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S C Williams

Publications and source records attributed to S C Williams.

At least 163 records · Page 9Linked to original sources
PubMed1996

Functional magnetic resonance image analysis of a large-scale neurocognitive network.

Many "higher-order" mental functions are subserved by large-scale neurocognitive networks comprising several spatially distributed and functionally specialized brain regions. We here report statistical and graphical methods of functional magnetic resonance imaging data analysis which can be used to elucidate the functional relationships (i.e., connectivity and distance) between elements of a neurocognitive network in a single subject. Data were acquired from a normal right-handed volunteer during periodic performance of a task which demanded visual and semantic processing of words and subvocalization of a decision about the meaning of each word. Major regional foci of activation were identified (by sinusoidal regression modeling and spatiotemporal randomization tests) in left extrastriate cortex, angular gyrus, supramarginal gyrus, superior and middle temporal gyri, lateral premotor cortex, and Broca's area. Principal component (PC) analysis was initially undertaken by singular value decomposition (SVD) of the "raw" time series observed at 170 activated voxels. This revealed a large functional distance (negative connectivity) between visual processing systems and all other brain regions in the space of the first PC. SVD of a matrix of fitted time series, and a matrix of six sinusoidal regression parameters estimated at each activated voxel, were developed as less noisy (more informative) alternatives to SVD of the "raw" data. Canonical variate analysis of denoised data was then used to clarify functional relationships between the major regional foci. Visual input analysis systems (extrastriate cortex and angular gyrus) were colocalized in the space of the first canonical variate (CV) and significantly separated from all other brain regions. Semantic analysis systems (supramarginal and temporal gyri) were colocalized and significantly separated in the space of the second CV from the subvocal output system (Broca's area). These results are provisionally interpreted in terms of underlying hemodynamic events and cognitive psychological theory.

Adult↗
PubMed1996

Simulation of MRI cluster plots and application to neurological segmentation.

The advent of magnetic resonance imaging has provided new opportunities for volume measurement of tissues, with applications increasing dramatically in recent years. Cluster classification techniques have proved the most popular for volume measurement, yet little attention has been paid to how the choice of images for analysis affects the quality and ease of segmentation. To address this issue, we have developed a system to simulate MRI cluster plots using multicompartmental anthropomorphic software models of anatomy, and components for image contrast, signal-to-noise ratio, image nonuniformity, tissue heterogeneity, imager field strength, the partial volume effect, correlation between proton density, T1 and T2, and a variety of data preprocessing techniques. The effect of these components on tissue cluster size, shape, orientation, and separation is demonstrated. The simulation allows an informed choice of pulse sequence, acquisition parameters, and data preprocessing for cluster classification to be made as well as providing an aid to interpretation of acquired data cluster plots and a valuable educational tool. The system has been used to choose suitable images for neurological segmentation of grey matter, white matter, CSF, and multiple sclerosis lesions using spin-echo, inversion recovery, and gradient-echo pulse sequences. Constraints on image selection are discussed.

Brain↗
PubMed1996

Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome.

Two subjects with narcoleptic syndrome and three healthy volunteers underwent functional magnetic resonance imaging during the simultaneous presentation of periodic auditory and visual stimuli both before and after administration of amphetamine. The effect of amphetamine in control subjects was a small reduction in the extent of sensory-induced activation. In the narcoleptic subjects, amphetamine led to an increase in the extent of induced activation within primary and association sensory cortex.

Acoustic Stimulation↗
PubMed1996

Magnetic resonance spectroscopy in psychiatry: basic principles and applications.

In vivo magnetic resonance spectroscopy (MRS) is a safe and non-invasive tool which can be used to study aspects of brain chemistry and metabolism. Although a relatively recent technique in the field of psychiatric research, it has already been used in the study of anxiety and affective disorders, dementia, schizophrenia, and neurodevelopmental disorders. This review outlines the basic principles of MRS and summarises the research findings in psychiatric disorders. Although mostly preliminary, these findings highlight the capacity of MRS to detect subtle neurobiological abnormalities in mental disorders. They also suggest a future role for MRS in differential diagnosis and monitoring illness progression. Initial MRS studies have also focused on the metabolic effects of psychiatric treatments and could provide information about their relationship to clinical variables.

Brain Chemistry↗
PubMed1996

Neurotoxic effects of gadopentetate dimeglumine: behavioral disturbance and morphology after intracerebroventricular injection in rats.

PURPOSE: To determine the neurotoxic potential of gadopentetate dimeglumine in an animal model that allowed the agent to avoid the blood-brain barrier. Gadopentetate dimeglumine is known to produce functional changes when injected into the cerebrospinal fluid, and we hypothesized that such changes might be associated with morphologic damage. METHODS: Conscious rats, surgically prepared with a lateral ventricular cannula, were given a slow injection of gadopentetate dimeglumine into the lateral ventricle, and behavioral and neuropathologic changes were noted. RESULTS: Gadopentetate dimeglumine produced signs of acute neurotoxicity over several hours (stereotyped movements and myoclonus), medium-term signs over several days (ataxia and tremor), and neuropathologic changes over 24 hours, with reactive changes persisting for 42 days. All of the above were dose-dependent over the range of 2.5 to 15 mumol/g brain. The lowest dose producing morphologic or behavioral changes was 5 mu mol/g brain. Iso-osmotic, isovolumetric injections of sucrose produced no such effects. Focal lesions occurred within the thalamus, brain stem, and spinal cord, with necrosis of glia, loss of myelin, and, usually, sparing of neurons and nerve fibers. Persisting ataxia was always associated with brain stem or spinal cord lesions. CONCLUSION: Intraventricular administration of contrast medium allows toxicity to be evaluated in areas such as the spinal cord that are not accessible by osmotic opening. While it is unlikely that these toxic effects would be seen at the doses used for clinical imaging by the intravenous route, gadopentetate dimeglumine clearly has some neurotoxic and neuropathologic potential. Although the acute excitation could be attributed to a transiently high local concentration of the agent at the injection site, the lesions were widely distributed through the brain and spinal cord and may reflect a region-specific neurotoxic action, possibly related to central pontine myelinolysis.

Animals↗
PubMed1995

Neural correlates of working memory in a visual letter monitoring task: an fMRI study.

Complex mental operations rely on the coordinated activity of widely distributed brain regions constituting neurocognitive networks. Using multislice echoplanar functional magnetic resonance imaging (fMRI) we have contrasted regional brain activity during a control and an experimental condition which differed with respect to the demands placed on verbal working memory. Subjects were seven right-handed healthy male volunteers. Analysis of group and individual data revealed activation in the anterior and posterior parasagittal cortex in all subjects, left parietal cortex (six subjects) and left dorsolateral prefontal cortex (five subjects). These results suggest that verbal working memory is subserved by a neurocognitive network comprising cortical regions involved in attention, executive function and short term mnemonic processes.

Adult↗
PubMed1995

Mouse chromosomal location of the CCAAT/enhancer binding proteins C/EBP beta (Cebpb), C/EBP delta (Cebpd), and CRP1 (Cebpe).

There are four known members of the C/EBP family of basic region-leucine zipper transcription factors: Cebpa, Cebpb, Cebpd, and Cebpe. Cebpa has previously been mapped to mouse chromosome 7. Here, we show that Cebpb maps to mouse chromosome 2, Cebpd to chromosome 16, and Cebpe to chromosome 14. The assignment of Cebpd to chromosome 16 identifies a new region of homology between mouse chromosome 16 and human chromosome 8.

Animals↗
PubMed1995

CRP2 (C/EBP beta) contains a bipartite regulatory domain that controls transcriptional activation, DNA binding and cell specificity.

Two members of the C/EBP family of basic region-leucine zipper proteins enriched in the liver, C/EBP (C/EBP alpha) and CRP2 (C/EBP beta), were previously shown to transactivate the albumin promoter in a cell type-dependent manner. These proteins function efficiently in HepG2 hepatoma cells, but inefficiently in HeLa (epithelial) and L (fibroblastic) cells. Here we have investigated the mechanism for cell-specific control of CRP2 activity. We show that CRP2 contains a negative regulatory region composed of two elements, RD1 and RD2. Deletions of RD2 relieve the inhibition of CRP2 activity in L cells, but do not affect CRP2 function in HepG2 cells. These deletions also increase the DNA binding activity of CRP2 approximately 3-fold, suggesting that RD2-mediated repression of DNA binding activity is responsible for CRP2 inhibition in L cells. The adjacent RD1 element functions independently of RD2 and modulates the CRP2 activation domain, which we show to be composed of three subdomains that are conserved within the C/EBP protein family. RD1 does not affect cell type specificity, but inhibits the transactivation potential of GAL4-CRP2 hybrid proteins by 50-fold. These findings suggest that CRP2 assumes a tightly folded conformation in which the DNA binding and activation domains are masked by interactions with the regulatory domain and that to function efficiently in HepG2 cells the protein must undergo an activation step. We propose that relief of inhibition conferred by the regulatory domains also accounts for CRP2 activation in response to extracellular signals.

Amino Acid Sequence↗
PubMed1995

Shunt treatment at two postnatal ages in hydrocephalic H-Tx rats quantified using MR imaging.

The H-Tx rat has inherited hydrocephalus with an onset in late gestation. Ventriculosubcutaneous shunts were placed in a group of hydrocephalic pups at 3-6 days after birth and in another group at 8-12 days after birth. Multislice proton magnetic resonance (MR) images were taken of shunt-treated pups at 7, 14, or 21 days and of age-matched control and untreated hydrocephalic rats and were subjected to quantitative analysis. Some rats were also imaged before surgery. The volume of the ventricles of untreated hydrocephalic pups increased linearly with age at a rate of 52 microliters/day. The ventricles of shunted pups were reduced from the preshunt condition and were around 20% of age-matched hydrocephalic rats. There was no significant difference in the post-shunt volume between early and late shunt groups. The cortical mantle thickness in both groups of shunt-treated rats was significantly thicker than in untreated pups and close to that of control rats. It is concluded that shunt treatment at both ages reversed the hydrocephalus as measured from MR images, although other evidence from fixed brains suggests that normal morphology may not be achieved at the cellular level even for early shunts.

Aging↗
PubMed1995

MRI assessment of the blood-brain barrier in a hamster model of scrapie.

Magnetic resonance (MR) imaging in combination with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement was used to investigate the integrity of the blood-brain barrier in a hamster model of scrapie (263K) during the clinical phase of the disease. The post Gd-DTPA images of the infected hamster brain showed marked enhancement, which was not present in control animals. These results suggest that blood-brain barrier function is disrupted in the clinically-affected animal.

Animals↗
PubMed1995

Analysis of fMRI time-series revisited.

This paper presents a general approach to the analysis of functional MRI time-series from one or more subjects. The approach is predicated on an extension of the general linear model that allows for correlations between error terms due to physiological noise or correlations that ensue after temporal smoothing. This extension uses the effective degrees of freedom associated with the error term. The effective degrees of freedom are a simple function of the number of scans and the temporal auto correlation function. A specific form for the latter can be assumed if the data are smoothed, in time, to accentuate hemodynamic responses with a neural basis. This assumption leads to an expedient implementation of a flexible statistical framework. The importance of this small extension is that, in contradistinction to our previous approach, any parametric statistical analysis can be implemented. We demonstrate this point using a multiple regression analysis that tests for effects of interest (activations due to word generation), while taking explicit account of some obvious confounds.

Arousal↗
PubMed1995

Haemodynamic and metabolic effects in diabetic ketoacidosis in rats of treatment with sodium bicarbonate or a mixture of sodium bicarbonate and sodium carbonate.

To examine factors determining the haemodynamic and metabolic responses to treatment of diabetic ketoacidosis with alkali, groups of anaesthetised and ventilated rats with either diabetic ketoacidosis (mean arterial pH 6.86-6.96, mean arterial blood pressure 63-67 mm Hg) or hypovolaemic shock due to blood withdrawal (mean pHa 7.25-7.27, mean arterial blood pressure 36-41 mm Hg) were treated with sodium chloride ('saline'), sodium bicarbonate or 'Carbicarb' (equimolar bicarbonate plus carbonate). In the diabetic ketoacidosis series, treatment with either alkali resulted in deterioration of mean arterial blood pressure and substantial elevation of blood lactate, despite a significant rise in myocardial intracellular pH determined by 31P-magnetic resonance spectroscopy. These effects were accompanied by falling trends in the ratios of myocardial phosphocreatine and ATP to inorganic phosphate. Erythrocyte 2,3-bisphosphoglycerate was virtually absent in animals with diabetic ketoacidosis of this severity and duration. In contrast, in shock due to blood withdrawal, infusion of saline or either alkali was accompanied by a transient elevation of mean arterial blood pressure and no significant change in the already elevated blood lactate; erythrocyte 2,3-bisphosphoglycerate was normal in these animals. The effect of alkalinization in rats with severe diabetic ketoacidosis was consistent with myocardial hypoxia, due to the combination of very low initial erythrocyte 2,3-bisphosphoglycerate, alkali-exacerbated left shift of the haemoglobin-oxygen dissociation curve and artificial ventilation. No evidence was found for any beneficial effect of 'Carbicarb' in either series of animals; 'Carbicarb' and sodium bicarbonate could be deleterious in metabolic acidosis of more than short duration.

3-Hydroxybutyric Acid↗
PubMed1995

Activation of area V5 by visual perception of motion demonstrated with echoplanar MR imaging.

Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically "run" and "frozen" during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.

Echo-Planar Imaging↗
PubMed1995

Organization of the human immunoglobulin lambda light-chain locus on chromosome 22q11.2.

The maps of the human immunoglobulin heavy-chain and kappa light-chain loci have recently been completed. We have now completed a map of the human lambda locus (IGL) located on chromosome 22q11.2. We mapped 52 V lambda genes from 10 V lambda families and 7 J lambda and C lambda genes on a 1140 kb contig constructed from eight YACs and 129 cosmid clones. The V lambda genes are arranged within 800 kb. Genes of the different V lambda families are organized in three clusters, V lambda II and III families (cluster A); V lambda I, V, VII and IX families (cluster B); V lambda IV, VI, VIII and X families (cluster C), in contrast to the dispersed organization of the different VH and V kappa families within the human VH and V kappa loci. We note that the most frequently used V lambda families (V lambda II and III) are proximal to the J lambda and C lambda genes. The VpreB gene, encoding part of the surrogate light chain, the GGT2 gene and the BCRL4 pseudogene were also mapped within the lambda locus.

Base Sequence↗