Biomedical subjects

Iain D Wilkinson

Publications and source records attributed to Iain D Wilkinson.

At least 19 recordsLinked to original sources

PubMed2006

Increased cerebellar vermis white-matter volume in men with schizophrenia.

We aimed to investigate cerebellar structural abnormalities and their functional significance in patients with schizophrenia. Forty right-handed men with schizophrenia and 40 sex, age and handedness matched controls underwent a volumetric magnetic resonance scan with 1 mm3 isotropic spatial resolution. Cerebellar grey- and white-matter volumes were analysed using voxel-based morphometry. Patients with schizophrenia completed a battery of neuropsychological tests assessing sustained attention (continuous performance test), memory (Hopkins memory test) and executive function (verbal fluency and Wisconsin card sorting tests). Patients with schizophrenia exhibited significantly increased cerebellar vermis white-matter volume compared with controls. By contrast, total cerebellar volume, and grey- and white-matter volumes of cerebellar hemispheres were not significantly different between groups. Increased vermis white-matter volume in patients was associated with poor verbal fluency performance. We concluded that increased white-matter in the cerebellar vermis, possibly suggesting anomalous connectivity, may be associated with verbal executive dysfunction in men with chronic schizophrenia.

Adult↗

PubMed2006

MR imaging of recent non-traumatic intracranial hemorrhage: early experience at 3 T.

Magnetic resonance imaging (MRI) using 3.0 T scanners in the clinical environment is in its infancy and is only available at a limited number of sites worldwide. There is great interest amongst radiologists about the perceived benefits of clinical imaging at 3.0 T; however, it remains to be seen whether the theoretical advantages will bring real gains. MRI in patients with non-traumatic intracranial hemorrhage (ICH) is difficult, yet, these patients benefit from non-invasive angiography. Conventional catheter angiography (CCA) remains the reference standard for excluding/confirming the presence of intracranial vascular abnormalities, but MR angiography at 3.0 T may offer opportunities for significant changes in patient management. We present our experiences of using 3.0 T MR angiography in 27 patients with acute or early subacute ICH.

Adult↗

PubMed2006

Effects of creatine supplementation on cerebral white matter in competitive sportsmen.

OBJECTIVES: To determine the neurobiochemical sequelae of oral creatine monohydrate supplementation in active athletes. DESIGN/PARTICIPANTS: Eighteen sportsmen underwent single-voxel proton magnetic resonance spectroscopy of the deep frontal cerebral white matter before and after 5 days of oral ingestion: 12 of 18 swallowed 4 x 5 g creatine monohydrate per day, and the remaining swallowed a placebo. MAIN OUTCOME MEASUREMENTS: Creatine, choline, and N-acetyl spectral resonances were evaluated at both long (135 ms) and short (20 ms) echo times. RESULTS: A mixed-design factorial ANOVA demonstrated no interaction over time in any of the measures (P at least 0.081). CONCLUSIONS: The results suggest that, for the given dosage regimen, ingested creatine augmentation does not alter the magnetic resonance visible creatine pool in the deep frontal cerebral white matter of young active sportsmen.

Administration, Oral↗

PubMed2006

Influence of human serum albumin on longitudinal and transverse relaxation rates (r1 and r2) of magnetic resonance contrast agents.

OBJECTIVES: Exogenous magnetic resonance (MR) contrast media (CM) are used to improve detection and delineation of physiological and pathologic structures. Temporary binding between CM and proteins such as human serum albumin (HSA) may alter the relaxation-enhancing properties of specific contrast agents. In this study, the presence and strength of HSA interaction with different CM was investigated. MATERIAL AND METHODS: Three contrast agents were chosen: Gd-DTPA, Gd-BT-DO3A, and Gd-BOPTA, each of which is known to have a different protein interaction. Samples were prepared using 7 different HSA concentrations, all at a constant CM concentration of 0.5 mmol/L. The relaxation rates, R1 and R2, of each sample were measured at 1.5 T. Virtual docking studies were performed to estimate the number of high affinity-binding sites of Gd-BOPTA and the surface of the HSA dimer. RESULTS: Gd-BOPTA caused the greatest increase in R1 and R2, which followed an exponential dependency with increasing HSA concentration. Between the range of 0 and 7 g/dL of HSA, Gd-DTPA and Gd-BT-DO3A showed a relative change in both relaxation rates of approximately 13% and 22% for R1 and 26% and 30% for R2, respectively. In contrast, Gd-BOPTA demonstrated a relative increase of approximately 108% and 363% for R1 and R2, respectively. Changes of HSA concentration within physiological range (3.5-5.5 g/dL) resulted in an increase of R1 and R2 of approximately 40% when using Gd-BOPTA. The docking study revealed that approximately 10 small hydrophobic pockets exist on the HSA surface where the aromatic tail of Gd-BOPTA can fit in and a stronger noncovalent binding can occur compared with Gd-DTPA and Gd-BT-DO3A. CONCLUSION: Relaxation rates of Gd-BOPTA showed a strong dependency on HSA. In contrast, Gd-DTPA and Gd-BT-DO3A demonstrated little or no relevant dependency. On the basis of these results, the influence of serum protein concentration should be considered in both research studies and in clinical use.

Contrast Media↗

PubMed2006

A functional magnetic resonance imaging study of social cognition in schizophrenia during an acute episode and after recovery.

OBJECTIVE: Difficulty with social interactions is a characteristic of schizophrenia. The authors used functional magnetic resonance imaging (fMRI) to investigate brain activation changes during a social cognition paradigm in patients with schizophrenia during and after an acute episode and their association with social and executive function. METHOD: In a longitudinal study design, 14 patients with schizophrenia experiencing an acute episode had an fMRI scan. They returned for a follow-up scan after clinical improvement. Fourteen healthy comparison subjects were also scanned twice with approximately the same time interval between scans as in the patient group. The authors employed a social cognition fMRI paradigm involving empathic and forgivability judgments. Schizophrenia symptoms, social functioning and illness insight scales, and the Wisconsin Card Sorting Test were used to examine whether improvement on these measures was associated with recovery of brain activation in response to the social cognition paradigm. RESULTS: After recovery from the acute episode, patients exhibited increased activation in the left medial prefrontal cortex, which was, in turn, significantly correlated with improved insight and social functioning. Decreased symptom severity and improved performance on the Wisconsin Card Sorting Test were not significantly associated with increased left medial prefrontal cortex activation. CONCLUSIONS: This is the first study to the authors' knowledge to use a social cognition paradigm to reveal improved left medial prefrontal cortex activation in schizophrenia after recovery from an acute episode. These results suggest that restored left medial prefrontal cortex activation may mediate improvement of insight and social functioning in patients with schizophrenia.

Adult↗

PubMed2006

Dexamethasone and enhancing solitary cerebral mass lesions: alterations in perfusion and blood-tumor barrier kinetics shown by magnetic resonance imaging.

OBJECTIVE: Glucocorticoid analogues are often administered to patients with intracranial space-occupying lesions. Clinical response can be dramatic, but the neurophysiological response is not well documented. This study sought to investigate the blood-lesion barrier, blood-brain barrier, and cerebral perfusion characteristics of patients who have undergone such therapy using magnetic resonance imaging. METHODS: Seventeen patients with intracranial mass-enhancing lesions underwent magnetic resonance imaging before and after 3 days of high-dose dexamethasone therapy. Assessments of blood-lesion barrier and blood-brain barrier integrity were based on a dynamic T1-weighted exogenous contrast technique that yielded the normalized maximal change in contrast uptake (T1-uptake). Perfusion was assessed using a dynamic T2*-weighted exogenous contrast technique to yield relative regional cerebral blood volume and first-moment mean transit time. Comparisons were made in T1-uptake, regional cerebral blood volume, and first-moment mean transit time of both enhancing lesion and contralateral normal-appearing white matter (CNAWM) obtained before and after dexamethasone. RESULTS: Significant reduction in T1-uptake was observed (19% decrease, P < 0.005) within enhancing pathological tissue, whereas no significant alteration was detected in CNAWM. Regional cerebral blood volume was significantly reduced in both enhancing tissue (28% decrease, P < 0.005) and in CNAWM (20% decrease, P < 0.001). Bolus first-moment mean transit time significantly increased (2.0 s prolongation, P < 0.05) in CNAWM, whereas there was no significant change (1.4 s prolongation, P > 0.05) within enhancing tissue. CONCLUSION: Glucocorticoid-analogue therapy not only affects the permeability of the blood-lesion barrier and lesion blood volume but also affects blood flow within normal-appearing contralateral parenchyma. There is a need for controls in steroid therapy in magnetic resonance imaging studies, which involve assessments of cerebrovascular function.

Adult↗

PubMed2005

Quantifiable change in functional brain response to empathic and forgivability judgments with resolution of posttraumatic stress disorder.

Previous functional neuroimaging studies of posttraumatic stress disorder (PTSD) have mainly focused on symptom-provocation paradigms in combat-related PTSD. We sought to elucidate the effect of non-combat-related PTSD on the physiology of social cognition. Thirteen patients with PTSD underwent functional magnetic resonance imaging (fMRI) while they engaged in tasks that (i) involve speculation on another's intention, (ii) invoke empathy and (iii) involve making judgments of the forgivability of others' actions; each versus 'baseline' social reasoning judgments. A post-therapy fMRI scan followed a course of modified cognitive behavioural therapy. Post-therapy, we found increased activation in brain regions predicted on the basis of foregoing work in healthy subjects. These included significant left middle temporal gyrus activation in post-therapy response to empathy judgments and posterior cingulate gyrus activation in post-therapy response to forgivability judgments. The specific regions of the human brain activated by empathy and forgivability judgments changed with symptom resolution in PTSD. Time and therapy are likely contributory factors that lead to a degree of 'normalisation' of the neural response to these social cognition tasks.

Adult↗

PubMed2005

Expanding the response space in chronic schizophrenia: the relevance of left prefrontal cortex.

OBJECTIVE: This study probed the ability of people with chronic schizophrenia to control their behavior in time by requiring them to deliberately vary responses within the temporal domain (i.e., to avoid regular inter-response intervals). METHODS: Thirteen schizophrenia patients performed single finger movements (at moments of their own choosing) in an event-related functional magnetic resonance imaging paradigm. Their performance was computed using the coefficient of variation of inter-response interval duration. RESULTS: Task performance was positively correlated with activation of left lateral prefrontal cortex. Post hoc analyses revealed an inverse correlation between activation in this region and severity of attentional impairment. CONCLUSION: These findings implicate left lateral prefrontal cortex in the modulation of the temporal response space in schizophrenia and imply greater attentional (executive) impairment among those who fail to modulate their behavior in time.

Adult↗

PubMed2005

Male and female voices activate distinct regions in the male brain.

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Acoustic Stimulation↗

PubMed2005

Modafinil modulates anterior cingulate function in chronic schizophrenia.

BACKGROUND: Schizophrenia is associated with widespread cognitive deficits that have an impact on social function. Modafinil promotes wakefulness and is reported to enhance cognition. AIMS: To study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia. METHOD: In a randomised double-blind placebo-controlled crossover design, 19 patients received either modafinil (100 mg) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging. RESULTS: Seventeen patients completed the study and another underwent acute relapse 4 days post-drug. Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task. The anterior cingulate cortex signal correlated with cognitive performance, although only a subset of patients exhibited 'enhancement'. CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation.

Adolescent↗

PubMed2005

Structural brain correlates of unconstrained motor activity in people with schizophrenia.

Avolition affects quality of life in chronic schizophrenia. We investigated the relationship between unconstrained motor activity and the volume of key executive brain regions in 16 male patients with schizophrenia. Wristworn actigraphy monitors were used to record motor activity over a 20 h period. Structural magnetic resonance imaging brain scans were parcellated and individual volumes for anterior cingulate cortex and dorsolateral prefrontal cortex extracted. Patients'total activity was positively correlated with volume of left anterior cingulate cortex. These data suggest that the volume of specific executive structures may affect (quantifiable) motor behaviours, having further implications for models of the 'will' and avolition.

Adult↗

PubMed2004

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.

Adult↗

PubMed2004

Spatial and temporal dissociation in prefrontal cortex during action execution.

It is widely accepted that dorsolateral prefrontal cortex (DLPFC) is activated at the time of action generation in humans. However, the previous functional neuroimaging studies that have supported this hypothesis temporally integrated brain dynamics and therefore could not demonstrate when DLPFC underwent activation relative to the emergence of voluntary behavior. Data that are time-locked to the instant of voluntary action execution do not reveal DLPFC activation at that moment. Rather, activated foci are seen at the frontal poles. We investigated this apparent conundrum through three differentially constrained experiments, utilizing functional magnetic resonance imaging to identify those prefrontal areas exhibiting functional change at the moment of spontaneous action execution. We observed profound functional dissociation between anterior and dorsolateral regions, compatible with their involvement at different points during the temporal evolution of action: bilaterally the frontal poles activated at the moment of execution, while simultaneously (and relative to a prior activation state) left DLPFC 'deactivated.'

Adult↗

PubMed2003

B1AC-MAMBA: B1 array combined with multiple-acquisition micro B0 array parallel magnetic resonance imaging.

The combination of an in-plane B(1) sensitivity encoding (SENSE) technique with a simultaneous multiple-slice B(0) field step technique (multiple-acquisition micro B(0) array (MAMBA)) has produced high scan time reduction factors (R < or = 8). In this study, two slices were acquired simultaneously in combination with x2 and x4 SENSE in-plane encoding using a MAMBA stepped B(0) field coil inside a four-channel phased-array coil system. Experiments were performed on a 1.5 T Infinion system (Philips Medical Systems, Cleveland, OH). The signal-to-noise ratio (SNR) was reduced with higher R factors, as was expected from the reduced number of acquisitions used to create the unaliased images. The combination of SENSE and MAMBA offers great promise for reducing scan times through parallel acquisition while at the same time reducing the number of RF channels required by a factor equal to the number of field steps employed. The B(1) array combined with MAMBA (B(1)AC-MAMBA) technique is applicable when the length of an object is much greater than its diameter, as in scanning limbs or in whole-body screening for disease.

Artifacts↗

PubMed2003

Approaching an ecologically valid functional anatomy of spontaneous "willed" action.

We used functional magnetic resonance imaging of healthy subjects to investigate the neural basis for spontaneous "willed" action. We hypothesised that such action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in addition to primary motor cortex. Furthermore, we predicted that PFC and SMA would demonstrate similar temporal response dynamics, distinct from primary motor cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as shorter response latencies compared with primary motor cortex. Six right-handed males participated in an event-related design and were required to generate spontaneous motor acts inside the scanner. By deciding "which" of two buttons to press, and "when" to press them, subjects generated sequences of action that were of high information content ("novelty" or "randomness"). Utilising a short repetition time (1 s), we acquired functional images that covered most of the frontal and parietal cortices. The onset of action was associated with significant activation in bilateral PFC, left primary motor cortex, and, close to the midline, SMA. Following action, mean time to half-maximum blood oxygenation level-dependent response was significantly earlier in left PFC and SMA than primary motor cortex. Our findings suggest that neural correlates of spontaneous willed action are distributed in executive and motor centres, and that temporal response dynamics differentiate "higher" regions from subordinate motor areas.

Adult↗

PubMed2003

A measure of curve fitting error for noise filtering diffusion tensor MRI data.

A parameter, chi2p, based on the fitting error was introduced as a measure of reliability of DT-MRI data, and its properties were investigated in simulations and human brain data. Its comparison with the classic chi2 revealed its sensitivity to both the goodness of fit and the pixel signal-to-noise-ratio (SNR), unlike the classic chi2, which is sensitive only to the goodness of fit. The new parameter was thus able to separate effectively pixels with coherent signals (having small fitting error and/or high SNR) from those with random signals (having inconsistent fitting and/or low SNR). A practical advantage of chi2p over the classic chi2 was that chi2p is quantified directly from the data of each pixel, without requiring accurate estimation of data-dependent parameters (such as noise variance), which often makes application of the classic chi2 problematic. Analytical approximations of chi2p enabled an objective (data-independent) and automated calculation of a threshold value, used for internal scaling of the chi2p map. Apart from assessing data reliability on a pixel-by-pixel basis, chi2p was used to develop an objective and generic methodology for the exclusion of pixels with unreliable DT information by discarding pixels with chi2p values exceeding the threshold. Pixels corresponding to very low SNR, and poorly fitted cerebrospinal fluid and surrounding brain tissue, had increased chi2p values and were successfully excluded, providing DT anisotropy maps free from artifactual anisotropic appearance.

Adult↗

PubMed2003

A neural basis for the perception of voices in external auditory space.

We used functional imaging of normal subjects to identify the neural substrate for the perception of voices in external auditory space. This fundamental process can be abnormal in psychosis, when voices that are not true external auditory objects (auditory verbal hallucinations) may appear to originate in external space. The perception of voices as objects in external space depends on filtering by the outer ear. Psychoses that distort this process involve the cerebral cortex. Functional magnetic resonance imaging was carried out on 12 normal subjects using an inside-the-scanner simulation of 'inside head' and 'outside head' voices in the form of typical auditory verbal hallucinations. Comparison between the brain activity associated with the two conditions allowed us to test the hypothesis that the perception of voices in external space ('outside head') is subserved by a temperoparietal network comprising association auditory cortex posterior to Heschl's gyrus [planum temporale (PT)] and inferior parietal lobule. Group analyses of response to 'outside head' versus 'inside head' voices showed significant activation solely in the left PT. This was demonstrated in three experiments in which the predominant lateralization of the stimulus was to the right, to the left or balanced. These findings suggest a critical involvement of the left PT in the perception of voices in external space that is not dependent on precise spatial location. Based on this, we suggest a model for the false perception of externally located auditory verbal hallucinations.

Acoustics↗

PubMed2003

Postmortem MR imaging of the fetal and stillborn central nervous system.

BACKGROUND AND PURPOSE: Changes in the public perception of postmortem procedures in the United Kingdom have led to reduced numbers of autopsies being performed in the fetus and neonate. When autopsy is performed in this group, the brain is now usually studied without being formalin-fixed, which limits the available information. We evaluated the diagnostic accuracy of postmortem MR imaging of the fetal brain and spine when compared with the reference standard, autopsy. METHODS: We obtained high-spatial-resolution T2-weighted images (in-plane resolution approximately 0.4 mm) of the brain and spine in 40 fetuses and stillborn neonates (14-42 weeks gestational age) who were referred for autopsy. The MR findings were compared with those of autopsy, the reference standard, which had been performed independently. RESULTS: In eight cases, the autopsy did not provide structural information of the brain or spine, because assessment of the unfixed tissue was impossible. There was agreement between MR and autopsy findings in 31 (97%) of 32 cases in which comparison could be made. Eleven cases showed normal brain, and 20 cases showed a wide range of developmental and acquired abnormalities. The sensitivity of MR was 100%, specificity 92%, positive predictive value 95%, and negative predictive value 100%. CONCLUSION: MR imaging has a useful role in providing structural information of the central nervous system in fetuses and stillborn neonates.

Autopsy↗