Repeated rTMS Sessions Research Articles

Repetitive transcranial magnetic stimulation alone and in combination with motor control exercise for the treatment of individuals with chronic non-specific low back pain (ExTraStim trial): study protocol for a randomised controlled trial

IntroductionWhile multiple pharmacological and non-pharmacological interventions treating chronic non-specific low back pain (CLBP) are available, they have been shown to produce at best modest effects. Interventions such as repetitive transcranial...

Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Impulse Inhibition in Abstinent Patients With Methamphetamine Addiction

Impulsivity during periods of abstinence is a critical symptom of patients who use methamphetamine (MA). To evaluate changes in impulse inhibition elicited by repetitive transcranial magnetic stimulation (rTMS) in patients with MA addiction. This randomized clinical trial was conducted in Da Lian Shan Addiction Rehabilitation Center, Nanjing, China, from December 1, 2018, to April 20, 2019. Effects of the intervention were examined at 3 time points: after a single session (day 1), 24 hours after 10 repeated sessions (day 11), and at 3 weeks of follow-up (day 31). Men with MA addiction and healthy male control participants were recruited for this study. Data analysis was performed from March 2019 to October 2019. Patients who use MA were randomized to undergo sham rTMS (36 patients) and or 1-Hz rTMS (37 patients) to the left prefrontal cortex, receiving daily TMS treatments for 10 consecutive days. The primary outcome was impulse inhibition, which is primarily embodied by accuracy reduction (ie, accuracy cost) from standard to deviant trials in a 2-choice oddball task (80% standard and 20% deviant trials). The study included 73 men with MA addiction (mean [SD] age, 38.49 [7.69] years) and 33 male healthy control participants without MA addiction (mean [SD] age, 35.15 [9.68] years). The mean (SD) duration of abstinence for the men with MA addiction was 9.27 (4.61) months. Compared with the control group, patients with MA addiction exhibited greater impulsivity (accuracy cost, 3.3% vs 6.2%). The single session of 1-Hz rTMS over the left prefrontal cortex significantly increased accuracy from 91.4% to 95.7% (F1,36 = 9.58; P < .001) and reaction time delay from 50 milliseconds to 77 milliseconds (F1,36 = 22.66; P < .001) in deviant trials. These effects were seen consistently after 10 sessions of 1-Hz rTMS treatment (day 11 vs day 1, t26 = 1.59; P = .12), and the behavioral improvement was maintained at least for 3 weeks after treatment (day 31 vs day 1, t26 = 0.26; P = .80). These improvement effects of impulse inhibition were coupled with a reduction in addictive symptoms as measured by cue-induced craving. The pretest accuracy cost was positively correlated with the change in impulse inhibition (r = 0.615; P < .001) and change in craving (r = 0.334; P = .01), suggesting that these 2 behaviors may be modified simultaneously. These findings suggest that repeated rTMS sessions have sustained effects on impulse inhibition in patients with MA addiction and provide novel data on impulsivity management strategies for addiction rehabilitation. ChiCTR-ROC-16008541.

Effects of Multi-Session Repetitive Transcranial Magnetic Stimulation on Motor Control and Spontaneous Brain Activity in Multiple System Atrophy: A Pilot Study.

Background: Impaired motor control is one of the most common symptoms of multiple system atrophy (MSA). It arises from dysfunction of the cerebellum and its connected neural networks, including the primary motor cortex (M1), and is associated with altered spontaneous (i.e., resting-state) brain network activity. Non-invasive repetitive transcranial magnetic stimulation (rTMS) selectively facilitates the excitability of supraspinal networks. Repeated rTMS sessions have been shown to induce long-term changes to both resting-state brain dynamics and behavior in several neurodegenerative diseases. Here, we hypothesized that a multi-session rTMS intervention would improve motor control in patients with MSA, and that such improvements would correlate with changes in resting-state brain activity.Methods: Nine participants with MSA received daily sessions of 5 Hz rTMS for 5 days. rTMS targeted both the cerebellum and the bilateral M1. Before and within 3 days after the intervention, motor control was assessed by the motor item of the Unified Multiple System Atrophy Rating Scale (UMSARS). Resting-state brain activity was recorded by blood-oxygen-level dependency (BOLD) functional magnetic resonance imaging. The “complexity” of resting-state brain activity fluctuations was quantified within seven well-known functional cortical networks using multiscale entropy, a technique that estimates the degree of irregularity of the BOLD time-series across multiple scales of time.Results: The rTMS intervention was well-attended and was not associated with any adverse events. Average motor scores were lower (i.e., better performance) following the rTMS intervention as compared to baseline (t8 = 2.3, p = 0.003). Seven of nine participants exhibited such pre-to-post intervention improvements. A trend toward an increase in resting-state complexity was observed within the motor network (t8 = 1.86, p = 0.07). Participants who exhibited greater increases in motor network resting-state complexity demonstrated greater improvement in motor control (r2= 0.72, p = 0.004).Conclusion: This pilot study demonstrated that a five-session rTMS intervention targeting the cerebellum and bilateral M1 is feasible and safe for those with MSA. More definitive, well-controlled trials are warranted to confirm our preliminary results that rTMS may alleviate the severity of motor dysfunction and modulate the multiscale dynamics of motor network brain activity.

Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation.

The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings.

Acute and chronic effects of repeated 1 Hz rTMS on the temporal cortex

Electroencephalography amplitude, phase synchronization, and directionality of phase coupling within and between hemispheres were compared for different frequency components in 27 healthy individuals before and after 5 days of daily 1 Hz repetitive transcranial magnetic stimulation (rTMS), and at 2 weeks after the last session. Instantaneous amplitudes of α (8-13 Hz) and β (13-30 Hz) frequency components were increased after daily rTMS, the effects of which were declining over time, suggesting an adapting response with repeated rTMS sessions. The phase synchronization of electroencephalography increased significantly in the α frequency, especially the upper-α band (11-13 Hz), in both the frontal and the temporal areas, predominantly in the ipsilateral hemisphere. Asymmetric directional interactions of the upper-α band were stronger from the stimulated area to the contralateral hemisphere. No significant differences were found at 2 weeks after rTMS in any of these values. Focal 1 Hz rTMS induces an enhancement in the ipsilateral dominant corticocortical interaction drastically by interhemispheric asymmetric coupling from the stimulated cortical area with an adapting response with repeated sessions. This kind of method can be valuable for possible clinical applications in various neuropsychiatric conditions to study the therapeutic mechanisms of 1 Hz rTMS.

Assessing Low‐frequency Repetitive Transcranial Magnetic Stimulation with Functional Magnetic Resonance Imaging: A Case Series

This case series assesses the effects of five consecutive days of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) with and without a 6-Hz primer. Although this paper studies able-bodied individuals, similar rTMS protocols are used to facilitate motor recovery in patients with hemiplegia following stroke. However, the cortical mechanisms associated with repeated daily doses of rTMS are not completely understood. Four right-handed healthy volunteers (two men, aged 20-50 years) participated in a double-blind case series of primed and unprimed rTMS. Functional magnetic resonance imaging was used to compare task-related haemodynamics during a simple motor task and resting-state cortical connectivity. Understanding the mechanisms of repeated rTMS sessions may serve as a precursor to development of rTMS paradigms involving motor cortex stimulation in patients with a range of neurologic dysfunction. Following five consecutive days of rTMS, all subjects had reduced task-related haemodynamics. Resting-state brain connectivity between motor regions was reduced only after primed rTMS. This is the first study to indicate that resting-state brain connectivity can distinguish the effect of primed and unprimed rTMS to a greater extent than task-related haemodynamics. Furthermore, priming may inhibit the connectivity between the area of the cortex underlying the rTMS site and remote brain regions. These findings benefit rTMS rehabilitation studies by examining haemodynamics on repeated days of stimulation and incorporating resting-state brain connectivity analysis to further understand underlying neural mechanisms. Furthermore, this work encourages the utilization of resting connectivity in future rTMS studies.

Enhancing plasticity through repeated rTMS sessions: The benefits of a night of sleep

Objective Previous work has demonstrated that corticospinal facilitation from 20 Hz repetitive transcranial magnetic stimulation (rTMS) was greater during a second rTMS session 24 h after the first. We sought to determine whether such metaplasticity is dependent on a particular phase of the normal sleep–wake/circadian cycle. Methods Twenty healthy participants received two sessions of 20 Hz rTMS over the hand motor cortex (M1) spaced 12 h apart, either over-day or overnight. Results Baseline corticospinal excitability did not differ by group or session. The time-of-day of Session 1 did not influence the relative increase in excitability following rTMS. However, the increase in excitability from the second rTMS session was 2-fold greater in the overnight group. Conclusions When a night with sleep follows rTMS to M1, the capacity to induce subsequent plasticity in M1 is enhanced, suggesting sleep–wake and/or circadian-dependent modulation of processes of metaplasticity. Significance TMS treatment of neuropsychiatric disorders entails repeated sessions of rTMS. Our findings suggest that the timing of sessions relative to the sleep–wake/circadian cycle may be a critical factor in the cumulative effect of treatment. Future studies using this paradigm may provide mechanistic insights into human metaplasticity, leading to refined strategies to enhance non-invasive stimulation therapies.

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression

There is growing interest worldwide in rTMS as a clinical treatment for depression. Apart from efficacy, its safety as a clinical treatment must be considered before its widespread use can be advocated. All published, sham-controlled rTMS depression trials were reviewed for reported side-effects and outcomes of formal neuropsychological testing. In addition, all reports of seizures occurring with rTMS were reviewed. Other safety concerns (effects on hearing; headache, pain, induced currents in electrical circuits, histotoxicity, electromagnetic field exposure, psychiatric complications, safety in pregnancy) are discussed. Common side-effects were of a minor nature, e.g. headache. There was a low incidence of accidental seizures and induced hypomania, both of which were associated with identified risk factors for which subjects should be screened. Long-term effects of repeated rTMS sessions are as yet unknown. When given within recommended guidelines, the overall safety profile of rTMS is good, and supports its further development as a clinical treatment.

Repetitive transcranial magnetic stimulation (rTMS): insights into the treatment of Parkinson’s disease by cortical stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a potent tool that can be used to modify activity of targeted cortical areas. Significant clinical effects have been obtained in patients with Parkinson's disease (PD) by stimulating different cortical regions with rTMS at inhibitory (low) or excitatory (high) frequency. These effects were thought to result from plastic changes in motor cortical networks. Actually cortical dysfunction has been documented in PD by neuroimaging and neurophysiologic studies showing either hypo- or hyper-activation of various brain areas. In addition, cortical excitability studies using transcranial magnetic stimulation disclosed significant alterations in intracortical facilitatory or inhibitory processes according to the resting state or to phases of movement preparation or execution. These observations clearly support the therapeutic potential of cortical neuromodulation in PD. Motor cortex stimulation could impact on any station within the cortico-basal ganglia-thalamo-cortical loops that are involved in motor control, providing alleviation of parkinsonian symptoms. Depending on the target, cortical stimulation might improve motor performance or other symptoms associated with PD, like depression. Clinical application of rTMS to treat PD patients is limited by the short duration of the effects beyond the time of stimulation, even if long-lasting improvements have been observed after repeated rTMS sessions. In any case, the place of cortical stimulation in the therapeutic management of PD patients remains to be determined, as an alternative or a complementary technique to deep brain stimulation. The rTMS technique could be used to better define the targets and the parameters of stimulation subsequently applied in chronic epidural stimulation.

Induction of Long-Lasting Changes of Visual Cortex Excitability by Five Daily Sessions of Repetitive Transcranial Magnetic Stimulation (rTMS) in Healthy Volunteers and Migraine Patients

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a normal habituation for 9 min. In the present study, we investigated whether repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5 consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz rTMS-induced dishabituation increased in duration over consecutive sessions and persisted between several hours (n=4) and several weeks (n=4) after the fifth session. In six out eight migraineurs, the normalization of VEP habituation by 10 Hz rTMS lasted longer after each daily stimulation but did not exceed several hours after the last session, except in two patients, where it persisted for 2 days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical excitability and VEP habituation pattern. Whether this effect may be useful in preventative migraine therapy remains to be determined.