The effect of transcranial magnetic stimulation and peripheral nerve stimulation on corticomuscular coherence in humans

Cortex and muscle show coupled oscillations in the 15–35 Hz frequency band during voluntary movements. To obtain evidence of the neuronal network responsible for this rhythmicity we investigated the effect of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation on the coupling between eletcroencephalographic (EEG) activity recorded from the scalp over the motor cortex and electromyographic (EMG) activity recorded from the tibialis anterior (TA) muscle in 15 healthy human subjects. TMS over the leg area at intensities between 0.95 and 1.1 × threshold for a motor evoked potential (MEP) in the TA increased corticomuscular coherence in the 15–35 Hz frequency band. This effect lasted on average for 300 ms, but could last up to 600–800 ms in some subjects. Stimulation of motor nerves from the ankle muscles suppressed corticomuscular coherence in the 15–35 Hz frequency range between leg area EEG and TA EMG for a period up to 600–800 ms. In addition, increased coherence around 10 Hz was observed for a period up to 250 ms after the stimulation. Stimulation of motor nerves in the arm and motor nerves from the ankle muscles in the other leg had no effect. The findings indicate that TMS has direct access to the neuronal circuitry in the motor cortex, which generates the corticomuscular coherence. This effect was caused either by direct activation of corticospinal cells or by activation of local neuronal circuitries in the motor cortex. The effects of peripheral nerve stimulation suggest that an alternative rhythm generator may entrain the cortical cells into a lower 10 Hz rhythm and disrupt the 15–35 Hz rhythm.     

Excitability changes in human peripheral nerve axons in a paradigm mimicking paired-pulse transcranial magnetic stimulation

A peripheral nerve model was developed to determine whether changes in axonal excitability could affect the findings in studies of cortical processes using paired-pulse transcranial magnetic stimulation (TMS). The recovery of axonal excitability from a conditioning stimulus smaller than the test stimulus was qualitatively similar to that with suprathreshold conditioning stimuli. There was an initial decrease in excitability, equivalent to refractoriness at conditioning-test intervals < 4 ms, an increase in excitability, equivalent to supernormality, at intervals of 5–20 ms and a second phase of decreased excitability, equivalent to late subnormality at intervals > 30 ms. H reflex studies using conditioning stimuli below threshold for the H reflex established that these excitability changes could be faithfully translated across an excitatory synapse. Changing membrane potential by injecting polarising current altered axonal excitability in a predictable way, and produced results similar to those reported for many disease states using paired-pulse TMS. Specifically, axonal hyperpolarisation produced a smaller decrease in excitability followed by a greater increase in excitability. This study supports the view that changes in excitability of the stimulated axons should be considered before synaptic mechanisms are invoked in the interpretation of findings from paired-pulse TMS studies.     

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10–25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50–60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.     

Reduced expression of Munc13-1 in human and porcine diabetic peripheral nerve

Peripheral neuropathy (PN) involves widespread peripheral nerve disorders affecting a large human population worldwide. In Europe and the United States, the first single most prominent cause of peripheral neuropathy is diabetes, affecting 60–70% patients with long-term diabetes followed by idiopathic neuropathy, peripheral nerve damage of unknown etiology, diagnosed in 10–40% of all patients admitted to hospitals with symptoms of peripheral nerve damage. The molecular mechanisms underlying the pathogenesis of this disorder are not yet fully understood, however a few potential molecular contributors, such as Munc13-1, have been recently suggested. Munc13-1 is a diacylglycerol (DAG) receptor and a multifunction active zone protein essential for synaptic vesicle priming and crucial for insulin release from pancreatic beta cells. Here, for the first time, we focused on the comparative expression of Munc13-1 in human and porcine peripheral nerves. Our results revealed significantly reduced number of Munc13-1 in human (64.26% ± 6.68%) and porcine (84.09% ± 2.21%) diabetic nerve fibers and lower number of the double stained, neuronal marker, Neurofilament (NF) and Munc13-1 positive, human (56.83% ± 3.77%) and porcine (65.87% ± 4.86%) nerve fibers. Optical density quantification of Western blots showed similar results. Our study indicates that Munc13-1, on account of its role in both insulin and neurotransmitter exocytosis and through its binding properties, may be an important factor contributing to the development or progression of diabetic neuropathy.     

On a possible mechanism for peripheral nerve stimulation during magnetic resonance imaging scans

When patients undergo a magnetic resonance imaging scan, they are subject to both strong static and temporal magnetic fields. The temporal fields are designed to vary at each point in the region being imaged. This is achieved by the use of gradient coils. However, when the gradient coils are switched very rapidly, the strongly time-varying magnetic fields produced can be responsible for stimulating nerves in the peripheral regions of the body. This paper gives a somewhat novel explanation for this phenomenon. The physical mechanism suggested is supported by an illustrative theoretical calculation.     

经颅磁刺激放电回路参数对线圈脉冲电流特性的影响

目的 本文分析了经颅磁刺激放电回路参数,包括放电回路中总电容（C）、放电电压（U）以及放电线圈的电感值（L）和电阻值（R）对线圈放电电流特性的影响,为经颅磁刺激放电回路参数的优化提供理论指导.方法 首先理论上对经颅磁刺激系统基本电路进行分析,得出放电电流与放电回路参数的关系式,然后通过仿真和实验相结合的方法,研究放电回路参数对线圈脉冲电流的影响.同时,利用傅里叶变换分析线圈脉冲放电电流的频域特性.结果 单独增大储能电容值,增大了线圈放电电流幅值,延长了脉冲电流上升沿时间和脉宽持续时间,减小了电流信号的主频.单独减小回路总电阻值,增大了脉冲电流的幅值,提高了电流信号的主频,但更容易使脉冲电流出现多次振荡.单独增大回路电感值,减小了脉冲电流幅值,延长了脉冲电流的上升沿时间和脉宽持续时间,电流信号主频先增大后减小.结论 在经颅磁刺激系统工程设计中,放电回路参数值要匹配,不同的回路参数取值直接影响线圈脉冲电流的特性.本研究对设计特定指标要求的经颅磁刺激系统具有理论参考价值.     

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.     

皮神经感觉传导速度和波幅检测对糖尿病周围神经病的诊断作用

目的：探讨皮神经感觉传导速度（SCV）,波幅（Amp)检测对糖尿病患者周围神经远端受损的早期诊断价值。方法：受试者为糖悄病患者组和正常对照组各25例,对前臂外侧皮神经和腓肠神经共100条,就其感觉传导速度（SVC）及其诱发的波幅（Amp)进行分析,并与胫神经,正中神经进行比较,结果：混合神经的异常率明显低于皮神经,尤以无周围神经症状的糖尿病者更加明显（P＜0．01）,结论：皮神经的SCV,Amp检测,对糖尿病周围神经远端受损的早期诊断可靠,灵敏度高。     

An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons.     

Influence of different distal nerve degeneration period on peripheral nerve collateral sprouts regeneration

The effects of the distal nerve degeneration on the regeneration of the collateral sprouts from the proximal nerve stump have been examined. The delayed cross-suture anastomosis technique was used in which the tibial nerve was denervated for 0-8 weeks before cross-suture of the freshly axotomized common peroneal and chronically denervated TIB nerve stumps. There was a remarkable decreasing of the regenerated myelinated axons number after the distal nerve suffered 8 weeks deterioration, suggesting that short-term denervation did not affect the collateral sprouts regeneration but more prolonged denervation profoundly reduced collateral sprouts regenerated in the distal nerve stump.     

Relationship between stimulus amplitude,stimulus frequency and neural damage during electrical stimulation of sciatic nerve of cat

The relation is investigated between stimulus frequency, stimulus pulse amplitude and the neural damage induced by continuous stimulation of the cat's sciatic nerve. The chronically implanted electrodes were pulsed continuously and the effects of the electrical stimulation were quantified as the amount of early axonal degeneration (EAD) present in the nerves seven days after the continuous stimulation. The primary effect of stimulating at 100 Hz rather than 50 Hz was to cause an increase in the slope of the plot of the amount of EAD versus stimulus lower. There was a small amount of EAD in three of the nerves stimulated at 20 Hz, but there was no detectable correlation between the amount of EAD and the stimulus amplitude. This suggests that continuous electrical stimulation of peripheral nerves at a low frequency induce little or no neural damage, even if the stimulus amplitude is very high. A preliminary presentation of the results has been made elsewhere (Agnew et al., 1993)     

Surface anodal stimulation of human peripheral nerves

Summary Retinal endings in the dorsal lateral geniculate nucleus (dLGN) of the rat were visualized by anterogradely transported horseradish peroxidase following injections in the optic tract. The morphological findings confirm the two types of retinal axons previously suggested by Golgi investigations. In the caudal third of the dLGN type 2b axons, with small dense clusters of boutons, are the only representatives of retinal fibres seen. In the rostral two thirds they are intermingled with the larger type 2a terminals, but tend to accumulate laterally, adjacent to the optic tract. This study supports the concept that large retinal ganglion cells probably give rise to 2a axons that may represent a Y-like channel, whereas 2b axons are derived from small ganglion cells, and may relay a W-like pathway.     

Magnetic stimulation of peripheral nerve; site of stimulation estimated from H reflex.

In order to find out the difference in the site of stimulation between electrical and magnetic stimulation of a peripheral nerve, H reflexes were recorded in 20 healthy persons. Electrical stimulation was performed with the stimulator placed along the tibial nerve (A) and at right angles to the tibial nerve (B). Magnetic stimulation (Magstim Model 200) was performed with a large (14 cm in diameter) magnetic coil (C) and a small (7 cm in diameter) magnetic coil (D). The magnetic coil was held parallel to the skin and its center was placed on the point where the cathode had been placed in the electrical stimulation. The mean value of the sum of M wave latency and H reflex latency in C was 1.4 msec, 1.7 msec and 0.8 msec shorter than those in A, B and D, respectively. The mean value of the sum of M wave latency and H reflex latency in D was 0.6 msec shorter than that in A and 0.9 msec shorter than that in B. When the center of the magnetic coil is placed over the peripheral nerve, two loci of the nerve, 7-8 cm apart from each other with the large magnetic coil and 3-4 cm apart from each other with the small magnetic coil, are considered to be stimulated simultaneously.     

Magnetic stimulation of the human peripheral nerves

In this report some preliminary data after magnetic stimulation of the peripheral nerves in 8 normal individuals are presented. Compound muscle action potentials were recorded by surface electrodes after magnetic and conventional electrical stimulation of the median, ulnar, peroneal, tibial, femoral and sciatic nerves, and the lumbosacral roots. The data clearly show the ability of the magnetic coil to stimulate the roots in sites relatively inaccessible to electrical stimulation and obtain consistent muscle response suggesting important clinical application of magnetic stimulation in lumbosacral root disorders. However, before the magnetic coil can be recommended for general use, a very careful study comparing the responses after conventional electrical stimulation with those obtained after magnetic stimulation of each nerve in the upper and lower limbs must be evaluated.     

人周围神经肿瘤的免疫组化观察

周围神经肿瘤光镜诊断有时存在困难 ,对周围神经肿瘤进行肿瘤标志或细胞内含物的检测有助于这类肿瘤的诊断、鉴别诊断、组织发生和生物学行为的判断。为此对 91例周围神经肿瘤进行了多种标志的检测。1　材料与方法91例周围神经肿瘤均为外科手术切除标本 ,包括孤立性神经纤维瘤 13例、神经鞘瘤 30例、颗粒细胞瘤 9例、节细胞神经瘤 5例、婴幼儿色素性神经外胚层瘤 4例、恶性周围神经鞘膜瘤 15例、神经母细胞瘤 8例、外周性原始神经外胚层瘤 7例。标本经 4%中性甲醛固定 ,石蜡包埋 ,切5 μｍ厚切片。除ＨＥ染色外 ,应用ＡＢＣ和ＰＡＰ法进行Ｓ…