Biophysical modeling of neural plasticity induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method capable of inducing plastic reorganisation of cortical circuits in humans. Changes in neural activity following TMS are often attributed to synaptic plasticity via process of long-term potentiation and depression (LTP/LTD). However, the precise way in which synaptic processes such as LTP/LTD modulate the activity of large populations of neurons, as stimulated en masse by TMS, are unclear. The recent development of biophysical models, which incorporate the physiological properties of TMS-induced plasticity mathematically, provide an excellent framework for reconciling synaptic and macroscopic plasticity. This article overviews the TMS paradigms used to induce plasticity, and their limitations. It then describes the development of biophysically-based numerical models of the mechanisms underlying LTP/LTD on population-level neuronal activity, and the application of these models to TMS plasticity paradigms, including theta burst and paired associative stimulation. Finally, it outlines how modeling can complement experimental work to improve mechanistic understandings and optimize outcomes of TMS-induced plasticity.     

双样本t检验和配对检验的异同性

概述:临床研究中经常遇到比较实验组和对照组之间的结果.双样本t检验(又称为独立样本t检验)和配对t检验可能是运用于比较两个样本之间均值的最广泛的统计方法.然而,这两种方法的运用会产生混淆,从而导致使用不当.本文中,我们讨论了这两种t检验之间的异同性,并运用三个范例来阐述双样本t检验和配对t检验的计算过程.     

李中宇教授对药治疗痹证经验

李中宇教授为全国第五批名老中医之一,从医50余年,临床经验丰富。治疗痹证多使用对药(桂枝、细辛,葛根、姜黄,白芍、甘草,等),现将其运用对药治疗痹证的临床经验作以总结。     

多种统计方法比较黄连姜制工序中影响生物碱含量的因素

目的：测定黄连不同姜制品中6种生物碱的含量,采用多种统计方法对数据进行分析,找出姜制工序中影响姜黄连质量的因素。方法：采用高效液相色谱法测定黄连不同姜制品中药根碱、非洲防己碱、表小檗碱、黄连碱、巴马汀及小檗碱的含量。运用主成分分析、聚类分析、LSD（Least-Significant Difference）检验、独立t检验对结果进行分析。结果：黄连经姜炙后,表小檗碱、黄连碱含量略有上升,药根碱、非洲防己碱、巴马汀、小檗碱含量略有下降,传统姜炙品中各成分含量均高于烘制品。聚类分析发现榨汁组和煮汁组可以聚为一类;烘法和炙法具有明显不同的聚类,对黄连姜制品中的6种生物碱之和进行LSD检验,亦表明烘法与炙法具有显著性差异。对榨汁组进行独立t 检验,结果表明姜汁与黄连饮片拌匀或闷润至透心在6种生物碱上无显著性差异,LSD与独立t 检验的结果与聚类分析的结果一致。结论：采用同一批次黄连炮制所得的姜制品中,姜的来源、不同方法制备的姜汁及闷润过程对6种生物碱影响不大,加热方式可能是影响姜黄连质量的因素。考虑到润至透心需加入大量水稀释姜汁,炒干所需工时较长,故辅料姜汁与黄连饮片拌匀吸尽即可。     

Effect of low-frequency gain and venting effects on the benefit derived from directionality and noise reduction in hearing aids

When the frequency range over which vent-transmitted sound dominates amplification increases, the potential benefit from directional microphones and noise reduction decreases. Fitted with clinically appropriate vent sizes, 23 aided listeners with varying low-frequency hearing thresholds evaluated six schemes comprising three levels of gain at 250 Hz (0, 6, and 12 dB) combined with two features (directional microphone and noise reduction) enabled or disabled in the field. The low-frequency gain was 0 dB for vent-dominated sound, while the higher gains were achieved by amplifier-dominated sounds. A majority of listeners preferred 0-dB gain at 250 Hz and the features enabled. While the amount of low-frequency gain had no significant effect on speech recognition in noise or horizontal localization, speech recognition and front/back discrimination were significantly improved when the features were enabled, even when vent-transmitted sound dominated the low frequencies. The clinical implication is that there is no need to increase low-frequency gain to compensate for vent effects to achieve benefit from directionality and noise reduction over a wider frequency range.     

Paired pulse depression in the somatosensory cortex: associations between MEG and BOLD fMRI

Interpretation of the blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) requires an understanding of the underlying neuronal activity. Here we report on a study using both magnetoencephalography (MEG) and BOLD fMRI, to measure the brain's functional response to electrical stimulation of the median nerve in a paired pulse paradigm. Interstimulus Intervals (ISIs) of 0.25, 0.5, 0.75, 1.0, 1.5 and 2.0 s are used to investigate how the MEG detected neural response to a second pulse is affected by that from a preceding pulse and if these MEG modulations are reflected in the BOLD response. We focus on neural oscillatory activity in the β-band (13-30 Hz) and the P35m component of the signal averaged evoked response in the sensorimotor cortex. A spatial separation of β ERD and ERS following each pulse is demonstrated suggesting that these two effects arise from separate neural generators, with ERS exhibiting a closer spatial relationship with the BOLD response. The spatial distribution and extent of BOLD activity were unaffected by ISI, but modulations in peak amplitude and latency were observed. Non-linearities in both induced oscillatory activity ERS and in the signal averaged evoked response are found for ISIs of up to 2 s when the signal averaged evoked response has returned to baseline, with the P35m component displaying paired pulse depression effects. The β-band ERS magnitude was modulated by ISI, however the ERD magnitude was not. These results support the assumption that BOLD non-linearity arises not only from a non-linear vascular response to neural activity but also a non-linear neural response to the stimulus with ISI up to 2 s.     

Antibodies to the neuronal cytoskeleton are elicited by Alzheimer paired helical filament fractions

Antibodies were raised to paired helical filament (PHF) enriched fractions obtained from brains of individuals with Alzheimer disease by extraction with ionic detergent followed by sucrose gradient centrifugation. Electron microscopic examination showed that the fractions were enriched in Alzheimer PHF but contained also lipofuscin, amyloid, granular material and membranous elements. Analysis of these fractions with SDS-PAGE stained with Coomassie blue showed only a faint band at approximately 60 kDa while most of the material was excluded from the stacking gel. BALB/c mice were injected weekly with 100 or 200 μg of these fractions or corresponding fractions from age-matched control brains. The 3 mice injected with Alzheimer brain, but not the 5 mice injected with control brain fractions, produced antibodies that reacted with central and peripheral nervous system axons, Alzheimer neurofibrillary tangles in intact tissue as well as with isolated, SDS-treated paired helical filaments. In gel strips antibodies from all 3 mice injected with Alzheimer brain fractions reacted with the 200-kDa and 168-kDa but not the 68-kDa neurofilament subunits. The 3 antisera reacted also with some forms of the microtubule-associated protein τ. Adsorptions with the insoluble fraction from Alzheimer but not from control brains blocked staining of axons and NFT by all 3 antisera. Adsorption with highly purified neurofilament proteins or with a preparation containing the 200-kDa 168-kDa neurofilament subunits blocked axon and NFT immunostaining only in one antiserum. Adsorptions with microtubule protein, heat-stable microtubule-associated protein, or a preparation of τ did not completely block immunostaining by any of the 3 antisera. These results demonstrate that fractions enriched with Alzheimer paired helical filaments contain insoluble neurofilament, τ and other yet unidentified antigens.