outcomes of interest were postoperative complications and adverse events measured using the Clavien-Dindo scale, treatment compliance, device usability according to the Systems Usability Scale (SUS) and clinical measures of bowel recovery. Forty patients were randomized and one withdrew, leaving 39 for analysis. Postoperative complications occurred in 9/19 (47.4%) participants receiving Sham and 11/20 (55.0%) receiving Active stimulation and were mostly minor. Compliance with treatment before surgery was 4.7±0.9days out of 5days in the Sham group and 4.7±1.1 in the Active group. Compliance with treatment after surgery was 4.1±1.1 and 4.4±1.5, respectively. Participants considered the intervention to be 'acceptable' according to the SUS. The most prominent differences in bowel recovery were days to first flatus (2.35±1.32 vs 1.65±0.88) and tolerance of solid diet (2.18±2.21 vs 1.75±0.91) for Sham and Active groups, respectively. This study supports the safety, treatment compliance and usability of self-administered nVNS in patients undergoing major colorectal surgery.

Activation response and functional connectivity change in rat cortex after bilateral transcranial direct current stimulation-An exploratory study.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique implicated as a promising adjunct therapy to improve motor function through the neuromodulation of brain networks. Particularly bilateral tDCS, which affects both hemispheres, may yield stronger effects on motor learning than unilateral stimulation. Therefore, the aim of this exploratory study was to develop an experimental model for simultaneous magnetic resonance imaging (MRI) and bilateral tDCS in rats, to measure instant and resultant effects of tDCS on network activity and connectivity. Naïve, male Sprague‐Dawley rats were divided into a tDCS (n = 7) and sham stimulation group (n = 6). Functional MRI data were collected during concurrent bilateral tDCS over the sensorimotor cortex, while resting‐state functional MRI and perfusion MRI were acquired directly before and after stimulation. Bilateral tDCS induced a hemodynamic activation response, reflected by a bilateral increase in blood oxygenation level‐dependent signal in different cortical areas, including the sensorimotor regions. Resting‐state functional connectivity within the cortical sensorimotor network decreased after a first stimulation session but increased after a second session, suggesting an interaction between multiple tDCS sessions. Perfusion MRI revealed no significant changes in cerebral blood flow after tDCS. Our exploratory study demonstrates successful application of an MRI‐compatible bilateral tDCS setup in an animal model. Our results indicate that bilateral tDCS can locally modulate neuronal activity and connectivity, which may underlie its therapeutic potential.

A Causal Role for the Right Dorsolateral Prefrontal Cortex in Avoidance of Risky Choices and Making Advantageous Selections

In everyday life, risky decision-making relies on multiple cognitive processes including sensitivity to reinforcers, exploration, learning, and forgetting. Neuroimaging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in exploration and risky decision-making, but the nature of its computations and its causal role remain uncertain. We provide evidence for the role of the DLPFC in value-independent, directed exploration on the Iowa Gambling Task (IGT) and we describe a new computational model to account for the competition of directed exploration and exploitation in guiding decisions. Forty-two healthy human participants were included in a right DLPFC, left DLPFC or sham stimulation groups using continuous theta-burst stimulation (cTBS). Immediately after cTBS, the IGT was completed. Computational modelling was used to account for exploration and exploitation with different combinations with value-based and sensitivity to reinforcers for each group. Applying cTBS to the left and right DLPFC selectively decreased directed exploration on the IGT compared to sham stimulation. Model-based analyses further indicated that the right (but not the left) DLPFC stimulation increased sensitivity to reinforcers, leading to avoidance of risky choices and promoting advantageous choices during the task. Although these findings are based on small sample sizes per group, they nevertheless elucidate the causal role of the right DLPFC in governing the exploration–exploitation tradeoff during decision-making in uncertain and ambiguous contexts.