Repetitive Transcranial Stimulation Research Articles

Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder and Tic Disorder: A Quick Review.

Repetitive transcranial megnetic stimulation (rTMS) has been widely used in patients with psychiatric disorders. Previous studies revealed good efficacy of rTMS for patients with obsession-compulsive disorder (OCD) and Tic disorder (TD). OCD and TD are closely related and considered to etiologically overlap. Patients with the co-occurrence of OCD and TD are often identified. Therefore, we conducted a quick review of rTMS for the treatment of these two diseases to compare the similarities and differences of rTMS for OCD and TD, which might provide an indication for the treatment of the co-occurrence of OCD and TD. We searched articles published in PubMed, Wanfang, and Web of Science from January 2001 to January 2022. Both inclusion criteria and exclusion criteria were developed to identify the relevant included studies. Data on the frequency, target area, sample size, and number of males, especially the rTMS treatment procedure or parameters, were extracted in the included studies. We included 26 studies on OCD and 12 studies on TD in this quick review. A total of 996 participants were included. Based on the review of the included studies, lowfrequency rTMS might be used more than high-frequency rTMS, and the supplementary motor area (SMA) might show better efficacy than the dorsolateral prefrontal cortex (DLPFC) in OCD. For patients with TD, low-frequency rTMS located in the SMA might show good efficacy both in OCD and TD. Our quick review elaborated the treatment efficacy of rTMS for both patients with OCD and those with TD. It seems that the SMA is an important target choice for both OCD and TD patients. Low-frequency rTMS might be used more than high-frequency rTMS in both OCD and TD patients. In future studies, we should explore more about the efficacy of rTMS for patients with co-occurring OCD and TD, especially for the efficacy of targeted SMA with low frequency.

Prolonged Suppression of Neuropathic Hypersensitivity upon Neurostimulation of the Posterior Insula in Mice.

Neurostimulation-based therapeutic approaches are emerging as alternatives to pharmacological drugs, but need further development to optimize efficacy and reduce variability. Despite its key relevance to pain, the insular cortex has not been explored in cortical neurostimulation approaches. Here, we developed an approach to perform repetitive transcranial direct current stimulation of the posterior insula (PI tDCS) and studied its impact on sensory and aversive components of neuropathic pain and pain-related anxiety and the underlying neural circuitry in mice using behavioral methods, pharmacological interventions and the expression of the activity-induced gene product, Fos. We observed that repetitive PI tDCS strongly attenuates the development of neuropathic mechanical allodynia and also reverses chronically established mechanical and cold allodynia for several weeks post-treatment by employing descending opioidergic antinociceptive pathways. Pain-related anxiety, but not pain-related aversion, were inhibited by PI tDCS. These effects were associated with a long-term suppression in the activity of key areas involved in pain modulation, such as the cingulate, prefrontal and motor cortices. These data uncover the significant potential of targeting the insular cortex with the objective of pain relief and open the way for more detailed mechanistic analyses that will contribute to improving cortical neurostimulation therapies for use in the clinical management of pain.

Repetitive transcranial direct current stimulation modulates the brain–gut–microbiome axis in obese rodents

BackgroundComplex interactions between the brain, gut and adipose tissue allow to recognize obesity as a neurometabolic disorder. The recent data have shown that gut microbiota can play a potential role in obesity development. Transcranial direct current stimulation (tDCS) is a safe and non-invasive technique to modulate the activity of cerebral cortex and other connected brain areas also in context of appetite control. The objective of this study was to evaluate the effects of repetitive anodal tDCS (AtDCS) of prefrontal cortex on feeding behavior, metabolic status and selected phyla of gut microbiota in rats with obesity induced by high-calorie diet (HCD).Methods32 female Wistar rats were equally divided into 4 subgroups depending on diet effect (lean versus obese) and type of stimulation (active versus sham tDCS versus no stimulation). Feed intake, body weight, blood lipoproteins and leptin levels as well as Firmicutes and Bacteroidetes in intestines and stool were examined.ResultsHCD changed feeding behavior and metabolic parameters typically for obesity-related ranges and resulted in an abundance of Firmicutes at the expanse of Bacteroidetes in the large intestine and stool. AtDCS decreased appetite, body weight, and cholesterol levels. In addition, AtDCS reduced ratio of the average number of Firmicutes to average number of Bacteroidetes in all examined tissues.ConclusionsRepetitive AtDCS is not only effective for appetite restriction but can also modulate gut microbiome composition which demonstrates the existence of the brain–gut–microbiome axis and points at this technique as a promising complementary treatment for obesity. However, the effects should be further replicated in human studies.

Clinical Study of Repetitive Transcranial Direct Current Stimulation Combined with Rehabilitation Therapy for Patients with Consciousness Disorder

<bold>Objective</bold> To explore the effect of repetitive transcranial direct current combined with rehabilitation therapy on promoting consciousness and improving spasticity in patients with consciousness disorder. <bold>Methods</bold> A retrospective analysis was performed on 42 patients with disturbance of consciousness，whom hospitalized in rehabilitation medicine department of Lanzhou University Second Hospital from April 2017 to April 2021. They were divided into observation group and control group according to whether they received transcranial direct current stimulation （tDCS），21 cases in each group. The control group were treated with conventional rehabilitation treatment and the observation group were treated with conventional rehabilitation therapy and tDCS，the anode was placed in the left primary motor cortex （M1） and the cathode was placed in the right shoulder region，current intensity of 2 mA，once daily，20 min once a day，5 times per week，for 6 weeks. Before and after treatment，the level of consciousness was assessed by the Coma Recovery Scale-Revised （CRS-R） and Glasgow Coma Scale （GCS），the Modified Ashworth Scale （MAS） was used to assess changes muscle tone of the right flexor elbow muscle. <bold>Results</bold> Before treatment，there were no significant difference in CRS-R and GCS scores between the two groups （<italic>P</italic>＞0.05）；After treatment，the scores of the two groups were improved，and the CRS-R and GCS scores of the observation group were better than the control group，the differences were statistically significant （<italic>P</italic>&lt;0.05）. In terms of clinical efficacy，there were 13 （38.10%） responders and 8 （61.90%） non responders in the observation group. In the control group，there were 2 （9.50%） patients with responded and 19 （90.50%） patients who did not respond，the difference between the two groups was significant difference （<italic>P</italic>&lt;0.05）. As for MAS score，there was no significant difference in MAS score of right flexor elbow muscle between the two groups before treatment （<italic>P</italic>＞0.05）; There was no significant difference in MAS score of bilateral flexor elbow muscle in the control group before and after treatment （<italic>P</italic>＞0.05），but there was significant difference in the observation group before and after treatment （<italic>P</italic>&lt;0.05）. Comparison among groups，MAS score of flexor elbow muscle in the observation group was better than the control group，the difference was significant difference （<italic>P</italic>&lt;0.05）. <bold>Conclusion</bold> Repetitive transcranial direct current stimulation combined with rehabilitation therapy can effectively improve the level of consciousness and spasticity of patients with consciousness disorder.

Long-term iTBS promotes neural structural and functional recovery by enhancing neurogenesis and migration via miR-551b-5p/BDNF/TrkB pathway in a rat model of cerebral ischemia-reperfusion injury

As a novel form of repetitive transcranial stimulation, intermittent theta burst stimulation (iTBS) has potentials to be widely used in patients with stroke. Yet little is known about the idiographic actions of iTBS with different stimulation parameters on rehabilitative aspects of stroke patients, nor is the molecular mechanism underlying. In the present study, effects of iTBS with different stimulation parameters were evaluate to identify the optimal protocol of iTBS against damage induced by ischemia/reperfusion (I/R). Herein we found the short-term iTBS application seemed to have no significant effects on outcomes of rats during acute phase after I/R, including the neurological deficits, cerebral infarction and edema. However, behavioral functional tests demonstrated that long-term iTBS treatment provided effective therapy during subacute stage after two weeks post-stroke onset, which possibly by increasing proliferation and migration of adult neural stem cells. To explore the possible mechanisms of, microRNAs (miRs) expressional profiles were analyzed by microarray technology. Further bioinformatic analysis of binding sites revealed miR-551b-5p directly targeted the brain-derived neurotrophic factor (BDNF), which was confirmed by luciferase reporter and qRT-PCR. Moreover, the level phosphorylated-TrkB, the downstream of BDNF, was elevated accompanied by above-mentioned changes of long-term iTBS. Taken together, experimental data reveals a direct link between miR-551b-5p and BDNF-mediated signaling cascade in early convalescence of stroke. Our findings provide new insights into the molecular mechanisms underlying curative effects of iTBS on stroke, thus aiding in the prognosis and personalized therapies.

The effect of low-frequency repetitive transcranial magnetic stimulation on left dorsolateral prefrontal cortex in patients with the obsessive-compulsive disorder: a double-blinded, sham-controlled clinical trial

BackgroundObsessive-compulsive disorder (OCD) is a complicated neuropsychiatric disorder, which its prevalence ranges from 2 to 4%. In 30–60% of patients due to intolerance of side effects or partial response to treat symptoms of the disease remain or relapse. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive therapeutic option to treat this condition. Transcranial magnetic stimulation can be applied for treating with no anesthesia. The current study intended to evaluate the effectiveness of low-frequency rTMS on the left dorsolateral prefrontal cortex as an adjunct treatment in combination with standard medication in patients with OCD.ResultsIn both groups of intervention and sham, the Y-BOCS scale was decreased. There was no significant difference between the two groups (P=0.82). Also after 15 sessions, the symptoms of OCD patients were improved. Although the treatment process was the same in the control group, none of the patients showed any serious complications, such as seizures, severe headache, neurological complication, or cognitive impairment during treatment.ConclusionsIt seems that treatment with 1 Hz rTMS on the left dorsolateral prefrontal cortex does not play an effective role in the recovery of OCD patients.Trial registrationName of the registry: Therapeutic effect comparison of the Repetitive Transcranial MagneticMagnetic Stimulation (RTMS) combination therapy with drug versus medication monotherapy in obsessive-compulsive disorder (OCD). Trial registration number: IRCT ID: IRCT20200728048240N1. Date of registration: 2020/8/8.

A comparative study of the effect of electroconvulsive therapy and transcranial direct current stimulation in the treatment of persons suffering from treatment-resistant depression.

Background:About 20%–30% of persons with major depression are said to have treatment-resistant depression (TRD) when they do not respond to antidepressants. These people continue to suffer in life and have poor quality of life. Although electroconvulsive therapy (ECT) is the most successful option in treating TRD, many people refuse ECT due to various reasons (stigma, the cost involved, and medical complications). Various studies combine treatment options such as psychotherapy, repetitive trans magnetic stimulation, ketamine, and transcranial direct current stimulation (tDCS) in an attempt to reduce symptoms for those people suffering from TRD. This study aims to compare the effectiveness of ECT and tDCS in TRD.Subjects and Methods:A total of 90 persons suffering from TRD were selected for the study. 46 persons received 6 ECTs and 44 persons received 10 sessions of tDCS. Treatment response was measured using baseline and postassessment scores of Hamilton depression rating scale and clinical global impression. The scores were used to determine the effectiveness of ECT in comparison to tDCS in TRD.Statistical Analysis:The mean ± standard deviation was analyzed and paired t-test was used to find the significance of treatment outcome in a group at a 95% confidence interval.Results:ECT was found to be more effective than tDCS in the reduction of depressive symptoms. tDCS showed a significant reduction in depressive symptoms (P < 0.001). ECT has yet again been proven to be effective in the treatment of TRD.Conclusion and Discussion:tDCS is effective in reducing depressive symptoms in persons suffering from TRD. However, ECT is superior in decreasing depressive symptoms in TRD when compared to tDCS.

Symposium

Objective:Neuromodulatory interventions like transcranial direct current stimulation (tDCS) is an emerging and potential therapeutic strategy to help in reducing craving and relapse prevention in patients of alcohol dependence syndrome (1–4). The potential target for alcohol dependence is the dorsolateral pre-frontal cortex (dlPFC) as frontal dysfunction is a hallmark of alcoholism, even in alcohol dependence subjects with no major clinical and global cognitive deficits (5). In this context, this study was designed to explore the effect of tDCS treatment on craving and relapse prevention and its correlation to dorsolateral prefrontal cortex (DLPFC) activation in alcohol dependent patients.Methodology:This study was a double blinded randomized sham control trial, conducted at National Institute of Mental Health and Neurosciences, Bangalore after approval by the Institute Ethics Committee. Twenty-four patients of alcohol dependence syndrome were recruited after informed consent. After detoxification patients underwent baseline fMRI scans. Followed by tDCS with intensity of 2mA and duration of 20 minutes per day was administered for 5 consecutive days with cathode over left dorsolateral prefrontal cortex (DLPFC) and anode over right DLPFC. On the 5th day post fMRI scans were repeated. Both investigator and subjects remained blind throughout the study period. During scans patients were exposed to visual alcohol cues using VICE (visual image- Induced craving for ethanol) paradigm. Pre- treatment and post-treatment scans were analysed using SPM-12 software.Results:At the beginning of the study, 24 subjects were selected but 2 subjects dropped out before post fMRI scan. The baseline comparison of socio-demographic and clinical variables found to have no differences among both groups.fMRI results: At baseline, the true and sham tDCS groups had comparable BOLD activation patterns and there were no between-group differences in activation pattern noted for alcohol vs. neutral cues contrast. Following 5 sessions of tDCS, there is significantly increased activation observed in true tDCS group, from Pre- to Post- treatment scans. Brain activity at DLPFC (Post-Pre) was positively associated with time to first alcohol lapse (p=0.048, Spearman’s rho =0.426). This suggests that greater the increase in brain activity at DLPFC after treatment with bilateral repetitive tDCS longer was the time to first lapse. Conclusion:This study has shown bilateral repetitive transcranial direct current stimulation in alcohol dependent subjects, activates dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) along with increase in the connectivity strength between medial frontal gyrus (MFG) and sub cortical reward centre (NAc), which facilitated abstinence from alcohol. So from this study we better understood the mechanism of tDCS in preventing relapse to alcohol by activation of dorsolateral prefrontal cortex and anterior cingulated cortex. Though the fMRI results were statistically significant for relapse and DLPFC activation, but it would be difficult to establish the clinical significance of the improvement in craving in the background of small sample size. Hence further studies with larger sample size are required in near future. Referrences: 1. Klauss J, Penido Pinheiro LC, Silva Merlo BL, Correia Santos GDA, Fregni F, Nitsche MA, et al. A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. Int J Neuropsychopharmacol. 2014;17(11):1793–803.2. Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, et al. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study. Drug Alcohol Depend. 2008;92(1–3):55–60.3. Nakamura-Palacios EM, Lopes IBC, Souza RA, Klauss J, Batista EK, Conti CL, et al. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction. J Neural Transm. 2016;123(10):1179–94.4. da Silva MC, Conti CL, Klauss J, Alves LG, do Nascimento Cavalcante HM, Fregni F, et al. Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. J Physiol. 2013;107(6):493–502.5. Nakamura-Palacios EM, Souza RSM, Zago-Gomes MP, de Melo AMF, Braga FS, Kubo TTA, et al. Gray Matter Volume in Left Rostral Middle Frontal and Left Cerebellar Cortices Predicts Frontal Executive Performance in Alcoholic Subjects. Alcohol Clin Exp Res [Internet]. 2014 Apr 1 ;38(4):1126–33. Available from: http://doi.wiley.com/10.1111/ acer.12308

A Compact Circuit for Boosting Electric Field Intensity in Repetitive Transcranial Magnetic Stimulation (rTMS).

The concept of a portable, wearable system for repetitive transcranial stimulation (rTMS) has attracted widespread attention, but significant power and field intensity requirements remain a key challenge. Here, a circuit topology is described that significantly increases induced electric field intensity over that attainable with similar current levels and coils in conventional rTMS systems. The resultant electric field is essentially monophasic, and has a controllable, shortened duration. The system is demonstrated in a compact circuit implementation for which an electric field of 94 V/m at a depth of 2 cm is measured (147 V/m at 1 cm depth) with a power supply voltage of 80 V, a maximum current of 500 A, and an effective pulse duration (half amplitude width) of 7 µsec. The peak electric field is on the same order as that of commercially available systems at full power and comparable depths. An electric field boost of 5x is demonstrated in comparison with our system operated conventionally, employing a 70 µsec rise time. It is shown that the power requirements for rTMS systems depend on the square of the product of electric field Ep and pulse duration tp, and that the proposed circuit technique enables continuous variation and optimization of the tradeoff between Ep and tp. It is shown that the electric field induced in a medium such as the human brain cortex at a specific depth is proportional to the voltage generated in a given loop of the generating coil, which allows insights into techniques for its optimization. This rTMS electric field enhancement strategy, termed 'boost rTMS (rbTMS)' is expected to increase the effectiveness of neural stimulation, and allow greater flexibility in the design of portable rTMS power systems.Clinical Relevance- This study aims to facilitate a compact, battery-powered rTMS prototype with enhanced electric field which will permit broader and more convenient rTMS treatment at home, in a small clinic, vessel, or field hospital, and potentially, on an ambulatory basis.

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

Comparative study between transcranial direct current and repetitive transcranial electromagnetic stimulation in the rehabilitation of primary fibromyalgia

Abstract Background Fibromyalgia syndrome (FMS) is a complex disorder where a widespread musculoskeletal pain (without a clear lesion basis) is associated with a great variety of symptoms including affective disturbances, central fatigue, cognitive dysfunction and even a particular skin reactivity to several chemical substances. Despite intense research effort, especially in the last years, the pathophysiology of the disease remains to be explained. The treatment recommendations were classified as pharmacological therapies, non-pharmacological treatments, and complementary non-pharmacological therapies. Also, particular interest has been raised by techniques able to perform effective modulation of brain areas through magnetic or electric currents applied to the scalp like transcranial magnetic and electrical stimulation such as direct current (TMS and tDCS). Objective: To compare the efficacy of Repetitive transcranial magnetic stimulation (r-TMS) and transcranial direct current stimulation (t-DCS) as non- invasive brain stimulation techniques in the rehabilitation of patients with primary (1ry) fibromyalgia (FM). Patients and Methods The present study included 30 patients with 1ry FM, equally divided into 2 groups. Group I included 15 patients who received 8 sessions of rTMS and Group II included 15 patients who received 8 sessions of anodal tDCS. Differences in visual analogue scale (VAS) of pain, tender point scale, Fibromyalgia Impact Questionnaire (FIQ) and Hospital Anxiety and Depression Scale (HADS) were assessed before and after completion of assigned treatment sessions. Results Pain VAS, tender point scale, FIQ and HADS showed significant decrease between baseline and follow-up assessments for both groups. Moreover, a significant change in all assessment scales was observed post treatment when compared between both groups with more significant improvement in the group received rTMS. Conclusion Both rTMS and tDCS techniques showed marked improvement in symptoms of pain, functional status and quality of life in patients with 1ry fibromyalgia. Both techniques can be considered as promising alternatives therapeutic options in the treatment of FM in order to reduce side effects of long-term use of drugs.

Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients.

Repetitive transcranial stimulation (rTMS) has been shown to produce an analgesic effect and therefore has a potential for treating chronic refractory pain. However, previous studies used various stimulation parameters (including cortical targets), and the best stimulation protocol is not yet identified. The present study investigated the effects of multi-session 20 Hz (2000 pulses) and 5 Hz (1800 pulses) rTMS stimulation of left motor cortex (M1-group) and left dorsolateral prefrontal cortex (DLPFC-group), respectively. The M1-group (n = 9) and DLPFC-group (n = 7) completed 13 sessions of neuronavigated stimulation, while a Sham-group (n = 8) completed seven sessions of placebo stimulation. The outcome was measured using the German Pain Questionnaire (GPQ), Depression, Anxiety and Stress Scale (DASS), and SF-12 questionnaire. Pain perception significantly decreased in the DLPFC-group (38.17%) compared to the M1-group (56.11%) (p ≤ 0.001) on the later sessions. Health-related quality of life also improved in the DLPFC-group (40.47) compared to the Sham-group (35.06) (p = 0.016), and mental composite summary (p = 0.001) in the DLPFC-group (49.12) compared to M1-group (39.46). Stimulation of the left DLPFC resulted in pain relief, while M1 stimulation was not effective. Nonetheless, further studies are needed to identify optimal cortical target sites and stimulation parameters.

Suppression of neuropathic pain and comorbidities by recurrent cycles of repetitive transcranial direct current motor cortex stimulation in mice

Transcranial, minimally-invasive stimulation of the primary motor cortex (M1) has recently emerged to show promise in treating clinically refractory neuropathic pain. However, there is a major need for improving efficacy, reducing variability and understanding mechanisms. Rodent models hold promise in helping to overcome these obstacles. However, there still remains a major divide between clinical and preclinical studies with respect to stimulation programs, analysis of pain as a multidimensional sensory-affective-motivational state and lack of focus on chronic phases of established pain. Here, we employed direct transcranial M1 stimulation (M1 tDCS) either as a single 5-day block or recurring blocks of repetitive stimulation over early or chronic phases of peripherally-induced neuropathic pain in mice. We report that repeated blocks of stimulation reverse established neuropathic mechanical allodynia more strongly than a single 5-day regime and also suppress cold allodynia, aversive behavior and anxiety without adversely affecting motor function over a long period. Activity mapping revealed highly selective alterations in the posterior insula, periaqueductal gray subdivisions and superficial spinal laminae in reversal of mechanical allodynia. Our preclinical data reveal multimodal analgesia and improvement in quality of life by multiple blocks of M1 tDCS and uncover underlying brain networks, thus helping promote clinical translation.

Navigated Transcranial Magnetic Stimulation Motor Mapping Usefulness in the Surgical Management of Patients Affected by Brain Tumors in Eloquent Areas: A Systematic Review and Meta-Analysis

Background: The surgical strategy for brain glioma has changed, shifting from tumor debulking to a more careful tumor dissection with the aim of a gross-total resection, extended beyond the contrast-enhancement MRI, including the hyperintensity on FLAIR MR images and defined as supratotal resection. It is possible to pursue this goal thanks to the refinement of several technological tools for pre and intraoperative planning including intraoperative neurophysiological monitoring (IONM), cortico-subcortical mapping, functional MRI (fMRI), navigated transcranial magnetic stimulation (nTMS), intraoperative CT or MRI (iCT, iMR), and intraoperative contrast-enhanced ultrasound. This systematic review provides an overview of the state of the art techniques in the application of nTMS and nTMS-based DTI-FT during brain tumor surgery.Materials and Methods: A systematic literature review was performed according to the PRISMA statement. The authors searched the PubMed and Scopus databases until July 2020 for published articles with the following Mesh terms: (Brain surgery OR surgery OR craniotomy) AND (brain mapping OR functional planning) AND (TMS OR transcranial magnetic stimulation OR rTMS OR repetitive transcranial stimulation). We only included studies regarding motor mapping in craniotomy for brain tumors, which reported data about CTS sparing.Results: A total of 335 published studies were identified through the PubMed and Scopus databases. After a detailed examination of these studies, 325 were excluded from our review because of a lack of data object in this search. TMS reported an accuracy range of 0.4–14.8 mm between the APB hotspot (n1/4 8) in nTMS and DES from the DES spot; nTMS influenced the surgical indications in 34.3–68.5%.Conclusion: We found that nTMS can be defined as a safe and non-invasive technique and in association with DES, fMRI, and IONM, improves brain mapping and the extent of resection favoring a better postoperative outcome.

Repetitive anodal transcranial direct current stimulation improves neurological recovery by preserving the neuroplasticity in an asphyxial rat model of cardiac arrest

BackgroundNon-shockable rhythms present an increasing proportion of out-of-hospital cardiac arrest (CA) patients, but are associated with poor prognosis and received limited therapeutic effect of targeted temperature management (TTM). Previous study showed repetitive anodal transcranial direct current stimulation (tDCS) improved neurological outcomes in animals with ventricular fibrillation. Here, we examine the effectiveness of tDCS on neurological recovery and the potential mechanisms in a rat model of asphyxial CA. MethodCardiopulmonary resuscitation was initiated after 5 min of untreated asphyxial CA. Animals were randomized to three experimental groups immediately after successful resuscitation (n = 12/group, 6 males): no-treatment control (NTC) group, TTM group, and tDCS group. Post resuscitation hemodynamics, quantitative electroencephalogram (EEG), neurological deficit score, and 96-h survival were evaluated. Brain tissues of additional animals undergoing same experimental procedure was harvested for enzyme-linked immunoassay-based quantification assays of neuroplasticity-related biomarkers and compared with the sham-operated rats (n = 6/group). ResultsWe observed that after resuscitation tDCS-treated animals exhibited significantly higher mean arterial pressure and left ventricular ejection fraction than NTC group and showed greatly improved EEG characteristics including weighted-permutation entropy and gamma band power, and neurologic deficit scores and 96-h survival rates compared to NTC and TTM groups. Furthermore, neuroplastic biomarkers including microtubule-associated protein 2, growth-associated protein 43, postsynaptic density protein 95 and synaptophysin, were significantly higher in tDCS group when compared with NTC and TTM groups. ConclusionIn this rat model of asphyxial CA, repetitive anodal tDCS commenced after resuscitation improved neurological recovery, and it may exert a neuroprotective effect by preserving the neuroplasticity.

Repetitive non-invasive prefrontal stimulation reverses neuropathic pain via neural remodelling in mice.

Chronic neuropathic pain presents a major challenge to pharmacological therapy and neurostimulation-based alternatives are gaining interest. Although invasive and non-invasive motor cortex stimulation has been the focus of several studies, very little is known about the potential of targeting the prefrontal cortex. This study was designed to elucidate the analgesic potential of prefrontal stimulation in a translational context and to uncover the neural underpinnings thereof. Here, we report that non-invasive, repetitive direct anodal current transcranial stimulation (tDCS) of the prefrontal cortex exerted analgesia in mice with neuropathic pain for longer than a week. When applied at chronic stages of neuropathic pain, prefrontal tDCS reversed established allodynia and suppressed aversion and anxiety-related behaviours. Activity mapping as well as in vivo electrophysiological analyses revealed that although the cortex responds to acute tDCS with major excitation, repetitive prefrontal tDCS brings about large-scale silencing of cortical activity. Different classes of different classes of GABAergic interneurons and classes of excitatory neurons differs dramatically between single, acute vs and repetitive tDCS. Repetitive prefrontal tDCS alters basal activity as well as responsivity of a discrete set of distant cortical and sub-cortical areas to tactile stimuli, namely the rostral anterior cingulate cortex, the insular cortex, the ventrolateral periaqueductal grey and the spinal dorsal horn. This study thus makes a strong case for harnessing prefrontal cortical modulation for non-invasive transcranial stimulation paradigms to achieve long-lasting pain relief in established neuropathic pain states and provides valuable insights gained on neural mechanistic underpinnings of prefrontal tDCS in neuropathic pain.

Repetitive Anodal Transcranial Direct Current Stimulation Hastens Isoflurane-Induced Emergence and Recovery and Enhances Memory in Healthy Rats.

Attaining a rapid and smooth return to consciousness after general anesthesia is a goal for clinical anesthesiologists. This study aimed to investigate the effects of repeated anodal transcranial direct current stimulation (atDCS) on emergence and recovery from isoflurane anesthesia in rats. Four days after surgery for atDCS socket implantation, rats received either sham stimulation or repetitive anodal direct electrical current of 0.2 mA intensity applied to the right motor cortex for 20 minutes/d for 10 consecutive days. Isoflurane potency and emergence and recovery from a 2-hour isoflurane challenge were evaluated 24 hours after the last atDCS session. Cognitive performance on novel object recognition and spontaneous alternation Y-maze tests were measured 48 hours after the last atDCS session. Locomotor activity was assessed via automated counting of electric infrared beam crossings. Data are expressed as mean ± standard error of mean (SEM). Isoflurane potency was not affected by atDCS (sham: 1.69% ± 0.06%, transcranial direct current stimulation [tDCS]: 1.73% ± 0.11%, mean difference [MD]: 0.045, 95% confidence interval [CI]: -0.22 to 0.30; P = .72). However, the time to appearance of emergence behavioral marker (eg, return of righting reflex) was hastened in rats receiving atDCS (sham: 486 ± 31 seconds, tDCS: 330 ± 45 seconds, MD: 157, 95% CI: 30-284; P = .008). Similarly, time to acknowledgment of adhesive tape ("sticky dot" applied while anesthetized) was also decreased in atDCS-treated rats as compared to sham (sham: 1374 ± 179 seconds, tDCS: 908 ± 151 seconds, MD: 466, 95% CI: 73-858; P = .015), indicating a faster recovery of isoflurane anesthesia. Rats treated with atDCS spent more time exploring the novel object and environment when compared to sham without affecting activity cycles, indicating visual and working memory can be enhanced by atDCS. Taken together, our findings suggest that atDCS over cortical areas might hasten recovery from isoflurane anesthesia and could potentially be used as a preventative strategy for disruptions in higher order functions related to sedation/anesthesia.

Neuronavigated Repetitive Transcranial Ultrasound Stimulation Induces Long-Lasting and Reversible Effects on Oculomotor Performance in Non-human Primates.

Since the late 2010s, Transcranial Ultrasound Stimulation (TUS) has been used experimentally to carryout safe, non-invasive stimulation of the brain with better spatial resolution than Transcranial Magnetic Stimulation (TMS). This innovative stimulation method has emerged as a novel and valuable device for studying brain function in humans and animals. In particular, single pulses of TUS directed to oculomotor regions have been shown to modulate visuomotor behavior of non-human primates during 100 ms ultrasound pulses. In the present study, a sustained effect was induced by applying 20-s trains of neuronavigated repetitive Transcranial Ultrasound Stimulation (rTUS) to oculomotor regions of the frontal cortex in three non-human primates performing an antisaccade task. With the help of MRI imaging and a frame-less stereotactic neuronavigation system (SNS), we were able to demonstrate that neuronavigated TUS (outside of the MRI scanner) is an efficient tool to carry out neuromodulation procedures in non-human primates. We found that, following neuronavigated rTUS, saccades were significantly modified, resulting in shorter latencies compared to no-rTUS trials. This behavioral modulation was maintained for up to 20 min. Oculomotor behavior returned to baseline after 18–31 min and could not be significantly distinguished from the no-rTUS condition. This study is the first to show that neuronavigated rTUS can have a persistent effect on monkey behavior with a quantified return-time to baseline. The specificity of the effects could not be explained by auditory confounds.

Theta burst stimulation in humans: a need for better understanding effects of brain stimulation in health and disease.

Repetitive transcranial stimulation (rTMS) paradigms have been used to induce lasting changes in brain activity and excitability. Previous methods of stimulation were long, often ineffective and produced short-lived and variable results. A new non-invasive brain stimulation technique was developed in John Rothwell's laboratory in the early 2000s, which was named 'theta burst stimulation' (TBS). This used rTMS applied in burst patterns of newly acquired 50Hz rTMS machines, which emulated long-term potentiation/depression-like effects in brain slices. This stimulation paradigm created long-lasting changes in brain excitability, using efficient, very rapid stimulation, which would affect behaviour, with the aim to influence neurological diseases in humans. We describe the development of this technique, including findings and limitations identified since then. We discuss how pitfalls facing TBS reflect those involving both older and newer, non-invasive stimulation techniques, with suggestions of how to overcome these, using personalised, 'closed loop' stimulation methods. The challenge in most non-invasive stimulation techniques remains in identifying their exact mechanisms of action in the context of neurological disease models. The development of TBS provides the backdrop for describing John's contribution to the field, inspiring our own scientific endeavour thanks to his unconditional support, and unfailing kindness.

Cerebellar neuromodulation improves naming in post-stroke aphasia.

Transcranial direct current stimulation has been shown to increase the efficiency of language therapy in chronic aphasia; however, to date, an optimal stimulation site has not been identified. We investigated whether neuromodulation of the right cerebellum can improve naming skills in chronic aphasia. Using a randomized, double-blind, sham-controlled, within-subject crossover study design, participants received anodal cerebellar stimulation (n = 12) or cathodal cerebellar stimulation (n = 12) + computerized aphasia therapy then sham + computerized aphasia therapy, or the opposite order. There was no significant effect of treatment (cerebellar stimulation versus sham) for trained naming. However, there was a significant order x treatment interaction, indicating that cerebellar stimulation was more effective than sham immediately post-treatment for participants who received cerebellar stimulation in the first phase. There was a significant effect of treatment (cerebellar stimulation versus sham) for untrained naming immediately post-treatment and the significant improvement in untrained naming was maintained at two months post-treatment. Greater gains in naming (relative to sham) were noted for participants receiving cathodal stimulation for both trained and untrained items. Thus, our study provides evidence that repetitive cerebellar transcranial direct stimulation combined with computerized aphasia treatment can improve picture naming in chronic post-stroke aphasia. These findings suggest that the right cerebellum might be an optimal stimulation site for aphasia rehabilitation and this could be an answer to handle heterogeneous participants who vary in their size and site of left hemisphere lesions.