Balanced excitation and inhibition: Model based analysis of local field potentials

We have developed a model of the local field potential (LFP) based on the conservation of charge, the independence principle of ionic flows and the classical Hodgkin-Huxley (HH) type intracellular model of synaptic activity. Insights were gained through the simulation of the HH intracellular model on the nonlinear relationship between the balance of synaptic conductances and that of post-synaptic currents. The latter is dependent not only on the former, but also on the temporal lag between the excitatory and inhibitory conductances, as well as the strength of the afferent signal. The proposed LFP model provides a method for decomposing the LFP recordings near the soma of layer IV pyramidal neurons in the barrel cortex of anaesthetised rats into two highly correlated components with opposite polarity. The temporal dynamics and the proportional balance of the two components are comparable to the excitatory and inhibitory post-synaptic currents computed from the HH model. This suggests that the two components of the LFP reflect the underlying excitatory and inhibitory post-synaptic currents of the local neural population. We further used the model to decompose a sequence of evoked LFP responses under repetitive electrical stimulation (5Hz) of the whisker pad. We found that as neural responses adapted, the excitatory and inhibitory components also adapted proportionately, while the temporal lag between the onsets of the two components increased during frequency adaptation. Our results demonstrated that the balance between neural excitation and inhibition can be investigated using extracellular recordings. Extension of the model to incorporate multiple compartments should allow more quantitative interpretations of surface Electroencephalography (EEG) recordings into components reflecting the excitatory, inhibitory and passive ionic current flows generated by local neural populations.     

Renal disposition of moxalactam in experimental animals as revealed by stop-flow analysis.

The mechanisms of moxalactam excretion were studied by stop-flow analysis in dogs, monkeys, and rabbits. In dogs, the amount of moxalactam excreted in the urine was almost equal to that estimated by glomerular filtration. There was no specific moxalactam peak corresponding to the p-aminohippuric acid (PAH) peak in the stop-flow patterns of the dogs. The PAH peak disappeared with administration of probenecid, but the moxalactam stop-flow pattern showed no change. In monkeys, no specific moxalactam peak corresponding to the PAH peak could be detected. In the stop-flow pattern of the rabbit, the peak moxalactam concentration corresponded with that of PAH and disappeared with probenecid. These results suggest that in dogs and monkeys renal excretion of moxalactam takes place mostly through glomerular filtration. In rabbits, however, there is a small renal tubular secretory component added to the primary element, glomerular filtration. These observations point to differences in the mechanisms of moxalactam excretion in different animal species.     

Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis

The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor kappaB activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.     

BOLD responses in the superior colliculus and lateral geniculate nucleus of the rat viewing an apparent motion stimulus

In rats, the superior colliculus (SC) is a main destination for retinal ganglion cells and is an important subcortical structure for vision. Electrophysiology studies have observed that many SC neurons are highly sensitive to moving objects, but complementary non-invasive functional imaging studies with larger fields of view have been rarely conducted. In this study, BOLD fMRI is used to measure the SC and nearby lateral geniculate nucleus' (LGN) hemodynamic responses, in normal adult Sprague Dawley (SD) rats, during a dynamic visual stimulus similar to those used in long-range apparent motion studies. The stimulation paradigm consists of four light spots arranged in a linear array and turned on and off sequentially at different rates to create five effective speeds of motion (7, 14, 41, 82, and 164°/s across the visual field). Stationary periods (same light spot always on) are interleaved between the moving periods. The speed response function (SRF), the hemodynamic response amplitude at each speed tested, is measured. Significant responses are observed in the SC and LGN at all speeds. In the SC, the SRF increases monotonically from 7 to 82°/s. The minimum response amplitude occurs at 164°/s. The results suggest that the SC is sensitive to slow moving visual stimuli but the hemodynamic response is reduced at higher speeds. In the LGN, the SRF exhibits a similar trend to that of the SC, but response amplitude during 7°/s stimulation is comparable to that during 164°/s stimulation. These findings are in good agreement with previous electrophysiology studies conducted on albino rats like the SD strain. This work represents the first fMRI study of stimulus speed dependence in the SC and is also the first fMRI study of motion responsiveness in the rat.     

Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis

Complex bimanual motor learning causes specific changes in activation across brain regions. However, there is little information on how motor learning changes the functional connectivity between these regions, and whether this is influenced by different sensory feedback modalities. We applied graph-theoretical network analysis (GTNA) to examine functional networks based on motor-task-related fMRI activations. Two groups learned a complex 90° out-of-phase bimanual coordination pattern, receiving either visual or auditory feedback. 3T fMRI scanning occurred before (day 0) and after (day 5) training. In both groups, improved motor performance coincided with increased functional network connectivity (increased clustering coefficients, higher number of network connections and increased connection strength, and shorter communication distances). Day×feedback interactions were absent but, when examining network metrics across all examined brain regions, the visual group had a marginally better connectivity, higher connection strength, and more direct communication pathways. Removal of feedback had no acute effect on the functional connectivity of the trained networks. Hub analyses showed an importance of specific brain regions not apparent in the standard fMRI analyses. These findings indicate that GTNA can make unique contributions to the examination of functional brain connectivity in motor learning.     

Functional anatomy of visual search: regional segregations within the frontal eye fields and effective connectivity of the superior colliculus

The ability to find targets embedded within complex visual environments requires the dynamic programming of visuomotor search behaviors. Functional magnetic resonance imaging was used to image subjects while they visually searched for targets embedded among foils. Visuomotor search activated the posterior parietal cortex and the frontal eye fields. Both regions showed a greater number of activated voxels on the right, consistent with the known pattern of right hemispheric dominance for spatial attention. The superior colliculus showed prominent activation in the search versus eye movement contrast, demonstrating, for the first time in humans, activation of this region specifically related to an exploratory attentional contingency. An analysis of effective connectivity demonstrated that the search-dependent variance in the activity of the superior colliculus was significantly influenced by the activity in a network of cortical regions including the right frontal eye fields and bilateral parietal and occipital cortices. These experiments also revealed the presence of a mosaic of activated sites within the frontal eye field region wherein saccadic eye movements, covert shifts of attention, and visuomotor search elicited overlapping but not identical zones of activation. In contrast to the existing literature on functional imaging, which has focused on covert shifts of spatial attention, this study helps to characterize the functional anatomy of overt spatial exploration.     

The time course of visual word recognition as revealed by linear regression analysis of ERP data

EEG correlates of a range of psycholinguistic word properties were used to investigate the time course of access to psycholinguistic information during visual word recognition. Neurophysiological responses recorded in a visual lexical decision task were submitted to linear regression analysis. First, 10 psycholinguistic features of each of 300 stimulus words were submitted to a principal component analysis, which yielded four orthogonal variables likely to reflect separable processes in visual word recognition: Word length, Letter n-gram frequency, Lexical frequency and Semantic coherence of a word's morphological family. Since the lexical decision task required subjects to distinguish between words and pseudowords, the binary variable Lexicality was also investigated using a factorial design. Word-pseudoword differences in the event-related potential first appeared at 160 ms after word onset. However, regression analysis of EEG data documented a much earlier effect of both Word length and Letter n-gram frequency around 90 ms. Lexical frequency showed its earliest effect slightly later, at 110 ms, and Semantic coherence significantly correlated with neurophysiological measures around 160 ms, simultaneously with the lexicality effect. Source estimates indicated parieto-temporo-occipital generators for the factors Length, Letter n-gram frequency and Word frequency, but widespread activation with foci in left anterior temporal lobe and inferior frontal cortex related to Semantic coherence. At later stages (>200 ms), all variables exhibited simultaneous EEG correlates. These results indicate that information about surface form and meaning of a lexical item is first accessed at different times in different brain systems and then processed simultaneously, thus supporting cascaded interactive processing models.     

Interaction between metronidazole and drugs eliminated by oxidative metabolism

Single-dose kinetics of 0.1 mg/kg intravenous diazepam, 10 mg/kg oral antipyrine, and 300 mg oral phenytoin were followed in healthy subjects before and after 400 mg metronidazole twice a day for 5 days. When data before metronidazole dosing were compared with those after metronidazole dosing, there were no changes in total plasma clearance of diazepam (0.53 and 0.65 ml/min/kg), antipyrine (39.0 and 38.0 ml/min/kg), or phenytoin (0.56 and 0.55 ml/min/kg). Plasma t 1/2s and volumes of distribution of the three drugs tested were not affected by metronidazole, but urinary excretion of 4-hydroxyantipyrine decreased after metronidazole dosing. There was no change in the elimination of phenytoin as its hydroxylated metabolite after metronidazole. It is concluded that, at therapeutic concentrations, metronidazole does not significantly inhibit oxidative drug metabolism.     

肠系膜上动、静脉水平夹角CT测量及意义

目的研究螺旋CT横断面上肠系膜上动、静脉与冠状线间夹角的测量在胰头疾病诊断中的意义。方法对行上腹部螺旋CT扫描的1127例成人,先确定冠状面为虚拟水平线,再对肠系膜上动、静脉连线与水平线间夹角予以测量分析。结果<60岁胰腺正常组成年人肠系膜上动、静脉水平夹角正常值范围为4.9°～34.7°;≥60岁胰腺正常组成年人肠系膜上动、静脉水平夹角正常值范围为-4.7°～17.3°;慢性胰腺炎组肠系膜上动、静脉水平夹角为-2.0°～17.6°;急性胰腺炎组肠系膜上动、静脉水平夹角为1.5°～48.5°;<60岁胰头恶性占位组肠系膜上动、静脉水平夹角为38.8°～42.8°;≥60岁组胰头恶性占位组肠系膜上动、静脉水平夹角为39.0°～53.6°。结论螺旋CT横断面上肠系膜上动、静脉与冠状线间夹角的测量对胰头病变的CT诊断具有一定的提示价值,是临床上诊断胰头病变的一种新思路。     

Functional interaction between serotonin-S2 and dopamine-D2 neurotransmission as revealed by selective antagonism of hyper-reactivity to tryptamine and apomorphine.

The functional significance of the interaction between serotonergic and dopaminergic neurotransmission is still uncertain. To document this interaction further, specific behavioral responses of rats to tryptamine and apomorphine were studied. The sequential injection of these agonists, at time intervals with minimal direct behavioral interference, was used to observe response changes with respect to a single challenge. The antagonists haloperidol, ritanserin and risperidone, with known actions on serotonin-S2 (5-HT2) and dopamine-D2 (D2) receptors were used to evaluate effective antagonism of single and sequential challenges. When tryptamine was preceded by an apomorphine challenge the effective doses of the 5-HT2 antagonists ritanserin and risperidone for 50% inhibition of the seizures increased by a factor of 2.5. The dose-response curve of haloperidol remained virtually unchanged, apparently because of the potent dopamine-D2 antagonism associated with these doses which may block the potentiating effect of apomorphine. When apomorphine was preceded by a tryptamine challenge, the total agitation score of the control animals increased by 59% on the average. Haloperidol was equally effective against the enhanced as against the unenhanced apomorphine response. Ritanserin reduced agitation only by the part corresponding to the tryptamine enhancement. Risperidone's activity against the enhanced agitation started at very low doses and was complete at a dose still about 2.5 times lower than that required against the single apomorphine challenge. Mutual enhancement of tryptamine and apomorphine appears to occur even at a time when the behavioral effects of the first agonist are no longer manifest. The enhanced agitation remains largely dopamine-D2-specific and the enhanced seizures serotonin 5-HT2-specific.(ABSTRACT TRUNCATED AT 250 WORDS)     

Automatic processing of grammar in the human brain as revealed by the mismatch negativity

The Mismatch Negativity (MMN), a neurophysiological indicator of cognitive processing, was used to investigate grammatical processes in the absence of focused attention to language. Subjects instructed to watch a silent video film and to ignore speech stimuli heard grammatical and ungrammatical spoken word strings that were physically identical up to a divergence point where they differed between each other by a minimal acoustic event, the presence or the absence of a final -s sound. The sentence we come was presented as a rare deviant stimulus against the background of frequently occurring ungrammatical strings, and, in a different experiment, the ungrammatical string *we comes was the deviant in the reverse design. To control for effects related to differences between the critical words, come and comes, control conditions were used in which the same words were presented out of linguistic context. At 100-150 ms after the divergence point, the ungrammatical deviant stimulus elicited a larger MMN than the correct sentence at left-anterior recording sites. This difference was not seen under the out-of-context conditions. In the time range 100-400 ms after stimulus divergence, a spatiotemporal pattern of grammatically related effects was documented by statistically significant interactions of the word and context variables. Minimum-Norm Current Estimates of the cortical sources of the grammaticality effects revealed a main source in the left frontal cortex. We use a neurobiological model of serial order processing to provide a tentative explanation for the data.     

A positive feedback loop between spinal cord nociceptive pathways and antinociceptive areas of the cat's brain stem

Electrophysiological evidence has been obtained suggesting the presence of reciprocal excitation between descending pathways from the nucleus raphe magnus (NRM) and adjacent reticular formation (Ret.F) and spinal cord neurones projecting to these brain stem areas. In decerebrate and decerebellate cats, 40 spinal cord neurones were recorded whose recording sites were in or close to lamina VIII of the lumbar spinal cord. All 40 neurones recorded in the lumbar cord were postsynaptically excited by electrical stimulation of the NRM, the Ret.F. or most commonly, of both. The excitation was mediated by fast-conducting fibres and lasted for over 100 msec after a single shock. The shortest latency responses were obtained following stimulation of the contralateral Ret.F. These neurones had complex peripheral inputs subjected to descending controls. All the neurones could be excited by deep pressure of the ipsilateral and/or contralateral hind limbs. Peripheral inhibitory inputs were also observed. Eighteen out of the 40 neurones had axons that projected to NRM and the adjacent Ret.F. Conduction velocities ranged between 31.6 and 91 m/sec. In addition, 11 other axons were recorded in the white matter of the cervical cord from neurones projecting to NRM and Ret.F. Conduction velocities of this group of axons ranged between 13 and 70 m/sec. The majority of the axons projecting to NRM and Ret.F. were found to join pathways in the ventro-lateral quadrant of the spinal cord either ipsi- or contralaterally to their Ret.F. destination. Recordings were also made from 12 neurones whose recording sites were located in the NRM and Ret.F. Their responses to electrical stimulation of sites within lamina VIII of the lumbar spinal cord were studied. Only excitatory responses could be evoked by such stimulation. These results are discussed in relation to the mechanisms of activation of central antinociceptive systems.     

Interaction between high-risk infants and their mothers: the NCAST as an assessment tool.

Using the NCAST Feeding, Teaching, and HOME Scales, we tested 37 high-risk infants matched with 37 healthy infants on gender, race, and socioeconomic status. All infants were 8 months old. A one-to-one matched case-control design was used to determine whether increased risk of impaired mother-infant interaction was associated with case status. Conditional logistic regression was used to control for possible confounding and to evaluate interaction. Of the 37 high-risk infant-mother dyads, 25 had a low score on one or more scales while only 10 of the control dyads had a low score on one or more of the three scales. The Feeding scale was the only assessment in which the association found in the univariate analysis persisted after adjusting for other variables. Because of its low cost and high efficiency, the NCAST battery appears to be valuable for directing more specialized intervention services in a high-risk infant population.     

Neural networks related to pro-saccades and anti-saccades revealed by independent component analysis

The saccadic eye movement system provides an excellent model for investigating basic cognitive processes and flexible control over behaviour. While the mechanism of pro-saccades (PS) is well known, in the case of the anti-saccade task (AS) it is still not clear which brain regions play a role in the inhibition of reflexive saccade to the target, nor what is the exact mechanism of vector inversion (i.e. orienting in the opposite direction). Independent component analysis (ICA) is one of the methods being used to establish temporally coherent brain regions, i.e. neural networks related to the task. In the present study ICA was applied to fMRI data from PS and AS experiments. The study revealed separate networks responsible for saccade generation into the desired direction, the inhibition of automatic responses, as well as vector inversion. The first function is accomplished by the eye fields network. The inhibition of automatic responses is associated with the executive control network. Vector inversion seems to be accomplished by the network comprising a large set of areas, including intraparietal sulcus, precuneus/posterior cingulate cortices, retrosplenial and parahippocampal. Those regions are associated with the parieto-medial temporal pathway, so far linked only to navigation. These results provide a new insight into understanding of the processes of the inhibition and vector inversion.     

电针对抑郁模型大鼠脑形态结构影响的磁共振成像研究

目的 通过MRI成像技术，观察电针“百会”、“印堂”穴对慢性应激抑郁模型大鼠脑形态结构的影响，从神经生理学的角度探讨针刺治疗抑郁症的机理。方法选择Open-field法评分相近的30只成年SD雄性大鼠并将其随机分为正常组、模型组和电针组，每组10只；应用分养和长期不可预见性中等强度应激建造大鼠抑郁模型，电针组参照《实验针灸学》取百会、印堂两穴进行针刺；以Open-field实验和糖水消耗实验等方法测定动物的行为变化；多片多回波的T2加权成像、扩散加权成像和翻转恢复的T1加权成像，对照研究各组大鼠脑内形态学及各脑区信号强度的改变。结果正常组大鼠的体重远高于电针组，且差异有统计学意义，模型组大鼠的体重虽然高于电针组，但差异无统计学意义；模型组大鼠的1％蔗糖水摄取量明显低于正常组和电针组，且差异有统计学意义，正常组高于电针组，但差异无统计学意义；采用Open-field法检测大鼠活动性，电针组、模型组分别与正常组比较，水平运动次数、垂直运动次数均明显降低并且差异有统计学意义。电针组与模型组相比较差异均无统计学意义；从rr2加权像上观察到大鼠脑裂扩大现象，但三组之间并无显著差异；模型组和电针组与正常组相比较，中脑水管的横截面积有增加，统计结果显示三组之间差异有统计学意义；对T2值的分析结果显示，电针组和正常组的海马区T2值接近，而模型组的海马区T2值与电针组和正常组相比较有增加，其海马区T2值与电针组相比较差异有统计学意义，其它脑区，如尾壳核、杏仁核和皮层，T2值在三组之间并无明显差别；对扩散加权像的数据处理结果显示，模型组和电针组海马区和颞叶及听觉皮质区的ADC值(表观扩散系数)相对于正常组有降低，并且与正常组相比差异都有统计学意义；而纹状皮质区的ADC值三组之间差异无统计学意义。结论MRI证实电针对抑郁模型大鼠的脑形态结构有影响，提示电针作为一种治疗手段在临床治疗抑郁症中取得的显著疗效，可能与电针作用于抑郁症患者脑部组织并影响了其相关组织的功能有关。但本实验体现的是好坏参半的结果，提示以大鼠为对象来研究针刺机理，必须注意人与大鼠的种属差异和受试主体的精神心理作用对实验指标乃至实验结论的影响。     

Characteristics of the interactions between acid glycosaminoglycans and proteins in normal human plasma as revealed by the behaviour of the protein-polysaccharide complexes in ultrafiltration and chromatographic procedures.

Acid glycosaminoglycans were isolated from normal human plasma: (a) following fractionation of plasma (with protease inhibitors) on Sephadex G-200; (b) by ultrafiltration through membranes with retention of molecules above 50 kDa, with and without previous addition of NaCl, Triton X-100, urea, or guanidine HCl; (c) by filtering on Ecteola-cellulose either untreated plasma or after treatment with NaCl, urea, Triton X-100, papain or NaOH. More than 95% of plasma glycosaminoglycans interact with plasma proteins to give complexes that exhibit reproducible behaviour on Sephadex G-200 and are retained by ultrafiltration membranes, which the 12-20 kDa polysaccharide chains do filter. High charge plasma glycosaminoglycans show ionic interactions with proteins, while low charge glycosaminoglycan interactions are resistant to Ecteola charged groups, to 0.5% Triton and 4 M urea, while not to 4 M guanidine HC1. Some glycosaminoglycan-protein complexes appear resistant to proteolysis, suggesting that they may originate from lymphocytes. The simple method utilized for plasma GAG measurement may represent an useful tool in clinical practice.