大鼠海马神经元群体对于高频电刺激的响应

脑深部电刺激（DBS）在帕金森和癫痫等疾病治疗中的应用不断发展,但DBS对于神经元的作用机制尚无定论。为了研究DBS对于大脑神经网络的作用,在麻醉大鼠海马CA1区的输入和输出轴突纤维上,分别施加正向和反向高频电刺激（HFS）,考察CA1区锥体神经元的同步动作电位（即群峰电位）发放情况。结果表明,50 Hz的正向HFS可以诱发持续发放的群峰电位,而100和200 Hz的正向HFS诱发的群峰电位却要少得多。在不同频率的反向HFS中,每个刺激脉冲均诱发群峰电位,但它们的幅值逐渐减小;而且,刺激频率越高,幅值减小得越快。可见,作用于轴突的HFS对于上游和下游神经元群体都具有兴奋作用,但频率越高,兴奋作用越小。这些结果,对于深入了解DBS的作用机制以及安全有效地推广其临床应用都具有重要的意义。     

脑深部刺激适应症局部场电位节律特征研究进展

脑深部电刺激(DBS)作为一种植入性的神经调控技术,在治疗脑功能障碍的同时,也为研究人员打开了局部场电位(LFP)探究大脑的窗口。基于美国食品药品监督管理局(FDA)批准的4种DBS适应症,包括帕金森病、肌张力障碍、特发性震颤和强迫症的治疗现状和致病机理假说,重点总结上述疾病患者相关脑区LFP的Theta节律、Alpha节律、Beta节律,Gamma节律以及更高频段节律的特征,分析各种节律与临床症状及行为的关联,得到DBS刺激靶点或相关脑区的LFP节律能够显著反映疾病特征的结论,还介绍首例实时全植入式的LFP研究工具和其最新研究结果。这些LFP特征为后续的病理研究、DBS机制探索和新疗法改进提供理论基础。最后,基于目前LFP研究的不足之处,提出未来LFP研究在DBS神经调控领域的潜在发展方向,对神经调控领域的发展具有重要的意义。     

经颅磁声电刺激对大鼠工作记忆局部场电位gamma节律的影响

经颅磁声电刺激(TMAES)是一种新型无创的神经调控技术,利用超声与静磁场相互耦合产生感应电场,调节相应脑区的神经节律振荡活动,从而影响大脑学习、记忆等认知功能。为探究经颅磁声电刺激对大鼠工作记忆(WM)行为学实验中gamma节律神经振荡活动的影响,将20只健康成年Wistar大鼠随机分为对照组和刺激组,刺激组大鼠接受0.05～0.15 T、1.33～13.33 W/cm²的经颅磁声电刺激,持续10 d,对照组不接受刺激;采集T型迷宫工作记忆任务中大鼠前额叶皮层(PFC)的局部场电位信号(LFPs),对比分析两组间的行为学差异、LFPs的时频分布和互信息相关性。结果显示,刺激组大鼠执行工作记忆任务达到正确率80%以上所需时间为(7.57±0.99) d,明显少于对照组(10.65±2.32) d(P<0.05);在经过选择点位置前后,2.66～13.33 W/cm²组、0.10～0.15 T组大鼠LFPs信号gamma频段的能量密度明显高于对照组的相应值(P<0.05),6.65～13.33 W/cm²组、0.10～0.15 T组大鼠gamma频段12通道信号间的相关性明显强于对照组的相应值(P<0.05)。研究结果表明,经颅磁声电刺激能够增强大鼠工作记忆中前额叶皮层神经元集群gamma节律振荡活动,为进一步探索经颅磁声电刺激调节大脑记忆功能的作用机制奠定基础。     

高频电刺激指导肾动脉射频消融的实验研究

目的:用电刺激的方法指导肾脏去神经术(renal denervation,RDN)中射频消融靶点的选择,同时比较电刺激与射频消融时血压变化的异同。方法:成年健康昆明犬6只,行肾动脉造影排除肾动脉畸形后,每侧肾动脉从远段开始,由远及近选择数个位点进行电刺激并消融。连续记录术中血压的变化,术后通过软件分析血压的变化情况。采用常规HE和Masson染色观察肾动脉壁结构及其周围组织;采用酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化染色观察消融后肾动脉去神经效果。结果:本实验中刺激/消融位点共计50个,其中对电刺激有反应的位点占34%,无反应位点占66%。对有反应位点进行120 s电刺激时,其收缩压按每20 s分段与基线血压相比分别变化(0.34±3.38)、(0.41±3.04)、(10.47±5.73)、(13.27±3.63)、(10.17±1.87)和(0.78±1.87)mm Hg;将120 s连续消融时的收缩压数据同样按每20 s与基线血压相比,变化分别为(0.88±3.44)、(-1.64±3.47)、(13.17±3.12)、(12.82±3.21)、(9.50±2.68)和(-6.09±2.21)mm Hg。无反应位点进行电刺激和射频消融时均无明显血压升高。组织病理学检查显示,有反应位点肾动脉神经面积为(0.51±0.28)mm~2,无反应位点处为(0.09±0.06)mm~2,差异有统计学显著性(P0.01);免疫组化染色表明消融部位神经TH的表达显著低于未消融部位(P0.01)。结论:高频电刺激可以标测肾交感神经,且电刺激指导下的射频消融能对肾动脉交感神经造成有效损伤。     

电刺激期间神经细胞单元锋电位的检测

大脑深部电刺激（DBS）已成功用于临床治疗帕金森等中枢神经系统疾病;但是DBS的作用机制尚无定论。为了考察电刺激期间神经细胞动作电位（即单元锋电位）发放的规律,本研究设计了一种插值法去除刺激伪迹和大幅值诱发波,并设定信号斜率的阈值来自动选定插值区的端点,尽可能缩短锋电位的不可测期（NP）。该算法用于大鼠海马CA1区正向和反向电刺激期间锋电位的分析,结果表明：它可以将紧随刺激的NP缩短约8 ms;而且与线性插值相比,样条插值对于锋电位检测的影响更小。此插值法能够有效地用于高频串刺激期间锋电位信号的检测,从而为深入研究DBS期间的神经元活动提供了一种简单实用的新方法。     

高频电刺激大鼠丘脑底核抑制背侧中缝核5-羟色胺表达

本研究探讨高频电刺激丘脑底核对大鼠背侧中缝核5-羟色胺(5-HT)表达的影响。实验动物分两组,刺激组给予高频电流(130Hz,100μA,60μs)刺激大鼠右侧丘脑底核,对照组大鼠右侧丘脑底核植入电极,但无电流输出。刺激结束后,用免疫组织化学方法染色背侧中缝核5-HT能神经元,检测背侧中缝核5-HT能神经元的数量和平均灰度值。结果显示电刺激组背侧中缝核5-HT阳性神经元数目与对照组比明显减少(t(13)=3.786,P=0.002),并且神经递质5-HT表达量减少,平均灰度值显著增高(t(13)=7.917,P<0.001)。本实验结果表明高频电刺激丘脑底核对背侧中缝核5-HT能神经元有抑制作用,在应用高频电刺激丘脑底核治疗Parkison病运动障碍时出现的情绪障碍可能与其有关。     

高频电刺激对PC12细胞形态及代谢水平的影响

目的:研究细胞外高频电刺激(HFS)对PC12类交感神经细胞的形态及代谢水平的影响.方法:将HFS作用于传代的PC12类交感神经细胞株,高频电流参数为130 Hz,500μA,60μs;每天固定时间刺激3 h,持续3 d.分别用H-E染色、免疫组织化学、电子显微镜等方法检测经HFS后PC12类交感神经细胞在光镜、电镜下的形态变化及细胞代谢水平的变化.结果:相比对照组,HFS后PC12类神经细胞光镜下突起长度显著缩短,突起个数明显减少;酪氨酸羟化酶免疫组织化学结果显示HFS后PC12细胞胞质灰度降低,提示酪氨酸羟化酶代谢水平下降;电镜下可见胞质中的线粒体、分泌颗粒减少,突起和突触减少.结论:HFS对PC12类交感神经细胞有抑制作用,它抑制PC12类交感神经细胞突起的生长以及颗粒分泌的代谢水平.     

定量分析神经元锋电位与局部场电位锁相关系的新方法

神经元动作电位(锋电位)的发放与局部场电位(LFP)节律之间的锁相关系反映了重要的神经编码信息,但目前的分析方法只能判断有无锁相性,而不能定量区别各种锁相性的强弱。本文利用锋电位触发的叠加平均(STA)信号,以STA信号与原始LFP信号的功率百分比值φ为指标,来评价这种锁相性的强弱。大鼠海马CA1区的实验数据以及仿真数据的验证结果均表明,指标φ与锁相性强弱之间存在单调关系,它能够提供有效的界值来区分是否锁相。由于计算该指标时无需事先滤波,它可以避免传统的区间统计法中人为限定LFP频率所造成的不利影响,为研究大脑神经信息编码的机制提供一种新的定量方法。     

节律性听觉刺激干预脑卒中患者非急性期的运动障碍

背景：近些年来,国外已将互动节律性听觉刺激用于康复治疗中枢神经损伤导致的运动行为障碍,中国康复医学界也陆续开展这方面的应用研究,但是将互动节律性听觉刺激用于脑卒中非急性期运动障碍的研究报道颇少。目的：研究节律性听觉刺激对脑卒中患者非急性期运动障碍的影响。方法：纳入2017年3月至2019年10月深圳恒生医院、吉林省中医药研究院附属医院、吉林省人民医院、吉林市中西医结合医院及吉林市龙潭中医院康复科的脑卒中偏瘫患者130例,年龄40-80岁,采用随机数字表法分为对照组(n=75)与试验组(n=55),对照组进行常规的康复训练(1次/d,5次/周),试验组在常规康复训练的基础上进行互动节律性听觉刺激训练(1次/d,5次/周),共训练8周。训练及训练结束后,评估两组患者Fugl-Meyer运动功能、Berg平衡、10 m步行速度、Tinetti步态、FAC步行功能、节律性听觉刺激运动反馈误差值及改良Barthel指数。结果与结论：(1)训练结束后,两组患者的Fugl-Meyer运动功能、Berg平衡、10 m步行速度、Tinetti步态、FAC步行功能、节律性听觉刺激运动反馈误差值及改良Bar...     

电刺激对军入血浆褪黑激素昼夜节律的影响

人体的生理与行为节律是由内源性昼夜节律钟产生与调控的。我们通过监测人体体核温度，就电针与光照胭肌对军人血浆褪黑激素节律的影响进行了研究，以探索电针调节人体节律的相位反应规律。实验结果显示，电针对军人血浆中的褪黑激素节律相位的影响具有明显的依时相性，其相位反应曲线呈光性模式。这一发现为治疗睡眠与节律混乱性疾病提供了新的思路。     

Patterns of neuronal firing in the human lateral thalamus during sleep and wakefulness

The firing patterns of thalamic neurons in mammals undergo a dramatic change as the animal's state changes between sleep and wakefulness. During sleep the normal tonic firing of thalamic neurons changes into a slower bursting mode characterized by repetitive activation of a low-threshold calcium (Ca²⁺) current. The present report describes the patterns of thalamic neuronal firing during sleep and wakefulness in one human patient. Extracellular single neuron activity was recorded during functional stereotactic surgery in the thalamus of a patient with chronic pain, who was observed to fall asleep during the recording. Evolutive power spectra of the thalamic slow wave were used in place of cortical encephalography to confirm the patient's states of sleep and wakefulness. Twenty-nine sites were observed in motor and somatosensory thalamus (Vop, Vim, and Vc) that were characterized by the presence of neurons with bursting activity when the patient was asleep. Such bursting was not observed in the patient when she was awakened. At 14 of these sites we were able to discriminate the bursting activity of single units. In each case the cell stopped firing or its bursting was replaced by a tonic firing pattern when the patient was awakened. In three cases the patient began to lapse back into sleep and the neuron resumed firing in a bursting pattern once again. None of these units had a peripheral receptive field (RF), while several other units recorded in nearby regions that did not fire in a bursting pattern during sleep had kinesthetic or cutaneous RFs. Analysis of the intraburst firing pattern revealed increasing interspike intervals (ISI) for successive action potentials in a burst and that the duration of the first ISI in the burst decreased as the number of ISIs increased. This pattern is similar to that reported to occur as a result of a calcium spike. These data have confirmed for the first time that state-dependent changes in thalamic firing exist in the human and that the physiological substrates at the thalamic level that are involved in human sleep are similar to those observed in animals.     

The role of GABAergic neuron on NMDA- and SP-induced phase delays in the suprachiasmatic nucleus neuronal activity rhythm in vitro

Gamma-aminobutyric acid (GABA), and its biosynthetic enzyme, glutamic decarboxylase, are widely distributed in the suprachiasmatic nucleus (SCN). In the present study, we examined the role of the GABA_A receptor on in vitro SCN responses to photic-like signals. We found that 100 μM GABA_A receptor antagonist bicuculline partially blocked field potentials evoked by optic nerve stimulation. NMDA- and SP-induced phase shifts of SCN neuronal activity rhythms, were blocked with 10 μM bicuculline. Application of 100 μM bicuculline alone induced phase advance of SCN neuronal activity rhythm. These results show that NMDA- and SP-induced phase shifts are blocked by bicuculline and suggest GABA has an important role as neurotransmitter in the neuronal network regulating phase shifts of the circadian clock.     

闭合性阴囊及睾丸损伤的高频超声诊断

目的探讨高频超声对阴囊、睾丸损伤的诊断价值。方法回顾性分析46例阴囊、睾丸损伤患者（年龄8～82岁，平均年龄35．6岁）的超声表现及手术发现。结果46例患者据阴囊、睾丸的声像图表现可分为：阴囊壁挫伤32例，阴囊壁血肿14例，睾丸挫伤5例，睾丸血肿7例，睾丸破裂27例等五种类型。阴囊、睾丸损伤的超声诊断与临床符合率为100％，而阴囊、睾丸损伤的超声分型与术后诊断符合率仅为93．5％。结论高频超声能准确诊断阴囊、睾丸的损伤，且能对大多数阴囊、睾丸损伤的程度进行分型，为临床选择治疗方案提供可靠依据。     

Effects of firing frequency on length-dependent myofascial force transmission between antagonistic and synergistic muscle groups

Effects of stimulation frequency on myofascial force transmission between rat peroneal and triceps surae and antagonistic anterior crural muscles, and between extensor digitorum longus (EDL) and tibialis anterior and extensor hallucis longus (TA + EHL) muscles were investigated for lengthening of all anterior crural muscles. Muscles contracted isometrically at firing rates of 10, 20, 30 and 100 Hz. EDL and TA + EHL were distally lengthened. Peroneal and triceps surae muscles attained a constant muscle-tendon complex length. Peroneal and triceps surae distal active force decreased significantly as a function of anterior crural muscle length, also at submaximal activation. The absolute decrease was highest for 100 Hz (peroneal muscles -0.87 N; triceps surae muscles -0.92 N), but the highest normalized decrease occurred at 10 Hz stimulation (peroneal muscles -34%; triceps surae muscles -18%). At all muscle lengths, a negative proximo-distal difference in EDL active force was present which decreased with lower firing frequencies (from -0.4 N at 100 Hz to -0.03 N at 10 Hz). The passive proximo-distal force difference attained positive values. EDL and TA + EHL length-force characteristics agree with effects of firing frequency, except for 10 Hz stimulation, where active force was higher than expected and optimum length shifted to lower muscle lengths. It is concluded that also at submaximal stimulation frequencies, extramuscular myofascial force transmission between peroneal and triceps surae muscles and antagonistic anterior crural muscles is substantial. Although lengthening of submaximally active anterior crural muscles decreases the net myofascially transmitted load on EDL, myofascial force transmission significantly alters effects of firing frequency on length-force characteristics.     

高频震荡通气技术研究现状分析与展望

以低平均气道压和小潮气量为主要特征的高频震荡通气(HFOV),自出现以来备受医务、科研人员的关注。本文就HFOV通气技术方面的研究现状与发展趋势进行了分析和展望,重点介绍与分析了有关HFOV的通气模型、通气机制和通气模式方面的研究现状。并藉此提出,在未来一段时期内,对HFOV通气技术的研究将主要集中在三个方面:建立多级、高阶、非线性的黏性阻力、惯性阻力和顺应性(RIC)通气模型;更为充分地揭示HFOV之所以能够有效通气的机制;研究实现低风险的无创HFOV。对HFOV通气技术的研究与发展,将为呼吸系统疾病患者提供一种不同于常频通气的通气方式。     

Reprint of "frequency tuning and firing pattern properties of auditory thalamic neurons: an in vivo intracellular recording from the guinea pig" [Neuroscience 151 (2008) 293-302

We investigated the firing pattern and frequency tuning properties of medial geniculate body (MGB) neurons, through in vivo intracellular recordings in anesthetized guinea pigs. Twenty-two of the 25 physiological characterized neurons were anatomically identified. Ten neurons were located in the ventral division of the medial geniculate body (MGv) (seven in pars ovoidea (OV) and three in the pars lateralis (LV)). Eight were located in the dorsal division (MGd), and four in the medial division (MGm). OV neurons showed a uniform, phasic ON response with high frequency selectivity. Functionally, they are interpreted as relaying spectral information with high reliability. LV neurons exhibited various patterns: phasic, tonic and excitatory postsynaptic potentials (EPSP) with a spike train. These high magnitude EPSPs are proposed to convey temporal information of the auditory signals with more encoding power. MGd neurons had relatively low best frequencies while MGm neurons had high intensity threshold, broader frequency selectivity, and a tonic response pattern. Tonic firing is likely to impose a strong impact onto wide cortical area and amygdala. When hyperpolarized with current injection, MGB neurons evoked low-threshold calcium spikes. Distinct change in these spike numbers was observed among MGv and MGd neurons as compared with MGm neurons, implying their differential roles. MGm neurons are more modulatory in nature, while the long lasting bursts of low-threshold calcium spikes observed in MGv and MGd neurons probably participate in propagating the sleep oscillations.     

The relationship between frequency of rapid eye movements in REM sleep and SWS rebound

Previous studies have shown a decrease in rapid eye movement (REM) frequency during desynchronized sleep in recovery nights following total or partial sleep deprivation. This effect has been ascribed to an increase in sleep need or sleep depth consequent to sleep length manipulations. The aims of this study were to assess REM frequency variations in the recovery night after two consecutive nights of selective slow-wave sleep (SWS) deprivation, and to evaluate the relationships between REM frequency and SWS amount and auditory arousal thresholds (AAT), as an independent index of sleep depth. Ten normal males slept for six consecutive nights in the laboratory: one adaptation, two baseline, two selective SWS deprivation and one recovery night. SWS deprivation allowed us to set the SWS amount during both deprivation nights close to zero, without any shortening of total sleep time. In the ensuing recovery night a significant SWS rebound was found, accompanied by an increase in AAT. In addition, REM frequency decreased significantly compared with baseline. This effect cannot be attributed to a variation in prior sleep duration, since there was no sleep loss during the selective SWS deprivation nights. Stepwise regression also showed that the decrease in REM frequency is not correlated with the increase in AAT, the traditional index of sleep depth, but is correlated with SWS rebound.     

工频电磁场长期作用影响工作记忆中局部场电位因果网络连接特征

电磁场(EMF)作用对神经系统功能的影响,现已成为电磁生物效应领域广泛关注的问题。本文旨在从神经信息网络连接角度探究工频EMF长期作用对大脑认知功能的影响及其机制。本文将斯普拉格·道利(SD)大鼠随机分为3组,其中模型Ⅰ组将SD大鼠置于2 mT工频EMF中作用24 d;模型Ⅱ组将SD大鼠置于2 mT工频EMF中作用48 d;对照组SD大鼠未经工频EMF作用。随后,采集不同组别SD大鼠执行工作记忆(WM)任务过程中前额皮层(PFC)16通道的局部场电位信号(LFPs),并基于定向传递函数(DTF)构建LFPs因果连接网络,最终通过对比各组SD大鼠在WM过程中LFPs信号因果网络特征参数及行为学表现的异同,探讨工频EMF长期作用对WM的影响。本文研究结果显示,模型Ⅱ组大鼠执行WM任务达到正确率80%以上所需时间及次数明显多于对照组。WM任务中,模型Ⅰ、Ⅱ组因果网络连接强度及全局效率值均明显低于对照组;且模型Ⅱ组中因果网络连接密度值明显低于模型Ⅰ组及对照组。结果表明,经2 mT工频EMF的长期作用,PFC的LFPs信号间因果网络连接强度及全局效率降低,并影响SD大鼠的行为学表现。本文的研究结果从神经网络信息传递的角度揭示了工频EMF作用影响大脑认知功能的可能机制,可为进一步研究其作用机制提供重要的支持。     

基于有限元方法的 theta 节律能量与导电媒质关系的研究

目的在认知功能研究中,与认知有很大关系的theta(4~12 Hz)节律的能量分析受到很多关注,该仿真研究了一个脑区theta能量与组织电特性的关系以深入了解theta能量所表达的物理意义。方法文章利用了COMSOL Multiphysics(FEMLAB)所提供的有限元方法 (finite element method,FEM)仿真了正弦振荡(4~8 Hz)的偶极子电流所形成的场电位(field potential,FP),分析了theta能量随导电媒质电导率特性变化的规律。结果 (1)Theta能量可随电导率的增大而减小,但随着各向异性的增强却没有下降。(2)与各向同性媒质对照,各向异性媒质的能量有变大可能。(3)偶极子电流的振幅和频率都对theta能量有影响。结论 Theta能量与导电媒质的特性和偶极子电流的特性均有关。