Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia

Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann's area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated.     

Spatial and Temporal Characteristics of Set-Related Inhibitory and Excitatory Inputs from the Dorsal Premotor Cortex to the Ipsilateral Motor Cortex Assessed by Dual-Coil Transcranial Magnetic Stimulation

The capacity to produce movements only at appropriate times is fundamental in successful behavior and requires a fine interplay between motor inhibition and facilitation. Evidence in humans indicates that the dorsal premotor cortex (PMCd) is involved in such preparatory and inhibitory processes, but how PMCd modulates motor output in humans is still unclear. We investigated this issue in healthy human volunteers, using a variant of the dual-coil transcranial magnetic stimulation (TMS) technique that allows testing the short-latency effects of conditioning TMS to the left PMCd on test TMS applied to the ipsilateral orofacial primary motor cortex (M1). Participants performed a delayed cued simple reaction time task. They were asked to produce a lip movement cued by an imperative GO-signal presented after a predictable SET-period, during which TMS was applied at different intervals. Results showed that the area of motor evoked potentials (MEPs) to test TMS was modulated by conditioning TMS. A transient inhibition cortico-bulbar excitability by PMCd stimulation was observed around the middle of the SET-period. Conversely, a ramping excitatory effect of PMCd stimulation appeared towards the end of the SET-period, as the time of the predicted GO-signal approached. The time-course of PMCd–M1 activity scaled to the varying SET-period duration. Our data indicate that inhibition and excitation of motor output during a delayed reaction time task are two distinct neural phenomena. They both originate in PMCd and are conveyed via cortico–cortical connections to the ipsilateral M1, where they are integrated to produce harmonic fluctuations of motor output.     

Efficient Mapping of the Motor Cortex with Navigated Biphasic Paired-Pulse Transcranial Magnetic Stimulation

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate cortical muscle representations. Usually, single TMS pulses are targeted to the motor cortex with the help of neuronavigation and by measuring motor evoked potential (MEP) amplitudes from the peripheral muscles. The efficacy of single-pulse TMS to induce MEPs has been shown to increase by applying facilitatory paired-pulse TMS (ppTMS). Therefore, the aim was to study whether the facilitatory ppTMS could enable more efficient motor mapping. Biphasic single-pulse TMS and ppTMS with inter-stimulus intervals (ISIs) of 1.4 and 2.8 ms were applied to measure resting motor thresholds (rMTs) as a percentage of the maximal stimulator output and to determine the cortical representation areas of the right first dorsal interosseous muscle in healthy volunteers. The areas, shapes, hotspots, and center of gravities (CoGs) of the representations were calculated. Biphasic ppTMS with ISI of 1.4 ms resulted in lower rMTs than those obtained with the other protocols (p?=?0.001). With ISI of 2.8 ms, rMT was lower than with single-pulse TMS (p?=?0.032). The ppTMS mapping was thus performed with lower intensity than when using single-pulse TMS. The areas, shapes, hotspots, and CoGs of the muscle representations were in agreement. Hence, biphasic ppTMS has potential in the mapping of cortical hand representations in healthy individuals as an alternative for single-pulses, but with lower stimulation intensity by utilizing cortical facilitatory mechanism. This could improve application of nTMS in subjects with low motor tract excitability.     

磁刺激中脑内感应电场的计算

本研究建立了脑部分层模型，提出了传统感应电场计算方法与时域有限差分法相结合计算磁刺激中脑部各点瞬态感应电场值的方法，对圆形线圈和8字形线圈在头内产生的感应电场进行了理论推导，有助于进一步探索脑部磁刺激最佳刺激方式和作用机理。     

Involvement of the Motor Cortex in the Bimanual Unloading Reaction: A Transcranial Magnetic Stimulation Study

The responses of the biceps brachii muscle of the upper arm to magnetic stimulation of the motor cortex during the postural pretuning and forearm unloading tasks were studied in humans. On active unloading, the amplitude of the evoked response decreased in parallel with a decrease in muscle activity. During stationary holding of the load, the muscle response changed in proportion to the load. When, on the background of stationary holding of the load, the other arm took on the same load, the amplitude of the evoked response in the biceps muscle of the arm holding the load decreased without any change in the muscle activity. Passive unloading was accompanied by similar changes in the response evoked by magnetic stimulation as seen with active unloading. The question of whether the decrease in muscle activity (postural pretuning) in active unloading may be associated with both direct corticospinal influences and influences mediated via subcortical structures is discussed. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 54, No. 6, pp. 759–766, November–December, 2004.     

单脉冲经颅磁刺激对视皮层神经活动抑制作用的初步实验研究

为了研究单脉冲经颅磁刺激(sTMS)对视皮层神经活动的影响,利用多通道生理记录仪,分别记录下11名右利手志愿者sTMS作用于视皮层前后的视觉诱发电位(VEP)。采用叠加平均和巴特沃斯低通滤波的方法处理后,对比分析这两种情况下的VEP峰时特征,发现sTMS刺激将引起VEP峰值发生的时间有一定延迟。初步的实验结果表明,sTMS对视皮层神经活动有抑制作用,从而引起VEP产生了滞后,为将经颅磁刺激应用于研究视觉中枢神经活动提供了实验证据。     

难治性抑郁症患者rTMS治疗前后双侧前额叶质子磁共振波谱定量研究

目的:探讨难治性抑郁症患者与正常对照之间神经生化代谢分布的差异,探索rTMS治疗前后难治性抑郁症局部脑代谢物的特异性.方法:应用1H-MRS检测34例难治性抑郁症患者双侧前额叶N-乙酰天门冬氨酸(NAA)、谷氨酸(Glx)、胆碱复合物(cho)、肌醇(ml)及肌酸(cr)5种代谢物,分别计算NAA、Glx、Cho、mI与Cr的比值,并与28名健康对照者比较.对34例难治性抑郁症患者进行4周共20次高频rTMS治疗.治疗前后分别评定汉密尔顿抑郁量表(HAMD).治疗后再次应用1H-MRS检测34例难治性抑郁症患者双侧前额叶代谢物分布特征.结果:①rTMS治疗前难治性抑郁症组患者左侧前额叶皮质mI/Cr比值明显低于健康对照组(P＜0.001).rTMS治疗组治疗有效患者mI/Cr比值增高,与健康对照比较无显著性差异.(②在控制年龄、病程的影响后,rTMS治疗组左侧前额叶mI/Cr改变与HAMD减分率成正相关(r=0.86,P=0.000).结论:难治性抑郁症患者可能存在前额叶胶质细胞代谢异常,有效的rTMS治疗可改善神经胶质细胞功能.     

经颅磁刺激中大鼠真实头模型感应电场分布的研究

经颅磁刺激是一种利用时变磁场产生的感应电流刺激大脑的技术,现在已经广泛地应用于精神疾病的治疗及脑功能的研究.本文建立了经颅磁刺激中大鼠真实头模型,并利用有限元方法计算了模型中感应电场的空间分布情况.该模型可用于动物实验方案的设计和实验结果的解释.     

重复经颅磁刺激合并帕罗西汀治疗 难治性强迫症的临床观察

目的 观察重复经颅磁刺激合并帕罗西汀治疗难治性强迫症的临床疗效。方法 回顾分析2016年10月~2017年10月在我院治疗的140例难治性强迫症患者临床资料,将其随机分为对照组和观察组,每组70例。对照组采用帕罗西汀治疗,观察组在对照组治疗基础上联合重复经颅磁刺激治疗。观察两组患者的临床效果,治疗前后的Yale-Bocs评分、生存质量评分以及不良反应发生情况。结果 观察组治疗总有效率为94.29%,高于对照组的71.43%,差异有统计学意义（P＜0.05）;治疗后观察组Yale-Bocs评分为（25.21±5.60）分,低于对照组的（32.44±5.40）分,差异有统计学意义（P＜0.05）;治疗后观察组生存质量评分为（15.87±1.82）分,高于对照组的（10.53±1.95）分,差异有统计学意义（P＜0.05）;观察组患者不良反应发生率与对照组对比,差异无统计学意义（P＞0.05）。结论 重复经颅磁刺激合并帕罗西汀治疗难治性强迫症效果显著,可显著降低患者强迫症评分,改善患者生存质量,且无严重不良反应,值得临床推广和应用。     

基于复杂网络的磁刺激内关穴脑皮层功能连接分析

将磁刺激技术、脑电图与传统穴位理论相结合,研究穴位刺激引发的大脑皮层功能网络协同调控过程。利用组独立成分分析、标准低分辨率脑电磁断层成像,对14名健康被试静息态、磁刺激内关穴的脑电信号进行反演,确定脑网络节点。通过短时傅里叶变换和互相关方法,计算α频段功率谱间的互相关系数,基于t检验、错误发现率,校正(FDR)构建脑网络连接边(P＜0.05, FDR校正),并对脑皮层功能连接进行分析。结果表明,磁刺激时与运动相关脑区节点的功能连接减少22.9%,与情绪、记忆相关脑区节点的功能连接增多93.8%,位于额叶和颞叶节点的功能连接增多21.2%。磁刺激内关穴引起的脑皮层功能网络拓扑结构变化与穴位自身功能相吻合,为揭示穴位调控机理提供新线索。     

Decreased Metabolism in the Posterior Medial Network with Concomitantly Increased Metabolism in the Anterior Temporal Network During Transient Global Amnesia

Perturbation of corticohippocampal circuits is a key step in the pathogenesis of transient global amnesia. We evaluated the spatial distribution of altered cerebral metabolism to determine the location of the corticohippocampal circuits perturbed during the acute stage of transient global amnesia. A consecutive series of 12 patients with transient global amnesia who underwent ¹⁸F-fluorodeoxyglucose positron emission tomography within 3 days after symptom onset was identified. We used statistical parametric mapping with two contrasts to identify regions of decreased and increased brain metabolism in transient global amnesia patients compared with 25 age-matched controls. Transient global amnesia patients showed hypometabolic clusters in the left temporal and bilateral parieto-occipital regions that belong to the posterior medial network as well as, hypermetabolic clusters in the bilateral inferior frontal regions that belong to the anterior temporal network. The posterior medial and anterior temporal networks are the two main corticohippocampal circuits involved in memory-guided behavior. Decreased metabolism in the posterior medial network might explain the impairment of episodic memory observed during the acute stage of transient global amnesia. Concomitant increased metabolism within the anterior temporal network might occur as a compensatory mechanism.     

颞叶癫痫患者全脑皮层厚度分析

观察并探讨颞叶癫痫(TLE)患者脑皮层厚度变化。 对71例颞叶癫痫患者(左侧癫痫组40例、右侧癫痫组31例)及17名健康对照组进行三维扰相梯度回波序列(3D-SPGR)扫描,采集数据通过Freesurfer软件进行大脑模型重建;再利用Brainstorm软件配准、平滑,以双样本独立t检验分别比较癫痫组与对照组,和癫痫组间皮层厚度的差异,并将具有统计学意义(P<0.01)的区域在标准脑模板上标注显示。 结果显示,与正常组比较,癫痫组均出现部分颞叶及颞叶意外脑区皮层厚度增大的现象,但异常脑区存在不同(左侧27个,右侧11个);癫痫组间比较,左侧癫痫组患者在左侧额下回眶部皮层增厚现象更为明显。 颞叶癫痫患者的情感及认知等障碍可能与多个脑区皮层增厚的问题有关。