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.     

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...     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Transcranial magnetic stimulation of visual cortex in migraine patients: a systematic review with meta-analysis

We systematically reviewed the literature to evaluate the prevalence of phosphenes and the phosphene threshold (PT) values obtained during single-pulse transcranial magnetic stimulation (TMS) in adults with migraine. Controlled studies measuring PT by single-pulse TMS in adults with migraine with or without aura (MA, MwA) were systematically searched. Prevalence of phosphenes and PT values were assessed calculating mean difference (MD) and odds ratio (OR) with 95 % confidence intervals (CI). Ten trials (277 migraine patients and 193 controls) were included. Patients with MA had statistically significant lower PT compared with controls when a circular coil was used (MD −28.33; 95 % CI −36.09 to −20.58); a similar result was found in MwA patients (MD −17.12; 95 % CI −23.81 to −10.43); using a figure-of-eight coil the difference was not statistically significant. There was a significantly higher phosphene prevalence in MA patients compared with control subjects (OR 4.21; 95 % CI 1.18–15.01). No significant differences were found either in phosphene reporting between patients with MwA and controls, or in PT values obtained with a figure-of-eight coil in MA and MwA patients versus controls. Overall considered, these results support the hypothesis of a primary visual cortex hyper-excitability in MA, providing not enough evidence for MwA. A significant statistical heterogeneity reflects clinical and methodological differences across studies, and higher temporal variabilities among PT measurements over time, related to unstable excitability levels. Patients should therefore be evaluated in the true interictal period with an adequate headache-free interval. Furthermore, skull thickness and ovarian cycle should be assessed as possible confounding variables, and sham stimulation should be performed to reduce the rate of false positives. Phosphene prevalence alone cannot be considered a measure of cortical excitability, but should be integrated with PT evaluation.     

经颅磁刺激在癫痫研究中的应用

目的：对经颅磁刺激技术在癫痫中的研究与应用的国内外近况做一介绍，以期为癫痫临床治疗开阔思路。 资料来源：应用计算机检索中国医院知识仓库1994／2004期间的相关文章，限定文章语言种类为中文，检索词为“经颅磁刺激、癫痫”，同时应用计算机检索Journals@Ovid Full Text 1980／2004期间的相关文章，检索词“Transcranial magnetic stimulation，epilepsy”，并限定文章语言种类为English。 资料选择：对资料进行初审，选择临床或动物试验研究以及综述文献查找全文。纳入标准：①有明确诊断标准。②随机对照实验或对照试验。③治疗组干预措施为经颅磁刺激或经颅磁刺激合并抗癫痫药物或经颅磁刺激合并安慰剂；对照组干预措施为抗癫痫药物、抗癫痫药合并模拟经颅磁刺激、单纯经颅磁刺激或不采用抗癫痫措施。④综述文献为近5年来经颅磁刺激技术在神经精神病学方面研究的综述全文。排除标准：①非对照研究。②治疗组或对照组的干预措施不符合纳入标准。 资料提炼：共收集到相关文献113篇，按上述标准纳入26篇，其余文献均被排除。 资料综合：26篇文章中12篇为综述全文，7篇总结了经颅磁刺激在神经精神科学方面的应用及进展，5篇经颅磁刺激在癫痫领域的研究。4篇为动物试验研究。8篇为临床随机对照研究，2篇为对照研究。 结论：经颅磁刺激在癫痫研究中是一种安全有效而可靠的非侵入性的新方法，为临床研究和治疗癫痫开辟了一条新途径。目前虽然存在一定副作用，但相信随着磁刺激设备和刺激技术的进一步改进，此技术将会有一个很好的发展前景。