High Frequency rTMS Research Articles

Personalized Repetitive Transcranial Magnetic Stimulation for Primary Progressive Aphasia.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome for which no effective treatment is available. We aimed to assess the effect of repetitive transcranial magnetic stimulation (rTMS), using personalized targeting. We conducted a randomized, double-blind, pilot study of patients with PPA receiving rTMS, with a subgroup of patients receiving active- versus control-site rTMS in a cross-over design. Target for active TMS varied among the cases and was determined during a pre-treatment phase from a list of potential regions. The primary outcome was changes in spontaneous speech (word count). Secondary outcomes included changes in other language tasks, global cognition, global impression of change, neuropsychiatric symptoms, and brain metabolism using FDG-PET. Twenty patients with PPA were enrolled (14 with nonfluent and 6 with semantic variant PPA). For statistical analyses, data for the two variants were combined. Compared to the control group (n = 7), the group receiving active-site rTMS (n = 20) showed improvements in spontaneous speech, other language tasks, patient and caregiver global impression of change, apathy, and depression. This group also showed improvement or stabilization of results obtained in the baseline examination. Increased metabolism was observed in several brain regions after the therapy, particularly in the left frontal and parieto-temporal lobes and in the precuneus and posterior cingulate bilaterally. We found an improvement in language, patient and caregiver perception of change, apathy, and depression using high frequency rTMS. The increase of regional brain metabolism suggests enhancement of synaptic activity with the treatment. NCT03580954 (https://clinicaltrials.gov/ct2/show/NCT03580954).

A combination of P300 and eye movement data improves the accuracy of auxiliary diagnoses of depression

BackgroundExploratory eye movements (EEMs) and P300 are often used to facilitate the clinical diagnosis of depression. However, There were few studies using the combination of EEMs and P300 to build a model for detecting depression and predicting a curative effect. MethodsSixty patients were recruited for 2 groups: high frequency repetitive transcranial magnetic stimulation(rTMS) combined with paroxetine group and simple paroxetine group. Clinical efficacy was evaluated by the Hamilton Depression scale-24(HAMD-24), EEMs and P300. The classification model of the auxiliary diagnosis of depression and the prediction model of the two treatments were developed based on a machine learning algorithm. ResultsThe classification model with the greatest accuracy for patients with depression and healthy controls was 95.24% (AUC = 0.75, recall = 1.00, precision = 0.95, F1-score = 0.97). The root mean square error (RMSE) of the model for predicting the efficacy of high frequency rTMS combined with paroxetine was 3.54 (MAE [mean absolute error] = 2.56, R2 = -0.53). The RMSE of the model for predicting the efficacy of paroxetine was 4.97 (MAE = 4.00, R2 = -0.91). ConclusionBased on the machine learning algorithm, P300 and EEMs data was suitable for modeling to distinguish depression patients and healthy individuals. However, it was not suitable for predicting the efficacy of high frequency rTMS combined with paroxetine or to predict the efficacy of paroxetine.

Repetitive transcranial magnetic stimulation on the modulation of cortical and spinal cord excitability in individuals with spinal cord injury.

Repetitive transcranial magnetic stimulation (rTMS) has been applied for modulating cortical excitability and treating spasticity in neurological lesions. However, it is unclear which rTMS frequency is most effective in modulating cortical and spinal excitability in incomplete spinal cord injury (SCI). To evaluate electrophysiological and clinical repercussions of rTMS compared to sham stimulation when applied to the primary motor cortex (M1) in individuals with incomplete SCI. A total of 11 subjects (35±12 years) underwent three experimental sessions of rTMS (10 Hz, 1 Hz and sham stimulation) in a randomized order at 90%intensity of the resting motor threshold and interspersed by a seven-day interval between sessions. The following outcome measures were evaluated: M1 and spinal cord excitability and spasticity in the moments before (baseline), immediately after (T0), 30 (T30) and 60 (T60) minutes after rTMS. M1 excitability was obtained through the motor evoked potential (MEP); spinal cord excitability by the Hoffman reflex (H-reflex) and homosynaptic depression (HD); and spasticity by the modified Ashworth scale (MAS). A significant increase in cortical excitability was observed in subjects submitted to 10 Hz rTMS at the T0 moment when compared to sham stimulation (p = 0.008); this increase was also significant at T0 (p = 0.009), T30 (p = 0.005) and T60 (p = 0.005) moments when compared to the baseline condition. No significant differences were observed after the 10 Hz rTMS on spinal excitability or on spasticity. No inter-group differences were detected, or in the time after application of 1 Hz rTMS, or after sham stimulation for any of the assessed outcomes. High-frequency rTMS applied to M1 was able to promote increased cortical excitability in individuals with incomplete SCI for at least 60 minutes; however, it did not modify spinal excitability or spasticity.

Effects of High-Frequency rTMS on Negative Symptoms and Cognitive Function in Hospitalized Patients With Chronic Schizophrenia: A Double-Blind, Sham-Controlled Pilot Trial.

This study aimed to evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral pre-frontal cortex (DLPFC) in ameliorating negative symptoms and cognitive impairments in patients with chronic schizophrenia. Fifty-two patients with chronic schizophrenia were randomly assigned to two groups: active rTMS group and sham rTMS group, with existing antipsychotic drugs combined 20 sessions of 10 Hz active/sham rTMS over DLPFC (20 min/session, 5 times/week). The PANSS, RBANS, and SCWT were used to evaluate the clinical symptoms and cognitive functions of the patients. Our results indicated significant improvements in clinical symptoms (PANSS total and subscale scores) and cognitive functions (RBANS total and subscale scores, card 1 and card 3 of the SCWT test) (All p <0.05) after 4-week intervention both in active and sham rTMS group. Moreover, the active rTMS group showed more effective on ameliorating negative symptoms (p = 0.002), immediate memory (p = 0.016) and delayed memory (p = 0.047) compared to the sham group. Interestingly, PANSS negative symptom scores was negatively correlated with RBANS language scores in the real stimulation group (p = 0.046). The study found that the high frequency rTMS stimulation over left DLPFC as a supplement to antipsychotics may have potential benefits in improving clinical symptoms and cognitive functions in patients with chronic schizophrenia.

Deep-TMS for Negative Symptoms of Schizophrenia

Background: Negative symptoms of schizophrenia(NSS) are resistant to current pharmacological interventions. Thirty percent of appropriately medicated schizophrenia patients are disabled due to negative symptoms(NS). Prefrontal and orbitofrontal cortical volumes are decreased in NSS. PET and SPECT studies demonstrate decreased metabolism in frontal and prefrontal areas, particularly the DLPFC, leading to the study of high frequency rTMS for NSS. Conflicting sham-controlled studies resulted in the 2019 rTMS evidence based treatment guidelines downgrading high frequency rTMS LDLPFC for NSS to a C, possibly efficacious.

Repetitive transcranial magnetic stimulation and its role in suicidality - A systematic review.

Repetitive transcranial magnetic stimulation (rTMS) as a brain stimulation modality is approved for the treatment of resistant depression and its efficacy in depression is also well supported in several studies. However, its effect on suicidality is still unclear, unlike electroconvulsive therapy. This paper provides a systematic review of the literature published till June 2021. Studies that used rTMS as either monotherapy or adjunctive treatment in patients with suicidality, irrespective of their diagnosis, were included. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines was followed. A total of 20 studies (N = 1584) were included for the qualitative synthesis. The quality of studies was assessed using the Cochrane Risk of Bias tool for Randomised control trials (RCT) and the Newcastle-Ottawa Scale tool for Non-Randomised studies (NRS). Of the 20 articles selected for qualitative synthesis, 11 were RCTs and 9 were NRS. The results are categorized in domains of type of the study, size of population, type of population, diagnosis, assessment scales, mode of rTMS, stimulus parameters, safety and efficacy. The high frequency rTMS at left dorsolateral prefrontal cortex as an adjunct to antidepressant medication is promising in reducing suicidal behaviour in treatment resistant depression. However, role of TMS targeting other areas of stimulation in mitigating suicide risk in other disorders could not be established due to scarcity of such studies. The results should be interpreted cautiously as considerable risk of bias was present in the reviewed studies.

Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Modulates Electroencephalographic Functional Connectivity in Alzheimer's Disease.

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer’s disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear.Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment.Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared.Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p < 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p < 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group.Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.

Effects of Noninvasive Brain Stimulation (NIBS) on Cognitive Impairment in Mild Cognitive Impairment and Alzheimer Disease: A Meta-analysis.

The purpose of this meta-analysis was to evaluate the beneficial effects and optimal stimulation protocol of noninvasive brain stimulation (NIBS) including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on patients with mild cognitive impairment and Alzheimer disease. PubMed, Web of Science, Embase, and the Cochrane Library were searched until March 2020. The cognitive outcomes were extracted and the standardized mean difference with 95% confidence interval was calculated. Twenty-eight studies were included. The result of NIBS showed significant effect on global cognition (P<0.05). Low-frequency rTMS over right dorsolateral prefrontal cortex (DLPFC), high-frequency rTMS (HF-rTMS) over left DLPFC, and the tDCS over left DLPFC and temporal lobe can significantly improve the memory function (P<0.05). HF-rTMS over left, right, or bilateral DLPFC can significantly improve the language function (P<0.05). Both HF-rTMS and tDCS over left DLPFC can obviously improve the executive function (P<0.05). Multiple sessions of rTMS with 80% to 100% intensity and anode tDCS with 2 mA current density are more suitable for all these functions. NIBS has a beneficial effect on cognitive performance in both mild cognitive impairment and Alzheimer disease patients. Distinct optimal stimulation parameters were observed for different cognitive functions.

Repetitive Transcranial Magnetic Stimulation With H-Coil Coupled With Cycling for Improving Lower Limb Motor Function After Stroke: An Exploratory Study

Repetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for the treatment of post-stroke motor deficits. Here, we explore safety, feasibility, and potential effectiveness of high-frequency rTMS (HF-rTMS) delivered with the Hesed coil (H-coil) during active cycling on paretic lower extremity (LE) motor function in chronic stroke. Twelve subjects with a first-ever stroke were recruited in this double-blind, placebo controlled, crossover study. Eleven sessions of HF-rTMS (40 2s-trains of 20Hz at 90% resting leg motor threshold) were delivered over the LE motor areas using the H-coil during active cycling for three weeks. Each subject underwent both real and sham rTMS treatments separated by a four-week washout period, in a random sequence. Vital signs were recorded before and after each rTMS session. Any discomfort related to stimulation and side effects were recorded. LE function was also evaluated with Fugl-Meyer assessment (FMA-LE), spasticity was assessed with modified-Ashworth scale and measures of gait speed and endurance (10-meter and 6-min walk tests, respectively) were recorded. No participant reported serious adverse effects. During real rTMS, 4 of 12 subjects reported mild side effects including transitory dizziness and muscle twitches on shoulder, so that intensity of stimulation initially set at 90% of RMT was reduced to 80% of RMT on average in these four subjects. Only real treatment was associated with a significant and sustained improvement in FMA-LL (67% responders vs. 9% of the sham). Spasticity significantly ameliorated only after the real rTMS. Real treatment did not offer advantages on walking timed measures when compared with sham. This exploratory study suggests that bilateral HF-rTMS combined with cycling is safe and potentially effective in ameliorating paretic LE motor function and spasticity, rather than gait speed or endurance, in chronic stroke.

Management of Pain and Related Disabilities in Primary Fibromyalgia Using Neuromodulator Techniques, Repetitive Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation

Background: Fibromyalgia syndrome (FMS) is a chronic condition that causes pain, stiffness, and tenderness in muscles, tendons, and joints. It is also characterized by disturbed sleep, fatigue, anxiety, depression, and disturbances in bowel function. Management of FMS is at present very challenging as it contains multiple etiological factors and psychological tendencies; though, a patient-centered approach is essential to deal with this problem. Objective: To compare the efficacy of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in improving pain and related disabilities in patients with primary (1ry) FM. Patients and Methods: Thirty patients with 1ry FM, 18 to 50 years old were randomized into 2 groups. Group I included 15 patients, who received 8 sessions (2/week for 4 consecutive weeks) of high frequency rTMS (10 Hz frequency) and Group II included 15 patients received 8 daily sessions of anodal tDCS (2 mA for 20 minutes) applied over the left primary motor cortex (M1). Results: Pain visual analogue scale (VAS), the revised Fibromyalgia Impact Questionnaire (FIQR), tender point scale, and Hospital Anxiety and Depression Scale (HADS) showed a 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 that received rTMS. Conclusion: Both rTMS and anodal tDCS of the left primary motor cortex showed marked improvement in symptoms of pain, functional disabilities and psychological status in patients with 1ry fibromyalgia. Both neuromodulator techniques can be considered as promising alternatives therapeutic options in the management of pain and related disabilities in FM.

Repetitive transcranial magnetic stimulation increases the brain\u2019s drainage efficiency in a mouse model of Alzheimer\u2019s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients.

Mechanisms of transcranial magnetic stimulation in the treatment of anorexia nervosa

AimsSevere and Enduring Anorexia Nervosa (SE-AN) is a challenging condition to treat, with limited therapeutic options, high morbidity, and the highest mortality rates of any psychiatric illness. Repetitive Transcranial Magnetic Stimulation (rTMS) is an emerging treatment option, as evidence demonstrates promising efficacy in improving mood and reducing core Anorexia Nervosa symptoms, as well as safety and tolerability to patients. We aimed to investigate the neurophysiological mechanisms of rTMS use in SE-AN patients by assessing changes in resting state functional connectivity, in the first functional neuroimaging analysis investigating rTMS effects in Anorexia Nervosa patients.Method26 females with a current diagnosis of SE-AN received 20 sessions of sham or real high frequency rTMS (10 hertz) to the left dorsolateral prefrontal cortex in a randomised double-blind trial. Resting-state functional magnetic resonance imaging was performed before and after rTMS. Neural correlates of rTMS treatment were identified using a seed-based functional connectivity analysis with the left dorsolateral prefrontal cortex and bilateral amygdalae as regions of interest. Functional connectivity differences were analysed using t-contrasts in a mixed ANOVA (flexible factorial analysis) to assess interactions between treatment group (real rTMS vs sham) and time-point (pre or post TMS).ResultNo statistically significant changes in resting-state functional connectivity were observed post-rTMS compared to baseline in participants receiving active rTMS compared to sham. Increased functional connectivity between the left amygdala and left pre-supplementary motor area was observed to reach cluster-wise significance (PFWE &lt; 0.05). However, after Bonferroni correction for multiple comparisons (3 seed regions), this did not reach the significance threshold PFWE &lt;0.017.ConclusionThis study highlights the need for further investigation of neurophysiological mechanisms, including resting-state functional connectivity modulation, resulting from rTMS to the dorsolateral prefrontal cortex in SE-AN patients. This requires higher powered studies to account for heterogeneity in treatment response. We have provided some indication that high frequency rTMS may have therapeutic benefit in SE-AN by modification of functional connectivity between prefrontal and limbic brain regions, resulting in improved top-down cognitive control over emotional processing and ability to enact goal-directed behaviours, enabling secondary reductions in eating disorder behaviours.

The impact of rTMS on patients with dual diagnosis of depressive disorder and substance use disorders

AimsWe aim to investigate the effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS) in reducing consumption and craving among patients with Substance Use Disorder (SUD) and comorbid depressive disorder.BackgroundDorsolateral prefrontal cortex (DLPFC) is greatly involved in SUD evolution (1). Research has turned to targeting this brain area with rTMS; a non-invasive brain stimulation technique that modulates cortical excitability by sending pulsatile electromagnetic fields through the skull and into the brain (2). rTMS is an FDA approved and safe treatment option for treatment-resistant depression (TRD) (3).MethodFifty-four patients were admitted over six-month period of time (June 2019- December 2019) to the inpatient unit of Erada center for treatment and rehabilitation of SUD in Dubai. All patients who fulfilled ICD-10 diagnoses of Depressive disorder and SUD were screened for further assessment.Positive drug screen was confirmed through urine analysis. Hospital Anxiety and Depression Scale (HADS) and Brief Substance Craving Scale (BSCS) were applied to all participants. Patients were contracted for 5-times weekly High frequency (10 Hz) rTMS for 4 weeks (total of 20 treatments). Those who managed to complete their contracted TMS sessions were matched for age and sex with similar number of patients who received standard treatment as usual (TAU). Stimulation was as per FDA clearance for rTMS application in TRD.ResultEight patients were excluded (previous head trauma). A total of 46 patients had TMS mapping; nine of whom completed 20 sessions.Opioids was the most commonly used drug in almost 52% of patients (n = 14), followed by amphetamines in almost 30% (n = 8) and Cannabis in 18.5% (n = 5).Among those who completed 20 rTMS sessions; HADS scores on anxiety and depression fell by 85% and 78% respectively. BSCS score fell by 98%. Relapse rate (defined by positive drug screen) at 3 months was 33%.For those who completed 10 sessions; there was only 50% reduction on BSCS scores and 66% relapse rate. There were no data available on their HADS scores (only collected at baseline and at completion of 20 sessions).Those who only had TAU; there were no reduction in their BSCS (average score of 7 at both baseline and after 2 weeks).ConclusionOur findings suggest that rTMS may be an effective and safe treatment for both depressive disorder and craving for SUD which is supported by other studies (3,4).Our study is probably the first of its kind within Middle East population with addiction problems.

Modification of rectal function and emotion by repetitive transcranial magnetic stimulation in humans

Gut microbiota may affect function of the dorsolateral prefrontal cortex (DLPFC). However, there have been a few studies on modification of brain-gut interactions with repetitive transcranial magnetic stimulation (rTMS) to the DLPFC. We hypothesized that stimulation of the right or left DPFC by rTMS modifies the brain-gut interactions in humans. Subjects were 25 healthy males. Viscerosensory evoked potential (VEP) with sham (0 mA) or actual (30 mA) electrical stimulation (ES) of the rectum was taken after sham, low frequency rTMS at 0.1 Hz, and high frequency rTMS at 10 Hz to the right or left DLPFC. Rectal tone was measured with a rectal barostat. Visceral perception and emotion were analyzed using ordinates scale, rectal barostat, and viscerosensory evoked potential. Low frequency rTMS to the right DLPFC significantly reduced the visceral sensation and emotion composite score evoked by ES at 30 mA (p < 0.05). Plasma ACTH was significantly increased by high frequency rTMS to the right or left DLPFC (p < 0.05). Rectal fine contractions were significantly induced by low frequency rTMS to the right or left DLPFC and high frequency rTMS to the right DLPFC (p < 0.05). These results suggest that stimulation of the right or left DPFC by rTMS modifies the brain-gut interactions in humans.

High frequency repetitive Transcranial Magnetic Stimulation promotes long lasting phrenic motoneuron excitability via GABAergic networks

Repetitive transcranial magnetic stimulation (rTMS) is a promising, innovative, and non-invasive therapy used clinically. Efficacy of rTMS has been demonstrated to ameliorate psychiatric disorders and neuropathic pain through neuromodulation of affected neural circuits. However, little is known about the mechanisms and the specific neural circuits via which rTMS facilitates these functional effects. The aim of this study was to begin revealing the mechanisms by which rTMS may tap into existing neural circuits, by using a well characterized spinal motor circuit – the phrenic circuit. Here we hypothesized that rTMS can be used to enhance phrenic motoneuron excitability in anesthetized Sprague Dawley rats. Multiple acute rTMS protocols were used revealing 10 Hz rTMS protocol induced a robust, long-lasting increase in phrenic motoneuron excitability, functionally evaluated by diaphragm motor evoked potentials (59.1 ± 21.1 % of increase compared to baseline 60 min after 10 Hz protocol against 6.0 ± 5.8 % (p = 0.007) for Time Control, -5.8 ± 7.4 % (p < 0.001) for 3 Hz, and 5.2 ± 12.5 % (p = 0.008) for 30 Hz protocols). A deeper analyze allowed to discriminate “responder” and “non-responder” subgroups among 10 Hz rTMS treated animals. Intravenous injections of GABAA and GABAB receptor agonists prior to 10 Hz rTMS treatment, abolished the enhanced phrenic motoneuron excitability, suggesting GABAergic input plays a mechanistic role in rTMS-induced phrenic excitability. These data demonstrate that a single high frequency rTMS protocol at 10 Hz increases phrenic motoneuron excitability, mediated by a local GABAergic “disinhibition”. By understanding how rTMS can be used to affect neural circuits non-invasively we can begin to harness the therapeutic potential of this neuromodulatory strategy to promote recovery after disease or injury to the central nervous system.

High frequency repetitive transcranial magnetic stimulation of dorsomedial prefrontal cortex for negative symptoms in patients with schizophrenia: A double-blind, randomized controlled trial

Negative symptoms are the major challenge in clinical management of schizophrenia. Dorsomedial prefrontal cortex (DMPFC) has been suggested to be highly involved in the mechanisms of negative symptoms of schizophrenia. However, the effect of repetitive Transcranial Magnetic Stimulation (rTMS) over DMPFC has not yet been well studied. In this double-blind, randomized controlled rTMS clinical trial, thirty-three participants (17 in active group and 16 in sham group) were enrolled. This study includes the rTMS treatment phase (lasts for 4 weeks) and a subsequently naturalistic follow-up phase (lasts for another 4 weeks). Schizophrenia patients with prominently negative symptoms were randomly assigned to receive 10 Hz or sham rTMS intervention. The score change in Scale of Negative Symptoms (SANS) was defined as the primary outcome measure. There was a significant decrease in negative symptoms, especially affective flattening and anhedonia in schizophrenia patients after DMPFC-rTMS intervention. Moreover, the negative symptoms improvement could maintain at least another 4 weeks. In addition, no memory impairment or serious adverse reaction of rTMS emerged. Our results suggest that high frequency rTMS over DMPF may represent a safe and effective treatment for negative symptoms in patients with schizophrenia.

Effects of repetitive transcranial magnetic stimulation (rTMS) on aphasia in stroke patients: A systematic review and meta-analysis

Objective: To evaluate the effects and safety of repetitive transcranial magnetic stimulation (rTMS) on aphasia in stroke patients. Methods: We searched databases from inception to January 28, 2021. Randomized control trials investigating the effects and safety of rTMS for aphasia patients after stroke were included. Study screening, data extraction, and risk of bias assessment were performed independently by two reviewers. Meta-analysis was conducted with Review Manager 5.3 software. The quality of the evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Twenty-eight studies with 1287 patients were included. All studies were assessed at low or unclear risk of bias in one or more domains. The meta-analysis exhibited rTMS was better than sham rTMS and conventional rehabilitation in language recovery. Low-frequency rTMS showed greater improvement in language recovery except for comprehension than sham rTMS. Low-frequency and bilateral rTMS were superior to conventional rehabilitation in language recovery. High-frequency rTMS was no better than sham rTMS and conventional rehabilitation for improving aphasia. The rTMS had better effects in naming, comprehension and aphasia quotient at 20 sessions. Eleven studies reported rTMS was safe for aphasia patients after stroke. The quality of evidence for all outcomes was low or very low, and publication bias may exist. Conclusions: rTMS may be relatively effective and safe for aphasia patients after stroke. However, these findings should be treated with caution due to high heterogeneity and potential biases.

Distinction of High- and Low-Frequency Repetitive Transcranial Magnetic Stimulation on the Functional Reorganization of the Motor Network in Stroke Patients.

Objective To investigate the functional reorganization of the motor network after repetitive transcranial magnetic stimulation (rTMS) in stroke patients with motor dysfunction and the distinction between high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS). Methods Thirty-three subcortical stroke patients were enrolled and assigned to the HF-rTMS group, LF-rTMS group, and sham group. Each patient of rTMS groups received either 10.0 Hz rTMS over the ipsilesional primary motor cortex (M1) or 1.0 Hz rTMS over the contralesional M1 for 10 consecutive days. A resting-state functional magnetic resonance imaging (fMRI) scan and neurological examinations were performed at baseline and after rTMS. The motor network and functional connectivities intramotor network with the core brain regions including the bilateral M1, premotor area (PMA), and supplementary motor area (SMA) were calculated. Comparisons of functional connectivities and Pearson correlation analysis between functional connectivity changes and behavioral improvement were calculated. Results Significant motor improvement was found after rTMS in all groups which was larger in two rTMS groups than in the sham group. The functional connectivities of the motor network were significantly increased in bilateral M1, SMA, and contralesional PMA after real rTMS. These changes were only detected in the regions of the ipsilesional hemisphere in the HF-rTMS group and in the regions of the contralesional hemisphere in the LF-rTMS group. Significantly changed functional connectivities of the intramotor network were found between the ipsilesional M1 and SMA and contralesional PMA, between contralesional M1 and contralesional SMA, between contralesional SMA and ipsilesional SMA and contralesional PMA in the HF-rTMS group in which the changed connectivity between ipsilesional M1 and contralesional PMA was obviously correlated with the motor improvement. In addition, the functional connectivity of the intramotor network between ipsilesional M1 and contralesional PMA was significantly higher in the HF-rTMS group than in the LF-rTMS group. Conclusion Both HF-rTMS and LF-rTMS have a positive effect on motor recovery in patients with subcortical stroke and could promote the reorganization of the motor network. HF-rTMS may contribute more to the functional connectivity reorganization of the ipsilesional motor network and realize greater benefit to the motor recovery.

A double-blind randomized clinical trial of high frequency rTMS over the DLPFC on nicotine dependence, anxiety and depression

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is a widely applied treatment protocol for chronic smoking and major depressive disorder. However, no previous study has measured the effects of rTMS on both nicotine consumption and anxiety/depression in the same volunteers despite the relationship between them. The aim of this work was to evaluate the efficacy of 10 daily sessions of HF-rTMS over the L-DLPFC in chronic cigarette smokers’ addiction and investigate the possible beneficial effects of this treatment procedure on symptoms of depression and anxiety in the same subjects. The study included 40 treatment-seeking nicotine-dependent cigarette smokers. Onset/duration of smoking, number of cigarettes/day, Fagerstrom Test of Nicotine Dependence (FTND), Tobacco Craving Questionnaire-Short Form (TCQ-SF), Hamilton depression and anxiety scales (HAM-D and HAM-A) were recorded. Participants were randomly assigned to the active or the sham treatment group. Those in the active group received 10 trains of 20 Hz stimulation, at 80% of the resting motor threshold (rMT) for 10 consecutive working days over L-DLPFC. Participants were reassessed immediately after treatment, and then 3 months later using all rating scales. There were no differences between active and sham groups at baseline. The cigarette consumption/day, and scores on FTND, and TCQ decreased significantly in both groups (p = 0.0001 for each) immediately after treatment. However, improvement persisted to 3 months in the active group but not in the sham group. Moreover, there was a significant reduction in HAM-D and HAM-A scores immediately after treatment in the active but not the sham group. Subjects with a longer history of smoking had a lower percent improvement in FTND (p = 0.005). Our findings revealed that HF-rTMS over L-DLPCF for 10 days reduced cigarette consumption, craving, dependence, and improved associated symptoms of anxiety and depression.ClinicalTrials.gov Identifier: NCT03264755 registered at 29/08/2017.

EFFECT OF HIGH FREQUENCY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION ON POST STROKE-DYSPHASIA

Background: Aphasia is characterized as language impairment. The bulk of stroke-induced cerebrovascular disease leads to its prevalence. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and painless method of altering the excitability of the cerebral cortex by inducing or enhancing neuroplasticity in brain. Objective: The goal of this research to assess the effect of high frequency repetitive transcranial magnetic stimulation (rTMS) on improving post-stroke dysphasia. Patients and methods: Our studies were conducted on sixty (60) patients suffering from post-cerebrovascular stroke dysphasia and were randomly divided into two groups. Group A (case group): Forty patients received stimulatory session’s high frequency) of rTMS (10Hz, 90 % of motor threshold) over the dominant language areas, and Group B (sham group): Twenty patients received sham rTMS on dominant language areas. Patients were selected from the Department of Neurology at Al-Azhar University Hospitals, and follow up was performed at outpatient clinics at (Bab Al-Shaaria and Al-Hussien university hospitals). Results: There were a significant changes in fluency, auditory verbal (AV) comprehension, sequential commands and aphasia qutions (AQ) before and after rTMS therapy in group A (P <0.05). There was significant difference in auditory verbal (AV) comprehension, sequential commands before and after shamTMS therapy in group B (P <0.05). Conclusion: Significant changes were found in fluency, auditory verbal comprehension, sequential commands and aphasia qutions between before and after TMS therapy in group A (case group).High frequency rTMS was beneficial for rehabilitating patients with post stroke aphasia.