Hz rTMS Research Articles

When Two Is Better Than One: A Pilot Study on Transcranial Magnetic Stimulation Plus Muscle Vibration in Treating Chronic Pelvic Pain in Women.

Chronic pelvic pain syndrome (CPPS) affects about 4–16% of adult women, and about one-third of them require medical assistance due to severe symptoms. Repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) has been shown to manage pain in refractory CPPS. Focal muscle vibration (FMV) has also been reported to relieve pelvic pain. The objective of this study was to assess the feasibility and effect of rTMS coupled with FMV to reduce pain in seven adult women with refractory CPPS. This pilot, open-labeled, prospective trial examined treatment by 5 Hz rTMS over SMA and 150 Hz FMV over the perineum, suprapubic, and sacrococcygeal areas, with one daily session for five consecutive days for three weeks. We assessed tolerance and subjective pain changes (as per visual analog scale, VAS) until one month post-treatment, with a primary endpoint at day 7. No patients experienced serious adverse effects or a significant increase in pain. Six out of seven patients experienced a VAS improvement of at least 10% at T7; three of these individuals experienced a VAS improvement of more than 30%. Overall, we found a significant VAS reduction of 15 points (95% CI 8.4–21.6) at T7 (t = 6.3, p = 0.001; ES = 2.3 (1.1–3.9)). Three of the women who demonstrated a significant VAS reduction at T7 retained such VAS improvement at T30. VAS decreased by six points (95% CI 1.3–10.7) at T30 (t = 3.1, p = 0.02; ES = 1.5 (0.2–2.6)). This coupled approach seems promising for pain management in adult women with refractory CPPS and paves the way for future randomized controlled trials.

Mechanisms of Repetitive Transcranial Magnetic Stimulation on Post-stroke Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

We aimed to identify neural mechanisms underlying clinical response to repetitive transcranial magnetic stimulation (rTMS) in post-stroke depression (PSD) by the Resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-two depressed patients after ischemic stroke were randomized in a 1:1 ratio to receive 20min of 5Hz rTMS or sham over left dorsolateral prefrontal cortex (DLPFC) in addition to routine supportive treatments. The clinical outcome was measured by the 17-item Hamilton Depression Rating Scale (HDRS-17), while the imaging results were acquired from rs-fMRI, including regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF) and seed-based dynamic functional connection (dFC). HRSD-17 scores were improved in the two groups after treatment (P < 0.01), while greater mood improvement was observed in the rTMS group (P < 0.05). Compared with the sham group, the rTMS group demonstrated regions with higher ReHo and fALFF values locating mainly in the left hemisphere and highly consistent with the default mode network (DMN) (p < 0.05). Using the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) as seeds, significant difference between the two groups in dFC within the DMN was found after treatment, including 10 connections with increased connectivity strength and 2 connections with reduced connectivity strength. The ReHo, fALFF and dFC values within DMN in the rTMS group were negatively correlated with the HDRS scores after treatment (P < 0.05). Our results indicated reductions in depressive symptoms following rTMS in PSD are associated with functional alterations of different depression-related areas within the DMN.

Alteration of gamma-aminobutyric acid in the left dorsolateral prefrontal cortex of individuals with chronic insomnia: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study

ObjectiveTo investigate changes in the level of gamma-aminobutyric acid (GABA) in the left dorsolateral prefrontal cortex (DLPFC) of patients with chronic insomnia treated with real repetitive transcranial magnetic stimulation (rTMS) as compared to sham-rTMS, as measured with 1H-Magnetic Resonance Spectroscopy (1H-MRS). MethodsForty chronic insomnia participants were randomized to either real or sham rTMS group. The rTMS was administered once per day Continuously for 14 days with the stimulation over the left DLPFC. Left DLPFC GABA level relative to creatine (Cr) was measured by 1H-MRS. Insomnia symptom was evaluated by Insomnia Severity Index (ISI). MRS and ISI were assessed among all participants before and after treatment. This study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100047255). ResultsAfter treatment, the ISI score in real rTMS group was markedly decreased as compared to pre-rTMS (t = −4.25, p < 0.001, Cohen's d = 0.90), whereas no significant change in ISI was observed in the group of sham rTMS. In addition, we observed a significant increase of GABA+/Cr concentration in the real rTMS group after stimulation (0.37 ± 0.11 to 0.40 ± 0.11, p = 0.039), but that of sham did not (0.38 ± 0.10 to 0.39 ± 0.11, p = 0.151). However, there was no significant association between the change of GABA+/Cr in left DLPFC and the changes of ISI scores in the two groups. Conclusion1 Hz rTMS has the potential to increase GABA + level in left DLPFC of patients with chronic insomnia, and warrants further investigation.

High-frequency repetitive transcranial magnetic stimulation mitigates depression-like behaviors in CUMS-induced rats via FGF2/FGFR1/p-ERK signaling pathway

High-frequency repetitive transcranial magnetic stimulation (rTMS) is a widely used and effective biological treatment for depression. Although previous studies have shown that astrocyte function may be modified by rTMS, the specific neurobiological mechanisms underlying its antidepressant action are not clear. Substantial evidence has accumulated indicating that neurotrophin dysfunction and neuronal apoptosis play a role in the development of depression. To evaluate this hypothesis, we applied a chronical unpredictable mild stress (CUMS) protocol to induce depression-like behaviors in rats, followed by the delivery of 10-Hz rTMS for 3 weeks. Behavioral outcome measures consisted of a sucrose preference test, forced swimming test, and open field test. Histological analysis focused on apoptosis, expression of GFAP and FGF2, and FGF2 pathway-related proteins. The results showed that after rTMS treatment, the rats’ sucrose preference increased, open field performance improved while the immobility time of forced swimming decreased. The behavioral changes seen in rTMS treated rats were accompanied by marked reductions in the number of TUNEL-positive neural cells and the level of expression of BAX and by an increase in Bcl2. Furthermore, the expression of GFAP and FGF2 was increased, along with activation of FGF2 downstream pathway. These results suggest that rTMS treatment can improve depression-like behavior, attenuate neural apoptosis, and reverse reduction of astrocytes in a rat model of depression. We hypothesize that the therapeutic action of rTMS in CUMS-induced rats is linked to the activation of the FGF2/FGFR1/p-ERK signaling pathway.

Impact of low-frequency rTMS on functional connectivity of the dentate nucleus subdomains in schizophrenia patients with auditory verbal hallucination

Despite low-frequency repetitive transcranial magnetic stimulation (rTMS) is effective in treating schizophrenia patients with auditory verbal hallucinations (AVH), the underlying neural mechanisms of the effect still need to be clarified. Using the cerebellar dentate nucleus (DN) subdomain (dorsal and versal DN) as seeds, the present study investigated resting state functional connectivity (FC) alternations of the seeds with the whole brain and their associations with clinical responses in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The results showed that the rTMS treatment improved the psychiatric symptoms (e.g., AVH and positive symptoms) and certain neurocognitive functions (e.g., visual learning and verbal learning) in the patients. In addition, the patients at baseline showed increased FC between the DN subdomains and temporal lobes (e.g., right superior temporal gyrus and right middle temporal gyrus) and decreased FC between the DN subdomains and the left superior frontal gyrus, right postcentral gyrus, left supramarginal gyrus and regional cerebellum (e.g., lobule 4–5) compared to controls. Furthermore, these abnormal DN subdomain connectivity patterns did not persist and decreased FC of DN subdomains with cerebellum lobule 4–5 were reversed in patients after rTMS treatment. Linear regression analysis showed that the FC difference values of DN subdomains with the temporal lobes, supramarginal gyrus and cerebellum 4–5 between the patients at baseline and posttreatment were associated with clinical improvements (e.g., AVH and verbal learning) after rTMS treatment. The results suggested that rTMS treatment may modulate the neural circuits of the DN subdomains and hint to underlying neural mechanisms for low-frequency rTMS treating schizophrenia with AVH.

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression.

To investigate the effect of 10Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) on suicidality in patients with treatment-resistant depression (TRD). We used data from a three-site randomized clinical trial comparing 10Hz rTMS and iTBS applied to the left dorsolateral prefrontal cortex (DLPFC) in patients with TRD. We compared the effect of 10Hz rTMS and iTBS on suicidality as measured by the suicide item of the Hamilton Depression Rating Scale 17-item (HDRS-17). Suicidality remitted in 71 (43.7%) participants randomized to 10Hz stimulation and 91 (49.1%) participants randomized to iTBS, without a significant difference between the proportions in the two groups (Χ2 =0.674, df=1, p=0.4117). There was a significant correlation between change in suicidality and change in depression severity for both modalities (10Hz, Pearson's r=0.564; iTBS, Pearson's r=0.502), with a significantly larger decrease in depression severity for those in whom suicidality remitted compared to those in whom it did not (t=10.912, df=276.8, p<0.001). Both 10Hz and iTBS rTMS were effective in reducing suicidality in TRD. Future trials of iTBS for depression should include discrete measures of suicidality.

Similar Outcomes in Treating Major Depressive Disorder With 10 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) Versus Intermittent Theta Burst Stimulation (iTBS): A Naturalistic Observational Study.

Results reported in the existing literature have shown intermittent theta burst stimulation (iTBS) to be noninferior to 10 Hz repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD) when targeted at the left dorsolateral prefrontal cortex. The goal of this naturalistic observational study was to further explore potential differences between these 2 treatment modalities in treating depression in a real-world cohort. The participants were 105 patients, 18 years of age or older with a diagnosis of MDD who received standard clinical 10 Hz rTMS or iTBS treatment between 2016 and 2020. Clinical outcomes of depression treatment were assessed on the basis of changes in scores on the Patient Health Questionnaire-9 and on the Montgomery-Asberg Depression Rating Scale. Reduction in depression symptoms was measured with the Patient Health Questionnaire-9 and Montgomery-Asberg Depression Rating Scale from baseline to end of treatment, and no discernible differences in percent change, response, remission, or minimum clinically important difference were found between the 10 Hz rTMS and iTBS treatment groups. Findings in an observational, real-world clinical sample showed no significant differences in outcomes between 10 Hz rTMS and iTBS targeted at the left dorsolateral prefrontal cortex in the treatment of MDD. Because of the shorter treatment time involved, the choice of iTBS may reduce hospital exposure and increase savings and the treatment capacity of clinics without sacrificing effectiveness.

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.

Therapeutic Role of Repetitive Transcranial Magnetic Stimulation in Alzheimer's and Parkinson's Disease: Electroencephalography Microstate Correlates.

IntroductionThe microstate analysis is a method to convert the electrical potentials on the multi-channel electrode array to topographical electroencephalography (EEG) data. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that can modulate brain networks. This study explores the pathophysiological changes through microstate analysis in two different neurodegenerative diseases, Alzheimer’s (AD) and Parkinson’s disease (PD), characterized by motor and cognitive symptoms and analysis the effect of rTMS on the impaired cognitive and motor functions.Materials and MethodsWe included 18 AD, 8 PD patients, and 13 age-matched controls. For both groups, we applied 5 Hz rTMS on the left pre-SMA in PD patients while 20 Hz rTMS on the left lateral parietal region in AD patients. Each patient was re-evaluated 1 week after the end of the sessions, which included a detailed clinical evaluation and measurement of EEG microstates.ResultsAt the baseline, the common findings between our AD and PD patients were altered microstate (MS) B, MS D durations and transition frequencies between MS A–MS B, MS C–MS D while global explained variance (GEV) ratio and the extent and frequency of occurrence of MS A, MS B, and MS D were separately altered in AD patients. Although no specific microstate parameter adequately differentiated between AD and PD patients, we observed significant changes in MS B and MS D parameters in PD patients. Further, we observed that Mini-Mental State Examination (MMSE) performances were associated with the transition frequencies between MS A–MS B and MS C–MS D and GEV ratio. After left parietal rTMS application, we have observed significantly increased visual memory recognition and clock drawing scores after left parietal rTMS application associated with improved microstate conditions prominent, especially in the mean duration of MS C in AD patients. Also, pre-SMA rTMS resulted in significant improvement in motor scores and frequency of transitions from MS D to MS C in PD patients.ConclusionThis study shows that PD and AD can cause different and similar microstate changes that can be modulated through rTMS, suggesting the role of MS parameters and rTMS as a possible combination in monitoring the treatment effect in neurodegenerative diseases.

Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities.

Despite decades of research efforts, current treatments for Alzheimer's disease (AD) are of limited effectiveness and do not halt the progression of the disease and associated cognitive decline. Studies have shown that repetitive transcranial magnetic stimulation (rTMS) may improve cognition. We conducted a pilot study to investigate the effect of rTMS on cognitive function in Veterans with numerous medical comorbidities. Participants underwent 20 sessions, over the course of approximately 4 weeks, of 10 Hz rTMS at the left dorsolateral prefrontal cortex with intensity of 120% resting motor threshold. Outcome measures including memory, language, verbal fluency, and executive functions were acquired at baseline, end of treatment, and 4 months after the last rTMS session. Twenty-six Veterans completed the study (13 in the active rTMS group, 13 in the sham rTMS group). The study protocol was well-tolerated. Active, compared to sham, rTMS showed improved auditory-verbal memory at the end of treatment and at 4-month follow-up. However, the active rTMS group demonstrated a trend in decreased semantic verbal fluency at the end of treatment and at 4-month follow up. These preliminary results show rTMS is safe in general in this elderly Veteran population with multiple co-morbidities. Patients in the sham group showed an expected, slight decline in the California Verbal Learning Test scores over the course of the study, whereas the active treatment group showed a slight improvement at the 4-month post-treatment follow up. These effects need to be confirmed by studies of larger sample sizes.

Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial. Patients received two sessions of active or sham 0.25Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events. Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p=0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p=0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed. Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Corticomotor plasticity as a predictor of response to high frequency transcranial magnetic stimulation treatment for major depressive disorder

BackgroundMany patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10 Hz and intermittent theta-burst stimulation (iTBS) protocols. MethodsThirteen TRD patients underwent two evaluations of corticomotor plasticity—assessed as the post-rTMS (10 Hz, iTBS) percent change (%∆) in motor evoked potential (MEP) amplitude elicited by single-pulse TMS. Following corticomotor plasticity evaluations, patients subsequently underwent a standard 6-week course of 10 Hz rTMS (4 s train, 26 s inter-train interval, 3000 total pulses, 120% of motor threshold) to the left dorsolateral prefrontal cortex. Treatment efficacy was assessed by the Beck Depression Inventory II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). The change in MEPs was compared between 10 Hz and iTBS conditions and related to the change in BDI-II and HAM-D scores. ResultsAnalyses of variance revealed that across all time-points, higher post-10 Hz MEP change was a significant predictor of greater improvement on the BDI-II (p < 0.001) and HAM-D (p = 0.022). This relationship was not observed with iTBS (p-values≥0.100). Post-hoc tests revealed the MEP change 20 min post-10 Hz was the strongest predictor of BDI-II improvement. LimitationsCortical excitability was measured from the motor cortex, rather than the dorsolateral prefrontal cortex, where treatment is applied. The 10 Hz and iTBS protocols were performed at different intensities consistent with common practice. ConclusionsModulation of corticomotor excitability by 10 Hz can predict response to rTMS treatment with 10 Hz rTMS.

Analgesic Effects of Repetitive Transcranial Magnetic Stimulation at Different Stimulus Parameters for Neuropathic Pain: A Randomized Study

ObjectivesThe aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain. Materials and MethodsWe conducted a randomized, blinded, crossover exploratory study. Four single sessions of M1-rTMS at different parameters were administered in random order. The tested stimulation conditions were as follows: 5-Hz with 500 pulses per session, 10-Hz with 500 pulses per session, 10-Hz with 2000 pulses per session, and sham stimulation. Analgesic effects were assessed by determining the visual analog scale (VAS) pain intensity score and Short-Form McGill Pain Questionnaire 2 (SF-MPQ2) score immediately before and immediately after intervention. ResultsWe enrolled 22 adults (age: 59.8 ± 12.1 years) with intractable neuropathic pain. Linear-effects models showed significant effects of the stimulation condition on changes in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.01). Tukey multiple comparison tests revealed that 10-Hz rTMS with 2000 pulses provided better pain relief than sham stimulation, with greater decreases in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.02). ConclusionsThe results of this study suggest that high-dose stimulation (specifically, 10-Hz rTMS at 2000 pulses) is more effective than lower-dose stimulation for treating neuropathic pain.

Effect of Cognition Recovery by Repetitive Transcranial Magnetic Stimulation on Ipsilesional Dorsolateral Prefrontal Cortex in Subacute Stroke Patients.

ObjectiveTo demonstrate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional dorsolateral prefrontal cortex (DLPFC) on neurological recovery in patients with subacute phase stroke.MethodsPatients with supratentorial hemispheric stroke who were hospitalized for intensive rehabilitation in the subacute phase were enrolled for this retrospective analysis. Two groups of patients were selected: the rTMS group who received high-frequency (20 Hz) rTMS ≥ 5 times over the ipsilesional DLPFC, and a control group who did not receive any rTMS. The patients were further divided into groups with right- or left-side brain lesions. Functional measurements for cognitive ability, mood, speech, and activities of daily living, which were assessed at baseline and at the 1-month follow-up as a routine clinical practice, were used for analyses.ResultsAmong 270 patients with available clinical data, 133 (women, 51; age, 61.0 ± 13.8 years) met the inclusion criteria and were enrolled for analysis. There were no differences in demographic data and functional scores at baseline between the rTMS (n = 49) and control (n = 84) groups. The rTMS group showed a higher gain in the mini-mental status examination (MMSE) total score and subscores of all domains, forward digit span, and FIM-cognition than the control group (P < 0.05). Among the patients with left hemispheric lesions (n = 57), the rTMS group showed better outcomes in cognition and depression through scores of total and “attention and concentration” subscores of MMSE, FIM-cognition, and the geriatric depression scale (P < 0.05). Among the patients with right hemispheric lesions (n = 76), the rTMS group showed better outcomes in cognition through the MMSE total score and subscores of “attention and concentration,” “registration,” and “recall,” and scores of both forward and backward digit spans (P < 0.05).ConclusionHigh-frequency rTMS over the ipsilesional DLPFC has beneficial effects on the recovery of cognition on both sides as well as mood in patients with left-sided hemispheric lesions.

The effectiveness of high-frequency left DLPFC-rTMS on depression, response inhibition, and cognitive flexibility in female subjects with major depressive disorder

BackgroundThe purpose of the present study was to investigate the effect of high-frequency repetitive transcranial magnetic stimulation on depression severity, response inhibition, and cognitive flexibility in subjects with major depressive disorder. MethodsTwenty-eight female subjects with major depressive disorder were randomly divided into experimental and control groups. High frequency (20 Hz) rTMS stimulation at 85% of the MT consisted of 25 trains of 5 s duration, a total of 2500 pulses/session or sham stimulation was applied over the left DLPFC for five consecutive days per week, for two weeks. Depression severity, response inhibition, and cognitive flexibility of subjects were assessed by Beck Depression Inventory, Go/NoGo, and Wisconsin sort cards (WCST) tests, respectively, pre- and post-TMS intervention. ResultsrTMS over the left DLPFC significantly decreased the depression severity at the Beck Depression Inventory, enhanced accuracy, and decreased reaction time at the Go/NoGo task. In the Wisconsin Card Sort Test, perseverative and non-perseverative errors and failure to maintain a set index significantly decreased following rTMS treatment. ConclusionsFindings indicate that 20-Hz rTMS treatment on the left DLPFC has a positive effect on depression severity, response inhibition, and cognitive flexibility in depressed subjects.

Effects of rTMS and tDCS on neuropathic pain after brachial plexus injury: a randomized placebo-controlled pilot study

Neuropathic pain after brachial plexus injury (NPBPI) is a highly disabling clinical condition and is increasingly prevalent due to increased motorcycle accidents. Currently, no randomized controlled trials have evaluated the effectiveness of non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in patients suffering from NPBPI. In this study, we directly compare the efficacy of 10-Hz rTMS and anodal 2 mA tDCS techniques applied over the motor cortex (5 daily consecutive sessions) in 20 patients with NPBPI, allocated into 2 parallel groups (active or sham). The order of the sessions was randomised for each of these treatment groups according to a crossover design and separated by a 30-day interval. Scores for “continuous” and “paroxysmal” pain (primary outcome) were tabulated after the last stimulation day and 30 days after. Secondary outcomes included the improvement in multidimensional aspects of pain, anxiety state and quality of life from a qualitative and quantitative approach. Active rTMS and tDCS were both superior to sham in reducing continuous (p < 0.001) and paroxysmal (p = 0.002; p = 0.02) pain as well as in multidimensional aspects of pain (p = 0.001; p = 0.002) and anxiety state (p = < 0.001; p = 0.005). Our results suggest rTMS and tDCS are able to treat NPBPI with little distinction in pain and anxiety state, which may promote the use of tDCS in brachial plexus injury pain management, as it constitutes an easier and more available technique.Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/, RBR-5xnjbc – Sep 3, 2018.

Concurrent TMS-EEG to reveal the neuroplastic changes in the prefrontal and insular cortices in the analgesic effects of DLPFC-rTMS.

The dorsolateral prefrontal cortex (DLPFC) is an important target for repetitive transcranial magnetic stimulation (rTMS) to reduce pain. However, the analgesic efficacy of DLPFC-rTMS needs to be optimized, in which the mechanisms of action remain unclear. Concurrent TMS and electroencephalogram (TMS-EEG) is able to evaluate neuroplastic changes beyond the motor cortex. Using TMS-EEG, this study was designed to investigate the local and distributed neuroplastic changes associated with DLPFC analgesia. Thirty-four healthy adults received DLPFC or sham stimulation in a randomized, crossover design. In each session, participants underwent cold pain and TMS-EEG assessment both before and after 10-Hz rTMS. We provide novel findings that DLPFC analgesia is associated with a smaller N120 amplitude in the contralateral prefrontal cortex as well as with a larger N120 peak in the ipsilateral insular cortex. Furthermore, there was a strong negative correlation between N120 changes of these two regions whereby the amplitude changes of this dyad were associated with increased pain threshold. In addition, DLPFC stimulation enhanced coherence between the prefrontal and somatosensory cortices oscillating in the gamma frequency. Overall, our data present novel evidence on local and distributed neuroplastic changes associated with DLPFC analgesia.

Modulating intrinsic functional connectivity with visual cortex using low-frequency repetitive transcranial magnetic stimulation.

IntroductionIntrinsic network connectivity becomes altered in pathophysiology. Noninvasive brain stimulation can modulate pathological functional networks in an attempt to restore the inherent response. To determine its usefulness for visual‐related disorders, we developed procedures investigating repetitive transcranial magnetic stimulation (rTMS) protocols targeting the visual cortex on modulating connectivity associated with the visual network and default mode network (DMN).MethodsWe compared two low‐frequency (1 Hz) rTMS protocols to the visual cortex (V1)—a single 20 min session and five successive 20 min sessions (accelerated/within‐session rTMS)—using multi‐echo resting‐state functional magnetic resonance whole‐brain imaging and resting‐state functional connectivity (rsFC). We also explored the relationship between rsFC and rTMS‐induced changes in key inhibitory and excitatory neurotransmitters, γ‐aminobutyric acid (GABA) and glutamate. GABA (GABA+) and glutamate (Glx) concentrations were measured in vivo using magnetic resonance spectroscopy.ResultsAcute disruption with a single rTMS session caused widespread connectivity reconfiguration with nodes of interest. Changes were not evident immediately post‐rTMS but were observed at 1 h post‐rTMS. Accelerated sessions resulted in weak alterations in connectivity, producing a relatively homeostatic response. Changes in GABA+ and Glx concentrations with network connectivity were dependent on the rTMS protocol.ConclusionsThis proof‐of‐concept study offers new perspectives to assess stimulation‐induced neural processes involved in intrinsic functional connectivity and the potential for rTMS to modulate nodes interconnected with the visual cortex. The differential effects of single‐session and accelerated rTMS on physiological markers are crucial for furthering the advancement of treatment modalities in visual cortex related disorders.

Repetitive Transcranial Magnetic Stimulation Modulates Frontal and Temporal Time-Varying EEG Network in Generalized Anxiety Disorder: A Pilot Study.

Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.

Theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for poststroke dysphagia: A randomized, double-blind, controlled trial.

Background:Repetitive transcranial magnetic stimulation (rTMS) of high-frequency (10 Hz) on suprahyoid motor cortex has been an evidence-based treatment for poststroke dysphagia. Intermittent theta burst stimulation (iTBS) can be performed in 3 minutes compared with 20 ± 5 minutes for 10 Hz rTMS. This study aimed to ensure the clinical efficacy, safety, and tolerability of iTBS compared with 10 Hz rTMS for patients with poststroke dysphagia.Method:In this randomized, double-blind, single-center, controlled trial, 47 participants were randomly assigned to iTBS (n = 24) and rTMS (n = 23) group. Each participant received iTBS or rTMS daily at suprahyoid motor cortex of affected hemisphere for 10 consecutive days. The outcomes were assessed at baseline, immediately, and 2 weeks after intervention, including water-swallowing test, standardized swallowing assessment, Mann assessment of swallowing ability, Murray Secretion Scale, Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and motor evoked potential (MEP) of bilateral suprahyoid muscle.Results:There were no significant differences between groups. There was a significant improvement on all rating scales and MEP after rTMS and iTBS. No significant differences on water-swallowing test, Mann assessment of swallowing ability, standardized swallowing assessment, Murray Secretion Scale scores, and MEP were observed between groups. In particular, there was significant differences on Penetration-Aspiration Scale scores (viscous liquid: mean difference = 1.016; 95% CI: 0.32–1.71; effect size: 0.360; P = .005) and the residue rate of pyriform fossa (viscous liquid: mean difference = 0.732; 95% CI: 0.18–1.28; effect size: 0.248; P = .010) in between-group. Comparing the differences over the changes of all rating scales, only the residue rate of epiglottis valley between groups was found to be significantly different (dilute liquid: mean difference = –0.567; 95% CI: –0.98 to –0.15; P = .009). There was no severe adverse effect and high dropout rates in both groups.Conclusion:The clinical efficacy, safety, and tolerability of iTBS showed non-inferior to 10 Hz rTMS for patients with poststroke dysphagia. The present study can be used to improve the clinicians’ knowledge and clinical decision skills on iTBS and rTMS for poststroke dysphagia.