Transcranial magnetic stimulation, synaptic plasticity and network oscillations

Transcranial magnetic stimulation (TMS) has quickly progressed from a technical curiosity to a bona-fide tool for neurological research. The impetus has been due to the promising results obtained when using TMS to uncover neural processes in normal human subjects, as well as in the treatment of intractable neurological conditions, such as stroke, chronic depression and epilepsy. The basic principle of TMS is that most neuronal axons that fall within the volume of magnetic stimulation become electrically excited, trigger action potentials and release neurotransmitter into the postsynaptic neurons. What happens afterwards remains elusive, especially in the case of repeated stimulation. Here we discuss the likelihood that certain TMS protocols produce long-term changes in cortical synapses akin to long-term potentiation and long-term depression of synaptic transmission. Beyond the synaptic effects, TMS might have consequences on other neuronal processes, such as genetic and protein regulation, and circuit-level patterns, such as network oscillations. Furthermore, TMS might have non-neuronal effects, such as changes in blood flow, which are still poorly understood.     

Role of distinct parietal areas in arithmetic: an fMRI-guided TMS study

Although several parietal areas are known to be involved in number processing, their possible role in arithmetic operations remains debated. It has been hypothesized that the horizontal segment of the intraparietal sulcus (hIPS) and the posterior superior parietal lobule (PSPL) contribute to operations solved by calculation procedures, such as subtraction, but whether these areas are also involved in operations solved by memory retrieval, such as multiplication, is controversial. In the present study, we first identified the parietal areas involved in subtraction and multiplication by means of functional magnetic resonance imaging (fMRI) and we found an increased activation, bilaterally, in the hIPS and PSPL during both arithmetic operations. In order to test whether these areas are causally involved in subtraction and multiplication, we used transcranial magnetic stimulation (TMS) to create, in each participant, a virtual lesion of either the hIPS or PSPL, over the sites corresponding to the peaks of activation gathered in fMRI. When compared to a control site, we found an increase in response latencies in both operations after a virtual lesion of either the left or right hIPS, but not of the PSPL. Moreover, TMS over the hIPS increased the error rate in the multiplication task. The present results indicate that even operations solved by memory retrieval, such as multiplication, rely on the hIPS. In contrast, the PSPL seems to underlie processes that are nonessential to solve basic subtraction and multiplication problems.     

Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study

Recent neuroimaging studies have revealed that acupuncture stimulation modulates human central nervous system including cerebral limbic/paralimbic and subcortical structures. Due to the wide and intricate connections with cerebrum, we hypothesized that anatomically specific areas in human cerebellum are also modulated by acupuncture stimulation beyond classical involvement of cerebellum in motor coordination. Functional MRI (fMRI) was used to investigate neural substrates responding to the acupuncture stimulation of Pericardium 6 (PC6, Neiguan), an acupoint relevant for the management of nausea including vestibular-related motion sickness. Sham stimulation near the acupoint and tactile stimulation on the skin of the acupoint were given as separate conditions. Psychophysical scores as well as the heart and respiratory rates were measured during each condition. Acupuncture manipulation on PC6, in comparison to the sham acupuncture and tactile stimulation conditions, selectively activated left superior frontal gyrus, anterior cingulate gyrus, and dorsomedial nucleus of thalamus. Acupuncture-specific neural substrates in cerebellum were also evident in declive, nodulus, and uvula of vermis, quadrangular lobule, cerebellar tonsil, and superior semilunar lobule. Negative MR signal changes, often seen during the acupuncture of analgesic points, were not observed in the present study. Our data suggest that cerebellum serves as important activation loci during the acupuncture stimulation of PC6, and clinical efficacy of PC6 may be mediated by the cerebellar vestibular neuromatrix.     

Functional roles of Broca's area and SMG: evidence from cortical stimulation mapping in a deaf signer.

The importance of the left hemisphere in language function has been firmly established and current work strives to understand regional specializations within the perisylvian language areas. This paper reports a case study of a deaf user of American Sign Language undergoing an awake cortical stimulation mapping procedure. Patterns of sign errors accompanying electrical stimulation of Broca's area and the supramarginal gyrus (SMG) are reported. Our findings show Broca's area to be involved in the motor execution of sign language. These data demonstrate that the linguistic specificity of Broca's area is not limited to speech behavior. In addition, unusual semantic-phonological errors were observed with stimulation to the SMG; these data may implicate the SMG in the binding of linguistic features in the service of language production. Taken together, these findings provide important insight into the linguistic specificity of Broca's area and the functional role of the supramarginal gyrus in language processing.     

重复经颅磁刺激对海洛因成瘾者左侧执行控制网络影响的Fmri研究

目的探讨重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)对海洛因成瘾者左侧执行控制网络(executive control network,ECN)的影响.材料与方法纳入海洛因成瘾者19例(rTMS组)和年龄、性别、受教育年限相匹配的健康对照组(hea...     

Combined functional magnetic resonance imaging and transcranial magnetic stimulation evidence of ipsilateral motor pathway with congenital brain disorder: A case report

We present the case of 28-year-old man with schizencephaly who had mild left hemiparesis with mirror movement. Brain mapping using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) for both hand muscles was done to evaluate his neurologic state. Motor evoked potential (MEP) from both abductor pollicis brevis (APB) muscles was obtained simultaneously. fMRI showed that the left primary sensorimotor cortex became active when the right fingers performed the flexion-extension exercise. The left primary sensorimotor cortex, left prefrontal area, and both supplementary motor areas were activated with flexion-extension exercise of the left hand. Brain mapping for both APB muscles using TMS showed that no MEP was evoked in the right hemisphere, but a APB total of 5 sites were evoked in the left hemisphere simultaneously. The optimal scalp site for both APB muscles was present at the same site. The MEPs of both muscles which were evoked by stimulation of the optimal scalp site, showed similar latencies, amplitudes, and figures of potential. The similarities in both MEPs and the same optimal scalp site support the assumption that MEPs of both APB muscles are produced by the corticospinal tract originating from the same motor cortex. Our results showed that the ipsilateral motor pathway extended from the unaffected left hemisphere to both hand muscles. This finding may reflect functional reorganization of motor area in a patient with congenital brain disorder.     

Cyclical changes of cortical excitability and metaplasticity in migraine: Evidence from a repetitive transcranial magnetic stimulation study

The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high-frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (?120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate-dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine-without-aura patients, 48 migraine-with-aura patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5-Hz rTMS trains of 10 stimuli given at 120% RMT. Patients with episodic migraine were studied in different phases of the migraine cycle: interictal, preictal, ictal, and postictal states. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whereas inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed, depending on attack frequency: facilitation in patients with low and inhibition in those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.     

Transcranial magnetic stimulation and stroke: a computer-based human model study

This paper explores how transcranial magnetic stimulation (TMS) induced currents in the brain are perturbed by electrical and anatomical changes following a stroke in its chronic stage. Multiple MRI derived finite element head models were constructed and evaluated to address the effects that strokes can have on the induced stimulating TMS currents by comparing stroke models of various sizes and geometries to a healthy head model under a number of stimulation conditions. The TMS induced currents were significantly altered for stimulation proximal to the lesion site in all of the models analyzed. The current density distributions were modified in magnitude, location, and orientation such that the population of neural elements that are stimulated will be correspondingly altered. The current perturbations were minimized for conditions tested where the coil was far removed from the lesion site, including models of stimulation contralateral to the lesioned hemisphere. The present limitations of TMS to the peri-lesional cortex are explored, ultimately concluding that conventional clinical standards for stimulation are unreliable and potentially dangerous predictors of the site and degree of stimulation when TMS is applied proximal to infarction site.     

Sensorimotor integration in Complex Regional Pain Syndrome: a transcranial magnetic stimulation study

There is evidence that patients with Complex Regional Pain Syndrome (CRPS) have altered central sensorimotor processing. Sensory input can influence motor output either through indirect pathways or through direct connections from the sensory to motor cortex. The purpose of this study was to investigate sensorimotor interaction via direct connections in patients with CRPS and to compare the results with normal subjects'. Direct short-latency sensory-motor interaction was evaluated in eight patients with CRPS1 affecting a hand. Modulation of EMG responses to transcranial magnetic stimulation (TMS) induced by concomitant median nerve stimulation was measured, the so-called, short-latency afferent inhibition (SAI). Results were compared with eight normal subjects who were age and sex matched with the patients. As expected, all the normal subjects' EMG responses to TMS with median nerve stimulation were smaller than responses to TMS alone. In seven of the eight CRPS patients EMG responses to TMS were suppressed when paired with median nerve stimulation. Only one CRPS patient's results showed no suppression of EMG responses. These results suggest that the disease mechanisms of CRPS1 do not typically affect the direct neural circuit between sensory and motor cortex and that normal sensorimotor interaction is occurring via this route.     

近5年经颅磁刺激治疗脑卒中的可视化分析

目的 对近5年经颅磁刺激治疗脑卒中相关研究的现状、热点及前沿进行可视化分析。方法 检索2018年1月1日至2022年12月31日Web of Science核心合集数据库中经颅磁刺激治疗脑卒中的相关文献,采用CiteSpace 6.1.R6软件进行可视化分析。结果 年发文量逐年上升,发文量最多的作者是Abo Masahiro,发文量最多的国家是中国,发文量最多的机构是中山大学。热点关键词为大脑皮质、功能性磁共振成像、皮质兴奋性、可塑性等。突现强度排在前5位的关键词依次为单侧空间忽略、脑卒中后、神经性疼痛、皮质可塑性、经胼胝体抑制。结论 经颅磁刺激治疗脑卒中相关研究的热度逐年上升,未来可关注经颅磁刺激对单侧空间忽略、神经性疼痛等的治疗效果,可进一步研究经颅磁刺激对皮质可塑性的影响。     

Deposition in and release of vitamin D3 from body fat: evidence for a storage site in the rat

Vitamin D in all body tissues was radio-labeled by supplementing completely vitamin D-deficient weanling rats with oral vitamin D(3)-4-(14)C for 2 wk. All vitamin D was then withheld, and radioactivity and vitamin D content in a variety of organs and tissues were measured. Adipose tissue was found to contain by far the greatest quantity of radioactivity throughout the 3 month experimental period. Immediately after supplementation, half of the total radioactivity in adipose tissue corresponded to unaltered vitamin D(3), and the other half to polar metabolites and esters of vitamin D(3) and unidentified peak II. 1 month later there was approximately the same proportion but a decrease in the total quantity of each form. We conclude that adipose tissue is the major storage site for vitamin D(3) in its several forms. Unaltered vitamin D(3) was the principal storage form observed and presumably a source available for conversion to other metabolites during deprivation.     

Changes in corticospinal excitability with short-duration high-frequency electrical muscle stimulation: a transcranial magnetic stimulation study

[Purpose] Afferent input caused by electrical stimulation of a peripheral nerve or a muscle modulates corticospinal excitability. However, a long duration of stimulation is required to induce these effects. The purpose of this study was to investigate the effect of short-duration high-frequency electrical muscle stimulation (EMS) on corticospinal excitability through the measurement of motor evoked potentials (MEP) in young healthy subjects. [Subjects] Eleven healthy right-handed subjects participated in this study. [Methods] EMS was applied to the abductor pollicis brevis (APB) muscle at 100 Hz with a pulse width of 100 μs for 120 s. The intensity of stimulation was just below the motor threshold. Transcranial magnetic stimulation was applied over the motor cortex, and MEP were recorded from the APB before, and immediately, 10, and 20 min after EMS. [Results] In the APB muscle, the MEP amplitude significantly decreased after EMS, and this effect lasted for 20 min. [Conclusion] The excitability of the corticospinal tract decreased after short-duration high-frequency EMS, and the effect lasted for 20 min. These results suggest that even short duration EMS can change the excitability of the corticospinal tract.Key words: Electrical muscle stimulation, Transcranial magnetic stimulation, Corticospinal excitability     

Functional magnetic stimulation: a new modality for enhancing systemic fibrinolysis.

OBJECTIVE: To investigate whether functional magnetic stimulation (FMS) of the leg muscles could enhance systemic fibrinolysis. DESIGN: A within-subject analysis of systemic fibrinolysis before and after 60 minutes of FMS. SETTING: The Functional Magnetic Stimulation and Special Coagulation Laboratories in the Spinal Cord Injury Service at a Veterans Administration health care facility. PARTICIPANTS: Twenty healthy volunteers were recruited. The exclusion criteria were: (1) personal or family history of venous or arterial thrombosis, (2) personal or family history of cardiac arrythmias, (3) current use of medication, and (4) the presence of a cardiac pacemaker or other metallic implants. MAIN OUTCOME MEASURES: Whole blood clot lysis time (WBCLT) and tissue plasminogen activator (t-PA) antigen determined at baseline and 10 and 60 minutes after FMS. RESULTS: A significant decrease was observed in the mean WBCLT after FMS. The WBCLT decreased from 17+/-1.3 h before FMS to 12+/-1.0 h and 11+/-0.8 h at 10 and 60 minutes post-FMS, respectively. The mean t-PA antigen levels did not show a significant change (p = .6701) from pre-FMS (6.7+/-0.91 ng/mL) to 10 min post-FMS (6.8+/-0.91 ng/mL) and 60 min post-FMS (7.0+/-1.02 ng/mL). Several patterns of fibrinolytic response to FMS were observed. They differed in relation to the degree of enhancement, the period at which maximum enhancement occurred, and the corresponding t-PA antigen levels observed. CONCLUSIONS: The FMS-induced contractions of the leg muscles enhanced systemic fibrinolysis ex vivo. The improvement in fibrinolysis occurred immediately after FMS and was also observed at 60 minutes post-FMS. FMS appears to produce a sustained enhancement of systemic fibrinolysis that may prove useful in deep-vein thrombosis prophylaxis.     

低频重复经颅磁刺激对脑卒中后失语症疗效的Meta分析

目的：通过系统评价研究低频重复经颅磁刺激（low frequency repetitive transcranial magnetic stimulation，LF-rTMS）对脑卒中后失语症（post stroke aphasia，PSA）患者语言功能的干预疗效。方法：计算机检索Pubmed、Embase、Cochrane library、中国知网（CNKI）、万方数据库（WanFang）、维普数据库（VIP）和中国生物医学文献数据库（CBM）中关于rTMS治疗PSA的随机对照试验，文献检索时限限定为从建库至2020年11月。由2名研究员独立按照纳入、排除标准筛选文献，并完成提取数据，核对数据和质量评价等过程，最终采用RevMan 5.3软件进行Meta分析以及相关结果展示。结果：本研究共纳入11篇随机对照试验，共纳入301例PSA患者。试验组干预措施为：常规言语康复训练结合LF-rTMS，对照组干预措施为：常规言语康复训练结合LF-rTMS假刺激。分析结果显示:相较于对照组,经LF-rTMS治疗后，试验组听理解评分（SMD=0.37，95%CI（0.07,0.67），P=0.02）、复述评分（SMD=0.36，95%CI（0.09,0.64），P=0.01）、命名评分（SMD=0.40，95%CI（0.17,0.63），P=0.00007）均显著提高（P<0.05）；试验组与对照组相比具有统计学意义。结论：总结已有相关研究，LF-rTMS治疗对改善PSA患者的语言功能具有明显的效果，对于听理解、复述、命名能力均有显著改善效果。但总体样本量较小，仍需大样本、多中心、以及科学规范化的高质量随机对照试验，进一步完善LF-rTMS治疗PSA患者语言功能的疗效验证。     

Transcranial magnetic stimulation for migraine: clinical effects

The objective was to assess the impact of transcranial magnetic stimulation (TMS) on pain and the autonomic nervous system (ANS) in migraine. Fortytwo people [mean age 41.43±11.69 (SD) years, 36 females] were randomised into high vs. low TMS stimulation groups and received 2 brief pulses of TMS. Thirty-three (33/42) individuals had heart-rate variability assessed, before and after stimulation. No group effects were found. Pain decreased by 75%; 32% of people after 1 treatment reported no headache after 24 h. Mean heart rate decreased from 79.05±10.27 to 72.89±11.35 beats/min. The low-frequency (LF) and the high-frequency (HF) areas derived from power spectral analyses increased [mean 6522±1277 to 8315±1009 beats/min² (LF) (p=0.001) and mean 5600±1568 to 8755±3071 beats/min² (HF) (p=0.001)]. The LF:HF ratio decreased from mean 1.31±0.51 to 1.13±0.48 (NS). TMS produces immediate, sustained reductions in pain and modification of the ANS.     

Neuronal genetic rescue normalizes brain network dynamics in a lysosomal storage disorder despite persistent storage accumulation

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Repetitive transcranial magnetic stimulation of motor cortex after stroke: a focused review

Repetitive Transcranial Magnetic Stimulation (rTMS) is known to modulate cortical excitability and has thus been suggested to be a therapeutic approach for improving the efficacy of rehabilitation for motor recovery after stroke. In addition to producing effects on cortical excitability, stroke may affect the balance of transcallosal inhibitory pathways between motor primary areas in both hemispheres: the affected hemisphere (AH) may be disrupted not only by the infarct itself but also by the resulting asymmetric inhibition from the unaffected hemisphere, further reducing the excitability of the AH. Conceptually, therefore, rTMS could be used therapeutically to restore the balance of interhemispheric inhibition after stroke. rTMS has been used in two ways: low-frequency stimulation (≤1 Hz) to the motor cortex of the unaffected hemisphere to reduce the excitability of the contralesional hemisphere or high-frequency stimulation (>1 Hz) to the motor cortex of the AH to increase excitability of the ipsilesional hemisphere. The purpose of this systematic review is to collate evidence regarding the safety and efficacy of high-frequency rTMS to the motor cortex of the AH. The studies included investigated the concurrent effects of rTMS on the excitability of corticospinal pathways and upper-limb motor function in adults after stroke. This review suggests that rTMS applied to the AH is a safe technique and could be considered an effective approach for modulating brain function and contributing to motor recovery after stroke. Although the studies included in this review provide important information, double-blinded, sham-controlled Phase II and Phase III clinical trials with larger sample sizes are needed to validate this novel therapeutic approach.