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Plasma arginine correlations in trauma and sepsis.

Arginine (ARG) is an amino acid (AA) with unique properties and with a key-role in the metabolic, immune and reparative response to trauma and sepsis. This study has been performed to characterize the correlations between plasma levels of ARG, of other AA and of multiple metabolic variables in trauma and sepsis. Two-hundred and sixty-three plasma amino-acidograms with a large series of additional biochemical and blood variables were obtained consecutively in 9 trauma patients who developed sepsis, undergoing total parenteral nutrition with dextrose, fat and a mixed AA solution containing 10.4% arginine. ARG was low soon after trauma, then it increased with increasing distance from trauma and with the development of sepsis. ARG was also directly related to the AA infusion rate (AAIR) and for any given AAIR, was lower after trauma than after the development of sepsis. ARG was also related directly to the plasma levels of most of the other AA, the best correlation being that with lysine (r(2) = 0.81, p < 0.001). These correlations were often shifted downwards (showing lower ARG for any given level of the other AA) in measurements performed after trauma, compared to those performed after development of sepsis; this effect was more pronounced for the correlations with branched chain AA. Correlations between ARG and non-AA variables were not particularly relevant. The best simultaneous correlates of ARG, among variables involved in plasma ARG availability, were citrulline level, AAIR and urinary 3-methylhistidine excretion (accounting for the effect of endogenous proteolysis) (multiple r(2) = 0.70, p < 0.001). Plasma ornithine (ORN), the AA more specifically linked to ARG metabolism, correlated with AAIR better than ARG and, for any given AAIR, was lower after trauma than after the development of sepsis. Correlations of ORN with other AA levels were poorer than those found for ARG, however ORN was directly related to white blood cell and platelet count, fibrinogen, transferrin, cholesterol and many AA clearances. These data show that changes in ARG in trauma and sepsis are correlated with changes in other AA and, within these correlations, reconfirm a tendency to lower ARG in trauma compared to sepsis. The strong correlation with lysine warrants a deeper assessment of the practical implications of interdependency between these two AA. The data also suggest that changes in plasma ORN in trauma and sepsis may reflect adequacy of AA substrate to support acute-phase and other synthetic processes.

Adolescent↗

Locally correlated activity in the goldfish tectum in the absence of optic innervation.

Despite a substantial literature on the role of correlated presynaptic activity in the patterning of nerve connections during synaptogenesis in the central nervous system, few studies have focuses on postsynaptic activity during this process. To address the possibility that the target exhibits correlated activity independently of presynaptic activity, extracellular activity was recorded from the main optic innervation layer stratum fibrosum et griseum superficiale (SFGS) in goldfish in which the optic nerve was crushed or the eye removed. At about 2 weeks after denervation, multiunit recordings revealed phasic temporally correlated discharge between different tectal units. Auto-correlation analysis of these trains showed a broad peak 75-100 ms wide confirming temporal correlation. Using cross-correlation analysis of two simultaneous recordings at different distances across tectum, this correlation was shown to be local. Strong positive correlations were detected over about 200 micron and decrease with greater distances disappearing beyond about 400 micron. These correlograms showed a broad symmetrical peak about 75-100 ms wide. This pattern of activity persisted from the day following nerve crush into the period of activity dependent reinnervation at 1 month. When the eye was removed, the pattern could be demonstrated for up to 3 months of denervation indicating the circuitry responsible for the correlated activity was quite stable in the absence of optic innervation. We conclude that tectal elements are capable of locally correlated discharge independently of optic innervation. We propose that locally correlated discharge represents cooperative groups of tectal cells and that these groups, rather than single cells, are the target of the activity dependent synaptic rearrangement such as ocular dominance columns which occurs during synaptogenesis.

Animals↗

Correlations between estimated and true dietary intakes.

PURPOSE: It is unclear how well questionnaire or so-called reference methods of dietary assessment correlate with true dietary intake. We develop a method to estimate such correlations. METHODS: An error model is described that uses data from a food frequency questionnaire (Q), a reference method (R), and a biological marker (M). The model does not assume the classical error model for either R or M, or that the correlation between errors in the questionnaire and reference data is zero. Credible intervals can be placed about correlations between R, Q, M and true dietary data (T), also about the correlations between errors in reference and questionnaire data. RESULTS: Application of this model to a validation data set mainly found correlations in the range 0.4 to 0.8, and that correlations (R,T) generally exceeded correlations (Q,T), providing evidence that R is more valid than Q. Estimated correlations between errors in R and Q were often far from zero suggesting that regression calibration to imperfect reference data is problematic unless these error correlations can be estimated. CONCLUSION: A biological marker in addition to dietary data, allows calculation of correlations between estimated and true dietary intakes under reasonable assumptions about errors. However, sensitivity analyses are necessary on one variable.

Adult↗

Pressure-induced correlation field splitting of vibrational modes: structural and dynamic properties in lipid bilayers and biomembranes.

Correlation field splittings of the vibrational modes of methylene chains in lipid bilayers, isolated lipid molecules in perdeuterated lipid bilayers, crystalline lipid, and interdigitated lipid bilayers have been investigated by pressure-tuning Fourier-transform infrared spectroscopy. The correlation field splittings of these modes are originating from the vibrational coupling interactions between the fully extended methylene chains with different site symmetry along each bilayer leaflet. The interchain-interactions of the methylene chains with the same site symmetry only contribute to frequency shift of the vibrational modes. The magnitude of the correlation field splitting is a measure of the strength of the interchain-interactions, and the relative intensities of the correlation field component bands provide information concerning the relative orientation of the zig-zag planes of the interacting methylene chains. It has been demonstrated in the present work that the correlation field splitting of the CH2 bending and rocking modes commonly observed in the vibrational spectra of lipid bilayers is the result of the intermolecular interchain-interactions among the methylene chains of the neighboring molecules. The intramolecular interchain-interactions between the sn-1 and sn-2 methylene chains within each molecule are weak. The correlation field splitting resulting from the intramolecular interchain-interactions exhibits a much smaller magnitude than that from the intermolecular interchain-interactions and is observed only at very high pressure. Interdigitation of the opposing bilayer leaflets disturbs significantly the intermolecular interchain-interactions and results in dramatic changes in the pressure profiles of the correlation field component bands of both the CH2 bending and rocking modes. The relative intensities of the correlation field component bands of these modes and the magnitude of the splitting are also altered significantly. These results provide further evidence that the correlation field splitting of the CH2 bending and rocking modes in the vibrational spectra of lipid bilayers is due to the intermolecular interchain-interactions. The present work has also demonstrated that the correlation field splitting of the vibrational modes in lipid bilayers is mainly contributed by the intermolecular interchain-interactions among the nearest neighboring molecules and that the long-range correlation interactions beyond the second neighboring molecules are insignificant.

Biophysical Phenomena↗

Neuronal and behavioral correlations in the medial prefrontal cortex and nucleus accumbens during cocaine self-administration by rats.

Up to 31 neurons per animal were simultaneously recorded from the medial prefrontal cortex and nucleus accumbens in 15 rats during i.v. cocaine self-administration sessions, using a multi-channel, single-unit recording technique. Alterations of neuronal activity (both excitatory and inhibitory) were found a few seconds before each lever press for cocaine infusion; we have called these pre-lever press neuronal activations "anticipatory responses". A detailed video analysis revealed that these neuronal firing alterations were associated with specific portions of the behavioral sequence performed before each lever press in both recording areas. Some of the simultaneously recorded neurons displayed similar firing patterns in relation to a given behavioral episode within the behavioral sequence (turning, raising head, etc.), while others fired at different times relative to each behavioral event. Cross-correlational analyses revealed inter-regional and intra-regional correlated firing patterns between pairs of simultaneously recorded medial prefrontal cortex and nucleus accumbens neurons. This correlated firing occurred in the neurons with and without anticipatory responses, although the incidence of correlations between anticipatory neuron pairs was much higher than that between non-anticipatory neuron pairs (18.4% vs 3.6%). Many correlated neuron pairs displayed a time lag in the peak of correlational activity that indicated a temporal sequence in correlated activity. In contradiction to our hypothesis, the temporal pattern of correlation reveals that there are more cases in which nucleus accumbens neurons fired ahead of medial prefrontal cortex neurons. The results suggest that multiple mesocorticolimbic neuronal circuits may code sequential steps during the behavioral sequence performed to obtain an infusion of cocaine. The observed correlated firing between the medial prefrontal cortex and the nucleus accumbens indicates that dynamic, coherent activity occurs within the mesocorticolimbic circuit. Because this circuit is hypothesized to drive drug-seeking behavior, we suggest that this correlated firing between the nucleus accumbens and the medial prefrontal cortex may participate in the control of cocaine self-administration. In addition, the finding that correlated activity within the nucleus accumbens more often precedes that of the medial prefrontal cortex suggests that the nucleus accumbens may play a prime role in the initiation of cocaine self-administration.

Animals↗

Correlations of trace element levels within and between different normal autopsy tissues analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES).

Imbalance in trace metal metabolism may lead to metal interactions that may be of patho-physiological importance. Knowledge of the relation between trace metals in normal tissues is needed to assess abnormal deviations associated with disease. In this study correlations between Cu, Co, Cr, Fe, Mn, Ni, Se, Zn, Al, Ba, Cd, Pb and Sr within the same and between 6 different, normal autopsy tissues were determined using Spearman rank correlation analysis based on analytical data obtained by inductively coupled plasma atomic emission spectrometry (ICP-AES). Fe-Co were correlated in most tissues. Cu-Mn, Zn-Cu, Zn-Mn and Zn-Cd were highly correlated in the kidney medulla. Ni-Ni, Sr-Sr and Cd-Cd were correlated between several tissues, while Fe-Fe, Zn-Zn and Cu-Cu were correlated between kidney cortex and medulla. Mn-Mn was highly correlated between the liver and brain front lobe, cerebellum and heart. High correlations were found for Ni-Co and for Se-Mn between the kidney cortex and brain front lobe and pancreas respectively. Inverse correlations were found for Se-Cd between kidney cortex and cerebellum, for Se-Cd and Cd-Zn between kidney medulla and heart, for Co-Sr and Fe-Sr between the liver and kidney cortex and heart respectively, and for Sr-Mn between kidney medulla and pancreas. A large number of trace elements are statistically correlated within and between different, normal tissues. Knowledge of these correlations may contribute to increase the understanding of kinetic interactions of trace metals in the body and the role of such interactions in normal and disturbed trace metal metabolism.

Adolescent↗

Monitor-to-monitor temporal correlation of air pollution in the contiguous US.

Numerous studies have reported short-term associations between ambient air pollution concentrations and mortality and morbidity. Particulate matter (PM) was often implicated as the most significant predictor of the health outcomes among the various air pollutants. However, a question remains as to the potential role played by the relative error of exposure estimation associated with each pollutant in defining their relative strengths of association. While most of the recent studies on PM exposure measurements have focused on the temporal correlation between personal exposures and the concentrations observed at ambient air quality monitors (within a few miles from the subjects), there have been few studies that systematically evaluated spatial uniformity of temporal correlation of air pollution within the scale of a city (several tens of miles) for which mortality or morbidity outcomes are aggregated in time-series studies. In this study, spatial uniformity of temporal correlation was examined by computing monitor-to-monitor correlation using available multiple monitors for PM(10) and gaseous criteria pollutants (NO(2), SO(2), CO, and O(3)) in the nationwide data between 1988 and 1997. For each monitor, the median of temporal correlation with other monitors within the Air Quality Control Region (AQCR) was computed. The resulting median monitor-to-monitor correlation was modeled as a function of qualitative site characteristics (i.e., land-use, location-setting, and monitoring-objective) and quantitative information (median separation distance, longitude/latitude or regional indicators) for each pollutant. Generalized additive models (GAM) were used to fit the smooth function of the separation distance and regional variation. The intercepts of the models across pollutants showed the overall rankings in monitor-to-monitor correlation on the average to be: O(3), NO(2), and PM(10), (r approximately 0.6 to 0.8)>CO (r<0.6)>SO(2) (r<0.5). Both the separation distance and regional variation were important predictors of the correlation. For PM(10), for example, the correlation for the monitors along the East Coast was higher by approximately 0.2 than western regions. The qualitative monitor characteristics were often significant predictors of the variation in correlation, but their impacts were not substantial in magnitude for most categories. These results suggest that the apparent regional heterogeneity in PM effect estimates, as well as the differences in the significance of health outcome associations across pollutants, may in part be contributed to by the differences in monitor-to-monitor correlations by region and across pollutants.

Air Pollutants↗

Brain correlates of stuttering and syllable production: gender comparison and replication.

This article reports a gender replication study of the P. T. Fox et al. (2000) performance correlation analysis of neural systems that distinguish between normal and stuttered speech in adult males. Positron-emission tomographic (PET) images of cerebral blood flow (CBF) were correlated with speech behavior scores obtained during PET imaging for 10 dextral female stuttering speakers and 10 dextral, age- and sex-matched normally fluent controls. Gender comparisons were made between the total number of voxels per region significantly correlated with speech performance (as in P. T. Fox et al., 2000) plus total voxels per region that were significantly correlated with stutter rate and not with syllable rate. Stutter-rate regional correlates were generally right-sided in males, but bilateral in the females. For both sexes the positive regional correlates for stuttering were in right (R) anterior insula and the negative correlates were in R Brodmann area 21/22 and an area within left (L) inferior frontal gyrus. The female stuttering speakers displayed additional positive correlates in L anterior insula and in basal ganglia (L globus pallidus, R caudate), plus extensive right hemisphere negative correlates in the prefrontal area and the limbic and parietal lobes. The male stuttering speakers were distinguished by positive correlates in L medial occipital lobe and R medial cerebellum. Regions that positively correlated with syllable rate (essentially stutter-free speech) in stuttering speakers and controls were very similar for both sexes. The findings strengthen claims that chronic developmental stuttering is functionally related to abnormal speech-motor and auditory region interactions. The gender differences may be related to differences between the genders with respect to susceptibility (males predominate) and recovery from chronic stuttering (females show higher recovery rates during childhood).

Adult↗

Negative genetic correlation between traits of the Drosophila head, and interspecific divergence in head shape.

For morphological traits that are negatively correlated, the genetic correlation (rg) between them might strongly influence patterns of morphological divergence and shape. Here, the pattern of divergence between two sibling species of cactophilic Drosophila, D. buzzatii and D. koepferae, is examined for two traits that are known to be negatively correlated in other Drosophila species: face width (FW) and width of both eyes (EW). Head width (HW, the sum of FW and EW, i. e. the total width of the head capsule) was also examined. Genetic and phenotypic correlations were estimated in the laboratory G2 generation of a sample of wild D. buzzatii derived from a population where D. koepferae is not present. Phenotypic correlations were also estimated in D. buzzatii and D. koepferae from another, very different, population where the species are sympatric. Consistent with studies in other Drosophila species, rg was negative and significant for the correlation between FW and EW, and positive (but nonsignificant at a matrix-wide P-value of 0.05) for the correlations of HW with both FW and EW. This well-defined correlation pattern was also consistent with the phenotypic correlations in both D. buzzatii and D. koepferae. No significant difference in these traits was detected between D. buzzatii populations, but head shape has diverged between D. buzzatii and D. koepferae. Specifically, the two negatively correlated traits, FW and EW, have evolved in opposite directions in these two species, with HW showing no significant interspecific difference. The overall picture of this divergence pattern shows a striking concordance with the present evidence of negative correlations between FW and EW, and is consistent with the notion of rg-related constraints on the pattern of interspecific differentiation.

Animals↗

Is there any group additive rules in the calculation of electron correlation energies of long straight chain alkane molecules?

According to the definition in the text, the correlation energy of 1s2C of carbon atoms, the primary and secondary C-H bonding electron pairs in some CH3, CH2 fragments and CH3(CH2)mCH3 (m=1-5) linear alkane molecules are calculated and analyzed. The transferability of the correlation energies of these electron pairs in the linear alkanes is investigated. The results indicate that the correlation energy of 1s2C is perfectly transferable in the respective methyl and methylene groups, while the correlation energies of the primary and secondary C-H bonding electron pairs are approximately transferable in methyl and methylene groups. The analysis of the results of group correlation energy shows that both of the correlation energies of methyl and methylene groups are transferable in these linear alkanes. The correlation energies of methylene group in CH3(CH2)mCH3 (m=1-5) molecules are slightly decreasing showing a converging trend to a "standard" methylene group in linear alkanes. The excellent fitting relationship between the total correlation energy and the number of methylene groups of the linear alkanes shows that the total correlation energy is a linear function of the number of methylene groups, which means that the total correlation energies of large linear alkanes can be reproduced and predicted by counting the numbers of methylene groups. In this way, total correlation energy of large linear alkane molecule can be approximately calculated using this simple group additive scheme with substantial saving in computational time.

Journal Article↗

Conditions for positive and negative correlations between fitness and heterozygosity in equilibrium populations.

The past decades have witnessed extensive efforts to correlate fitness traits with genomic heterozygosity. While positive correlations are revealed in most of the organisms studied, results of no/negative correlations are not uncommon. There has been little effort to reveal the genetic causes of these negative correlations. The positive correlations are regarded either as evidence for functional overdominance in large, randomly mating populations at equilibrium, or the results of populations at disequilibrium under dominance. More often, the positive correlations are viewed as a phenomenon of heterosis, so that it cannot possibly occur under within-locus additive allelic effects. Here we give exact genetic conditions that give rise to positive and negative correlations in populations at Hardy-Weinberg and linkage equilibria, thus offering a genetic explanation for the observed negative correlations. Our results demonstrate that the above interpretations concerning the positive correlations are not complete or even necessary. Such a positive correlation can result under dominance and potentially under additivity, even in populations where associated overdominance due to linked alleles at different loci is not significant. Additionally, negative correlations and heterosis can co-occur in a single population. Although our emphasis is on equilibrium populations and for biallelic genetic systems, the basic conclusions are generalized to non-equilibrium populations and for multi-allelic situations.

Adaptation, Biological↗

Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population.

OBJECTIVE: The relationship between osteoprotegerin (OPG) and lipid profile, insulin sensitivity, adipocytokines and sex steroids has been poorly studied and subject to controversy. The purpose of this study was to look at the correlates of OPG in an elderly male population. DESIGN: One hundred and fifty-one nondiabetic, elderly Lebanese men (age range 50-83) were recruited in this cross-sectional study based on voluntary enrolment. MEASUREMENTS: In all the subjects, serum OPG levels were measured and related to clinical parameters (age, waist, body mass index (BMI), systolic and diastolic blood pressure), as well as to metabolic and hormonal parameters. The following fasting laboratory measurements were performed: plasma glucose and insulin levels, total cholesterol, triglycerides and HDL cholesterol, adiponectin, leptin, as well as sex steroids (testosterone, SHBG, free androgen index, ooestradiol, DHEAS), GH and IGF-1. QUICKI index was calculated as a measure of insulin sensitivity. RESULTS: OPG levels were significantly correlated with age (r = 0.28, P < 0.0001) but not with BMI, waist, systolic or diastolic blood pressure. There was a trend towards higher OPG levels in subjects without, compared to subjects with the metabolic syndrome (3.58 +/- 1.28 vs. 3.26 +/- 1.04 pmol/l, P = 0.09). OPG was negatively correlated with fasting glucose and triglyceride levels (r = -0.18, P = 0.031 and r = -0.19, P = 0.02, respectively) and positively correlated with the QUICKI index (r = 0.17, P = 0.033), HDL cholesterol (r = 0.21, P = 0.009) and adiponectin levels (r = 0.27, P = 0.001). No significant correlations were reported with total or LDL cholesterol levels and with leptin levels. After adjustment for age, OPG is still correlated with triglycerides (r = -0.19, P = 0.02), glucose (r = -0.21, P = 0.011) and adiponectin (r = 0.19, P = 0.02). Finally, OPG was positively associated with SHBG (r = 0.31, P < 0.001) and negatively associated with free androgen index (r =-0.346, P < 0.001); both correlations persisted after adjustment for age (r = 0.21, P = 0.009 and r = -0.23, P = 0.005, respectively). No significant correlation was found between OPG and oestradiol levels while a weak negative correlation was demonstrated with DHEAS (r = -0.18, P = 0.025). Also, no significant correlation was found between OPG and GH or IGF-1 values. In a multiple regression analysis with a stepwise model, the main determinants of OPG were free androgen index and adiponectin (P < 0.0001 and P = 0.015, respectively). CONCLUSION: Our results show that circulating OPG levels are favourably associated with some components of the metabolic syndrome. Also, for the first time, an association between OPG and adiponectin is described. Finally, the negative correlation we found between OPG and free androgen index may suggest a potential role of OPG in the increase in cardiovascular disease related to ageing and sex steroid deficiency.

Adiponectin↗

Estimation of genetic correlation: interpretation of experiments using selectively bred and inbred animals.

There is increasing interest in determining the extent to which multiple characters related to drug sensitivity are influenced by common genes. The principal method for testing for the existence of such genetic correlations has been examination of pairs of mouse or rat lines selectively bred for sensitivity or resistance to a single behavioral effect of a drug. When a pair of selected lines is found to differ significantly on some trait other than the one on which they were selected, it is commonly concluded that significant genetic correlation between the traits exists, implying the action of a common set of genes on the two responses. In addition, results from comparisons of lines of animals selected for trait X and tested for trait Y may be compared with results from lines selected for trait Y and tested for trait X. As the number of correlated responses in selected lines increases, it becomes more important to adhere to sensible, consensual guidelines for interpreting such line differences. The principles underlying phenotypic and genotypic correlational analyses with selected lines are discussed. A scheme is presented to allow standardization across laboratories of inferences about the relative strength of genetic association from experiments with selected lines. Statistical and practical experimental issues are addressed. Estimates of genetic correlations may also be derived from the correlation of mean trait values across a panel of inbred strains. Existing data have sometimes found estimates of genetic correlations made with one approach to be inconsistent with those estimated in other ways. Possible reasons for this are discussed. Finally, the relationship between phenotypic correlations and genetic correlations is discussed. Phenotypic and genetic correlations for a pair of traits may differ widely, and may even be opposite in sign. Both are characteristic of the population from which they are sampled. Phenotypic correlations estimated within selected lines may change over time, as the additive genetic variance in the selected trait is exhausted. A specific example of this phenomenon is given.

Alcoholic Intoxication↗

Correlated discharges among putative pyramidal neurons and interneurons in the primate prefrontal cortex.

Neurophysiological recordings have revealed that the discharges of nearby cortical cells are positively correlated in time scales that range from millisecond synchronization of action potentials to much slower firing rate co-variations, evident in rates averaged over hundreds of milliseconds. The presence of correlated firing can offer insights into the patterns of connectivity between neurons; however, few models of population coding have taken account of the neuronal diversity present in cerebral cortex, notably a distinction between inhibitory and excitatory cells. We addressed this question in the monkey dorsolateral prefrontal cortex by recording neuronal activity from multiple micro-electrodes, typically spaced 0.2-0.3 mm apart. Putative excitatory and inhibitory neurons were distinguished based on their action potential waveform and baseline discharge rate. We tested each pair of simultaneously recorded neurons for presence of significant cross-correlation peaks and measured the correlation of their averaged firing rates in successive trials. When observed, cross-correlation peaks were centered at time 0, indicating synchronous firing consistent with two neurons receiving common input. Discharges in pairs of putative inhibitory interneurons were found to be significantly more strongly correlated than in pairs of putative excitatory cells. The degree of correlated firing was also higher for neurons with similar spatial receptive fields and neurons active in the same epochs of the behavioral task. These factors were important in predicting the strength of both short time scale (<5 ms) correlations and of trial-to-trial discharge rate covariations. Correlated firing was only marginally accounted for by motor and behavioral variations between trials. Our findings suggest that nearby inhibitory neurons are more tightly synchronized than excitatory ones and account for much of the correlated discharges commonly observed in undifferentiated cortical networks. In contrast, the discharge of pyramidal neurons, the sole projection cells of the cerebral cortex, appears largely independent, suggesting that correlated firing may be a property confined within local circuits and only to a lesser degree propagated to distant cortical areas and modules.

Animals↗

Effects of noise correlations on information encoding and decoding.

Response variability is often correlated across populations of neurons, and these noise correlations may play a role in information coding. In previous studies, this possibility has been examined from the encoding and decoding perspectives. Here we used d prime and related information measures to examine how studies of noise correlations from these two perspectives are related. We found that for a pair of neurons, the effect of noise correlations on information decoding can be zero when the effect of noise correlations on the information encoded obtains its largest positive or negative values. Furthermore, there can be no effect of noise correlations on the information encoded when it has an effect on information decoding. We also measured the effect of noise correlations on information encoding and decoding in simultaneously recorded neurons in the supplementary motor area to see how well d prime accounted for the information actually present in the neural responses and to see how noise correlations affected encoding and decoding in real data. These analyses showed that d prime provides an accurate measure of information encoding and decoding in our population of neurons. We also found that the effect of noise correlations on information encoding was somewhat larger than the effect of noise correlations on information decoding, but both were relatively small. Finally, as predicted theoretically, the effects of correlations were slightly greater for larger ensembles (3-8 neurons) than for pairs of neurons.

Action Potentials↗

Correlation analysis of corticotectal interactions in the cat visual system.

We have studied the temporal relationship between visual responses in various visual cortical areas [17, 18, postero medial lateral suprasylvian (PMLS), postero lateral lateral suprasylvian (PLLS), 21a]) and the superficial layers of the cat superior colliculus (SC). To this end, simultaneous recordings were performed in one or several visual cortical areas and the SC of anesthetized paralyzed cats, and visually evoked multiunit responses were subjected to correlation analysis. Significant correlations occurred in 117 (24%) of 489 cortex-SC pairs and were found for all cortical areas recorded. About half of the significant correlograms showed an oscillatory modulation. In these cases, oscillation frequencies covered a broad range, the majority being in the alpha- and beta-band. On average, significant center peaks in cross-correlograms had a modulation amplitude of 0.34. Our analysis revealed a considerable intertrial variability of correlation patterns with respect to both correlation strength and oscillation frequency. Furthermore, cortical areas differed in their corticotectal correlation patterns. The percentage of cells involved a corticotectal correlation, as well as the percentage of significantly modulated correlograms in such cases, was low for areas 17 and PMLS but high for areas 18 and PLLS. Analysis of the cortical layers involved in these interactions showed that consistent temporal relationships between cortical and collicular responses were not restricted to layer V. Our data demonstrate a close relationship between corticotectal interactions and intracortical or intracollicular synchronization. Trial-by-trial analysis from these sites revealed a clear covariance of corticotectal correlations with intracortical synchronization. The probability of observing corticotectal interactions increased with enhanced local cortical and collicular synchronization and, in particular, with interareal cortical correlations. Corticotectal correlation patterns resemble in many ways those described among areas of the visual cortex. However, the correlations observed are weaker than those between nearby cortical sites, exhibit usually broader peaks and for some cortical areas show consistent phase-shifts. Corticotectal correlations represent population phenomena that reflect both the local and global temporal organization of activity in the cortical and collicular network and do not arise from purely monosynaptic interactions. Our findings show that both striate and extrastriate inputs affect the superficial SC in a cooperative manner and, thus, do not support the view that responses in the superficial SC depend exclusively on input from the primary visual areas as implied by the concept of "two corticotectal systems." We conclude that the corticotectal projections convey temporal activation patterns with high reliability, thus allowing the SC evaluation of information encoded in the temporal relations between responses of spatially disseminated cortical neurons. As a consequence, information distributed across multiple cortical areas can affect the SC neurons in a coherent way.

Animals↗

Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria.

We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer's disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a subgroup of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.

Aged↗

Performance evaluation of commercial short-oligonucleotide microarrays and the impact of noise in making cross-platform correlations.

BACKGROUND: Despite the widespread use of microarrays, much ambiguity regarding data analysis, interpretation and correlation of the different technologies exists. There is a considerable amount of interest in correlating results obtained between different microarray platforms. To date, only a few cross-platform evaluations have been published and unfortunately, no guidelines have been established on the best methods of making such correlations. To address this issue we conducted a thorough evaluation of two commercial microarray platforms to determine an appropriate methodology for making cross-platform correlations. RESULTS: In this study, expression measurements for 10,763 genes uniquely represented on Affymetrix U133A/B GeneChips and Amersham CodeLink UniSet Human 20 K microarrays were compared. For each microarray platform, five technical replicates, derived from the same total RNA samples, were labeled, hybridized, and quantified according to each manufacturers' standard protocols. The correlation coefficient (r) of differential expression ratios for the entire set of 10,763 overlapping genes was 0.62 between platforms. However, the correlation improved significantly (r = 0.79) when genes within noise were excluded. In addition to levels of inter-platform correlation, we evaluated precision, statistical-significance profiles, power, and noise levels for each microarray platform. Accuracy of differential expression was measured against real-time PCR for 25 genes and both platforms correlated well with r values of 0.92 and 0.79 for CodeLink and GeneChip, respectively. CONCLUSIONS: As a result of this study, we recommend using only genes called 'present' in cross-platform correlations. However, as in this study, a large number of genes may be lost from the correlation due to differing levels of noise between platforms. This is an important consideration given the apparent difference in sensitivity of the two platforms. Data from microarray analysis need to be interpreted cautiously and therefore, we provide guidelines for making cross-platform correlations. In all, this study represents the most comprehensive and specifically designed comparison of short-oligonucleotide microarray platforms to date using the largest set of overlapping genes.

Brain↗