Low-frequency rTMS Research Articles

Therapeutic effect of repetitive transcranial magnetic stimulation on non-lesional focal refractory epilepsy

The effects of repetitive transcranial magnetic stimulation (rTMS) on epilepsy remain unclear. This study was performed to investigate the effects of low-frequency rTMS on non-lesional focal epilepsy.This was a prospective open-label longitudinal study with four patients with multi-drug-resistant non-lesional focal epilepsy and no control group. The patients received daily doses of 900 pulses of 0.5-Hz stimulation for 10 days over the epileptic foci in neocortical areas determined by electrical source analysis. The outcomes were measured in terms of seizure reduction. The incidences of seizures were measured at baseline (4 weeks), intervention (2 weeks), and follow up (8 weeks).Seizure reduction was observed in three of four subjects. The effects of rTMS persisted over a follow-up period of 8 weeks. One of the four patients did not respond to rTMS and showed no seizure reduction.The low frequency rTMS would be an effective treatment for non-lesional focal refractory epilepsy, may be an adjunctive treatment with conventional medical treatment for refractory epilepsy. These results are therefore useful for planning treatment strategies for patients with refractory epilepsy, as well as for treatment of epilepsy.

Can psychological features predict antidepressant response to rTMS? A Discovery-Replication approach.

Few studies focused on the relationship between psychological measures, major depressive disorder (MDD) and repetitive transcranial magnetic stimulation (rTMS) response. This study investigated several psychological measures as potential predictors for rTMS treatment response. Additionally, this study employed two approaches to evaluate the robustness of our findings by implementing immediate replication and full-sample exploration with strict p-thresholding. This study is an open-label, multi-site study with a total of 196 MDD patients. The sample was subdivided in a Discovery (60% of total sample, n = 119) and Replication sample (40% of total sample, n = 77). Patients were treated with right low frequency (1 Hz) or left high frequency (10 Hz) rTMS at the dorsolateral prefrontal cortex. Clinical variables [Beck Depression Inventory (BDI), Neuroticism, Extraversion, Openness Five-Factor Inventory, and Depression, Anxiety, and Stress Scale, and BDI subscales] were obtained at baseline, post-treatment, and at follow-up. Predictors were analyzed in terms of statistical association, robustness (independent replication), as well as for their clinical relevance [positive predictive value (PPV) and negative predictive value (NPV)]. Univariate analyses revealed that non-responders had higher baseline anhedonia scores. Anhedonia scores at baseline correlated negatively with total BDI percentage change over time. This finding was replicated. However, anhedonia scores showed to be marginally predictive of rTMS response, and neither PPV nor NPV reached the levels of clinical relevance. This study suggests that non-responders to rTMS treatment have higher baseline anhedonia scores. However, anhedonia was only marginally predictive of rTMS response. Since all other psychological measures did not show predictive value, it is concluded that psychological measures cannot be used as clinically relevant predictors to rTMS response in MDD.

Abstract #79: Efficacy of Low-Frequency rTMS over the Right Dorsolateral Prefrontal Cortex following Mild Traumatic Brain Injury

Introduction: Mild traumatic brain injury (mTBI) is a common cause of disability that can result in physical, psychological, and cognitive impairment. Current treatments for mTBI are often ineffective or produce adverse side effects. Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) can improve cognition, and rTMS is increasingly being used for the treatment of mood disorders. Here, we sought to investigate the feasibility and tolerability of using low frequency (LF) rTMS (suggested to be a safe protocol for people with a higher chance of seizures) in individuals with mTBI, and to study whether LF rTMS over the right dorsolateral prefrontal cortex (DLPFC) could help reduce post-concussion and cognitive symptoms in this patient population.

Potentials of rTMS for neurodevelopmental disorders and road to clarification of TMS neuropathology

Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), or tic disorders are common in children and adolescents. However, treatment strategies remain limited for these disorders. Herein, we would like to discuss potential of repetitive transcranial magnetic stimulation (rTMS) for children with neurodevelopmental disorders and strategy for clarification of neurophysiology to develop more effective treatment protocols. Recently, rTMS has been emerged as an alternative potential treatment for neurodevelopmental disorders. We systematically reviewed the literature on rTMS for children with neurodevelopmental disorders published up to February 2018. In children with ASD, low-frequency rTMS and intermittent theta burst stimulation (iTBS) to the DLPFC may have therapeutic impact on symptoms such as lethargy or repetitive behavior. In children with ADHD, low-frequency left DLPFC rTMS and high-frequency right DLPFC rTMS could improve inattention, hyperactivity, and impulsivity. In children with tic disorders, low-frequency rTMS applied to bilateral supplementary motor area improved tic symptoms. In addition, severe adverse effects by rTMS have not been reported in the included studies. This systematic review suggests that rTMS may be beneficial in children with neurodevelopmental disorders especially ASD. Further, cortical excitation/inhibition (E/I) imbalances may contribute to various clinical symptoms observed in individuals with ASD, however, the precise neural basis supporting E/I balance of cortex remains unclear. We conducted a meta-analysis on TMS neurophysiology studies of their motor cortex such as MEPs and short-interval intracortical inhibition (SICI) between individuals with ASD and controls. There was no difference in MEP amplitude between the two groups while SICI was significantly reduced in individuals with ASD compared to controls. Since SICI mainly reflects GABA(A) receptor-mediated function, our findings are congruent with previous studies that demonstrated potential deficits in GABA receptor-mediated function in ASD. Collectively, to develop more sophisticated rTMS protocols targeting the pathophysiology of these disorders are highly demanded.

Different Modulation Mechanisms on Functional Motor Network between High and Low Frequency rTMS in Stroke Patients with Motor Dysfunction

Different Modulation Mechanisms on Functional Motor Network between High and Low Frequency rTMS in Stroke Patients with Motor Dysfunction

Comparison of effect of a single-session of high- or low-frequency rTMS on cortical excitability in people with Parkinson’s disease – A randomised placebo controlled trial

Comparison of effect of a single-session of high- or low-frequency rTMS on cortical excitability in people with Parkinson’s disease – A randomised placebo controlled trial

Right sided (RDLPFC) low frequency (1Hz) rTMS in the third trimester of pregnancy; a case report

Right sided (RDLPFC) low frequency (1Hz) rTMS in the third trimester of pregnancy; a case report

Low-frequency rTMS to ventral medial frontal cortex induces depression-like behavioral and physiological state in monkeys

The medial frontal cortex (MFC), including the anterior cingulate cortex (ACC), has long been implicated in emotional, motivational and social behavior. And the abnormal functioning of rostroventral regions of the ACC, the pregenual and subgenual ACCs, has been repeatedly reported in patients with mood disorders. In this study, we aimed to causally examine how the MFC is involved in the regulation of mood and affective state in monkeys by using repetitive transcranial magnetic stimulation (rTMS) as a tool to manipulate local cortical activity. Low-frequency (1 Hz) 1200-pulse rTMS was delivered to the monkey MFC through two types of the TMS coil. The dorsal and ventral regions of the anterior part of the MFC (d+vMFC) was stimulated with a 70-mm double-cone coil, which can stimulate deep brain regions. The same location was also stimulated with a 70-mm figure-of-eight coil to stimulate only the dorsal region of the anterior MFC. The within-cage spontaneous activity, motivational level, sociability, and plasma cortisol level were examined as indices of mood and affective state. As a result, we found significant decrease in the within-cage spontaneous activity, motivational level, and sociability, and a significant increase in the evening plasma cortisol level when the d+vMFC was stimulated. We also found that the reduction of within-cage spontaneous activity and the increase in evening plasma cortisol level induced by the d+vMFC stimulation returned to the baseline level by the administration of ketamine, which recently has been considered as a fast-reacting antidepressant. These results indicate that the ventral MFC including the rostroventral region of the ACC is critically involved in the regulation of mood and affect in monkeys, and the inhibition of its activity can be regarded as a model of major depression.

Effects of low-frequency repetitive transcranial magnetic stimulation on depression- and anxiety-like behaviors in epileptic rats.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a treatment option for depression and anxiety. However, its role in epilepsy comorbid with depression and anxiety is unclear. Therefore, we evaluated whether low-frequency rTMS can alleviate depression- and anxiety-like behavior in epileptic rats. Forty-eight adult rats were allocated at random to four groups: Control, Pentylenetetrazol (PTZ), PTZ-rTMS and PTZ-Sham. The control group received intraperitoneal injections of normal saline, while the other groups received intraperitoneal injections of pentylenetetrazol (35 mg/kg/d) once a day for 15 days. Low-frequency rTMS or sham stimulation were administered to the PTZ-rTMS and PTZ-Sham group, respectively, over the two-week period. The open-field test (OFT), elevated plus-maze test (EPM) and forced swimming test (FST) were carried out before the experiment, on the 8th and 15th day to assess depression- and anxiety-like behavior in the rats. Two weeks of low-frequency rTMS treatment could not impair the increases of seizure severity in epileptic rats. However, relative to the PTZ and PTZ-Sham group, the two-week low-frequency rTMS treatment significantly reduced the immobility time in the forced swimming test and attenuated the progressive decrease in total distance traveled, frequency of rearing, velocity in the open-field test, number of entries in the open arms (%) and the time spent in the open arms (%) in the elevated plus-maze test of the PTZ-rTMS group. We proposed that low-frequency rTMS can benefit epileptic rats via amelioration of comorbid depression and anxiety, but it can not alleviate the seizure severity.

Diagnostic and therapeutic issues of using transcranial magnetic stimulation in patients with writer's cramp

To assess diagnostic and therapeutic values of transcranial magnetic stimulation (TMS) in patients with writer's cramp (WC). Twelve right-handed patients with WC were enrolled in the study. All patients underwent low-frequency repetitive TMS (rTMS) over the premotor cortex of the hemisphere contralateral to the affected hand. The clinical efficacy was assessed using the Writer's Cramp Rating Scale (WCRS) and the Medical Outcomes Study-Short Form (MOS-SF-36). Before and after the last rTMS session, motor mapping of abductor pollicis brevis muscle (APB) was performed using navigated TMS (nTMS). Localization, area, and amplitude-weighted area of the APB muscle cortical representations were compared with the healthy controls. The dynamics of the mentioned above parameters after the rTMS course was assessed. Ten sessions of low-frequency rTMS over premotor cortex reduced the severity of WC clinical symptoms, with a duration of effect of at least 1 month (p<0.05). There was no significant difference between the area and the weighted area of cortical muscle representations between patients and healthy controls or in patients before and after rTMS. When assessing the localization of cortical muscle representations, two trends were noted: in 4 patients, the localization remained stable, with a shift in the center of gravity of less than 4 mm; in the other 8 patients, a shift in the center of gravity of more than 5 mm was noted. No significant correlations between the stability of the cortical muscle representations (the magnitude of the shift in the center of gravity) and the improvement on the WCRS scale were found. The low-frequency rTMS over the premotor cortex of the hemisphere contralateral to the affected hand can be used as an adjuvant therapy for WC. The TMS-motor mapping study did not show its diagnostic value.

Effects of Hand Intrinsic Muscle Facilitation and Functional Task Training on Cerebral Motor Evoked Potential after 1 Hz Low-Frequency rTMS in Stroke Patients

The purpose of this study was to investigate the effects of hand intrinsic muscles facilitation and functional task training with 1 Hz repetitive transcranial magnetic stimulation (rTMS) on cerebral motor cortex activity in stroke patients and to investigate the effectiveness of stroke rehabilitation. In this study, 20 adult stroke patients were randomly selected and divided into two groups of 10 each other. In the experimental group, hand intrinsic muscles facilitation and functional task training were performed after 1 Hz low frequency for 20 minutes and simple upper limb task training was performed in the control group. To investigate the changes of cerebral motor cortex activity after intervention, we measured Motor evoked potential (MEP) amplitude and latency. In both groups, MEP amplitude increased and MEP latency decreased after intervention. There was a significant difference between the two groups in MEP amplitude and latency (p 0.01) (p 0.05). Therefore, hand intrinsic muscles facilitation and functional task training with 1 Hz low frequency (rTMS) of stroke patients showed positive results in MEP amplitude and latency change of the injured cerebral cortex after stroke.

Effect of Combined Therapy of Robot and Low-Frequency Repetitive Transcranial Magnetic Stimulation on Hemispatial Neglect in Stroke Patients.

ObjectiveTo investigate the effect of upper limb rehabilitation combining robot with low-frequency repetitive transcranial magnetic stimulation (rTMS) on unilateral spatial neglect in stroke patients.MethodsPatients who had hemispatial neglect after right hemisphere stroke were randomly divided into rTMS only group, robot only group, and combined group. All groups received conventional neglect therapy and additional treatment for each group. rTMS group received rTMS therapy. Robot group received robot therapy, while combined group received both therapies. The effect of therapy was assessed with Motor-Free Visual Perception Test-3 (MVPT-3), line bisection test, star cancellation test, Catherine Bergego Scale (CBS), Mini-Mental State Examination (MMSE), and the Korean version of Modified Barthel Index (K-MBI). These measurements were evaluated before and after treatment.ResultsFor each group, 10 patients were recruited. There were no significant differences in baseline characteristics or initial values among the three groups. Two weeks after the therapy, all groups showed significant improvement in MVPT-3, line bisection test, star cancellation test, CBS, MMSE, and K-MBI. However, changes in measurements showed no significant differences among groups.ConclusionTreatment effect of the combined therapy of robotic therapy and low-frequency rTMS therapy for hemispatial neglect was not statistically different from that of each single treatment. Resultsof this study did not prove the superiority of any of the three treatments. Further study with large number of patients is needed to evaluate the superiority of these treatments.

Low-frequency rTMS stimulation over superior parietal cortex medially improves time reproduction and increases the right dorsolateral prefrontal cortex predominance

Aim of the study: Previous studies have shown that several cortical regions are involved in temporal tasks in multiple timescales. However, the hemispheric predominance of the dorsolateral prefrontal cortex (DLPFC) during time reproduction after repetitive low-frequency transcranial magnetic stimulation (rTMS) is relatively unexplored. Here, we study the effects of 1 Hz rTMS and sham stimulation applied medially over the superior parietal cortex (SPC) on the DLPFC alpha and beta band asymmetry and on time reproduction.Materials and methods: For this purpose, we have combined rTMS with electroencephalography in 20 healthy subjects who performed the time reproduction task in two conditions (sham and 1 Hz).Results: The worst performance was observed in sham and 1Hz conditions for longer time intervals (p < .05), with the 1Hz condition subjects sub-reproducing the time interval, closer to the target interval (p < .05). The right DLPFC hemispheric predominance was found in both conditions, but after low-frequency rTMS, the right hemisphere predominance increased in the 1Hz condition (p < .05).Conclusions: Results of this study suggest that rTMS applied over the SPC influences time interval interpretation and the DLPFC functions. Future studies would explore the effects of the rTMS application to other cortical areas, and study how it influences time interval interpretation.

Long-Term Relief of Painful Bladder Syndrome by High-Intensity, Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Right and Left Dorsolateral Prefrontal Cortices.

Aim: To show the value of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) to treat bladder pain syndrome (BPS), characterized by suprapubic pain, urgency and increased micturition frequency.Methods: A 68-year-old woman with BPS underwent 16 sessions of high-intensity, low-frequency (1 Hz) rTMS of the DLPFC, first on the right hemisphere (one daily session for 5 days, followed by one weekly session for 5 weeks), and then on the left hemisphere (one monthly session for 6 months).Results: At the end of the rTMS protocol, suprapubic pain completely vanished, micturition frequency dramatically decreased (by 60–80%), while fatigue and sleep quality improved (by 57–60%). The patient reported an overall satisfaction rate of 80% and her activities of daily living tending to normalize.Conclusion: This is the first report showing that high-intensity, low-frequency rTMS delivered on the DLPFC region of both hemispheres can relieve most symptoms of BPS (pain, urinary symptoms, and interference with physical functioning) in clinical practice.

Effect of Low Frequency Repetitive Transcranial Magnetic Stimulation on Depression and Cognition of Patients with Traumatic Brain Injury: A Randomized Controlled Trial.

BackgroundThis study was conducted to investigate the effects of low frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex on depression and cognition in patients with traumatic brain injury.Material/MethodsTo accomplish this, 13 patients who were diagnosed with traumatic brain injury were divided into an experimental group (n=7) and a control group (n=6). The experimental group received rTMS during a 30-minute session 5 days per week for 2 weeks; the control group received sham rTMS. The patients were then evaluated for depression using the Montgomery-Asberg Depression Rating Scale (MADRS) and for cognitive function using the Trail Making Test (TMT) and the Stroop Color Word Test (SCWT).ResultsA significant decrease in MADRS, TMT, and SCWT was observed after the intervention in the experimental group (P<0.01), and there was a significant difference in the change value of MADRS, TMT, and SCWT compared to the control group (P<0.01). Moreover, the effect size for gains in the experimental group and control group was very strong for MADRS, TMT, and SCWT (effect size=1.44, 1.49, and 1.24 respectively).ConclusionsThe results of this study suggest that application of low frequency rTMS to the right dorsolateral prefrontal cortex of patients with traumatic brain injury has a positive effect on depression and cognition.

Augmentation Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation Over Presupplementary Motor Area in Obsessive-Compulsive Disorder: A Randomized Controlled Trial.

The current study investigated the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over bilateral presupplementary motor area (pre-SMA) in patients suffering from obsessive-compulsive disorder (OCD) with partial/poor response to pharmacotherapy, in a double-blinded randomized sham controlled trial. Forty subjects with OCD, who were on stable medications with partial/poor response to pharmacotherapy were randomly divided into 2 groups (n = 20 in each group), to receive either active or sham low-frequency rTMS over bilateral pre-SMA. Thirty-six patients were eligible for intent-to-treat analysis. There was no significant difference in relevant demographic and clinical variables between the 2 groups at baseline. There were no statistically significant differences between the 2 groups after 3 weeks of treatment in the Yale-Brown Obsessive Compulsive Scale score (time*group interaction, F2.48,84.16 = 0.80, P = 0.40) and other secondary outcome measures including responder rates and depressive and anxiety symptoms. Low-frequency rTMS over pre-SMA may not be effective as an augmenting agent in partial/poor responders to SRIs. This study underlines the need to explore alternate rTMS protocols in OCD.

Low-Frequency rTMS of the Primary Motor Area Does Not Modify the Response of the Cerebral Cortex to Phasic Nociceptive Stimuli.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique of cortical stimulation. Although the exact mechanism of action is not clearly understood, it has been postulated that rTMS action on pain depends most on stimulation sites and stimulation parameters. Most studies concern high-frequency rTMS of the primary motor cortex (M1). High-frequency rTMS over motor cortex seems to induce an analgesic effect while contrasting results were reported after low-frequency rTMS. The aim of the current study was to investigate the effects of 1 Hz rTMS stimulation over the left primary motor cortex on subjective laser pain rating and laser evoked potential (LEP) amplitudes in healthy subjects. Subjects underwent two different sessions (real and sham rTMS) according to a cross-sectional design. In each session, LEPs and laser-pain rating to stimulation of both right and left hand dorsum were collected before 1 Hz rTMS over the left M1 area (baseline), which lasted 20 min. Then, LEPs and laser-pain rating were measured immediately after rTMS (T0), after 20 min from T0 (T0+20), and after 40 min from T0 (T0+40). We could not find any modification of both laser-pain rating and LEP parameters (latencies and amplitudes) following 1 Hz rTMS. Therefore, our results show that the low-frequency rTMS of the M1 area does not change the response of the cerebral cortex to pain.

Low frequency rTMS combined with visual scanning training in patients with post-stroke visuospatial neglect. A randomized, double-blind, placebo-controlled study

Low frequency rTMS combined with visual scanning training in patients with post-stroke visuospatial neglect. A randomized, double-blind, placebo-controlled study

Repetitive transcranial magnetic stimulation (rTMS) modulates hippocampal structural synaptic plasticity in rats.

Repetitive transcranial magnetic stimulation (rTMS) was shown to have therapeutic potential for some neurological and psychiatric disorders. Previous studies reported that low-frequency rTMS (</=1 Hz) affected synaptic plasticity in rats, however, there were few investigations to examine the possible effects of rTMS on structural synaptic plasticity changes in rats, which included the effects on synaptic morphology in the hippocampus, synaptic protein markers and Ca(2+)/calmodulin-dependent protein II (CaMKII). Sprague-Dawley rats were subject to 500 pulses of 0.5 Hz rTMS for 15 days, or sham stimulation. After last stimulation, transmission electron microscope (TEM) and real-time PCR were used to determine the effects of rTMS on synaptic plasticity. Results showed that rTMS could cause the change of structural synaptic plasticity, increase the expression of synaptic protein markers: synaptophysin (SYN) and increase the expression of CaMKII, relative to normal rats. suggesting a modulatory effect of chronic rTMS on synaptic plasticity that may be attributed to the increased expression of CaMKII in rats.

Repetitive transcranial magnetic stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.

BackgroundSeveral studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect in Alzheimer’s disease (AD). Nevertheless, the clinical benefit of rTMS for AD remains inconclusive.ObjectiveThis systematic review and meta-analysis aimed to evaluate the efficacy and safety of rTMS in AD.MethodsWe searched PubMed, Embase and Cochrane for randomized controlled trials (RCTs) of rTMS for AD. We calculated pooled estimates of mean difference (MD) with 95% confidence intervals (CI). The protocol was registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42018089990).ResultsFive RCTs involving 148 participants were included in this review. Compared with sham stimulation, high-frequency rTMS led to a significant improvement in cognition as measured by ADAS-cog (MD = -3.65, 95% CI -5.82 to -1.48, p = 0.001), but not MMSE (MD = 0.49, 95% CI -1.45 to 2.42, p = 0.62). High-frequency rTMS also improved the global impression in comparison to the placebo (MD = -0.79, 95% CI -1.24 to -0.34, p = 0.0006). There was no significant difference in mood (MD = -1.36, 95% CI -3.93 to 1.21, p = 0.30) and functional performance (MD = 0.59, 95% CI -1.21 to 2.38, p = 0.52) between high-frequency rTMS and sham groups. Only one trial included low-frequency rTMS reported no significant improvement in cognition, mood and functional performance. Few mild adverse events were observed in both the rTMS and sham groups.ConclusionsRTMS is relatively well tolerated, with some promise for cognitive improvement and global impression in patients with AD. Our findings also indicate the variability between ADAS-cog and MMSE in evaluating global cognitive impairment.