Low-frequency rTMS Research Articles

Which repetitive transcranial magnetic stimulation modality affects vasomotor reactivity in healthy subjects and how long does it last?

Objectives The aim of our study was to evaluate the effects of low and high-frequency repetitive transcranial magnetic stimulation (rTMS) on hypoxia-induced changes in bilateral cerebrovascular reserve up to 24 h in the same individuals. Methods Right-handed ten healthy male individuals participated in the study. All participants had neither drug therapy nor a concomitant disease and none of them had a variation in the circle of Willis, intracranial stenosis, arteriovenous malformation, or aneurysm which may have an impact on transcranial doppler ultrasound (TCD) examination and transcranial magnetic stimulation (TMS) recording. Results There was a statistically significant difference in the breath‐holding index (BHI) between before and after 0, 15, 30 min after 1 Hz repetitive stimulation (p < 0.05). When applying 5 Hz repetitive stimulation there was no difference before and after BHI values (p > 0.05). There were no differences in bilateral, ipsilateral, or contralateral middle cerebral artery (MCA) mean cerebral blood flow velocity (CBFV) after low or high-frequency rTMS application (p > 0.05). Conclusion The main result of the study was that low-frequency rTMS reduced vasomotor reactivity (VMR) for the very first 30 min and then this effect disappears. And the high-frequency rTMS did not affect VMR at all. Significance The effect of rTMS on VMR may continue up to 30 min but then return to the baseline and can be used safely.

Assessing differential effects of single and accelerated low-frequency rTMS to the visual cortex on GABA and glutamate concentrations.

BackgroundThe application of repetitive transcranial magnetic stimulation (rTMS) for therapeutic use in visual‐related disorders and its underlying mechanisms in the visual cortex is under‐investigated. Additionally, there is little examination of rTMS adverse effects particularly with regards to visual and cognitive function. Neural plasticity is key in rehabilitation and recovery of function; thus, effective therapeutic strategies must be capable of modulating plasticity. Glutamate and γ‐aminobutyric acid (GABA)‐mediated changes in the balance between excitation and inhibition are prominent features in visual cortical plasticity.Objectives and methodWe investigated the effects of low‐frequency (1 Hz) rTMS to the visual cortex on levels of neurotransmitters GABA and glutamate to determine the therapeutic potential of 1 Hz rTMS for visual‐related disorders. Two rTMS regimes commonly used in clinical applications were investigated: participants received rTMS to the visual cortex either in a single 20‐min session or five accelerated 20‐min sessions (not previously investigated at the visual cortex). Proton (1H) magnetic resonance spectroscopy for in vivo quantification of GABA (assessed via GABA+) and glutamate (assessed via Glx) concentrations was performed pre‐ and post‐rTMS.ResultsGABA+ and Glx concentrations were unaltered following a single session of rTMS to the visual cortex. One day of accelerated rTMS significantly reduced GABA+ concentration for up to 24 hr, with levels returning to baseline by 1‐week post‐rTMS. Basic visual and cognitive function remained largely unchanged.ConclusionAccelerated 1 Hz rTMS to the visual cortex has greater potential for approaches targeting plasticity or in cases with altered GABAergic responses in visual disorders. Notably, these results provide preliminary insight into a critical window of plasticity with accelerated rTMS (e.g., 24 hr) in which adjunct therapies may offer better functional outcome. We describe detailed procedures to enable further exploration of these protocols.

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity

PurposeRepetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated to be effective in body weight control in individuals with obesity. Most clinical trials on rTMS provided a reassuring safety profile. In the present work, we present an extensive analysis on both severe and mild Adverse Events (AEs) in obese individuals treated with rTMS.MethodsWe examined the intensity, duration, correlation with the treatment, up to 1 year after the end of rTMS treatment.ResultsDescriptive analysis included a total of 63 subjects undergoing a 5-week deep rTMS experimental treatment for obesity (age 48.3 ± 10.4 years; BMI 36.3 ± 4.4 kg/m2): 31 patients were treated with high-frequency rTMS (HF), 13 with low-frequency rTMS (LF), and 19 were sham treated (Sham). Thirty-two subjects (50.8%) reported a total of 52 AEs, including mainly moderate (51.9%) events. The most frequently reported side effects were headaches of moderate intensity (40.4%) and local pain/discomfort (19.2%) and resulted significantly more frequent in HF group compared to other groups (p < 0.05). No significant differences among groups were found for the other reported AEs: drowsiness, insomnia, paresthesia, vasovagal reactions, hypertensive crisis. No AEs potentially related to the rTMS arised up to 1 year from the end of the treatment.ConclusionsThis is the first comprehensive safety analysis in obese patients treated with rTMS. The analysis did not reveal any unexpected safety concerns. Only headaches and local pain/discomfort have been significantly more frequent in the HF group, confirming the good tolerability of rTMS even in the obese population potentially more susceptible to side effects of brain stimulation.

Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm

BackgroundNeural oscillations reflect rapidly changing brain excitability states. We have demonstrated previously with EEG-triggered transcranial magnetic stimulation (TMS) of human motor cortex that the positive vs. negative peak of the sensorimotor μ-oscillation reflect corticospinal low-vs. high-excitability states. In vitro experiments showed that induction of long-term depression (LTD) by low-frequency stimulation depends on the postsynaptic excitability state.Objective/Hypothesis: We tested the hypothesis that induction of LTD-like corticospinal plasticity in humans by 1 Hz repetitive TMS (rTMS) is enhanced when rTMS is synchronized with the low-excitability state, but decreased or even shifted towards long-term (LTP)-like plasticity when synchronized with the high-excitability state. MethodsWe applied real-time EEG-triggered 1-Hz-rTMS (900 pulses) to the hand area of motor cortex in healthy subjects. In a randomized double-blind three-condition crossover design, pulses were synchronized to either the positive or negative peak of the sensorimotor μ-oscillation, or were applied at random phase (control). The amplitude of motor evoked potentials was recorded as an index of corticospinal excitability before and after 1-Hz-rTMS. Results1-Hz-rTMS at random phase resulted in a trend towards LTD-like corticospinal plasticity. RTMS in the positive peak condition (i.e., the low-excitability state) induced significant LTD-like plasticity. RTMS in the negative peak condition (i.e., the high-excitability state) showed a trend towards LTP-like plasticity, which was significantly different from the other two conditions. ConclusionThe level of corticospinal depolarization reflected by phase of the μ-oscillation determines the degree of corticospinal plasticity induced by low-frequency rTMS, a finding that may guide future personalized therapeutic stimulation.

Low-Frequency Repetitive Transcranial Magnetic Stimulation over Right Dorsolateral Prefrontal Cortex in Parkinson's Disease.

Background Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic tool for Parkinson's disease (PD), and many stimulation targets have been implicated. We aim to explore whether low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) improves motor and nonmotor symptoms of individuals with PD. Methods We conducted a randomized, single-blind, sham-controlled parallel trial to compare the effect of 10 consecutive daily sessions of 1 Hz rTMS over right DLPFC on individuals with idiopathic PD between active and sham rTMS group. Primary outcomes were changes in Unified Parkinson's Disease Rating Scale (UPDRS) part III and Nonmotor Symptom Questionnaire (NMSQ). Secondary outcomes were changes in UPDRS total score, Hamilton Rating Scale for Depression (HRSD), Pittsburgh Sleep Quality Index (PSQI), and Montreal Cognitive Assessment (MoCA). Assessments were completed at baseline, after treatment, and at 1 month, 3 months, and 6 months after treatment. Results A total of 33 participants with PD were randomized. All participants completed the study and no severe adverse effect was noticed. Compared to baseline, active rTMS showed significant improvements in UPDRS part III and NMSQ at 1 month. Change of scores on UPDRS part III, HRSD, and PSQI persisted for 3 months after rTMS intervention. The beneficial effect on cognitive performance assessed by MoCA was maintained for at least 6 months in the follow-up. No significant changes were observed in the group with sham rTMS. Conclusions Low-frequency rTMS of right DLPFC could be a potential selection in managing motor and nonmotor symptoms in PD.

Low-frequency rTMS inhibits the anti-depressive effect of ECT. A pilot study.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has been shown to have a statistically and clinically significant anti-depressant effect. The present pilot study was carried out to investigate if right prefrontal low-frequency rTMS as an add-on to electroconvulsive therapy (ECT) accelerates the anti-depressant effect and reduces cognitive side effects. In this randomised, controlled, double-blind study, thirty-five patients with major depression were allocated to ECT+placebo or ECT+low-frequency right prefrontal rTMS. The severity of depression was evaluated during the course using the Hamilton scale for depression (the 17-item as well as the 6-item scale) and the major depression inventory (MDI). Furthermore, neuropsychological assessment of cognitive function was carried out. The study revealed no significant difference between the two groups for any of the outcomes, but with a visible trend to lower scores for MDI after treatment in the placebo group. The negative impact of ECT on neurocognitive functions was short-lived, and scores on logical memory were significantly improved compared to baseline 4 weeks after last treatment. The ECT-rTMS group revealed generally less impairment of cognitive functions than the ECT-placebo group. The addition of low-frequency rTMS as an add-on to ECT treatment did not result in an accelerated response. On the contrary, the results suggest that low-frequency rTMS could inhibit the anti-depressant effect of ECT.

Frontal\u2013striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS

Repetitive transcranial magnetic stimulation (rTMS), when applied to left dorsolateral prefrontal cortex (LDLPFC), reduces negative symptoms of schizophrenia, but has no effect on positive symptoms. In a small number of cases, it appears to worsen the severity of positive symptoms. It has been hypothesized that high-frequency rTMS of the LDLPFC might increase the dopaminergic neurotransmission by driving the activity of the left striatum in the basal ganglia (LSTR)—increasing striatal dopaminergic activity. This hypothesis relies on the assumption that either the frontal–striatal connection or the intrinsic frontal and/or striatal connections covary with the severity of positive symptoms. The current work aimed to evaluate this assumption by studying the association between positive and negative symptoms severity and the effective connectivity within the frontal and striatal network using dynamic causal modeling of resting state fMRI in a sample of 19 first episode psychosis subjects. We found that the total score of positive symptoms of schizophrenia is strongly associated with the frontostriatal circuitry. Stronger intrinsic inhibitory tone of LDLPFC and LSTR, as well as decreased bidirectional excitatory influence between the LDLPFC and the LSTR is related to the severity of positive symptoms, especially delusions. We interpret that an increase in striatal dopaminergic tone that underlies positive symptoms is likely associated with increased prefrontal inhibitory tone, strengthening the frontostriatal ‘brake’. Furthermore, based on our model, we propose that lessening of positive symptoms could be achieved by means of continuous theta-burst or low-frequency (1 Hz) rTMS of the prefrontal area.

A Case of Psychogenic Myoclonus Responding to a Novel Transcranial Magnetic Stimulation Approach: Rationale, Feasibility, and Possible Neurophysiological Basis.

Repetitive transcranial magnetic stimulation (rTMS) can relieve motor symptoms related to psychogenic movement disorders (PMDs), but the subtending neurophysiological basis is unclear. We report on a 50-year-old woman with a diagnosis of psychogenic myoclonus in the right lower limb, who was treated with a daily session (in the late morning/early afternoon) of 1 Hz rTMS over the left premotor cortex (PMC), five times a week for 6 weeks. Clinical data and EEG at rest were collected before and immediately and 2-month after the rTMS protocol completion. The patient reported a significant reduction of involuntary movement frequency and intensity and the related disability burden up to the follow-up. In parallel, any abnormality in terms of source current density within and connectivity between the frontal and parietal areas was reset. The short follow–up period, the lack of extensive neurophysiological measures, and the lack of control treatment represent the main limitation of the study. However, low-frequency rTMS over PMC seems a safe and promising approach for the management of psychogenic myoclonus owing to the combination of cortical neuromodulation and non-specific mechanisms suggesting cognitive-behavioral effects.

The effect of repetitive transcranial magnetic stimulation on upper extremity motor function in stroke patients: A meta-analytical review

Repetitive magnetic stimulation (rTMS) is a non-invasive brain stimulation technique, which can alter excitability in the motor cortex and is a potential treatment for motor impairment in stroke patients. However, the effect of rTMS on upper extremity function in stroke patients remains controversial. This study systematically reviewed and meta-analyzed the current findings on the effectiveness of rTMS for restoring upper extremity motor function in stroke patients. A comprehensive literature search up to March 2010 of PubMed, the Cochrane Library, Scirus and the Chinese Electronic Periodical Services (CEPS) was performed. The articles from these searches were used to obtain additional articles. The quality of each study was assessed by criteria suggested by Jadad and the American Academy of Neurology for grading therapeutic trials. Biostat meta-analysis software version 2.0 was used to perform meta-analysis. Nine studies were included. The overall random effects model revealed a significant positive treatment effect of rTMS when applied to primary motor cortex (M1) (Hedges' g = 0.590, 95% CI = 0.133 - 1.048, p= 0.011). In subgroup analysis, positive treatment effects were seen in acute stroke (Hedges' g = 0.91, 95% CI = 0.339 - 1.481, p = 0.002) and on the nonlesional M1 cortex (Hedges' g = 0.807, 95% CI = 0.054 - 1.560, p = 0.036). It is concluded that when applied to the nonlesional hemisphere, low frequency rTMS may improve the upper extremity motor function of patients with acute stroke.

Changes of resting-state EEG microstates induced by low-frequency repetitive transcranial magnetic stimulation.

Repetitive Transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that can influence cortical excitability. Low-frequency rTMS (stimulation frequency ≤1Hz) induces long-lasting inhibitory effects on cortical excitability. At the same time, EEG microstates have been studied and have been thought to corresponding to functional relevant brain-states. In order to investigate dynamic changes in EEG microstates after low-frequency rTMS, 20 healthy subjects received 1-Hz rTMS over the right motor area, and electroencephalography (EEG) in resting condition with eyes open was recorded before rTMS (Pre) and at 0 min, 20 min, 40 min, and 60 min after rTMS (Post0, Post20, Post40, and Post60). Resting state EEG data of all five sessions were computed using a clustering algorithm. Four EEG microstates were found and labeled with the letters A, B, C and D. No significant difference in duration was found among five sessions for four microstates. For microstates A, and B, there is an increase in the mean duration immediately after rTMS. And for microstate C, the mean duration at Post0 and Post60 was significantly higher than that before rTMS. For microstate D, there is an increase in the mean duration at 60min after rTMS. These results showed that we reproduced the same four microstate maps best representing the resting state EEG as found by others and that low-frequency rTMS produced long-lasting alterations in the mean duration of EEG microstates. It implies that low-frequency rTMS increases the stability of EEG microstates.

Non-invasive brain stimulation as add-on therapy for subacute post-stroke aphasia: a randomized trial (NORTHSTAR).

Non-invasive brain stimulation (NIBS) with speech therapy might improve recovery from post-stroke aphasia. This three-armed sham-controlled blinded prospective proof-of-concept study tested 1 Hz subthreshold repetitive transcranial magnetic stimulation (rTMS) and 2-mA cathodal transcranial direct current stimulation (ctDCS) on the right pars triangularis in subacute post-stroke aphasia. Sixty-three patients with left middle cerebral artery infarcts were recruited in five hospitals (Canada/United States/Germany, 01-2014/03-2018) and randomized to receive rTMS (N = 20), ctDCS (N = 24) or sham stimulation (N = 19) with ST for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Secondary outcome variable was the percent change in the Unified Aphasia Score. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment with a pre-planned subgroup analysis for lesion location (affecting Broca's area or not). Naming was significantly improved by rTMS (median = 1.91/interquartile range = 0.77/p = .01) at 30 days versus ctDCS (median = 1.11/interquartile range = 1.51) and sham stimulation (median = 1.02/interquartile range = 1.71). All other primary results were non-significant. The rTMS effect was driven by the patient subgroup with intact Broca's area where NIBS tended to improve UnAS (median = 33.2%/interquartile range = 46.7%/p = .062) versus sham stimulation (median = 12.5%/interquartile range = 7.9%) at day 30. Conversely, in patients with infarcted Broca's area, UnAS tended to improve more with sham stimulation (median = 75.0%/interquartile range = 86.9%/p = .053) versus NIBS (median = 12.7%/interquartile range = 31.7).Conclusion: We found a delayed positive effect of low-frequency rTMS targeting the right pars triangularis on the recovery of naming performance in subacute post-stroke aphasia. This intervention may be beneficial only in patients with morphologically intact Broca's area.

Repetitive transcranial magnetic stimulation of the prefrontal cortex for fibromyalgia syndrome: a randomised controlled trial with 6-months follow up

ObjectivesFibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS.MethodsNinety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months).ResultsIn Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed.ConclusionRight DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation .Trial registration: Ref No: CTRI/2013/12/004228.

Is twice daily LF-rTMS a viable treatment option for treatment-resistant OCD? Results from an open-label feasibility study.

Several reports point to the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant obsessive-compulsive disorder (OCD). This study aimed to evaluate the safety and efficacy of rTMS targeting the dmPFC in the treatment of treatment-resistant OCD patients. Twelve patients received 20 sessions of low-frequency (LF) rTMS (1Hz, 1200 pulses) in a twice daily protocol during 10weekdays. Y-BOCS and IDS scores modestly but significantly decreased after treatment and at follow-up and HADS anxiety improved at follow-up. LF rTMS may improve OCD, anxiety, and depressive symptoms in treatment-resistant OCD and was a safe and well-tolerated treatment.

Effect of repetitive transcranial magnetic stimulation on the kynurenine pathway in stroke patients.

Repetitive transcranial magnetic stimulation (rTMS) improves depressive symptoms and motor function in stroke patients. While metabolic derangement of the kynurenine pathway has been reported in stroke patients, the effect of rTMS on this pathway remains unknown. This study was performed to investigate the effect of rTMS on serum levels of kynurenine and tryptophan in stroke patients. Sixty-two stroke patients received rTMS in addition to intensive rehabilitation and 33 stroke patients received intensive rehabilitation alone for 14 days. The rTMS involved low-frequency stimulation (at 1 Hz) of the primary motor cortex on the unaffected side of the cerebrum. The depressive state of the patients was evaluated with the Beck Depression Inventory (BDI) before and after treatment. Motor function of the patients was evaluated with Fugl-Meyer Assessment (FMA). Serum levels of kynurenine and tryptophan levels were also measured before and after treatment. The serum tryptophan level decreased in the group receiving rTMS to the right brain and increased in the group receiving rTMS to the left brain. The serum kynurenine/tryptophan ratio was elevated in the group receiving rTMS to the right brain. The BDI indicated improvement of depressive symptoms in the rehabilitation alone group and the group receiving rTMS to the right brain plus rehabilitation. The FMA improved in all groups. The effect of low-frequency rTMS on the kynurenine pathway may differ depending on whether it is applied to the right or left cerebral hemisphere.

A Randomized Sham-controlled Trial of 1-Hz and 10-Hz Repetitive Transcranial Magnetic Stimulation (rTMS) of the Right Dorsolateral Prefrontal Cortex in Civilian Post-traumatic Stress Disorder: Un essai randomisé contrôlé simulé de stimulation magnétique transcrânienne repetitive (SMTr) de 1 Hz et 10 Hz du cortex préfrontal dorsolatéral droit dans le trouble de stress post-traumatique chez des civils.

Despite effective psychological and pharmacological treatments, there is a large unmet burden of illness in post-traumatic stress disorder (PTSD). Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention and a putative treatment strategy for PTSD. The evidence base to date suggests that rTMS targeting the dorsolateral prefrontal cortex (DLPFC), in particular the right DLPFC, leads to improvements in PTSD symptoms. However, optimal stimulation parameters have yet to be determined. In this study, we examine the efficacy of high- and low-frequency rTMS of the right DLPFC using a randomized, double-blind, sham-controlled design in civilian PTSD. We conducted a 2-week single-site randomized sham-controlled trial of rTMS targeting the right DLPFC. We recruited civilians aged 19 to 70 with PTSD and randomized subjects with allocation concealment to daily 1-Hz rTMS, 10-Hz rTMS, or sham rTMS. The primary outcome was improvement in Clinician Administered PTSD Scale-IV (CAPS-IV). Secondary outcomes included change in depressive and anxiety symptoms. We recruited 31 civilians with PTSD. One 1-Hz-treated patient developed transient suicidal ideation. Analyses revealed significant improvement in CAPS-IV symptoms in the 1-Hz group relative to sham (Hedges' g = -1.07) but not in the 10-Hz group. This was not attributable to changes in anxious or depressive symptomatology. Ten-Hz stimulation appeared to improve depressive symptoms compared to sham. Low-frequency rTMS is efficacious in the treatment of civilian PTSD. Our data suggest that high-frequency rTMS of the right DLPFC is worthy of additional investigation for the treatment of depressive symptoms comorbid with PTSD.

Low-Frequency Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Tinnitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background Chronic tinnitus affects approximately 10-15% of the population. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a promising and well-tolerated therapeutic strategy for chronic tinnitus. However, a recent large-scale multicenter clinical trial showed a negative result. Objective This systematic review is aimed at assessing the efficacy and safety of low-frequency rTMS in chronic tinnitus. Methods We searched PubMed, Embase, and Cochrane Library for randomized controlled studies of rTMS treatment of chronic tinnitus. A pooled analysis of standardized mean difference (SMD) was performed with 95% confidence intervals (CI). Results Ten RCTs involving 567 participants were included in this review. Compared with sham stimulation, rTMS showed no significant efficacy in tinnitus severity and disability measured by Tinnitus Handicap Inventory (THI) in short-term (SMD = −0.04, 95% CI -0.23 to 0.16, P = 0.72), medium-term (SMD = −0.13, 95% CI -0.43 to 0.17, P = 0.41), and long-term (SMD = −0.16, 95% CI -0.38 to 0.05, P = 0.14) follow-up. Tinnitus severity and disability measured by Tinnitus Questionnaire (TQ) also showed no significant improvement in short-term (SMD = −0.11, 95% CI -0.31 to 0.10, P = 0.30), medium-term (SMD = −0.10, 95% CI -0.37 to 0.16, P = 0.44), and long-term (SMD = −0.20, 95% CI -0.40 to 0.01, P = 0.06) follow-up. Additionally, no statistically significant difference was shown in the changes of tinnitus loudness assessed by a visual analogue scale (VAS) between rTMS and sham groups in the short-term (SMD = −0.28, 95% CI -0.59 to 0.02, P = 0.07), medium-term (SMD = −0.26, 95% CI -0.59 to 0.07, P = 0.13), and long-term (SMD = −0.20, 95% CI -0.53 to 0.13, P = 0.24) follow-up. Few mild or moderate adverse events were observed in both the rTMS and sham groups. Conclusion Low-frequency rTMS is well tolerated but not effective in treating chronic tinnitus based on the current analysis of pooled data. Further studies with modified and uniform protocols are required to investigate the potential benefit of rTMS in chronic tinnitus.

Motor recovery and antidepressant effects of repetitive transcranial magnetic stimulation on Parkinson disease: A PRISMA-compliant meta-analysis.

Clinical symptoms of Parkinson disease (PD) included both motor and nonmotor symptoms. Previous studies indicated inconsistent results for the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor and depression in PD. The study aimed to assess the therapeutic effect of rTMS with different mode on motor and depression in PD using a meta-analysis. Articles published before July 2019 were searched based on the following databases (PubMed, Web of Science, Medline, Embase, and Google Scholar). The therapeutic effects were assessed by computing the standard mean difference (SMD) and a 95% confidence interval (CI). The present study indicated that rTMS showed significant therapeutic effects on motor in PD (SMD 2.05, 95% CI 1.57-2.53, I = 93.0%, P < .001). Both high-frequency (HF)-rTMS and low-frequency rTMS showed therapeutic effects on motor; stimulation over primary motor cortex (M1), supplementary motor area, dorsal lateral prefrontal cortex (DLPFC) or M1+DLPFC showed therapeutic effects; stimulation during "on" and "off" states showed therapeutic effects; the study showed long-term effect of rTMS on motor in PD. In addition, the study indicated that rTMS showed significant therapeutic effects on depression in PD (SMD 0.80, 95% CI 0.31-1.29, I = 89.1%, P < .001). Stimulation over left DLPFC showed significant therapeutic effects on depression in PD; only HF-rTMS showed therapeutic effects; ages, disease durations, numbers of pulses, and session durations displayed influence on the therapeutic effects of rTMS on depression in PD; the therapeutic effects on depression was long term. However, no significant difference in therapeutic effects on depression were showed between rTMS and oral Fluoxetine (SMD 0.74, 95% CI -0.83 to 2.31, I = 92.5%, P < .001). The rTMS showed significant therapeutic effects on motor in PD. HF-rTMS showed a significant positive antidepressive effect in PD only over DLPFC.

Acute Exercise Protects Newly Formed Motor Memories Against rTMS-induced Interference Targeting Primary Motor Cortex

Acute cardiovascular exercise can promote motor memory consolidation following motor practice, and thus long-term retention, but the underlying mechanisms remain sparsely elucidated. Here we test the hypothesis that the positive behavioral effects of acute exercise involve the primary motor cortex and the corticospinal pathway by interfering with motor memory consolidation using non-invasive, low frequency, repetitive transcranial magnetic stimulation (rTMS). Forty-eight able-bodied, young adult male participants (mean age = 24.8 y/o) practiced a visuomotor accuracy task demanding precise and fast pinch force control. Following motor practice, participants either rested or exercised (20 min total: 3 × 3 min at 90% VO2peak) before receiving either sham rTMS or supra-threshold rTMS (115% RMT, 1 Hz) targeting the hand area of the contralateral primary motor cortex for 20 min. Retention was evaluated 24 h following motor practice, and motor memory consolidation was operationalized as overnight changes in motor performance. Low-frequency rTMS resulted in off-line decrements in motor performance compared to sham rTMS, but these were counteracted by a preceding bout of intense exercise. These findings demonstrate that a single session of exercise promotes early motor memory stabilization and protects the primary motor cortex and the corticospinal system against interference.

Cost-utility analysis of curative and maintenance repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant unipolar depression: a randomized controlled trial protocol

BackgroundDepression is a debilitating and costly disease for our society, especially in the case of treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy in treatment-resistant unipolar and non-psychotic depression. It can be applied according to two therapeutic strategies after an initial rTMS cure: a further rTMS cure can be performed at the first sign of relapse or recurrence, or systematic maintenance rTMS (M-rTMS) can be proposed. TMS adjuvant to treatment as usual (TAU) could improve long-term prognosis. However, no controlled study has yet compared the cost-effectiveness of these two additional rTMS therapeutic strategies versus TAU alone.Methods/designThis paper focuses on the design of a health-economic, prospective, randomized, double-blind, multicenter study with three parallel arms carried out in France. This study assesses the cost-effectiveness of the adjunctive and maintenance low frequency rTMS on the right dorsolateral prefrontal cortex versus TAU alone. A total of 318 patients suffering from a current TRD will be enrolled. The primary endpoint is to investigate the incremental cost-effectiveness ratio (ICER) (ratio costs / quality-adjusted life-years [QALY] measured by the Euroqol Five Dimension Questionnaire) over 12 months in a population of patients assigned to one of three arms: systematic M-rTMS for responders (arm A); additional new rTMS cure in case of mood deterioration among responders (arm B); and a placebo arm (arm C) in which responders are allocated in two subgroups: sham systematic M-rTMS and supplementary rTMS course in case of mood deterioration. ICER and QALYs will be compared between arm A or B versus arm C. The secondary endpoints in each three arms will be: ICER at 24 months; the cost-utility ratio analysis at 12 and 24 months; 5-year budget impact analysis; and prognosis factors of rTMS. The following criteria will be compared between arm A or B and arm C: rates of responders; remission and disease-free survival; clinical evolution; tolerance; observance; treatment modifications; hospitalization; suicide attempts; work stoppage; marital / professional statues; and quality of life at 12 and 24 months.DiscussionThe purpose of our study is to check the cost-effectiveness of rTMS and we will discuss its economic impact over time. In the case of significant decrease in the depression costs and expenditures associated with a good long-term prognosis (sustained response and remission) and tolerance, rTMS could be considered as an efficient treatment within the armamentarium for resistant unipolar depression.Trial registrationClinicalTrials.gov, NCT03701724. Registered on 10 October 2018. Protocol Amendment Version 2.0 accepted on 29 June 2019.

Altered response to repetitive transcranial magnetic stimulation in patients with chronic primary insomnia

BackgroundWe aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls. MethodsMedian peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T0), after the first train of a single rTMS session (T1), and after the whole rTMS procedure (T2). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s. ResultsResting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T0. A reduction of MEP size was observed at both T1 and T2 in all subjects, but this was significantly less pronounced in patients than in control subjects. ConclusionsThe lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI.