Hz rTMS Research Articles

Efficacy of repetitive transcranial magnetic stimulation combined with peripheral magnetic stimulation on movement symptom and exploration of the optimal population in Parkinson's disease: A randomized controlled trial.

This study explores the efficacy of repetitive transcranial magnetic stimulation (rTMS) and rTMS combined with repetitive peripheral magnetic stimulation (rPMS) (hereinafter referred to as rTMS + rPMS) on motor symptoms and quality of life in Parkinson's disease (PD), and explores whether there are differences between the two treatment methods; At the same time, analyze data from different subgroups to explore the influencing factors, in order to find the most suitable treatment group. Eighty patients with PD were randomly divided into rTMS and rTMS + rPMS groups and administered 10 Hz rTMS, and 10 Hz rTMS + 25 Hz rPMS, respectively, for 10 days. Before and after treatment, the PD Motor Function Rating Scale (UPDRS Part III, 10m Walk Timing Test, Stand Up Walk Test Evaluation Scale (TUG)) and PD Quality of Life Questionnaire (PDQ-39) were used to evaluate the motor symptoms and quality of life. After quantifying the treatment effect, a comparative analysis of the efficacy before and after treatment was conducted. Simultaneously, we divided the two treatment groups into different subgroups, compared the subgroups under the same treatment method, analyzed the relevant factors affecting the treatment method, and found the most suitable treatment group. (1) After rTMS or rTMS + rPMS, all scoring scales improved compared to those before treatment (P < .05). Compared to rTMS, rTMS + rPMS resulted in greater improvements in overall motor function (UPDRS III) and quality of life (PDQ-39) (P < .05). (2) Patients with rigidity-based type as the main type may be the most suitable for these two treatment methods (P < .05).(3) There was no significant difference in treatment efficiency between the two treatment methods for patients with PD at different disease stages, sexes, or treatment ages(P > .05). Both rTMS and rTMS + rPMS can improve movement symptoms and quality of life in patients with PD. rTMS + rPMS was more beneficial for improving the overall motor function. Patients with rigidity-based type as the main type may be the most suitable for these two treatment methods. The therapies work in all age groups, all gender and irrespective of the disease stage with varying levodopa equivalent daily doses as well.

TMS in the Kingdom of Denmark: an overview of current clinical practice

Purpose Repetitive TMS (rTMS) has been demonstrated to be an effective treatment of several neuropsychiatric disorders. Its safety and efficacy are well established, and multiple rTMS devices have been approved by both Conformitè Europëenne Mark and U.S. Food and Drug Administration. We aimed to survey TMS practice in Psychiatry in the Kingdom of Denmark and compare it with the international state of the art. Methods A survey of rTMS clinical practice in 2023 was sent to all general adult psychiatry departments practicing TMS in the Danish Realm (Denmark = 10, Faroe Islands = 0, Greenland = 0). Results Response rate was 100%. rTMS was available in 37% of psychiatric departments and 3 out of 5 Danish Regions. Admission criteria required a diagnosis of unipolar depression with a degree of treatment-resistance or unacceptable side-effects to antidepressant treatment. Common contraindications included: cochlear implants (100%), pacemaker and neurostimulators (80%), other ferromagnetic/implanted devices in head, neck, or thorax (70%), active substance misuse (60%), and electrolytic disturbances (50%). Three rTMS protocols were identified: 10 Hz rTMS delivered over the L-DLPFC, iTBS delivered over the L-DLPFC and 1 Hz rTMS delivered over the right-DLPFC. 383 patients were treated with TMS. Conclusions rTMS is unequally available in the public healthcare of the Kingdom of Denmark. Existing strategies for solving inequalities could address such issues. Unipolar depression was the only psychiatric disorder treated with rTMS in 2023. rTMS practice in the Danish Realm considers the use of evidence-based protocols and is consistent with recommendations from international expert guidelines.

Analgesic effects of high-frequency rTMS on pain anticipation and perception

Previous studies suggest that pain perception is greatly shaped by anticipation, with M1 and DLPFC involved in this process. We hypothesized that high-frequency rTMS targeting these regions could alter pain anticipation and thereby reduce pain perception. In a double-blind, sham-controlled study, healthy participants received 10 Hz rTMS to M1, DLPFC, or a sham treatment. Assessments were conducted before, immediately after, and 60 min after stimulation, including laser-evoked potentials, pain ratings, and anticipatory EEG. M1-rTMS immediately reduced laser-evoked P2 amplitude, increased sensorimotor high-frequency α-oscillation power, and accelerated peak alpha frequency in the midfrontal region during pain anticipation. In contrast, DLPFC-rTMS reduced the N2-P2 complex and pain ratings 60 min post-stimulation, an effect associated with prolonged microstate C duration during pain anticipation—a microstate linked to default mode network activity. Thus, M1-rTMS immediately modulates anticipatory α-oscillations and laser-evoked potentials, while DLPFC-rTMS induces delayed analgesic effects partially by modulating default mode network activity.

Primed low frequency repetitive transcranial magnetic stimulation rebalances cortical excitatory-inhibitory circuitry and improves functional outcomes in infantile cerebral palsy patients: A randomized controlled trial

BackgroundMultiple prenatal and postnatal etiologies in cerebral palsy (CP) patients cause neural tissue damage and alterations in cortical neuronal activity and plasticity, leading to motor and cognitive deficits early in life. Repetitive transcranial magnetic stimulation (rTMS) to the lesioned or contralesional hemisphere has been shown to alleviate these functional deficits. However, the underlying mechanisms of the beneficial effects of rTMS via realigning intracortical and interhemispheric circuitry and excitability remain unclear. The present study explored the ability of primed low-frequency rTMS to modulate intracortical excitatory-inhibitory circuitry, interhemispheric and corticospinal integrity, and plasticity in infantile hemiplegic CP. MethodsThe current study was a randomized, placebo-controlled trial with infantile hemiplegic CP patients. The active group received 6 Hz primed low-frequency 1Hz rTMS delivered to the contralesional primary motor cortex for 4 weeks, in 10 sessions. The placebo group received sham stimulation. Both groups also underwent 10 sessions of modified-constraint induced movement therapy (mCIMT). Pre- and post-intervention assessments were conducted using the Quality of Upper Extremity Skills Test to evaluate sensory and motor function, and the Modified Ashworth Scale (MAS) to assess spasticity. Additionally, cortical excitability and plasticity were measured using single- and paired-pulse TMS. ResultsWe found a significant increase in Quality of Upper Extremity Skills Test scores, CP Quality of Life Child (CP QOL-Child) scores, and grip strength, and a decrease in MAS scores in the active rTMS group compared with the sham group. Single- and paired-pulse paradigms revealed a significant decrease in resting and active motor threshold, a reduction in the cortical silent period, and short- and long-interval intracortical inhibition in the intervention group compared with the sham group. ConclusionPrimed low-frequency rTMS in the contralesional hemisphere combined with mCIMT shows potential for modulating motor neuronal excitability, rebalancing intracortical excitatory-inhibitory circuitry, and enhancing functional outcomes in children with infantile hemiparetic CP.

Increased Amygdala Activation during Symptom Provocation Predicts Response to Combined Repetitive Transcranial Magnetic Stimulation and Exposure Therapy in Obsessive-Compulsive Disorder in a Randomized Controlled Trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS), combined with exposure and response prevention (ERP), is a promising treatment modality for treatment-refractory obsessive-compulsive disorder (OCD). Yet, not all patients respond sufficiently to this treatment. We investigated whether brain activation during a symptom provocation task could predict treatment response. MethodsSixty-one adults with OCD (22 male/ 39 female) underwent symptom provocation with OCD- and fear-related visual stimuli during fMRI prior to an 8-week combined rTMS and ERP treatment regimen. Participants received one of the three following rTMS treatments as part of a randomized controlled trial: (1) 10Hz rTMS (110% resting motor threshold (RMT)) to the left dorsolateral prefrontal cortex (DLPFC); (2) 10Hz rTMS (110% RMT) to the left pre-supplementary motor area (preSMA); or (3) 10Hz control rTMS (60% RMT) to the vertex. Multiple regression and correlation were used to examine the predictive value of task-related brain activation for treatment response in the following ROIs: dorsomedial prefrontal cortex, amygdala, DLPFC, and preSMA. ResultsThe different treatment groups responded equally to treatment. Higher pre-treatment task-related activation of the right amygdala to OCD-related stimuli showed a positive association with treatment response in all groups. Exploratory whole-brain analyses showed positive associations between activation in multiple task-relevant regions and treatment response. Only dorsal anterior cingulate cortex activation to fear-related stimuli showed a negative association with treatment outcome. ConclusionsHigher pre-treatment right amygdala activation during symptom provocation predicts better treatment response to combined rTMS and ERP in OCD.

Effects of repetitive transcranial magnetic stimulation therapy on weight and lipid metabolism in patients with treatment-resistant depression: A preliminary single-center retrospective cohort study.

This study aimed to elucidate the effects of repetitive transcranial magnetic stimulation (rTMS) on weight, body mass index (BMI), and lipid metabolism in patients with treatment-resistant depression (TRD). This retrospective observational study included patients with TRD who received rTMS treatment at the Jikei University Hospital from September 2018 to August 2021. The patients were diagnosed based on the DSM-5 and ICD-10 criteria and treated using the NeuroStar TMS System. For 3-6 weeks, 10-Hz rTMS was administered to the left dorsolateral prefrontal cortex at 120% motor threshold. The primary outcomes were changes in weight and BMI, whereas the secondary outcomes included changes in total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, thyroid function indicators, as well as HAMD-17, HAMD-24, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Statistical analysis was conducted using paired t-tests and repeated measures ANOVA. Among the 34 patients (20 men and 14 women) included, no significant changes were observed in weight or BMI after rTMS treatment (average weight reduction: -0.50 kg, 95% CI: -0.14 to 0.56, p = 0.24; average BMI reduction: -0.21, 95% CI: -0.10 to 0.61, p = 0.15). However, significant reductions in total, HDL, and LDL cholesterol levels and FT4 were observed. Furthermore, the HAMD-17, HAMD-24, and MADRS scores significantly increased post-treatment. rTMS treatment did not affect weight or BMI in patients with TRD but is believed to improve lipid metabolism.

Ipsilesional 5 Hz Repetitive Transcranial Magnetic Stimulation for Motor Dysfunction in Subacute Intracerebral Hemorrhage: An Exploratory Trial

ObjectiveTo explore whether ipsilesional 5 Hz repetitive transcranial magnetic stimulation (rTMS) therapy can improve motor function in patients with intracerebral hemorrhage (ICH) and observe any adverse reactions. DesignA 4-week randomized, controlled, single-blind (evaluator) trial with a 1-month follow-up. SettingA tertiary hospital rehabilitation center. ParticipantsForty-nine patients with first ICH were recruited and randomly separated into an experimental (n=25; 19 men, 6 women) or control group (n=24; 17 men, 7 women), with age range of 30 to 75 years, and mean duration after hemorrhage onset of 47 (range 17-86) days. InterventionsThe experimental group received ipsilesional 5 Hz rTMS therapy and conventional rehabilitation training. The hot spot of the abductor pollicis brevis and tibialis anterior muscles on the affected hemisphere of the brain received 1500 pulses of stimulation each day, for a total of 3000 pulses. The stimulations applied to the affected abductor pollicis brevis and tibialis anterior hot spots were separated by >2 hours. The stimulation frequency was 5 Hz, each sequence lasting 2 seconds, with a sequence interval of 5 seconds, for a total duration of 36 minutes every day. The control group only received conventional rehabilitation training. Main Outcome MeasuresThe primary endpoint was the change in Brunnstrom stage. Secondary endpoints included Fugl-Meyer Assessment, Barthel Index, and Berg Balance Scale. All assessments were performed at baseline, after intervention (day 29) and 1 month after intervention (day 60). ResultsImprovements over baseline in all scores at day 29 and 60 were significantly greater in the 5 Hz rTMS group than in the control group. No significant side effects were reported during the experiment and 1 month after the experiment. ConclusionsApplying 5 Hz high-frequency rTMS to the affected hemisphere within 3 months after the onset of ICH appears safe and may significantly improve motor function and activities of daily living.

Individualized rTMS Intervention Targeting Sleep Deprivation-Induced Vigilance Decline: Task fMRI-Guided Approach.

Sleep deprivation (SD) is prevalent in our increasingly round-the-clock society. Optimal countermeasures such as ample recovery sleep are often unfeasible, and brief naps, while helpful, do not fully restore cognitive performance following SD. Thus, we propose that targeted interventions, such as repetitive transcranial magnetic stimulation (rTMS), may enhance cognitive performance recovery post-SD. We recruited 50 participants for two SD experiments. In the first experiment, participants performed a psychomotor vigilance task (PVT) under three conditions: normal sleep (resting wakefulness), after 24 h of SD, and following a subsequent 30-min nap. We analyzed dynamic changes in PVT outcomes and cerebral responses across conditions to identify the optimal stimulation target. Experiment 2 adopted the same protocol except that, after the nap, 10-Hz, sham-controlled, individualized rTMS was administrated. Then, an analysis of variance was conducted to investigate the ability of stimulation to improve the PVT reaction times. Through task-related functional magnetic resonance imaging, we identified cerebral responses within the right middle frontal gyrus (MFG) as the optimal stimulation target. Subsequent application of individualized 10-Hz rTMS over the right MFG attenuated SD-induced deterioration of vigilance. Our findings suggest that combining a brief nap with individualized rTMS can significantly aid the recovery of vigilance following SD. This approach, through modulating neural activity within functional brain networks, is a promising strategy to counteract the cognitive effects of SD.

Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial.

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) protocols targeting primary motor cortex (M1) are used in rehabilitation of neurological diseases for their therapeutic potential, safety, and tolerability. Although lower intensity LF-rTMS can modulate M1 neurophysiology, results are variable, and a systematic assessment of its dose effect is lacking. To determine the dose-response of LF-rTMS on stimulated and non-stimulated M1. In a sham-controlled randomized double-blind crossover study the effect of LF-TMS protocols were determined in 20 right-handed older healthy participants. In 3 sessions, 1 Hz rTMS at 80% (rTMS80), 90% (rTMS90) of motor threshold or sham stimulation were applied to left upper extremity M1. Outcome measures were curve parameters of the stimulus-response curve (maximum motor evoked potential [MEPMAX], slope and the intensity to evoke 50% MEPMAX), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI). Within LF-rTMS sessions, rTMS90, increased MEPMAX in the stimulated M1. Furthermore, rTMS90, increased the slope in the non-stimulated M1. LF-rTMS effects on SICI were dependent on the participants' baseline SICI, hemisphere, and intensity of conditioning pulse. Finally, rTMS90 increased whereas rTMS80 decreased IHI, for both IHI directions. These changes were dependent on baseline IHI and hemisphere and were no longer significant when baseline IHI was accounted for. Intensity of subthreshold LF-rTMS has differential effects on excitation and inhibition of stimulated and non-stimulated M1. The effects were small and were only demonstrated within the LF-rTMS sessions but were not different when compared to sham. rTMS related changes in SICI and IHI were dependent on baseline level. NCT02544503, NCT01726218.

Comparative analysis of the impact of repetitive transcranial magnetic stimulation and burst transcranial magnetic stimulation at different frequencies on memory function and neuronal excitability of mice

Transcranial magnetic stimulation (TMS) as a non-invasive neuroregulatory technique has been applied in the clinical treatment of neurological and psychiatric diseases. However, the stimulation effects and neural regulatory mechanisms of TMS with different frequencies and modes are not yet clear. This article explores the effects of different frequency repetitive transcranial magnetic stimulation (rTMS) and burst transcranial magnetic stimulation (bTMS) on memory function and neuronal excitability in mice from the perspective of neuroelectrophysiology. In this experiment, 42 Kunming mice aged 8 weeks were randomly divided into pseudo stimulation group and stimulation groups. The stimulation group included rTMS stimulation groups with different frequencies (1, 5, 10 Hz), and bTMS stimulation groups with different frequencies (1, 5, 10 Hz). Among them, the stimulation group received continuous stimulation for 14 days. After the stimulation, the mice underwent new object recognition and platform jumping experiment to test their memory ability. Subsequently, brain slice patch clamp experiment was conducted to analyze the excitability of granulosa cells in the dentate gyrus (DG) of mice. The results showed that compared with the pseudo stimulation group, high-frequency (5, 10 Hz) rTMS and bTMS could improve the memory ability and neuronal excitability of mice, while low-frequency (1 Hz) rTMS and bTMS have no significant effect. For the two stimulation modes at the same frequency, their effects on memory function and neuronal excitability of mice have no significant difference. The results of this study suggest that high-frequency TMS can improve memory function in mice by increasing the excitability of hippocampal DG granule neurons. This article provides experimental and theoretical basis for the mechanism research and clinical application of TMS in improving cognitive function.

A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study.

This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10-20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham. Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment. Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response. Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.

A preliminary comparison of the clinical efficacy of repetitive transcranial magnetic stimulation with facial feature point localization and navigated localization in the treatment of depression

ObjectiveTo compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression. Methods42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05. ResultsThe absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines. ConclusionThere was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.

The alterations of repetitive transcranial magnetic stimulation on the energy landscape of resting-state networks differ across the human cortex.

Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention tool for the noninvasive modulation of brain activity and behavior in neuroscience research and clinical settings. However, the resting-state dynamic evolution of large-scale functional brain networks following rTMS has rarely been investigated. Here, using resting-state fMRI images collected from 23 healthy individuals before (baseline) and after 1 Hz rTMS of the left frontal (FRO) and occipital (OCC) lobes, we examined the different effects of rTMS on brain dynamics across the human cortex. By fitting a pairwise maximum entropy model (pMEM), we constructed an energy landscape for the baseline and poststimulus conditions by fitting a pMEM. We defined dominant brain states (local minima) in the energy landscape with synergistic activation and deactivation patterns of large-scale functional networks. We calculated state dynamics including appearance probability, transitions and duration. The results showed that 1 Hz rTMS induced increased and decreased state probability, transitions and duration when delivered to the FRO and OCC targets, respectively. Most importantly, the shortest path and minimum cost between dominant brain states were altered after stimulation. The absolute sum of the costs from the source states to the destinations was lower after OCC stimulation than after FRO stimulation. In conclusion, our study characterized the dynamic trajectory of state transitions in the energy landscape and suggested that local rTMS can induce significant dynamic perturbation involving stimulated and distant functional networks, which aligns with the modern view of the dynamic and complex brain. Our results suggest low-dimensional mapping of rTMS-induced brain adaption, which will contribute to a broader and more effective application of rTMS in clinical settings.

Investigating the effects of excitatory and inhibitory somatosensory rTMS on somatosensory functioning in the acute and subacute phases of stroke: a preliminary double-blind and randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10-Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. https://www.chictr.org.cn/showproj.html?proj=166474, ChiCTR2200059098.

Safety and efficacy of targeting the supplementary motor area with double-cone deep transcranial magnetic stimulation vs figure-eight coil in treatment of obsessive-compulsive disorder with comorbid major depressive disorder

Background and objectiveThe Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone “deep” TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD). MethodsSixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted. ResultsSubjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups. ConclusionsSMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation.

Differential analgesic effects of high-frequency or accelerated intermittent theta burst stimulation of M1 on experimental tonic pain: Correlations with cortical activity changes assessed by TMS-EEG

Accelerated intermittent theta burst stimulation (AiTBS) has attracted much attention in the past few years as a new form of brain stimulation paradigm. However, it is unclear the relative efficacy of AiTBS on cortical excitability compared to conventional high-frequency rTMS. Using concurrent TMS and electroencephalogram (TMS-EEG), this study systematically compared the efficacy on cortical excitability and a typical clinical application (i.e. pain), between AiTBS with different intersession interval (ISIs) and 10-Hz rTMS. Participants received 10-Hz rTMS, AiTBS-15 (3 iTBS sessions with a 15-min ISI), AiTBS-50 (3 iTBS sessions with a 50-min ISI), or Sham stimulation over the primary motor cortex on four separate days. All four protocols included a total of 1800 pulses but with different session durations (10-Hz rTMS ​= ​18, AiTBS-15 ​= ​40, and AiTBS-50 ​= ​110 ​min). AiTBS-50 and 10-Hz rTMS were more effective in pain reduction compared to AiTBS-15. Using single-pulse TMS-induced oscillation, our data revealed low gamma oscillation as a shared cortical excitability change across all three active rTMS protocols but demonstrated completely opposite directions. Changes in low gamma oscillation were further associated with changes in pain perception across the three active conditions. In contrast, a distinct pattern of TMS-evoked potentials (TEPs) was revealed, with 10-Hz rTMS decreasing inhibitory N100 amplitude and AiTBS-15 reducing excitatory P60 amplitude. These changes in TEPs were also covarying with low gamma power changes. Sham stimulation indicated no significant effect on either cortical excitability or pain perception. These results are relevant only for provoked experimental pain, without being predictive for chronic pain, and revealed a change in low gamma oscillation, particularly around the very particular frequency of 40 ​Hz, shared between AiTBS and high-frequency rTMS. Conversely, cortical excitability (balance between excitation and inhibition) assessed by TEP recording was modulated differently by AiTBS and high-frequency rTMS paradigms.

Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study

BackgroundDisorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies.MethodsTwenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated.ResultsOne-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031).ConclusionsApplying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy.Trial registrationwww.ClinicalTrials.gov, identifier: NCT05187000.

Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study

BackgroundNew daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients.MethodsThis was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks.ResultsFifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point’s reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively.ConclusionrTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms.Trial registrationCTRI/2023/05/053247.

Restoration of abnormal sleep EEG power in patients with insomnia disorder after 1Hz rTMS over left DLPFC.

Hyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear. Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated. Abnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep. The relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

Induction and stabilization of delta frequency brain oscillations by phase-synchronized rTMS and tACS

BackgroundBrain oscillations in the delta frequency band have been linked with deep sleep and consolidation of declarative memory during sleep. However, the causal relationship of these associations remains not competely clarified, primarily due to constraints by technical limitations of brain stimulation approaches suited to induce and stabilize respective oscillatory activity in the human brain. The objective of this study was to establish a non-invasive brain stimulation protocol capable of reliably inducing, and stabilizing respective oscillatory activity in the delta frequency range. HypothesisWe aimed to develop an efficient non-invasive brain stimulation (NIBS) protocol for delta frequency induction and stabilization via concurrent, phase-locked repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS). We hypothesized that rTMS induces oscillatory resting-state activity in the delta frequency and that tACS stabilizes this effect, as has been shown before for alpha and theta frequencies. Methods19 healthy participants took part in a repeated-measures experimental protocol. We applied rTMS pulses synchronized with the peak or trough phase of 0.75Hz tACS over the bilateral prefrontal cortex. Resting state EEG in eyes-open (EO) and eyes-closed (EC) conditions was recorded before, immediately after and every 10 min for up to 1 h after intervention. ResultsrTMS phase-synchronized to the trough of the tACS waveform significantly increased delta frequency activity for up to 60 min in both EO and EC conditions after stimulation. The effects extended from frontal to temporal regions and this enhancement of oscillatory activity was shown to be specific for the delta frequency range. ConclusionConcurrent, trough-synchronized 0.75 Hz rTMS combined with tACS may be a reliable protocol to induce long-lasting oscillatory activity in the delta frequency range. The results of the current study might perspectively be relevant for clinical treatment of sleep disturbances which are accompanied by pathologically altered brain oscillations, and enhancement of memory consolidation.