Quadro-pulse stimulation is more effective than paired-pulse stimulation for plasticity induction of the human motor cortex

OBJECTIVE: Repetitive paired-pulse transcranial magnetic stimulation (TMS) at I-wave periodicity has been shown to induce a motor-evoked potential (MEP) facilitation. We hypothesized that a greater enhancement of motor cortical excitability is provoked by increasing the number of pulses per train beyond those by paired-pulse stimulation (PPS). METHODS: We explored motor cortical excitability changes induced by repetitive application of trains of four monophasic magnetic pulses (quadro-pulse stimulation: QPS) at 1.5-ms intervals, repeated every 5s over the motor cortex projecting to the hand muscles. The aftereffects of QPS were evaluated with MEPs to a single-pulse TMS, motor threshold (MT), and responses to brain-stem stimulation. These effects were compared to those after PPS. To evaluate the QPS safety, we also studied the spread of excitation and after discharge using surface electromyograms (EMGs) of hand and arm muscles. RESULTS: Sizes of MEPs from the hand muscle were enhanced for longer than 75min after QPS; they reverted to the baseline at 90min. Responses to brain-stem stimulation from the hand muscle and cortical MEPs from the forearm muscle were unchanged after QPS over the hand motor area. MT was unaffected by QPS. No spreads of excitation were detected after QPS. The appearance rate of after discharges during QPS was not different from that during sham stimulation. CONCLUSIONS: Results show that QPS can safely induce long-lasting, topographically specific enhancement of motor cortical excitability. SIGNIFICANCE: QPS is more effective than PPS for inducing motor cortical plasticity.     

Spinal Cord Stimulation in a Mouse Chronic Neuropathic Pain Model

Objective. Development of a spinal cord stimulation (SCS) system in a mouse model of chronic neuropathic pain. Materials and Methods. Male C57BL/6 mice (N = 6) underwent a partial ligation of the sciatic nerve. Development of mechanical hyperalgesia was tested using the withdrawal response to tactile stimuli with the von Frey test. An SCS system was implanted on day 14. On day 16, the mice were stimulated for 30 min (f = 50 Hz; pulse width 0.2 msec and stimulation at 2/3 of motor threshold). Repeated measure analysis of variance (anova ) and paired Student's t‐test with Bonferroni correction were used to evaluate the development of mechanical hyperalgesia and the therapeutic effect of SCS. Results. Five out of six mice developed marked mechanical hyperalgesia in the nerve‐lesioned paw that persisted for the duration of the study (16 days). No changes contralateral to the injury were observed. In four out of five mice, a successful implantation of the electrodes followed by stimulation was achieved. Then, SCS resulted in a fast and robust increase of withdrawal threshold back to pre‐injury levels. After termination of the SCS, the withdrawal threshold of the ipsilateral paw slowly decreased. No effect of SCS on the contralateral paw was noted. Conclusion. The development of a mouse SCS system is described that is practical in use, is reproducible, and shows a comparative therapeutic effect in treatment of chronic neuropathic pain as reported in rat.     

轻刺激——从克罗米芬到来曲唑

长方案、短方案已在临床使用了20余年,这类超排卵方案采用降调节抑制内源性卵泡刺激素(FSH)、黄体生成素(LH)合成和释放,降低了过早排卵导致的周期取消,但也导致了促性腺激素用量大增、促排卵时间延长,即使是卵巢储备正常者也可能出现超排卵反应低下导致周期取消;卵巢储备低下患者则因不能超排而无缘体外受精胚胎移植(IVF-ET);同时,垂体抑制使卵巢反应增加,重度卵巢过度刺激综合征(OHSS)发生率增加.因传统的超排卵技术有上述不足,最近几年关于微刺激或轻刺激的讨论逐渐增多,轻微卵巢刺激的理念已被业界所认可[1-3].     

RF refocused echoes of J-coupled spin systems: effects on RARE-based spectroscopic imaging.

A numerical simulation tool was developed to calculate the echo amplitudes of J-coupled resonances within a series of radiofrequency (RF) refocused echoes. The signal modulation due to J-coupling in rapid acquisition with relaxation enhancement (RARE) is suppressed only when the inverse of the pulse interval (tau) is large compared to both the chemical shift (CS) difference (Deltadelta) of the coupled spins and the coupling constant. In contrast, the echo amplitudes in ultrafast low-flip-angle RARE (U-FLARE) oscillate around a quasi-steady-state value that is greater than zero (neglecting relaxation and diffusion) even when Deltadelta > 1/tau. The flip-angle distribution over the measured slice caused by the use of Gaussian-shape slice-selective refocusing pulses further reduces the echo oscillations. When the pulse interval falls short of the fast pulse rate regime, spectroscopic U-FLARE provides an improved spatial impulse response in the phase-encoding (PE) direction compared to spectroscopic RARE.     

Neurophysiological aspects of chronic motor cortex stimulation

Chronic motor cortex stimulation is a treatment option for neuropathic drug-resistant pain and possibly associated movement disorders. Preliminary studies suggest the possibility to treat symptoms of Parkinson disease in selected patients. Recently, MCS has been suggested to enhance motor recovery in patients with poststroke hemiparesis. One or more electrodes are placed extradurally over the motor cortex through a burr hole or a small craniotomy, and then connected to a totally implantable neurostimulator. The accurate positioning of the stimulating electrodes over the motor cortex is the key point of the surgical procedure. Motor cortex identification results from the integration of anatomical, neuroradiological, functional, and neurophysiological data, taking into account the huge population variability. Intraoperative neurophysiological mapping of the motor cortex is of paramount importance, in spite of very sophisticated neuroradiological mathematical reconstructions of the motor area. We discuss and compare the different techniques that are utilized by different authors. Moreover, clinical neurophysiology is also helpful in evaluating the results of this neuromodulation procedure and in hypothesizing the mechanisms that are put in play by MCS.     

Changes in Glucose Metabolism in Cerebral Cortex and Cerebellum Correlate With Tremor and Rigidity Control by Subthalamic Nucleus Stimulation in Parkinson's Disease: A Positron Emission Tomography Study

Objective. Employing [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess the correlation between the effect of deep brain stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N = 8). Materials and Methods. On the basis of patients’ diary records, we performed FDG‐PET during the off‐period of motor activity with on‐ or off‐stimulation by STN‐DBS on separate days and analyzed the correlation between changes in motor symptoms and alterations in the rCMRGlc. Result. When FDG‐PET was performed, the motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower with on‐stimulation than with off‐stimulation (p < 0.001, Wilcoxon single‐rank test). STN‐DBS increased the rCMRGlc in the posterior part of the right middle frontal gyrus, which corresponded to the premotor area, and the right anterior lobe of the cerebellum (p < 0.005, paired t‐test). No region exhibited a decrease in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting tremor and rigidity of the left extremities showed a significant correlation with the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p < 0.05, respectively, Spearman's rank correlation). Conclusions. STN‐DBS either activates the premotor area or normalizes the deactivation of the premotor area. These FDG‐PET findings obtained are consistent with the idea that STN‐DBS modifies the activities of neural circuits involved in motor control.     

肝硬化患者的脑电活动地形图

对２０例无临床肝性脑病的失代偿期肝硬化患者进行脑电活动地形图（ＢＥＡＭ）检查，并与３３例正常人作对照，以探讨亚临床肝性脑病（ＳＨＥ）的诊断价值。结果表明，２０例肝硬化患者中，ＢＥＡＭ正常５例，轻度异常５例，轻￣中度异常５例，中度异常５例，总异常率为７５％（１５／２０）。ＢＥＡＭ异常的分布特点以弥漫性分布为主要表现，主要为慢频域（δ．θ．δ＋θ／α＋β）活动增强，Ｚ值增高，只有３例波及α频域。提示：     

Characterisation of pre- and post-synaptic α-adrenoceptors in modulation of the rat ileum longitudinal and circular muscle activities

Previous study has shown that α_2D-adrenoceptors are involved in modulation of peristalsis in the rat ileum. The aim of the present study was to determine the tissue location of α-adrenoceptors in the rat ileum by using a recently devised method. The pre-synaptic α-adrenoceptors were characterised by measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses, 10 Hz, 8-10 s trains) contractions of the longitudinal and circular muscles and the affinities of antagonists. Post synaptic α-adrenoceptors were identified by screening agonists and antagonists in carbachol-contracted tissues. In the circular muscle the order of potencies for inhibiting transmurally-induced contraction was: clonidine ≥ oxymetazoline ≥ UK 14,304 ≥ guanfacine > talipexole > phenylephrine > azepexole. The potency ratios relative to clonidine correlated to those previously derived using the rat ileum peristaltic reflex preparation. Most of the α-adrenoceptor agonists, however, caused only small inhibitions of the longitudinal muscle contraction in response to transmural stimulation, except phenylephrine and azepexole. RX 821002, yohimbine, rauwolscine, BRL 44408, phentolamine, idazoxan, ARC 239, and prazosin inhibited the effect of clonidine on the circular muscle response with apparent pK_B values best correlated with pK_B or pK_i values derived from the rat ileum peristaltic reflex preparation and other tissues known to have the α_2D-subtype. The rank order of potencies at inhibiting carbachol-induced responses of both muscle layers was: phenylephrine ≥ oxymetazoline > clonidine ≥ talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 μM. The EC₅₀ value of each agonist on the longitudinal muscle was not significantly different to the corresponding value on the circular muscle. Prazosin was more potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both muscle layers of carbachol-contracted tissues. It is concluded that the recently identified α_2D-adrenoceptors of the rat ileum are located on cholinergic neurons controlling circular muscle contraction. The study also demonstrated the presence of postsynaptic α₁-adrenoceptors involved in mediating relaxation in both muscle layers. Received: 4 November 1996 / Accepted: 10 April 1997     

Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We investigated the functional and morphological effects of α-latrotoxin (αLTX), a spider neurotoxin believed to cause massive release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor N^ω-nitro-L-arginine (L-NOARG: 0.3 mM) both αLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine, no contraction was observed, and under these conditions αLTX and EFS induced relaxation. At low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 μM ω-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG or ω-conotoxin GVIA, the αLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and ω-conotoxin GVIA further reduced or abolished the relaxation. In preparationstreated with tetrodotoxin or scorpion venom, believed to inactivate nerves by acting on sodium channels, αLTX and EFS had no effects. αLTX-induced relaxation was not associated with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation. A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and ω-conotoxin GVIA. Ultrastructural analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle. In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. αLTX caused a major loss of both types of vesicle. The present data suggest that αLTX has the ability to release not only adrenergic and cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra. Received: 13 January 1997 / Accepted: 17 April 1997