Frequency-specific effects of low-intensity rTMS can persist for up to 2 weeks post-stimulation: A longitudinal rs-fMRI/MRS study in rats

BackgroundEvidence suggests that repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, alters resting brain activity. Despite anecdotal evidence that rTMS effects wear off, there are no reports of longitudinal studies, even in humans, mapping the therapeutic duration of rTMS effects.ObjectiveHere, we investigated the longitudinal effects of repeated low-intensity rTMS (LI-rTMS) on healthy rodent resting-state networks (RSNs) using resting-state functional MRI (rs-fMRI) and on sensorimotor cortical neurometabolite levels using proton magnetic resonance spectroscopy (MRS).MethodsSprague-Dawley rats received 10 min LI-rTMS daily for 15 days (10 Hz or 1 Hz stimulation, n = 9 per group). MRI data were acquired at baseline, after seven days and after 14 days of daily stimulation and at two more timepoints up to three weeks post-cessation of daily stimulation.Results10 Hz stimulation increased RSN connectivity and GABA, glutamine, and glutamate levels. 1 Hz stimulation had opposite but subtler effects, resulting in decreased RSN connectivity and glutamine levels. The induced changes decreased to baseline levels within seven days following stimulation cessation in the 10 Hz group but were sustained for at least 14 days in the 1 Hz group.ConclusionOverall, our study provides evidence of long-term frequency-specific effects of LI-rTMS. Additionally, the transient connectivity changes following 10 Hz stimulation suggest that current treatment protocols involving this frequency may require ongoing “top-up” stimulation sessions to maintain therapeutic effects.     

Safety and Efficacy of Accelerated Repetitive Transcranial Magnetic Stimulation Protocol in Elderly Depressed Unipolar and Bipolar Patients

Objective

Major depressive disorder (MDD) is a prevalent condition in older adults. Although antidepressant drugs are commonly prescribed, efficacy is variable, and older patients are more prone to side effects. Repetitive transcranial magnetic stimulation (rTMS) is an alternative therapy used increasingly in the treatment of MDD. Even though recent studies have shown efficacy of rTMS in elderly depressed patients, the safety and efficacy of accelerated rTMS has not been studied in this population.

The influence of endogenous estrogen on high-frequency prefrontal transcranial magnetic stimulation

BackgroundThe use of repetitive transcranial magnetic stimulation (rTMS) as both therapeutic and experimental tools has grown enormously over the past decade. However, variability in response to rTMS is one challenge that remains to be solved. Estrogen can impact neural plasticity and may also affect plastic changes following rTMS. The present study investigated whether estrogen levels influence the neurophysiological effects of high-frequency (HF) rTMS in the left dorsolateral prefrontal cortex (DLPFC).HypothesisIt was hypothesised that individuals with higher endogenous estrogen would demonstrate greater rTMS-induced changes in cortical reactivity.Methods29 healthy adults (15M/14F) received HF-rTMS over left DLPFC. Females attended two sessions, one during a high-estrogen (HE) phase of the menstrual cycle, another during a low-estrogen (LE) phase. Males attended one session. Estrogen level was verified via blood assay. TMS-EEG was used to probe changes in cortical plasticity and comparisons were made using cluster-based permutation statistics and Bayesian analysis.ResultsIn females, a significant increase in TMS-evoked P60 amplitude, and decrease in N45, N100 and P180 amplitudes was observed during HE. A less pervasive pattern of change was observed during LE. No significant changes in TEPs were seen in males. Between-condition comparisons revealed higher likelihood of the change in N100 and/or P180 being larger in females during HE compared to both females during LE and males.ConclusionsThese preliminary findings indicate that a greater neuroplastic response to prefrontal HF-rTMS is seen in women when estrogen is at its highest compared to men, suggesting that endogenous estrogen levels contribute to variability in response to HF-rTMS.     

Enhancing cognitive training effects in Alzheimer’s disease: rTMS as an add-on treatment

The treatment of Alzheimer’s disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning.The present study provides important hints on the promising therapeutic use of rTMS in AD.     

Neuronal tuning: Selective targeting of neuronal populations via manipulation of pulse width and directionality

IntroductionMotor evoked potentials (MEP) in response to anteroposterior transcranial (AP) magnetic stimulation (TMS) are sensitive to the TMS pulse shape. We are now able to isolate distinct pulse properties, such as pulse width and directionality and evaluate them individually. Different pulse shapes induce different effects, likely by stimulating different populations of neurons. This implies that not all neurons respond in the same manner to stimulation, possibly, because individual segments of neurons differ in their membrane properties.ObjectivesTo investigate the effect of different pulse widths and directionalities of TMS on MEP latencies, motor thresholds and plastic aftereffects of rTMS.MethodsUsing a controllable pulse stimulator TMS (cTMS), we stimulated fifteen subjects with quasi-unidirectional TMS pulses of different pulse durations (40 μs, 80 μs and 120 μs) and determined thresholds and MEP AP latencies. We then compared the effects of 80 μs quasi-unidirectional pulses to those of 80 μs pulses with different pulse directionality characteristics (0.6 and 1.0 M ratios). We applied 900 pulses of the selected pulse shapes at 1 Hz.ResultsThe aftereffects of 1 Hz rTMS depended on pulse shape and duration. 40 and 80 μs wide unidirectional pulses induced inhibition, 120 μs wide pulses caused excitation. Bidirectional pulses induced inhibition during the stimulation but had facilitatory aftereffects. Narrower pulse shapes caused longer latencies and higher resting motor thresholds (RMT) as compared to wider pulse shapes.ConclusionsWe can tune the aftereffects of rTMS by manipulating pulse width and directionality; this may be due to the different membrane properties of the various neuronal segments such as dendrites.SignificanceTo date, rTMS frequency has been the main determinant of the plastic aftereffects. However, we showed that pulse width also plays a major role, probably by recruiting novel neuronal targets.     

Fast left prefrontal rTMS acutely suppresses analgesic effects of perceived controllability on the emotional component of pain experience

The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of perceived controllability regarding pain, stress, and learned helplessness. Although the left dorsolateral prefrontal cortex is a common TMS target for treating clinical depression as well as modulating pain, little is known about whether TMS over this area may affect perceived controllability. The present study explored the immediate effects of fast TMS over the left dorsolateral prefrontal cortex on the analgesic effects of perceived pain controllability. Twenty-four healthy volunteers underwent a laboratory pain task designed to manipulate perception of pain controllability. Real TMS, compared with sham, suppressed the analgesic benefits of perceived control on the emotional dimension of pain, but not the sensory/discriminatory dimension. Findings suggest that, at least acutely, fast TMS over the left dorsolateral prefrontal cortex may interrupt the perceived-controllability effect on the emotional dimension of pain experience. Although it is not clear whether this cortical area is directly involved with modulating perceived controllability or whether downstream effects are responsible for the present findings, it appears possible that left dorsolateral prefrontal TMS may produce analgesic effects by acting through a cortical perceived-control circuit regulating limbic and brainstem areas of the pain circuit. Despite evidence that prefrontal TMS can have analgesic effects, fast left prefrontal TMS appears to acutely suppress analgesia associated with perceived-control. This effect may be limited to the emotional dimension of pain experience.     

重复经颅磁刺激对正常人定量脑电图的影响

目的:探讨重复经颅磁刺激(repetitivetranscranialmagneticstimulation,rTMS)对正常人脑电活动的影响及其安全性。方法:对12名健康受试者左额叶予20Hz,100次/串、共5串、100%运动阈值的rTMS,并观察其刺激前后定量脑电图(qEEG)变化。结果:正常人rTMS后短时间内左额区β波频率增加刺激前β波为主者2名(2/12),刺激后8名(8/12)(χ2=4.285,P<0.05);磁刺激前后各脑区的δ,θ,α,β频带的绝对功率值差异无显著性意义(P>0.05),各脑区(δ+θ)/(α+β)比值无明显改变(t=1.433～2.132,均P>0.05),刺激过程中无明显不适。结论:rTMS对健康人脑电活动有一定调节作用,在一定强度和频率内rTMS是一种比较安全的方法。