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At least 1,135 records · Page 63Linked to original sources

PubMed2006

A method to produce evolving functional connectivity maps during the course of an fMRI experiment using wavelet-based time-varying Granger causality.

Functional magnetic resonance imaging (fMRI) is widely used to identify neural correlates of cognitive tasks. However, the analysis of functional connectivity is crucial to understanding neural dynamics. Although many studies of cerebral circuitry have revealed adaptative behavior, which can change during the course of the experiment, most of contemporary connectivity studies are based on correlational analysis or structural equations analysis, assuming a time-invariant connectivity structure. In this paper, a novel method of continuous time-varying connectivity analysis is proposed, based on the wavelet expansion of functions and vector autoregressive model (wavelet dynamic vector autoregressive-DVAR). The model also allows identification of the direction of information flow between brain areas, extending the Granger causality concept to locally stationary processes. Simulation results show a good performance of this approach even using short time intervals. The application of this new approach is illustrated with fMRI data from a simple AB motor task experiment.

Adult↗

PubMed2006

Dynamic causal modelling of evoked responses in EEG/MEG with lead field parameterization.

Dynamical causal modeling (DCM) of evoked responses is a new approach to making inferences about connectivity changes in hierarchical networks measured with electro- and magnetoencephalography (EEG and MEG). In a previous paper, we illustrated this concept using a lead field that was specified with infinite prior precision. With this prior, the spatial expression of each source area, in the sensors, is fixed. In this paper, we show that using lead field parameters with finite precision enables the data to inform the network's spatial configuration and its expression at the sensors. This means that lead field and coupling parameters can be estimated simultaneously. Alternatively, one can also view DCM for evoked responses as a source reconstruction approach with temporal, physiologically informed constraints. We will illustrate this idea using, for each area, a 4-shell equivalent current dipole (ECD) model with three location and three orientation parameters. Using synthetic and real data, we show that this approach furnishes accurate and robust conditional estimates of coupling among sources and their orientations.

Auditory Perception↗

PubMed2006

Causal visual interactions as revealed by an information theoretic measure and fMRI.

In the present study, we evaluated the direction of the effective connectivity between fMRI activations in neural structures mediating preserved visual function in a patient with homonymous hemianopsia due to a posterior cerebral artery stroke. Although the lesion affected the primary visual cortex, the visual abilities of this patient included above-chance verbal reports of movement and color change as well as the discrimination of movement direction in his hemianopic field. These abilities were coupled with awareness (Riddoch syndrome). The strength and the direction of the interactions between visual regions were assessed by applying directed transinformation (T), a nonparametric information theoretic causal measure sensitive to linear as well as to nonlinear interactions. In the healthy hemisphere, T identified a strong flow of information from visual area V1 to V5 during stimulation by visual movement and from V1 to V4/V8 during stimulation by color change. In addition, during color change stimulation, a bi-directional flow was observed between V4/V8 and V5, suggesting crosstalk between these regions. In the lesioned hemisphere, the color change stimulation evoked a stronger flow from V5 to V4/V8 and a flow from V4/V8 to V2. These observations provide support for the hypothesis that visual information is mediated via subcortical pathways that bypass V1 and project first to higher-tier visual areas V5 and V4/V8 then subsequently to lower-tier area V2.

Adult↗

PubMed2006

Dynamic causal modeling: a generative model of slice timing in fMRI.

Dynamic causal modeling (DCM) of functional magnetic resonance imaging (fMRI) data allows one to make inferences about the architecture of distributed networks in the brain, in terms of effective connectivity. fMRI data are usually acquired using echo planar imaging (EPI). EPI sequences typically acquire slices at different times over a few seconds. DCM, in its original inception, was not informed about these slice timings and assumed that all slices were acquired simultaneously. It has been shown that DCM can cope with slice timing differences of up to 1 s. However, many fMRI studies employ a repetition time (TR) of 3 to 5 s, which precludes a straightforward DCM of these data. We show that this limitation can be overcome easily by including slice timing in the DCM. Using synthetic data we show that the extended DCM furnishes veridical posterior means, even if there are large slice-timing differences. Model comparisons show that, in general, the extended DCM out-performs the original model. We contrast the modeling of slice timing, in the context of DCM, with the less effective approach of 'slice-timing correction', prior to modeling. We apply our procedure to real data and show that slice timings are important parameters. We conclude that, generally, one should use DCM with slice timing.

Humans↗

PubMed2006

Direct intracranial, FMRI, and lesion evidence for the causal role of left inferotemporal cortex in reading.

Models of the "visual word form system" postulate that a left occipitotemporal region implements the automatic visual word recognition required for efficient reading. This theory was assessed in a patient in whom reading was explored with behavioral measures, fMRI, and intracranial local field potentials. Prior to surgery, when reading was normal, fMRI revealed a normal mosaic of ventral visual selectivity for words, faces, houses, and tools. Intracranial recordings demonstrated that the left occipitotemporal cortex responded with a short latency to conscious but also to subliminal words. Surgery removed a small portion of word-responsive occipitotemporal cortex overlapping with the word-specific fMRI activation. The patient developed a marked reading deficit, while recognition of other visual categories remained intact. Furthermore, in the post-surgery fMRI map of visual cortex, only word-specific activations disappeared. Altogether, these results provide direct evidence for the causal role of the left occipitotemporal cortex in the recognition of visual words.

Brain Mapping↗

PubMed2005

Perhaps correlational but not causal: no effect of dyslexic readers' magnocellular system on their eye movements during reading.

During reading, dyslexic readers exhibit more and longer fixations and a higher percentage of regressions than normal readers. It is still a matter of debate, whether these divergent eye movement patterns of dyslexic readers reflect an underlying problem in word processing or whether they are - as the proponents of the magnocellular deficit hypothesis claim - associated with deficient visual perception that is causal for dyslexia. To overcome problems in the empirical linkage of the magnocellular theory with reading, a string processing task is presented that poses similar demands on visual perception (in terms of letter identification) and oculomotor control as reading does. Two experiments revealed no differences in the eye movement patterns of dyslexic and control readers performing this task. Furthermore, no relationship between the functionality of the participants' magnocellular system assessed by the coherent motion task and string processing were found. The perceptual and oculomotor demands required during string processing were functionally equivalent to those during reading and the presented consonant strings had similar visual characteristics as reading material. Thus, a strong inference can be drawn: Dyslexic readers do not seem to have difficulties with the accurate perception of letters and the control of their eye movements during reading - their reading difficulties therefore cannot be explained in terms of oculomotor and visuo-perceptual problems.

Adolescent↗

PubMedDate not supplied

The development and factor structure of the Functional Assessment for multiple causaliTy (FACT).

Since behavioral intervention is linked to the findings of a functional assessment, the reality of behaviors maintained by multiple functions is a frequent and troublesome issue for clinicians and researchers. Current methods of functional assessment provide little help in the way of providing information useful for prioritizing intervention strategies for problematic behaviors maintained by multiple functions. In an effort to account for this deficiency, we developed the Functional Assessment for multiple CausaliTy (FACT). The FACT is an informant-based, forced-choice measure designed to identify the most prominent function associated with the occurrence of problem behaviors. In the present study, we describe the factor structure and internal consistency of the FACT. Suggestions are provided for future validation strategies.

Adolescent↗

PubMed2004

Role and limitations of epidemiology in establishing a causal association.

Cancer risk assessment is one of the most visible and controversial endeavors of epidemiology. Epidemiologic approaches are among the most influential of all disciplines that inform policy decisions to reduce cancer risk. The adoption of epidemiologic reasoning to define causal criteria beyond the realm of mechanistic concepts of cause-effect relationships in disease etiology has placed greater reliance on controlled observations of cancer risk as a function of putative exposures in populations. The advent of molecular epidemiology further expanded the field to allow more accurate exposure assessment, improved understanding of intermediate endpoints, and enhanced risk prediction by incorporating the knowledge on genetic susceptibility. We examine herein the role and limitations of epidemiology as a discipline concerned with the identification of carcinogens in the physical, chemical, and biological environment. We reviewed two examples of the application of epidemiologic approaches to aid in the discovery of the causative factors of two very important malignant diseases worldwide, stomach and cervical cancers. Both examples serve as paradigms of successful cooperation between epidemiologists and laboratory scientists in the pursuit of the understanding of cancer etiology.

Carcinogens↗

PubMed2006

A new gene for Tourette's syndrome: a window into causal mechanisms?

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by impairing motor-vocal tics. Locating genetic loci by associating the phenotype with DNA translocations, inversions, gain or losses, State et al. identified SLITRK1 as a candidate gene in an individual with GTS and inv(13) (q31.1; q33.1). This gene was also associated with abnormal axonal-dendritic development in embryonic mouse cells. Although SLITRK1 is not a major causal gene for GTS, it can shed light on our understanding of the gene-based neural correlates of this disease.

Animals↗

PubMed2026

Bidirectional causal relationships between plasma proteins, neuroimaging metrics and risk of Alzheimer's disease.

BACKGROUND: Changes in neuroimaging metrics are among the first detectable pathophysiological alterations in Alzheimer's disease (AD). Proteins are closely linked to fluctuations in neuroimaging metrics. Therefore, the analysis of the proteomic signature associated with neuroimaging metrics holds significant promise for uncovering therapeutic targets that contribute to AD. METHODS: GWAS data concerning the Brain Imaging Data Structure (BIDs). The AD cohort comprised a total of 401,661 individuals diagnosed with AD, alongside 10,520 control participants. For a bidirectional MR analysis involving neuroimaging metrics, proteomics, and AD, the methods utilized included inverse variance weighted (IVW), MR Egger, weighted median, weighted mode, and the Wald ratio approaches. RESULTS: We identified 12 neuroimaging metrics that demonstrate significant relevance to AD (thickness of the left total hemisphere, volume of the right thalamus, and et al.). These metrics are structural magnetic resonance imaging (MRI) biomarkers that remain stable throughout the entire course of AD, from the preclinical stage through mild cognitive impairment (MCI) to dementia. Additionally, we found a substantial number of 1633 proteins that also show a noteworthy causal relationship with AD. Functional enrichment analysis indicated that these proteins were predominantly focused within various pathways linked to AD, encompassing those involved in the synaptic vesicle cycle, synaptic membranes, neurotransmitter release, and the activity of GABA receptors. In addition, our research indicates that the significant relationships observed between the identified proteins and AD are influenced by neuroimaging metrics. Notably, we found that these neuroimaging metrics play a crucial role in mediating a substantial 67% of the inverse relationship that exists between PTPRC and the phenotypic characteristics associated with AD. CONCLUSIONS: This study successfully establishes a connection between proteomic and neuroimaging metrics, as well as the AD that influence them. By creating this relationship, the research offers important information that aids in comprehending the intricate mechanisms involved in AD.

Alzheimer Disease↗

PubMed2005

First isolation of Mycoplasma capricolum subsp. capricolum, one of the causal agents of caprine contagious agalactia, on the island of Lanzarote (Spain).

During an unusually long period of bad weather, several outbreaks of caprine contagious agalactia (CCA) were reported in a number of flocks on the island of Lanzarote (Canary Islands, Spain). Clinical and subclinical mastitis in lactating goats and some cases of arthritis and pneumonia in kids were observed in the affected flocks. Mycoplasma capricolum subsp. capricolum was isolated as the main causal agent of the outbreaks, associated with M. mycoides subsp. mycoides "large colony type" (Mmm LC) in two flocks. This is the first report of an isolation of M. capricolum subsp. capricolum on the island of Lanzarote. The finding is of epidemiological importance and could complicate plans to control the disease. The significance of this mycoplasma species in association with CCA must now be studied in detail.

Animals↗

PubMed2006

Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle.

Syndactyly in Holstein cattle is an autosomal recessive abnormality characterized by the fusion of the functional digits. This disorder has been previously mapped to the telomeric part of bovine chromosome 15. Here, we describe the fine-mapping of syndactyly in Holstein cattle to a 3.5-Mb critical interval using a comparative mapping approach and an extended pedigree generated by embryo transfer. We report genetic evidence for the exclusion of two genes previously suggested as candidates (EXT2 and ALX4) and describe the identification of a doublet mutation in complete linkage disequilibrium with syndactyly in one gene of the critical interval: LRP4. Finally, based on recent discoveries concerning the mouse mutants dan and mdig and a mouse knockout for Lrp4, we present solid evidence that the subsequent substitution in LRP4 exon 33 is a strong candidate causal mutation for syndactyly in Holstein cattle.

Amino Acid Sequence↗

PubMed2004

Formaldehyde and leukemia: an improbable causal relationship.

Formaldehyde has been the subject of numerous toxicological and epidemiological investigations for almost 25 years. Though most toxicology studies have focused on the effects of the chemical on the nasal tract and respiratory system, epidemiology investigations have been more extensive evaluating the association between formaldehyde and cancers not only of the nasal cavities, nasopharynx, and lung, but also of the brain, prostate, pancreas, and hematopoietic system. Recently, three studies have been published which report on the possible association between exposure to formaldehyde and an increased incidence of leukemia, specifically myeloid leukemia. The article summarizes the results of these three studies, evaluates the evidence for causality based on recognized epidemiologic criteria, and provides an assessment that the association between formaldehyde and the increased incidence of leukemia reported in these studies is not plausible.

Carcinogens, Environmental↗

PubMed1997

Is oxidative stress causally linked to unstable angina pectoris? A study in 100 CAD patients and matched controls.

OBJECTIVE: Unstable angina pectoris often leads to acute myocardial infarction. Since lipid peroxidation is thought to be causally related to chronic and acute events in atherosclerosis and coronary artery disease, we measured lipid peroxidation products and vitamin E in 100 patients with coronary artery disease and compared them to a matched control group. METHODS: 50 consecutive patients with stable angina pectoris (SAP) and 50 consecutive patients with unstable angina pectoris (UAP) were studied and compared to 100 clinically healthy individuals. In addition to conventional lipid and lipoprotein analysis, malondialdehydes were measured as thiobarbituric acid reactive substances (TBARS). Lipid hydroperoxides were assayed with the colorimetric methylene blue method. alpha-Tocopherol was quantitated by HPLC after extraction of serum with hexane-ethanol. In the patient group conjugated dienes were also measured. RESULTS: As expected, patients had significantly higher cholesterol, triglyceride LDL-C and Lp(a) values and lower HDL-C values than controls. When patients were divided into groups with SAP and UAP respectively, peroxides and TBARS were significantly higher in the latter group as compared to patients with SAP and to controls. Conjugated dienes were also significantly higher in patients with UAP as compared to patients with SAP. Total plasma alpha-tocopherol was comparable in all three groups, whereas the alpha-tocopherol content per LDL particle was lowest in patients with UAP, followed by patients with SAP and then controls. CONCLUSION: It is concluded that lipid peroxidation parameters are increased in patients with UAP and discriminate SAP from UAP patients.

Aged↗

PubMed1981

Post-pill amenorrhea: a causal study.

The distribution of distinguishable disorders in 102 patients with post-pill amenorrhea has been compared with that in 166 other patients with secondary amenorrhea, including 123 patients who had never used oral conception. In the post-pill group there was a 13% to 21% excess of patients who had a functional disorder without any weight loss or psychological disturbance to account for it and who typically were estrogenized and demonstrated intact feedback systems by their ovulatory response to clomiphene (the so-called cycle initiation defect). This excess might be explained by biased selection of oral contraception, but it seems wiser to assume a causal relationship, which amounts to a true risk of post-pill amenorrhea in less than 1 per 1000 users. No risk was revealed of primary ovarian failure, hyperprolactinemia, or pituitary tumor.

Adolescent↗

PubMed1985

Evidence that lysolecithin is an important causal agent of atherosclerosis.

We examine the hypothesis of Portman et al. (1970) that lysolecithin is a causal agent of atherosclerosis. Four lines of argument support this hypothesis. (1) Lysolecithin is present, taken up and can act. Large amounts of lysolecithin are formed in plasma concomitant with triglyceride transport and it is readily taken up by arteries and retained for some time. Lysolecithin in aortic intima increases several-fold early in the induction of atherosclerosis in animals. From model system studies it is plausible that physiological doses of lysolecithin have physiologically significant effects. (2) At least one plausible mechanism of action can be formulated: stimulation of smooth muscle cell division due to lysolecithin-increased Ca2+ uptake. (3) The hypothesis is consistent with, and rationalizes, many literature observations in that inferred lysolecithin levels or production rates are appropriately correlated with a variety of positive and negative risk factors to a degree highly unlikely by chance. We found no data contradicting the hypothesis and only one piece weakening it. (4) A mechanism is outlined showing that low density lipoprotein receptor deficiency, the severest known risk factor, should cause the delivery of very high lysolecithin doses to artery walls. We conclude that the evidence, although indirect, is strong enough to give direct tests a high priority.

Animals↗

PubMed1996

Cigarette smoking is not associated with hyperinsulinemia: evidence against a causal relationship between smoking and insulin resistance.

Previous reports of a relationship between cigarette smoking and hyperinsulinemia and insulin resistance provide an important possible mechanism by which smoking could be associated with the metabolic cardiovascular syndrome and hence with ischemic heart disease. However, few previous studies have been able to adjust for all the possible confounding factors related both to smoking and to insulin resistance. Therefore, we examined this association in a population-based cohort study of 1,122 individuals aged 40 to 65 years who underwent a 75-g oral glucose tolerance test with specific measurement of insulin, 32,33-split proinsulin, and intact proinsulin concentrations. Physical activity was quantified using the Paffenbarger questionnaire, and smoking status and alcohol consumption were determined using the Health and Lifestyle Survey questionnaire; 17.4% of the population were current smokers and 32.4% were ex-smokers. Current smoking was associated with reduced overall obesity as indicated by the body mass index (BMI) but an increase in central adiposity as measured by the waist to hip ratio (WHR). There were also significant associations between cigarette smoking and the pattern of alcohol intake and physical inactivity. In unadjusted analyses, current smoking was associated with lower fasting and 120-minute insulin and also 120-minute glucose compared with levels in nonsmokers. Adjustment for confounding by age and BMI reduced these differences, but they were increased by adjustment for central obesity. We conclude from this study that a causal relationship between cigarette smoking and insulin resistance is unlikely.

Cohort Studies↗

PubMed2005

[Electrophysiological signs of muscle channelopathies by causal mutation].

Nondystrophic myotonias and familial periodic paralyses are disorders of muscle excitability caused by mutations in genes coding for voltage-gated ion channels. Electromyographic (EMG) diagnosis of these diseases is based on needle searching of myotonic discharges and on several exercise tests, performed by surface recording of compound muscle action potential (CMAP) before and after voluntary contractions of various durations. After a short exercise test (10 seconds contraction), three abnormal changes of CMAP have been defined in muscle channelopathies: 1) appearance of repetitive discharges (post-exercise myotonic potentials, PEMP), 2) transient or long-lasting amplitude reduction, 3) long-lasting amplitude increase. These abnormalities become more marked or decline with exercise repetition (repeated brief exercise test), depending on the causal mutation. After long exercise test (5 minutes contraction), three other abnormalities of CMAP amplitude have been described: 1) immediate increase, 2) immediate decrease, 3) progressive or delayed decrease. Combining the responses to the different tests has disclosed five main EMG types of muscle channelopathies (I to V), that correlated with different pathophysiological mechanisms and with subgroups of mutations. This classification may guide molecular diagnosis in clinical practice.

Action Potentials↗