Biomedical subjects

Clare E Mackay

Publications and source records attributed to Clare E Mackay.

10 recordsLinked to original sources

PubMed2006

Connectivity-based parcellation of human cortex using diffusion MRI: Establishing reproducibility, validity and observer independence in BA 44/45 and SMA/pre-SMA.

The identification of specialized, functional regions of the human cortex is a vital precondition for neuroscience and clinical neurosurgery. Functional imaging modalities are used for their delineation in living subjects, but these methods rely on subject cooperation, and many regions of the human brain cannot be activated specifically. Diffusion tractography is a novel tool to identify such areas in the human brain, utilizing underlying white matter pathways to separate regions of differing specialization. We explore the reproducibility, generalizability and validity of diffusion tractography-based localization in four functional areas across subjects, timepoints and scanners, and validate findings against fMRI and post-mortem cytoarchitectonic data. With reproducibility across modalities, clustering methods, scanners, timepoints, and subjects in the order of 80-90%, we conclude that diffusion tractography represents a useful and objective tool for parcellation of the human cortex into functional regions, enabling studies into individual functional anatomy even when there are no specific activation paradigms available.

Adult↗

PubMed2006

White matter pathway asymmetry underlies functional lateralization.

Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in brain tissue. White matter pathway asymmetry was investigated in a normalized image data set of 30 right-handed young healthy individuals. We identified, for the first time, a rightwardly asymmetric pathway connecting the posterior temporal lobe to the superior parietal lobule. This pathway may be related to auditory spatial attention and working memory for which there is evidence for a rightward laterality from functional imaging studies. Additional leftward asymmetries connecting the parietal and frontal lobes to the temporal lobe may be more closely related to laterality of language.

Adult↗

PubMed2006

Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.

Amyotrophic Lateral Sclerosis↗

PubMed2006

Antidepressant drug treatment modifies the neural processing of nonconscious threat cues.

BACKGROUND: The amygdala is believed to play a key role in processing emotionally salient, threat-relevant, events that require further online processing by cortical regions. Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala, but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information. METHODS: The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging. A double-blind, between-groups design was used with volunteers randomized to 20 mg/day citalopram versus placebo. RESULTS: Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo. Citalopram also reduced responses within the hippocampus and medial prefrontal cortex (mPFC) specifically during the fear-relevant stimuli. These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan. By contrast, there was no effect of citalopram on the neural or behavioral response to the happy facial expressions. CONCLUSIONS: These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans. Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety.

Adolescent↗

PubMed2005

Automatic analysis of cerebral asymmetry: an exploratory study of the relationship between brain torque and planum temporale asymmetry.

Leftward occipital and rightward frontal lobe asymmetry (brain torque) and leftward planum temporale asymmetry have been consistently reported in postmortem and in vivo neuroimaging studies of the human brain. Here automatic image analysis techniques are applied to quantify global and local asymmetries, and investigate the relationship between brain torque and planum temporale asymmetries on T1-weighted magnetic resonance (MR) images of 30 right-handed young healthy subjects (15 male, 15 female). Previously described automatic cerebral hemisphere extraction and 3D interhemispheric reflection-based methods for studying brain asymmetry are applied with a new technique, LowD (Low Dimension), which enables automatic quantification of brain torque. LowD integrates extracted left and right cerebral hemispheres in columns orthogonal to the midsagittal plane (2D column maps), and subsequently integrates slices along the brain's anterior-posterior axis (1D slice profiles). A torque index defined as the magnitude of occipital and frontal lobe asymmetry is computed allowing exploratory investigation of relationships between this global asymmetry and local asymmetries found in the planum temporale. LowD detected significant torque in the 30 subjects with occipital and frontal components found to be highly correlated (P<0.02). Significant leftward planum temporale asymmetry was detected (P<0.05), and the torque index correlated with planum temporale asymmetry (P<0.001). However, torque and total brain volume were not correlated. Therefore, although components of cerebral asymmetry may be related, their magnitude is not influenced by total hemisphere volume. LowD provides increased sensitivity for detection and quantification of brain torque on an individual subject basis, and future studies will apply these techniques to investigate the relationship between cerebral asymmetry and functional laterality.

Adult↗

PubMed2005

Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies.

OBJECTIVE: Voxel-based morphometry is a method for detecting group differences in the density or volume of brain matter. The authors reviewed the literature on use of voxel-based morphometry in schizophrenia imaging research to examine the capabilities of this method for clearly identifying specific structural differences in patients with schizophrenia, compared with healthy subjects. The authors looked for consistently reported results of relative deficits in gray and white matter in schizophrenia and evaluated voxel-based morphometry methods in order to propose a future strategy for using voxel-based morphometry in schizophrenia research. METHOD: The authors reviewed all voxel-based morphometry studies of schizophrenia that were published to May 2004 (15 studies). The studies included a total of 390 patients with a diagnosis of schizophrenia and 364 healthy volunteers. RESULTS: Gray and white matter deficits in patients with schizophrenia, relative to healthy comparison subjects, were reported in a total of 50 brain regions. Deficits were reported in two of the 50 regions in more than 50% of the studies and in nine of the 50 regions in one study only. The most consistent findings were of relative deficits in the left superior temporal gyrus and the left medial temporal lobe. Use of a smaller smoothing kernel (4-8 mm) led to detection of a greater number of regions implicated in schizophrenia. CONCLUSIONS: This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.

Amygdala↗

PubMed2003

Application of a new image analysis technique to study brain asymmetry in schizophrenia.

The hypothesis that normal brain torque (i.e. rightward frontal and leftward occipital asymmetry) is anomalous in schizophrenia (Crow, 1997. Trends in Neuroscience, 20, 339-343) was tested by application of a novel image analysis technique on three-dimensional magnetic resonance images obtained in 26 adult patients with chronic schizophrenia (18 males, 8 females) and 24 controls (14 males, 10 females). Right and left cerebral hemisphere tissue was extracted via non-linear co-registration with a mask image, and maps were computed of inter-hemispheric differences in tissue volume in an array of columns of voxels orthogonal to the mid-plane (2D), and profiles of coronal slice volumes (1D). Furthermore, integration of two-dimensional column maps gave approximate lobar asymmetries, and occipital and frontal asymmetries were combined to give a volumetric measure of brain torque. Significant brain torque was revealed in male and female control and patient groups, and did not correlate with brain size. Frontal and occipital asymmetries were significantly correlated in all groups. Both frontal and occipital components of torque were significantly increased in males than females. Patients tended to have reduced torque, particularly the leftward occipital component. Furthermore, 3/26 patients (but no controls) had reversed torque (leftward frontal and rightward occipital asymmetry). Contrary to Crow's hypothesis, brain torque was not significantly reduced in patients with schizophrenia relative to controls, although reversal of torque was found in three cases. Future studies with larger sample sizes should consider sexual dimorphism and specific symptoms in relation to asymmetry.

Brain↗

PubMed2003

Comparison of MR imaging against physical sectioning to estimate the volume of human cerebral compartments.

The purpose of this study was to compare magnetic resonance imaging (MRI) against physical sectioning techniques to estimate the volume of human cerebral hemisphere compartments (cortex, subcortex, and their union, called "total"). The volume of these compartments was estimated postmortem for six human subjects from MRI virtual sections and from physical sections using the Cavalieri design with point counting. Cursory paired t tests revealed no significant differences between the two methods for any of the three compartments considered, although P = 0.06 for the subcortex. A sharper analysis incorporating recent error prediction formulae revealed a significant discrepancy between the two methods in the estimation of subcortex and total volume for three of the specimens. Yet, none of these analyses is adequate to detect possible biases. The incorporation of an explanatory variable, namely hemisphere weight, and the adoption of a specific gravity rho = 1.04 g/cm(3) for the material, enabled us to carry out an allometric analysis for the total compartment which revealed a significant bias of the MRI data. The new error prediction formulae are illustrated by way of example, and their accuracy is checked by a resampling experiment on a data set of 274 MRI sections.

Aged↗

PubMed2003

Brain volume, asymmetry and intellectual impairment in relation to sex in early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that early-onset schizophrenia arises from a disturbance in the normal trajectory of cerebral development. AIMS: To investigate brain structure, asymmetry and IQ in early-onset schizophrenia. METHOD: Volumes of left and right cerebral hemispheres and IQ were assessed in 33 participants with early-onset DSM-IV schizophrenia and 30 members of a matched, normal control group. RESULTS: Total brain volume was significantly smaller in the group with early-onset disease ('cases') relative to the control group (4.5%), especially for the left hemisphere in males (6.0%). A significant sex x diagnosis interaction in hemisphere asymmetry revealed that the female cases group had significantly reduced rightward asymmetry relative to the female control group and that the male cases tended to have reduced leftward asymmetry relative to the male control group. Decreased left hemisphere volume in males and decreased rightward hemispheric asymmetry in females correlated with reduced IQ. CONCLUSIONS: Sexually dimorphic alterations in asymmetry correlate with degree of intellectual impairment in early-onset schizophrenia.

Adolescent↗

PubMed2002

Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy.

We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis technique, to investigate gray matter abnormalities in patients with temporal lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by application of the Cavalieri method of modern design stereology. VBM results (P < 0.05, corrected) indicated preferential gray matter concentration (GMC) reduction in anterior hippocampus in patients with left HA and posterior hippocampus in patients with right HA. GMC reduction was also found in right dorsal prefrontal cortex in left and right HA patients. Prefrontal atrophy may be due to epileptiform excitotoxic discharges from the reciprocally connected pathological hippocampus, and may be the underlying biological cause for executive dysfunction in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and pericallosal regions was common to both left and right HA groups relative to controls, and is hypothesized to reflect diminished gray-white matter demarcation, underlying white matter atrophy, or structural displacement due to cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was observed in left HA patients, while ipsilateral temporal lobe GMC excess was observed in right HA patients. This work demonstrates methodological consistency between automated VBM and manual stereological analysis of the hippocampus in group comparisons, indicates widespread extrahippocampal gray matter abnormalities in unilateral HA, and suggests that there may be inherent differences in the effect of TLE on temporal lobe structures depending on the side of HA.

Adolescent↗