Biomedical subjects

Steve C R Williams

Publications and source records attributed to Steve C R Williams.

12 recordsLinked to original sources

PubMed2004

Imaging localised dynamic changes in the nucleus accumbens following nicotine withdrawal in rats.

This study utilises pharmacological functional magnetic resonance imaging (fMRI) to examine the neurobiological mechanisms through which nicotine produces dependence. Using an established regime to induce physical dependence to nicotine in rats (osmotic minipumps delivering 3.16 mg/kg/day nicotine for 7 days SC), animals were subsequently anaesthetised under urethane and positioned in a stereotaxic frame to allow collection of gradient echo whole brain images with a 4.7-T MRI spectrometer. Rats were initially scanned for 34 min (40 baseline image volumes, 1 volume per 51 s) then challenged with mecamylamine (1.0 mg/kg SC) or saline (1 ml/kg) and scanned for a further 68 min (80 image volumes). Mecamylamine precipitated highly significant positive changes in fMRI blood oxygen level dependent (BOLD) contrast that were predominantly localised to the NAc of nicotine-dependent rats. Saline-treated rats challenged with the same dose of mecamylamine exhibited similar but smaller increases in BOLD contrast although such changes were less defined around the NAc. Precipitated withdrawal also elicited statistically significant negative BOLD contrast changes in widespread cortical regions. These findings are consistent with previous neurochemical reports on decreases in dopamine in the NAc during nicotine withdrawal. This fMRI study further highlights the potential and power to image the neurobiological events during nicotine dependence.

Analysis of Variance↗

PubMed2004

Heterozygous PAX6 mutation, adult brain structure and fronto-striato-thalamic function in a human family.

Recent progress in developmental neurobiology and neuroimaging can be drawn together to provide new insight into the links between genetically specified processes of embryonic brain development and adult human brain structure and function. We used magnetic resonance imaging (MRI) to show that individuals with aniridia and deficits in executive and social cognition, due to heterozygous mutation of the neurodevelopmental control gene PAX6, have structural abnormalities of grey matter in anterior cingulate cortex, cerebellum and medial temporal lobe, as well as white matter deficits in corpus callosum. Functional MRI demonstrated reduced activation of fronto-striato-thalamic systems during performance of overt verbal fluency and nonsense sentence completion; the most consistent abnormality of verbal executive activation was located in the thalamus. These results provide the first evidence for brain functional differences in humans with PAX6 mutation that are compatible both with anatomical abnormalities in the same subjects and, more circumstantially, with the known roles of murine Pax6 in regional differentiation, axonal guidance and other aspects of early forebrain development. Highly conserved homeobox genes may be critical for normal ontogenesis of large-scale neurocognitive networks supporting phylogenetically advanced mental functions.

Adolescent↗

PubMed2004

In vivo monitoring of cellular transplants by magnetic resonance imaging and positron emission tomography.

Cellular loss is a common pathological observation in many disease conditions. Recent evidence that these cells can be replaced has generated huge excitement over possible clinical applications. The use of stem or progenitor cells, which can differentiate into site-appropriate phenotypes required to "repair" the damaged tissue, has already demonstrated potential in animal models, but many aspects of this novel treatment strategy require further elucidation. Most importantly, the monitoring of the safety of cellular transplants in patients remains a challenge. Traditional histological methods do not address the dynamic nature of transplant-induced recovery and highlight the necessity of in vivo imaging to probe the survival, migration and functional consequences of transplanted cells. This paper reviews how non-invasive imaging technology can be used to serially assess intact living organisms in order to visualise and monitor cellular transplants.

Animals↗

PubMed2003

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects.

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.

Adult↗

PubMed2003

Functional magnetic resonance imaging of verbal fluency and confrontation naming using compressed image acquisition to permit overt responses.

Verbal fluency and confrontation naming, two tests of word retrieval, are of great utility in the field of cognitive neuroscience. However, in the context of functional magnetic resonance imaging (fMRI), movement artefact has necessitated the use of covert paradigms, which has limited clinical application. We developed two overt fMRI paradigms that allowed for performance measurement and hence were appropriate for use with patient groups. The paradigms incorporated a blocked-design and compressed-acquisition methodology where cues were presented and responses made in a "silent" period allowing for performance measurement. The slow response pace was specifically designed for older and potentially cognitively impaired participants. Verbal fluency was associated with activation in the middle frontal gyrus (Brodmann areas 46 and 9), anterior cingulate gyrus and inferior frontal gyrus (area 44 and 45). Confrontation naming activated areas of the temporo-occipital cortices (areas 18, 19, and 37) and the inferior frontal gyrus. The two paradigms successfully activated regions involved in executive and word retrieval processes and overcame the potential artefacts resulting from overt speech during image acquisition, providing useful neuropsychological tools to investigate cognitive deficits in clinical populations.

Acoustic Stimulation↗

PubMed2003

Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics.

Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans.

Adrenergic Uptake Inhibitors↗

PubMed2002

Acoustic noise and functional magnetic resonance imaging: current strategies and future prospects.

Functional magnetic resonance imaging (fMRI) has become the method of choice for studying the neural correlates of cognitive tasks. Nevertheless, the scanner produces acoustic noise during the image acquisition process, which is a problem in the study of auditory pathway and language generally. The scanner acoustic noise not only produces activation in brain regions involved in auditory processing, but also interferes with the stimulus presentation. Several strategies can be used to address this problem, including modifications of hardware and software. Although reduction of the source of the acoustic noise would be ideal, substantial hardware modifications to the current base of installed MRI systems would be required. Therefore, the most common strategy employed to minimize the problem involves software modifications. In this work we consider three main types of acquisitions: compressed, partially silent, and silent. For each implementation, paradigms using block and event-related designs are assessed. We also provide new data, using a silent event-related (SER) design, which demonstrate higher blood oxygen level-dependent (BOLD) response to a simple auditory cue when compared to a conventional image acquisition.

Auditory Pathways↗

PubMed2002

Sex differences in functional brain activation during a lexical visual field task.

Functional MRI was used to investigate sex differences in brain activation during a paradigm similar to a lexical-decision task. Six males and 6 females performed two runs of the lexical visual field task (i.e., deciding which visual field a word compared with a pseudoword was presented to). A sex difference was noted behaviorally: The reaction time data showed males had a marginal right visual field advantage and women a left visual field advantage. Imaging results showed that men had a strongly left-lateralized pattern of activation, e.g., inferior frontal and fusiform gyrus, while women showed a more symmetrical pattern in language related areas with greater right-frontal and right-middle-temporal activation. The data show evidence of task-specific sex differences in the cerebral organization of language processing.

Adult↗

PubMed2002

Novelty-related activation within the medial temporal lobes.

Functional magnetic resonance imaging (fMRI) was used to examine whether (1) verbal associative encoding activates the medial temporal lobes (MTL) and related regions more than non-associative encoding, (2) verbal associative novelty is related to enhanced MTL activation, and (3) verbal item novelty is related to enhanced MTL activation and, if so, whether these activations are in different or overlapping sites. No increase in MTL activation was found during verbal associative encoding relative to non-associative encoding, although associative encoding was related to a relative increase in activation in the posterior cingulate cortex. In contrast, verbal associative novelty was found to activate the MTL and posterior cingulate cortex. Verbal item novelty did not significantly activate any brain region. The verbal associative novelty-related effect occurred despite subjects having little awareness of associative novelty. The verbal associative novelty-related activation in the MTL may be related either to unconscious novelty detection or to a priming effect at encoding. We argue that if the priming explanation is correct then this may account for our failure to observe an associative encoding MTL activation.

Adult↗

PubMed2002

Spatial normalization and averaging of diffusion tensor MRI data sets.

Diffusion tensor magnetic resonance imaging (DT-MRI) is unique in providing information about both the structural integrity and the orientation of white matter fibers in vivo and, through "tractography", revealing the trajectories of white matter tracts. DT-MRI is therefore a promising technique for detecting differences in white matter architecture between different subject populations. However, while studies involving analyses of group averages of scalar quantities derived from DT-MRI data have been performed, as yet there have been no similar studies involving the whole tensor. Here we present the first step towards realizing such a study, i.e., the spatial normalization of whole tensor data sets. The approach is illustrated by spatial normalization of 10 DT-MRI data sets to a standard anatomical template. Both qualitative and quantitative approaches are described for assessing the results of spatial normalization. Techniques are then described for combining the spatially normalized data sets according to three definitions of average, i.e., the mean, median, and mode of a distribution of tensors. The current absence of, and hence need for, appropriate statistical tests for comparison of results derived from group-averaged DT-MRI data sets is then discussed. Finally, the feasibility of performing tractography on the group-averaged DT-MRI data set is investigated and the possibility and implications of generating a generic map of brain connectivity from a group of subjects is considered.

Adult↗

PubMed2002

A functional magnetic resonance imaging study of overt letter verbal fluency using a clustered acquisition sequence: greater anterior cingulate activation with increased task demand.

Regional cerebral activation during a cognitive task can vary with task demand and task performance. In a functional magnetic resonance imaging study, we examined the effect of manipulating task demand on activation during verbal fluency by using "easy" and "hard" letters. A "clustered" image acquisition sequence allowed overt verbal responses to be made in the absence of scanner noise which facilitated "on-line" measurement of task performance. Eleven right-handed, healthy male volunteers participated. Twice as many errors were produced with hard as with easy letters (20.8 +/- 13.6 and 10.1 +/- 10.7% errors, respectively). For both conditions, the distribution of regional activation was comparable to that reported in studies of covert verbal fluency, but with greater engagement of subcortical areas. The hard condition was associated with greater dorsal anterior cingulate activation than the easy condition. This may reflect the greater demands of the former, particularly in terms of arousal responses with increased task difficulty and the monitoring of potential response errors.

Adult↗

PubMed2002

Functional magnetic resonance neuroimaging of drug dependence: naloxone-precipitated morphine withdrawal.

This study investigated the potential utility of fMRI as a neuroimaging technique to examine drug dependence using a robust animal model of drug withdrawal. Two groups of rats chronically pretreated with incremental doses of morphine sulfate (2, 7, 15, 30, 40, 50, 50, and 50 mg/kg--subcutaneous injection) were subjected to opioid precipitated withdrawal (using the opioid antagonist, naloxone) and subsequently behaviorally assessed or gradient-echo imaged under urethane anesthesia. Whole brain, group statistical parametric maps revealed statistically significant changes in signal intensity following administration of 1 mg/kg naloxone (corrected for multiple comparisons: P < 0.05, T > 5.03). Control groups within the fully crossed designs did not exhibit any statistically significant changes in behavior or signal intensity changes. Regional patterns of modulated activity include the retrosplenial, piriform, insular, entorhinal, cingulate, visual and auditory cortices, posterior fields of the hippocampus, and in particular the dentate gyrus. Such areas are consistent with biochemical correlates of morphine withdrawal and time profiles derived from our behavioral observations (P < 0.02). A notable lack of signal intensity changes in a number of subcortical areas suggests a possible confound associated with fMRI under anesthesia. This paper reports the first whole brain fMRI examination of an animal model of drug withdrawal, we believe there is considerable scope for extrapolation of our methods to a multitude of pharmacological applications-most notably in conjunction with other techniques in the development of potential therapeutic agents for drug dependence.

Animals↗