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S C Williams

Publications and source records attributed to S C Williams.

At least 37 records · Page 2Linked to original sources

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI.

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

Adolescent↗

Further characterisation of a thromboembolic model of stroke in the rat.

We have used magnetic resonance imaging (MRI) techniques to characterise a rat model of thromboembolic stroke. The consequences of acute perfusion deficit associated with a middle cerebral artery occlusion (MCAo) by a newly formed thrombus was mapped by interrogation of the tissue oxygenation status using gradient echo methods and production of T2* maps. Final infarct size was subsequently assessed at 24-h post-ischaemia by histology with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Animals displayed an infarct volume of 178.7+/-84.2 mm(3) (mean+/-S.D.) with a large coefficient of variation (47%) and range of values (85.6--265.5 mm(3)). This variability provided us with an opportunity to assess the relationships between early imaging observations and eventual infarct size. For a single cerebral slice, at the centre of the MCA territory, a relationship between the area of reduced T2* at 1 and 2 h post MCAo correlated highly with final lesion area (Spearman rank correlation, r=0.98, P<0.01, n=9). Lesion volumes in the thromboembolic MCAo model were compared with a 120-min occlusion, 22-h reperfusion protocol using an intraluminal thread MCAo approach. For the thromboembolic model, the total lesion volume was found to be smaller (178.7+/-84.2 vs. 243.3+/-50.1 mm(3), mean+/-S.D., Student's t-test P=0.046) and showed a greater variability (coefficient of variations: 47% vs. 21%). These data underline the relative variability of this embolic model and provide important preliminary information regarding the value of early changes in T2* in predicting eventual infarct size.

Animals↗

Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo.

Endocardial cells are thought to contribute at least in part to the formation of the endocardial cushion mesenchyme. Here, we created Tie2-Cre transgenic mice, in which expression of Cre recombinase is driven by an endothelial-specific promoter/enhancer. To analyze the lineage of Cre expressing cells, we used CAG-CAT-Z transgenic mice, in which expression of lacZ is activated only after Cre-mediated recombination. We detected pan-endothelial expression of the Cre transgene in Tie2-Cre;CAG-CAT-Z double-transgenic mice. This expression pattern is almost identical to Tie2-lacZ transgenic mice. However, interestingly, we observed strong and uniform lacZ expression in mesenchymal cells of the atrioventricular canal of Tie2-Cre;CAG-CAT-Z double-transgenic mice. We also detected lacZ expression in the mesenchymal cells in part of the proximal cardiac outflow tract, but not in the mesenchymal cells of the distal outflow tract and branchial arch arteries. LacZ staining in Tie2-Cre;CAG-CAT-Z embryos is consistent with endocardial-mesenchymal transformation in the atrioventricular canal and outflow tract regions. Our observations are consistent with previously reported results from Cx43-lacZ, Wnt1-Cre;R26R, and Pax3-Cre;R26R transgenic mice, in which lacZ expression in the cardiac outflow tract identified contributions in part from the cardiac neural crest. Tie2-Cre transgenic mice are a new genetic tool for the analyses of endothelial cell-lineage and endothelial cell-specific gene targeting.

Animals↗

Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study.

BACKGROUND: Formal thought disorder (FTD) is a core symptom of schizophrenia, but its pathophysiology is little understood. We examined the neural correlates of FTD using functional magnetic resonance imaging. METHODS: Blood oxygenation level-dependent contrast was measured using functional magnetic resonance imaging while 6 patients with schizophrenia and 6 control subjects spoke about 7 Rorschach inkblots for 3 minutes each. In patients, varying degrees of thought-disordered speech were elicited during each "run." In a within-subject design, the severity of positive FTD was correlated with the level of blood oxygenation level-dependent contrast in the 2 runs that showed the highest variance of FTD in each patient. RESULTS: The severity of positive FTD in patients was negatively correlated (P<.001) with signal changes in the left superior and middle temporal gyri. Positive correlations were evident in the cerebellar vermis, the right caudate body, and the precentral gyrus. CONCLUSIONS: The severity of positive FTD was inversely correlated with the level of activity in the Wernicke area, a region implicated in the production of coherent speech. Reduced activity in this area might contribute to the articulation of incoherent speech. Because of the small sample size, these findings should be considered preliminary.

Adult↗

Time courses of left and right amygdalar responses to fearful facial expressions.

Despite the many studies highlighting the role of the amygdala in fear perception, few have examined differences between right and left amygdalar responses. Using functional magnetic resonance imaging (fMRI), we examined neural responses in three groups of healthy volunteers (n = 18) to alternating blocks of fearful and neutral faces. Initial observation of extracted time series of both amygdalae to these stimuli indicated more rapid decreases of right than left amygdalar responses to fearful faces, and increasing magnitudes of right amygdalar responses to neutral faces with time. We compared right and left responses statistically by modeling each time series with (1) a stationary fit model (assuming a constant magnitude of amygdalar response to consecutive blocks of fearful faces) and (2) an adaptive model (no assumptions). Areas of significant sustained nonstationarity (time series points with significantly greater adaptive than stationary model fits) were demonstrated for both amygdalae. There was more significant nonstationarity of right than left amygdalar responses to neutral, and left than right amygdalar responses to fearful faces. These findings indicate significant variability over time of both right and left amygdalar responses to fearful and neutral facial expressions and are the first demonstration of specific differences in time courses of right and left amygdalar responses to these stimuli.

Adult↗

Diffusion-weighted magnetic resonance imaging detects early neuropathology following four vessel occlusion ischemia in the rat.

Early neuropathology following a prolonged duration of four-vessel occlusion (4 VO) ischemia in the rat was charted using magnetic resonance imaging (MRI). Animals received either 30 minutes of 4 VO (N = 6) or sham operation (N = 6) prior to in vivo assessment. Proton density and T(2) and combined T(2)/diffusion-weighted (T(2)/DW) MRI were performed at 6, 24, and 72 hours postocclusion. T(2)/DW imaging was the most effective sequence for delineating between injured and intact tissues, indicating neuropathology in the dorsolateral striatum at 24 hours and in the CA1/CA2 subfields of the hippocampus at 72 hours following ischemia. Apparent diffusion coefficient values were significantly reduced in the striatum (P = 0.03) and hippocampus (P = 0.005) at 24 and 72 hours, respectively. This is the first report, to our knowledge, of T(2)/DW imaging detecting lesions following 4 VO in accord with the known temporal evolution of ischemic brain damage.

Animals↗

Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks.

Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.

Adult↗

Delaying the initiation of progesterone supplementation results in decreased pregnancy rates after in vitro fertilization: a randomized, prospective study.

OBJECTIVE: To compare IVF outcome between two protocols for luteal phase supplementation, one beginning on day 3 after oocyte retrieval and the other beginning on day 6 after retrieval. DESIGN: Prospective, randomized study. SETTING: University-based assisted reproductive technology center. PATIENT(S): One hundred twenty-six consecutive patients undergoing IVF between January and July 2000. INTERVENTION(S): Patients were randomized to begin luteal phase support using vaginal progesterone beginning either on day 3 after oocyte retrieval or on day 6 after oocyte retrieval. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates and implantation rates. RESULT(S): All patients randomized underwent transfer. There were no differences in age, oocytes retrieved, or embryos transferred between the two groups. Those patients receiving luteal phase support with progesterone beginning on day 6 after retrieval had a significantly lower clinical pregnancy rate per transfer compared with those beginning support on day 3 after retrieval (44.8% vs. 61.0%, respectively). This difference in pregnancy rates was greater in those patients undergoing a luteal gonadotropin releasing hormone (GnRH) agonist down-regulation protocol (47.5% vs. 71.4%, day 6 vs. day 3, respectively). Beginning support on day 6 also significantly decreased implantation rates in the GnRH agonist group (21.0% vs. 34.0%, day 6 vs. day 3, respectively). CONCLUSION(S): Pregnancy rates are significantly decreased by initiating luteal-phase progesterone supplementation on day 6 after oocyte retrieval during in vitro fertilization cycles.

Adult↗

Engagement of right temporal cortex during processing of linguistic context.

Language processing involves the interplay of areas in both cerebral hemispheres. Whereas the left temporal lobe is necessary for most language tasks, the right hemisphere seems to be additionally activated during processing of paragraphs and metaphors. We studied the neural correlates of word generation and selection in a sentence context, using functional magnetic resonance imaging (fMRI). Cerebral activation was measured while seven healthy, right handed volunteers read and completed sentence stems, with relatively low Cloze frequency, out loud. During a GENERATION condition, subjects were required to generate a word which completed a sentence stem appropriately. During a DECISION condition, subjects selected and articulated one of two presented terminal words. A READING condition in which subjects read an appropriate completion aloud, served as baseline. When GENERATION was compared to READING or DECISION, the left middle frontal, anterior cingulate, precuneus and right lateral temporal cortex were activated. During DECISION relative to READING, the left inferior frontal and middle/superior temporal cortex bilaterally were activated. The prominent engagement of the right lateral temporal cortex during the GENERATION conditions may reflect the processing of linguistic context, and particularly the activation of multiple meanings in the course of producing an appropriate completion.

Adult↗

Brain activation during automatic and controlled processing of semantic relations: a priming experiment using lexical-decision.

Semantic relations may be studied using the experimental technique known as semantic priming, in which a word 'primes' the processing of a related target (e.g. lion-tiger), following a short delay. Priming may be automatic or, with longer delays, under more controlled processing. This study used functional magnetic resonance imaging (fMRI) to examine the cerebral activation during two lexical-decision semantic priming experiments, with a short and long delay, representing automatic and controlled processing, respectively. A further two un-primed lexical-decision tasks were performed to distinguish cerebral activation specific to semantic priming itself from those utilised during lexical-decision processes. Distinct regions of anterior cingulate cortex (ACC) were critical to automatic and controlled semantic priming, whilst the putamen and hippocampal complex responded differently to unrelated and semantically related prime-target pairs. Lexical-decision alone revealed activation in posterior temporal cortex especially on the left, in agreement with previous neuroimaging studies. The results provide a plausible neural substrate for common semantic relations independent of task demands and further emphasise the regional functional specialisation of the ACC.

Adult↗

Differential frontal activation in schizophrenia and bipolar illness during verbal fluency.

INTRODUCTION: The precise nature of frontal lobe dysfunction in schizophrenia remains unclear. We have previously demonstrated, using fMRI, a task-specific attenuation of frontal activation in schizophrenic patients. By using an identical methodology in matched bipolar subjects, we sought to determine whether this finding is specific to schizophrenia or a correlate of psychosis in general. METHOD: Five dextral male bipolar patients and matching groups of schizophrenic subjects and controls were studied using fMRI. Echoplanar images were acquired while subjects performed two paced tasks: covert verbal fluency and a semantic decision task. Generic brain activation maps were constructed from individual images by sinusoidal regression analysis. Between-group differences in the mean power of experimental response were identified on a voxel-wise basis by an analysis of variance (ANOVA). RESULTS: The bipolar patients showed extensive prefrontal activation during verbal fluency which was significantly greater than in controls. There was no difference in the prefrontal BOLD response during the semantic decision task. CONCLUSIONS: These data indicate that bipolar patients show a strikingly different pattern of frontal responses compared to those with schizophrenia and provide further evidence that abnormal frontal activation in psychotic disorders is more apparent during verbal fluency than semantic decision.

Adult↗

A functional study of auditory verbal imagery.

BACKGROUND: We used functional MRI to examine the functional anatomy of inner speech and different forms of auditory verbal imagery (imagining speech) in normal volunteers. We hypothesized that generating inner speech and auditory verbal imagery would be associated with left inferior frontal activation, and that generating auditory verbal imagery would involve additional activation in the lateral temporal cortices. METHODS: Subjects were scanned, while performing inner speech and auditory verbal imagery tasks, using a 1.5 Tesla magnet. RESULTS: The generation of inner speech was associated with activation in the left inferior frontal/insula region, the left temporo-parietal cortex, right cerebellum and the supplementary motor area. Auditory verbal imagery in general, as indexed by the three imagery tasks combined, was associated with activation in the areas engaged during the inner speech task, plus the left precentral and superior temporal gyri (STG), and the right homologues of all these areas. CONCLUSIONS: These results are consistent with the use of the 'articulatory loop' during both inner speech and auditory verbal imagery, and the greater engagement of verbal self-monitoring during auditory verbal imagery.

Adult↗

Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis.

BACKGROUND: Neuroimaging studies of tuberous sclerosis complex (TSC) have previously focused mainly on tubers or subependymal nodules. Subtle pathological changes in the structure of the brain have not been studied in detail. Computationally intensive techniques for reliable morphometry of brain structure are useful in disorders like TSC, where there is little prior data to guide selection of regions of interest. METHODS: Dual-echo, fast spin-echo MRI data were acquired from 10 TSC patients of normal intelligence and eight age-matched controls. Between-group differences in grey matter, white matter and cerebrospinal fluid were estimated at each intracerebral voxel after registration of these images in standard space; a permutation test based on spatial statistics was used for inference. CSF-attenuated FLAIR images were acquired for neuroradiological rating of tuber number. RESULTS: Significant deficits were found in patients, relative to comparison subjects, of grey matter volume bilaterally in the medial temporal lobes, posterior cingulate gyrus, thalamus and basal ganglia, and unilaterally in right fronto-parietal cortex (patients -20%). We also found significant and approximately symmetrical deficits of central white matter involving the longitudinal fasciculi and other major intrahemispheric tracts (patients -21%); and a bilateral cerebellar region of relative white matter excess (patients +28%). Within the patient group, grey matter volume in limbic and subcortical regions of deficit was negatively correlated with tuber count. CONCLUSIONS: Neuropathological changes associated with TSC may be more extensive than hitherto suspected, involving radiologically normal parenchymal structures as well as tubers, although these two aspects of the disorder may be correlated.

Adult↗

Distributed grey and white matter deficits in hyperkinetic disorder: MRI evidence for anatomical abnormality in an attentional network.

BACKGROUND: Previous neuroimaging studies of children with attention deficit hyperactivity disorder (ADHD) have demonstrated anatomic and functional abnormalities predominantly in frontal and striatal grey matter. Here we report the use of novel image analysis methods, which do not require prior selection of regions of interest, to characterize distributed morphological deficits of both grey and white matter associated with ADHD. METHODS: Eighteen children with a refined phenotype of ADHD, who also met ICD-10 criteria for hyperkinetic disorder (mean age 10.4 years), and 16 normal children (mean age 10.3 years) were compared using magnetic resonance imaging. The groups were matched for handedness, sex, height, weight and head circumference. Morphological differences between groups were estimated by fitting a linear model at each voxel in standard space, applying a threshold to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels, and testing cluster 'mass', or the sum of suprathreshold voxel statistics in each 2D cluster, by repeated random resampling of the data. RESULTS: The hyperkinetic children had significant grey matter deficits in right superior frontal gyrus (Brodmann area (BA) 8/9), right posterior cingulate gyrus (BA 30) and the basal ganglia bilaterally (especially right globus pallidus and putamen). They also demonstrated significant central white matter deficits in the left hemisphere anterior to the pyramidal tracts and superior to the basal ganglia. CONCLUSIONS: This pattern of spatially distributed grey matter deficit in the right hemisphere is compatible with the hypothesis that ADHD is associated with disruption of a large scale neurocognitive network for attention. The left hemispheric white matter deficits may be due to dysmyelination.

Adolescent↗

Functional magnetic resonance imaging of odor identification: the effect of aging.

BACKGROUND: Sense of smell declines with age and impairment in olfaction has been observed in some neurodegenerative disorders such as Alzheimer's disease. Functional neuroimaging techniques enable researchers to observe brain regions activated by olfactory stimuli. METHODS: We gave three mainly olfactory-mediated odors (limonene, methylsalicylate, and eugenol) to six young and six elderly subjects and observed the areas activated by using blood oxygen level dependent contrast functional magnetic resonance imaging. RESULTS: The group mapping of young subjects showed extensive activation in the orbitofrontal cortex, commonly believed to be the olfactory cortex, some limbic areas (the hippocampus and the thalamus), regions involved with gustatory sensation (the anterior insula and the inferior postcentral gyrus), superior and inferior temporal gyri, and cerebellum. In the elderly group, only the left inferior temporal gyrus and the primary visual cortex reached accepted significance levels. CONCLUSIONS: We have therefore confirmed previous reports of brain regions involved in olfactory processing in young volunteers and demonstrated decreased activation in elderly volunteers.

Adult↗

Vaginal misoprostol enhances intrauterine insemination.

This study examined whether the prostaglandin E(1) analogue misoprostol (400 microgram), when placed vaginally at the time of intrauterine insemination (IUI) improves pregnancy rates. A prospective, placebo-controlled, randomized and double-blind study involving 274 women in 494 IUI cycles resulted in a total of 64 pregnancies (13% per cycle). Misoprostol cycles totalled 253, with 43 pregnancies (17% per cycle), whereas placebo cycles totalled 241, with 21 pregnancies (9% per cycle). The cumulative pregnancy rate with misoprostol treatment was significantly greater than with placebo (P = 0.004, Cox proportional hazards regression). The benefit of misoprostol was seen in clomiphene cycles (14 versus 4%, P = 0.006), and was indicated in FSH cycles (33 versus 15%, borderline significance) and natural cycles (15.6 versus 7.7%, not significant), but was not seen in clomiphene/FSH cycles (18.2 versus 23.5%, not significant). Misoprostol treatment did not increase pain score on the day of IUI (1.1 versus 1.4) and at 1 day post IUI (0.6 versus 0.8). Complications were rare in both groups [six (2%) subject cycles in the misoprostol cycles compared with two (1%) in the placebo group]. It is concluded that the use of vaginal misoprostol may improve the chance for pregnancy in women having IUI in a wide variety of cycle types.

Administration, Intravaginal↗