Project description:BACKGROUND:Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use. OBJECTIVE:We report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS. METHODS:Fifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. MEP's were induced with single TMS pulses and measured using surface electromyography. MEP modulation was calculated as the change of mean MEP amplitude after MC rTMS. RESULTS:MEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. This was found both in univariate analyses (Spearman regression: rho = 0.43, p < 0.005) and a multivariable linear regression model (? = 0.25, p < 0.0001) controlling for baseline depression severity, age and resting motor threshold. CONCLUSIONS:These findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS.
Project description:PurposeThe cognitive neuropsychological model of depression suggests that the cognitive deficits observed in depressed subjects are the result of attenuated top-down cognitive control resulting in increased bottom-up emotional processing. Remediation of cognitive impairments in cold cognition has been proposed as a valuable treatment for depression. The study aimed to examine the effects of clinical response to repetitive transcranial magnetic stimulation (rTMS) on cold cognition over the course of 8 weeks in medication-refractory depressed subjects.Materials and methodsTwenty-two medication-refractory depressed subjects received twenty sessions of high-frequency rTMS targeting the left dorsolateral prefrontal cortex, one of the key nodes of the cognitive control network. Cold cognition and antidepressant treatment response were monitored at baseline, week 2, 4 and 8. Clinical response was defined as ≥50% reduction in Montgomery-Åsberg Depression Rating Scale score at week 8. Longitudinal changes in cold cognition were modeled using (generalized) linear mixed models. It was hypothesized that the excitatory effects of rTMS would improve cognition in the domains of executive function, memory, and attention. Additionally, responders were expected to show larger cognitive improvements than nonresponders.ResultsA decrease in median latency was observed on a task that measured executive function, irrespective of treatment response status. Further, responders showed significantly larger improvements in A-Prime (the ability to detect target sequences) on a sustained attention task. Post hoc analysis indicated higher levels of rumination in non-responders.ConclusionOur findings suggest that distractions during tasks with low perceptual complexity affected nonresponders disproportionately possibly due to higher rumination levels. Overall, cold cognition in medication-resistant depressed subjects was minimally affected by rTMS, substantiating the safety of rTMS treatment.LimitationsThe sample size was small, and the study did not include a control group.
Project description:Repetitive transcranial magnetic stimulation (rTMS) is a commonly- used treatment for major depressive disorder (MDD). However, our understanding of the mechanism by which TMS exerts its antidepressant effect is minimal. Furthermore, we lack brain signals that can be used to predict and track clinical outcome. Such signals would allow for treatment stratification and optimization. Here, we performed a randomized, sham-controlled clinical trial and measured electrophysiological, neuroimaging, and clinical changes before and after rTMS. Patients (N = 36) were randomized to receive either active or sham rTMS to the left dorsolateral prefrontal cortex (dlPFC) for 20 consecutive weekdays. To capture the rTMS-driven changes in connectivity and causal excitability, resting fMRI and TMS/EEG were performed before and after the treatment. Baseline causal connectivity differences between depressed patients and healthy controls were also evaluated with concurrent TMS/fMRI. We found that active, but not sham rTMS elicited (1) an increase in dlPFC global connectivity, (2) induction of negative dlPFC-amygdala connectivity, and (3) local and distributed changes in TMS/EEG potentials. Global connectivity changes predicted clinical outcome, while both global connectivity and TMS/EEG changes tracked clinical outcome. In patients but not healthy participants, we observed a perturbed inhibitory effect of the dlPFC on the amygdala. Taken together, rTMS induced lasting connectivity and excitability changes from the site of stimulation, such that after active treatment, the dlPFC appeared better able to engage in top-down control of the amygdala. These measures of network functioning both predicted and tracked clinical outcome, potentially opening the door to treatment optimization.
Project description:BackgroundTo examine the antidepressant efficacy and response predictors of R-DLPFC-LF rTMS for antidepressant-nonresponding BD.MethodsWe conducted a single-blind randomized sham-controlled trial for 54 (28 sham, 26 active) patients with antidepressant-nonresponding BD (baseline MADRS ≥ 20). Patients received 15 daily sessions of active or sham neuronavigated rTMS (Figure-of-8 coil, five 1 Hz 60 s 110% RMT trains). Outcome measures included depressive response (≥ 50% MADRS reduction, CGI ≤ 2) and remission (MADRS < 7, CGI = 1) rates, treatment emergent hypo/mania (YMRS), depressive and anxiety symptoms (HAM-A).Results48 patients (25 sham, 23 active) completed treatment, with 3 drop-outs each in active and sham groups. Active rTMS did not produce superior response or remission rates at endpoint or 6 or 12 weeks (ps > 0.05). There was no significant group * time interaction (ps > 0.05) in a multivariate ANOVA with MADRS, HAMA and YMRS as dependent variables. Exploratory analysis found MADRS improvement to be moderated by baseline anxiety (p = 0.02) and melancholia (p = 0.03) at week 3, and depressive onset at weeks 6 (p = 0.03) and 12 (p = 0.04). In subjects with below-mean anxiety (HAMA < 20.7, n = 24), MADRS improvement from active rTMS was superior to sham at week 3 (ITT, t = 2.49, p = 0.04, Cohen's d = 1.05). No seizures were observed. Groups did not differ in treatment-emergent hypomania (p = 0.1).LimitationsLarger sample size might be needed to power subgroup analyses. Moderation analyses were exploratory. Single-blind design. Unblinding before follow-up assessments due to ethical reasons.Conclusions1-Hz 110% RMT (5 × 60 s trains) R-DLPFC-LF rTMS was not effective for antidepressant non-responding BD but may be further investigated at increased dosage and/or in BD patients with low anxiety. Trial registration CCRB Clinical Trials Registry, CUHK, CUHK_CCT00440. Registered 04 December 2014, https://www2.ccrb.cuhk.edu.hk/registry/public/279.
Project description:BackgroundProlonged intermittent theta-burst stimulation (piTBS) and repetitive transcranial magnetic stimulation (rTMS) are effective antidepressant interventions for major depressive disorder (MDD). Cognition-modulated frontal theta (frontalθ) activity had been identified to predict the antidepressant response to 10-Hz left prefrontal rTMS. However, whether this marker also predicts that of piTBS needs further investigation.MethodsThe present double-blind randomized trial recruited 105 patients with MDD who showed no response to at least one adequate antidepressant treatment in the current episode. The recruited patients were randomly assigned to one of three groups: group A received piTBS monotherapy; group B received rTMS monotherapy; and group C received sham stimulation. Before a 2-week acute treatment period, electroencephalopgraphy (EEG) and cognition-modulated frontal theta changes (Δfrontalθ) were measured. Depression scores were evaluated at baseline, 1 week, and 2 weeks after the initiation of treatment.ResultsThe Δfrontalθ at baseline was significantly correlated with depression score changes at week 1 (r = -0.383, p = 0.025) and at week 2 for rTMS group (r = -0.419, p = 0.014), but not for the piTBS and sham groups. The area under the receiver operating characteristic curve for Δfrontalθ was 0.800 for the rTMS group (p = 0.003) and was 0.549 for the piTBS group (p = 0.619).ConclusionThe predictive value of higher baseline Δfrontalθ for antidepressant efficacy for rTMS not only replicates previous results but also implies that the antidepressant responses to rTMS could be predicted reliably at baseline and both piTBS and rTMS could be effective through different neurobiological mechanisms.
Project description:BackgroundClinical 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.MethodsArticles 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).ResultsThe 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).ConclusionThe rTMS showed significant therapeutic effects on motor in PD. HF-rTMS showed a significant positive antidepressive effect in PD only over DLPFC.
Project description:BackgroundIt had been assumed that suppressing the undamaged contralesional motor cortex by repetitive low-frequency transcranial magnetic stimulation (rTMS) or increasing the excitability of the damaged hemisphere cortex by high-frequency rTMS will promote function recovery after stroke.ObjectivesTo assess the efficacy and safety of rTMS for improving function in people with stroke.Search methodsWe searched the Cochrane Stroke Group Trials Register (April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), the Chinese Stroke Trials Register (April 2012), MEDLINE (1950 to May 2012), EMBASE (1980 to May 2012), Science Citation Index (1981 to April 2012), Conference Proceedings Citation Index-Science (1990 to April 2012), CINAHL (1982 to May 2012), AMED (1985 to May 2012), PEDro (April 2012), REHABDATA (April 2012) and CIRRIE Database of International Rehabilitation Research (April 2012). In addition, we searched five Chinese databases, ongoing trials registers and relevant reference lists.Selection criteriaWe included randomised controlled trials comparing rTMS therapy with sham therapy or no therapy. We excluded trials that reported only laboratory parameters.Data collection and analysisTwo review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreements by discussion.Main resultsWe included 19 trials involving a total of 588 participants in this review. Two heterogenous trials with a total of 183 participants showed that rTMS treatment was not associated with a significant increase in the Barthel Index score (mean difference (MD) 15.92, 95% CI -2.11 to 33.95). Four trials with a total of 73 participants were not found to have a statistically significant effect on motor function (standardised mean difference (SMD) 0.51, 95% CI -0.99 to 2.01). Subgroup analyses of different stimulation frequencies or duration of illness also showed no significant difference. Few mild adverse events were observed in the rTMS groups, with the most common events being transient or mild headaches (2.4%, 8/327) and local discomfort at the site of the stimulation.Authors' conclusionsCurrent evidence does not support the routine use of rTMS for the treatment of stroke. Further trials with larger sample sizes are needed to determine a suitable rTMS protocol and the long-term functional outcome.
Project description:Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used in the study and treatment of neurological conditions including major depression, stroke, epilepsy, schizophrenia, multiple sclerosis, Parkinson’s, and Alzheimer’s disease, as well as other, non-neurological disorders. Among the effects of rTMS, low-frequency protocols (≤ 1Hz) are generally understood to result in cortical inhibition, whereas high-frequency protocols (≥ 3Hz) increase cortical excitability. However, the complex molecular basis of rTMS is largely unexplored. Using three complementary rat models, in vitro, ex vivo, and in vivo, we show complex patterns of hippocampal and neocortical transcriptional response to stimulation in glutamatergic and GABAergic signaling pathways, as well as multiple inflammatory pathways, among others. This broad-based molecular survey helps provide a foundation to tease out the complex molecular mechanisms of the effects of rTMS.
Project description:Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used in the study and treatment of neurological conditions including major depression, stroke, epilepsy, schizophrenia, multiple sclerosis, Parkinson’s, and Alzheimer’s disease, as well as other, non-neurological disorders. Among the effects of rTMS, low-frequency protocols (≤ 1Hz) are generally understood to result in cortical inhibition, whereas high-frequency protocols (≥ 3Hz) increase cortical excitability. However, the complex molecular basis of rTMS is largely unexplored. Using three complementary rat models, in vitro, ex vivo, and in vivo, we show complex patterns of hippocampal and neocortical transcriptional response to stimulation in glutamatergic and GABAergic signaling pathways, as well as multiple inflammatory pathways, among others. This broad-based molecular survey helps provide a foundation to tease out the complex molecular mechanisms of the effects of rTMS.