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:Sensory feedback is critical for motor learning, and thus to neurorehabilitation after stroke. Whether enhancing sensory feedback by applying excitatory repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional primary sensory cortex (IL-S1) might enhance motor learning in chronic stroke has yet to be investigated. The present study investigated the effects of 5 Hz rTMS over IL-S1 paired with skilled motor practice on motor learning, hemiparetic cutaneous somatosensation, and motor function. Individuals with unilateral chronic stroke were pseudo-randomly divided into either Active or Sham 5 Hz rTMS groups (n = 11/group). Following stimulation, both groups practiced a Serial Tracking Task (STT) with the hemiparetic arm; this was repeated for 5 days. Performance on the STT was quantified by response time, peak velocity, and cumulative distance tracked at baseline, during the 5 days of practice, and at a no-rTMS retention test. Cutaneous somatosensation was measured using two-point discrimination. Standardized sensorimotor tests were performed to assess whether the effects might generalize to impact hemiparetic arm function. The active 5 Hz rTMS + training group demonstrated significantly greater improvements in STT performance {response time [F (1, 286.04) = 13.016, p < 0.0005], peak velocity [F (1, 285.95) = 4.111, p = 0.044], and cumulative distance [F (1, 285.92) = 4.076, p = 0.044]} and cutaneous somatosensation [F (1, 21.15) = 8.793, p = 0.007] across all sessions compared to the sham rTMS + training group. Measures of upper extremity motor function were not significantly different for either group. Our preliminary results suggest that, when paired with motor practice, 5 Hz rTMS over IL-S1 enhances motor learning related change in individuals with chronic stroke, potentially as a consequence of improved cutaneous somatosensation, however no improvement in general upper extremity function was observed.
Project description:ObjectiveThis study was aimed to summarize and analyze the quality of the available evidence in systematic reviews (SRs) of repetitive transcranial magnetic stimulation (rTMS) on the non-motor cortex (non-M1) for neuropathic pain (NP) through an evidence mapping approach.MethodsWe follow the Global Evidence Mapping (GEM) methodology. Searches were conducted in PubMed, EMBASE, Epistemonikos, and the Cochrane Library. The study type was restricted to SRs with or without meta-analysis. All literature published before January 23, 2021, were included. The methodological quality of the included SRs was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2). Data were extracted according to a defined population-intervention-comparison-outcome (PICO) framework from primary studies that included SRs. The same PICO was categorized into PICOs according to interventions (stimulation target, frequency, number of sessions (short: 1-5 sessions, medium: 5-10 sessions, and long: >10 sessions)) and comparison (sham rTMS or other targets). The evidence mapping was presented in tables and a bubble plot.ResultsA total of 23 SRs were included. According to the AMSTAR-2, 20 SRs scored "very low" in terms of methodological quality, 2 SRs scored "low," and 1 SR scored "high." A total of 17 PICOs were extracted. The dorsolateral prefrontal cortex (DLPFC) is the most studied of the non-motor cortex targets. PICOs of DLPFC, premotor cortex (PMC), frontal cortex, and secondary somatosensory cortex (S2) were mainly categorized with a "potentially better" conclusion. High-frequency (5-20 Hz) rTMS of non-M1 usually lead to "potentially better" conclusions.ConclusionsDLPFC, PMC, frontal cortex, and S2 seem to be promising new targets for rTMS treatment of certain NP. Evidence mapping is a useful and reliable methodology to identify and present the existing evidence gap that more research efforts are necessary in order to highlight the optimal stimulation protocols for non-M1 targets and standardize parameters to fill the evidence gaps of rTMS. Further investigation is advised to improve the methodological quality and the reporting process of SRs.
Project description:Repetitive transcranial magnetic stimulation (rTMS) influences the brain temporally beyond the stimulation period and spatially beyond the stimulation site. Application of rTMS over the primary motor cortex (M1) has been shown to lead to plastic changes in interregional connectivity over the motor system as well as alterations in motor performance. With a sequential combination of rTMS over the M1 and functional magnetic resonance imaging (fMRI), we sought changes in the topology of brain networks and specifically the association of brain topological changes with motor performance changes. In a sham-controlled parallel group experimental design, real or sham rTMS was administered to each of the 15 healthy subjects without prior motor-related dysfunctions, over the right M1 at a high frequency of 10 Hz. Before and after the intervention, fMRI data were acquired during a sequential finger motor task using the left, nondominant hand. Changes in the topology of brain networks were assessed in terms of global and local efficiency, which measures the efficiency in transporting information at global and local scales, respectively, provided by graph-theoretical analysis. Greater motor performance changes toward improvements after real rTMS were shown in individuals who exhibited more increases in global efficiency and more decreases in local efficiency. The enhancement of motor performance after rTMS is supposed to be associated with brain topological changes, such that global information exchange is facilitated, while local information exchange is restricted.
Project description:Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) can modulate cortical excitability and is thought to influence activity in other brain areas. In this study, we investigated the anatomical and functional effects of rTMS of M1 and the time course of after-effects from a 1-Hz subthreshold rTMS to M1. Using an "offline" functional magnetic resonance imaging (fMRI)-rTMS paradigm, neural activation was mapped during simple finger movements after 1-Hz rTMS over the left M1 in a within-subjects repeated measurement design, including rTMS and sham stimulation. A significant decrease in the blood oxygen level dependent (BOLD) signal due to right hand motor activity during a simple finger-tapping task was observed in areas remote to the stimulated motor cortex after rTMS stimulation. This decrease in BOLD signal suggests that low frequency subthreshold rTMS may be sufficiently strong to elicit inhibitory modulation of remote brain regions. In addition, the time course patterns of BOLD activity showed this inhibitory modulation was maximal approximately 20?minutes after rTMS stimulation.
Project description:BackgroundNon-invasive neuromodulation is an emerging therapy for children with early brain injury but is difficult to apply to preschoolers when windows of developmental plasticity are optimal. Transcranial static magnetic field stimulation (tSMS) decreases primary motor cortex (M1) excitability in adults but effects on the developing brain are unstudied.Objective/hypothesisWe aimed to determine the effects of tSMS on cortical excitability and motor learning in healthy children. We hypothesized that tSMS over right M1 would reduce cortical excitability and inhibit contralateral motor learning.MethodsThis randomized, sham-controlled, double-blinded, three-arm, cross-over trial enrolled 24 healthy children aged 10-18 years. Transcranial Magnetic Stimulation (TMS) assessed cortical excitability via motor-evoked potential (MEP) amplitude and paired pulse measures. Motor learning was assessed via the Purdue Pegboard Test (PPT). A tSMS magnet (677 Newtons) or sham was held over left or right M1 for 30 min while participants trained the non-dominant hand. A linear mixed effect model was used to examine intervention effects.ResultsAll 72 tSMS sessions were well tolerated without serious adverse effects. Neither cortical excitability as measured by MEPs nor paired-pulse intracortical neurophysiology was altered by tSMS. Possible behavioral effects included contralateral tSMS inhibiting early motor learning (p < 0.01) and ipsilateral tSMS facilitating later stages of motor learning (p < 0.01) in the trained non-dominant hand.ConclusiontSMS is feasible in pediatric populations. Unlike adults, tSMS did not produce measurable changes in MEP amplitude. Possible effects of M1 tSMS on motor learning require further study. Our findings support further exploration of tSMS neuromodulation in young children with cerebral palsy.
Project description:Repetitive transcranial magnetic stimulation (rTMS) can noninvasively stimulate the brain and transiently amplify or block behaviors mediated through a region. We hypothesized that a single high-frequency rTMS session over the left dorsolateral prefrontal cortex (DLPFC) would reduce cue craving for cigarettes compared with a sham TMS session.Sixteen non-treatment-seeking, nicotine-dependent participants were randomized to receive either real high-frequency rTMS (10 Hz, 100% resting motor threshold, 5-sec on, 10-sec off for 15 min; 3000 pulses) or active sham (eSham) TMS over the DLPFC in two visits with 1 week between visits. The participants received cue exposure before and after rTMS and rated their craving after each block of cue presentation.Stimulation of the left DLFPC with real, but not sham, rTMS reduced craving significantly from baseline (64.1±5.9 vs. 45.7±6.4, t = 2.69, p = .018). When compared with neutral cue craving, the effect of real TMS on cue craving was significantly greater than the effect of sham TMS (12.5±10.4 vs. -9.1±10.4; t = 2.07, p = .049). More decreases in subjective craving induced by TMS correlated positively with higher Fagerström Test for Nicotine Dependence score (r = .58, p = .031) and more cigarettes smoked per day (r = .57, p = .035).One session of high-frequency rTMS (10 Hz) of the left DLPFC significantly reduced subjective craving induced by smoking cues in nicotine-dependent participants. Additional studies are needed to explore rTMS as an aid to smoking cessation.
Project description:Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical plasticity in clinical and non-clinical populations. Clinically, rTMS is delivered to targeted regions of the cortex at high intensities (>1?T). We have previously shown that even at low intensities, rTMS induces structural and molecular plasticity in the rodent cortex. To determine whether low intensity rTMS (LI-rTMS) alters behavioural performance, daily intermittent theta burst LI-rTMS (120?mT) or sham was delivered as a priming or consolidating stimulus to mice completing 10 consecutive days of skilled reaching training. Relative to sham, priming LI-rTMS (before each training session), increased skill accuracy (~9%) but did not alter the rate of learning over time. In contrast, consolidating LI-rTMS (after each training session), resulted in a small increase in the rate of learning (an additional ~1.6% each day) but did not alter the daily skill accuracy. Changes in behaviour with LI-rTMS were not accompanied with long lasting changes in brain-derived neurotrophic factor (BDNF) expression or in the expression of plasticity markers at excitatory and inhibitory synapses for either priming or consolidation groups. These results suggest that LI-rTMS can alter specific aspects of skilled motor learning in a manner dependent on the timing of intervention.
Project description:BackgroundRepetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain disorders by modulating the activity of disease-specific brain networks, yet the rTMS frequencies used are delivered in a binary fashion - excitatory (>1 Hz) and inhibitory (≤1 Hz).ObjectiveTo assess the effective connectivity of the motor network at different rTMS stimulation rates during positron-emission tomography (PET) and confirm that not all excitatory rTMS frequencies act on the motor network in the same manner.MethodsWe delivered image-guided, supra-threshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements. Path analysis - using structural equation modeling (SEM) - was employed to determine the effective connectivity of the motor network at all rTMS frequencies. Once determined, the final model of the motor network was used to assess any differences in effective connectivity at each rTMS frequency.ResultsThe exploratory SEM produced a very well fitting final network model (χ(2) = 18.04, df = 21, RMSEA = 0.000, p = 0.647, TLI = 1.12) using seven nodes of the motor network. 5 Hz rTMS produced the strongest path coefficients in four of the seven connections, suggesting that this frequency is the optimal rTMS frequency for stimulation the motor network (as a whole); however, the premotor cerebellum connection was optimally stimulated at 10 Hz rTMS and the supplementary motor area caudate connection was optimally driven at 15 Hz rTMS.Conclusion(s)We have demonstrated that 1) 5 Hz rTMS revealed the strongest path coefficients (i.e. causal influence) on the nodes of the motor network, 2) stimulation at "excitatory" rTMS frequencies did not produce increased CBF in all nodes of the motor network, 3) specific rTMS frequencies may be used to target specific none-to-node interactions in the stimulated brain network, and 4) more research needs to be performed to determine the optimum frequency for each brain circuit and/or node.
Project description:The net effect of altered interhemispheric interactions between homologous motor cortical areas after unilateral stroke has been previously reported to contribute to residual hemiparesis. Using this framework, we hypothesized that navigated 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the contralesional hemisphere would induce a stronger physiological and behavioural response in patients with residual motor deficit than in healthy subjects, because an imbalance in interhemispheric excitability may underlie motor dysfunction.Navigated rTMS was conducted in 8 chronic stroke patients (67.50±13.77 years) and in 8 comparable normal subjects (57.38±9.61 years). We evaluated motor function (Finger tapping, Nine Hole Peg test, Strength Index and Reaction Time) as well as the excitatory and inhibitory function (resting motor threshold, motor evoked potential amplitude, intra-cortical inhibition and facilitation, and silent period) of the stimulated and non-stimulated motor cortex before and after navigated rTMS.rTMS induced an increase in excitability in the ipsilesional (non-stimulated) motor cortex and led to improved performance in the finger tapping task and pinch force task. These physiological and behavioral effects were more prominent (or robust) in the group of stroke patients than in the control group.Navigated low-frequency rTMS involving precise and consistent targeting of the contralesional hemisphere in stroke patients enhanced the cortical excitability of the ipsilesional hemisphere and the motor response of the hemiparetic hand.