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Biomedical subjects

John Ashburner

Publications and source records attributed to John Ashburner.

12 recordsLinked to original sources

Variational free energy and the Laplace approximation.

This note derives the variational free energy under the Laplace approximation, with a focus on accounting for additional model complexity induced by increasing the number of model parameters. This is relevant when using the free energy as an approximation to the log-evidence in Bayesian model averaging and selection. By setting restricted maximum likelihood (ReML) in the larger context of variational learning and expectation maximisation (EM), we show how the ReML objective function can be adjusted to provide an approximation to the log-evidence for a particular model. This means ReML can be used for model selection, specifically to select or compare models with different covariance components. This is useful in the context of hierarchical models because it enables a principled selection of priors that, under simple hyperpriors, can be used for automatic model selection and relevance determination (ARD). Deriving the ReML objective function, from basic variational principles, discloses the simple relationships among Variational Bayes, EM and ReML. Furthermore, we show that EM is formally identical to a full variational treatment when the precisions are linear in the hyperparameters. Finally, we also consider, briefly, dynamic models and how these inform the regularisation of free energy ascent schemes, like EM and ReML.

Bayes Theorem↗

Unified segmentation.

A probabilistic framework is presented that enables image registration, tissue classification, and bias correction to be combined within the same generative model. A derivation of a log-likelihood objective function for the unified model is provided. The model is based on a mixture of Gaussians and is extended to incorporate a smooth intensity variation and nonlinear registration with tissue probability maps. A strategy for optimising the model parameters is described, along with the requisite partial derivatives of the objective function.

Algorithms↗

Neurolinguistics: structural plasticity in the bilingual brain.

Humans have a unique ability to learn more than one language--a skill that is thought to be mediated by functional (rather than structural) plastic changes in the brain. Here we show that learning a second language increases the density of grey matter in the left inferior parietal cortex and that the degree of structural reorganization in this region is modulated by the proficiency attained and the age at acquisition. This relation between grey-matter density and performance may represent a general principle of brain organization.

Age Factors↗

Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans.

The amygdala, which plays a critical role in emotional learning and social cognition, is structurally and functionally sexually dimorphic in humans. We used magnetic neuroimaging and molecular genetic analyses with healthy subjects and patients possessing X-chromosome anomalies to find dosage-sensitive genes that might influence amygdala development. If such X-linked genes lacked a homologue on the Y-chromosome they would be expressed in one copy in normal 46,XY males and two copies in normal 46,XX females. We showed by means of magnetic neuroimaging that 46,XY males possess significantly increased amygdala volumes relative to normal 46,XX females. However, females with Turner syndrome (45,X) have even larger amygdalae than 46,XY males. This finding implies that haploinsufficiency for one or more X-linked genes influences amygdala development irrespective of a direct or indirect (endocrinological) mechanism involving the Y-chromosome. 45,X females also have increased grey matter volume in the orbitofrontal cortex bilaterally, close to a region implicated in emotional learning. They are as poor as patients with bilateral amygdalectomies in the recognition of fear from facial expressions. We attempted to localize the gene(s) responsible for these deficits in X-monosomy by means of a deletion mapping strategy. We studied female patients possessing structural X-anomalies of the short arm. A genetic locus (no greater than 4.96 Mb in size) at Xp11.3 appears to play a key role in amygdala and orbitofrontal structural and (by implication) functional development. Females with partial X-chromosome deletions, in whom this critical locus is deleted, have normal intelligence. Their fear recognition is as poor as that of 45,X females and their amygdalae are correspondingly enlarged. This 4.96 Mb region contains, among others, the genes for monoamine oxidase A (MAOA) and B (MAOB), which are involved in the oxidative deamination of several neurotransmitters, including dopamine and serotonin. Abnormal activity of these neurotransmitters has been implicated in the aetiology of several neurodevelopmental disorders in which social cognitive deficits are prominent. These associated deficits include a specific lack of fear recognition from facial expressions. We show that the thrombocytic activity of MAOB is proportionate to the number of X-chromosomes, and hypothesize that haploinsufficiency of this enzyme in 45,X females predisposes to their deficits in social cognition.

Adolescent↗

Changes in cerebral morphology consequent to peripheral autonomic denervation.

Pure autonomic failure (PAF) is characterized by an acquired, selective, peripheral denervation of the autonomic nervous system. Patients with PAF fail to generate bodily states of arousal via the autonomic nervous system in response to physical or cognitive effort. We used voxel-based morphometry to test the hypothesis that changes in the morphology of brain regions involved in autonomic control would arise as a consequence to the longstanding absence of peripheral autonomic responses in PAF patients. Optimized voxel-based morphometry of structural magnetic resonance scans was used to test for regional differences in grey and white matter in 15 PAF patients and matched controls. There were no group differences observed in global measures of grey matter, white matter, or cerebrospinal fluid (CSF). We identified morphometric differences reflecting regional decreases in grey matter volume and concentration in anterior cingulate and insular cortices in PAF patients relative to controls. Morphometric differences in brainstem and subcortical regions did not reach statistical significance. Our findings suggest that peripheral autonomic denervation is associated with grey matter loss in cortical regions encompassing areas that we have previously shown are functionally involved in generation and representation of bodily states of autonomic arousal. The nature of these changes cannot be determined from morphometric analysis alone, but we suggest that they reflect experience-dependent change consequent upon loss of afferent input to brain regions involved in representation of autonomic states.

Adult↗

Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution.

The analysis of functional magnetic resonance imaging (fMRI) time-series data can provide information not only about task-related activity, but also about the connectivity (functional or effective) among regions and the influences of behavioral or physiologic states on that connectivity. Similar analyses have been performed in other imaging modalities, such as positron emission tomography. However, fMRI is unique because the information about the underlying neuronal activity is filtered or convolved with a hemodynamic response function. Previous studies of regional connectivity in fMRI have overlooked this convolution and have assumed that the observed hemodynamic response approximates the neuronal response. In this article, this assumption is revisited using estimates of underlying neuronal activity. These estimates use a parametric empirical Bayes formulation for hemodynamic deconvolution.

Bayes Theorem↗

How to correct susceptibility distortions in spin-echo echo-planar images: application to diffusion tensor imaging.

Diffusion tensor imaging is often performed by acquiring a series of diffusion-weighted spin-echo echo-planar images with different direction diffusion gradients. A problem of echo-planar images is the geometrical distortions that obtain near junctions between tissues of differing magnetic susceptibility. This results in distorted diffusion-tensor maps. To resolve this we suggest acquiring two images for each diffusion gradient; one with bottom-up and one with top-down traversal of k-space in the phase-encode direction. This achieves the simultaneous goals of providing information on the underlying displacement field and intensity maps with adequate spatial sampling density even in distorted areas. The resulting DT maps exhibit considerably higher geometric fidelity, as assessed by comparison to an image volume acquired using a conventional 3D MR technique.

Algorithms↗

Computer-assisted imaging to assess brain structure in healthy and diseased brains.

Neuroanatomical structures may be profoundly or subtly affected by the interplay of genetic and environmental factors, age, and disease. Such effects are particularly true in healthy ageing individuals and in those who have neurodegenerative diseases. The ability to use imaging to identify structural brain changes associated with different neurodegenerative disease states would be useful for diagnosis and treatment. However, early in the progression of such diseases, neuroanatomical changes may be too mild, diffuse, or topologically complex to be detected by simple visual inspection or manually traced measurements of regions of interest. Computerised methods are being developed that can capture the extraordinary morphological variability of the human brain. These methods use mathematical models sensitive to subtle changes in the size, position, shape, and tissue characteristics of brain structures affected by neurodegenerative diseases. Neuroanatomical features can be compared within and between groups of individuals, taking into account age, sex, genetic background, and disease state, to assess the structural basis of normality and disease. In this review, we describe the strengths and limitations of algorithms of existing computer-assisted tools at the most advanced stage of development, together with available and foreseeable evidence of their usefulness at the clinical and research level.

Algorithms↗

Image distortion correction in fMRI: A quantitative evaluation.

A well-recognized problem with the echo-planar imaging (EPI) technique most commonly used for functional magnetic resonance imaging (fMRI) studies is geometric distortion caused by magnetic field inhomogeneity. This makes it difficult to achieve an accurate registration between a functional activation map calculated from an EPI time series and an undistorted, high resolution anatomical image. A correction method based on mapping the spatial distribution of field inhomogeneities can be used to reduce these distortions. This approach is attractive in its simplicity but requires postprocessing to improve the robustness of the acquired field map and reduce any secondary artifacts. Furthermore, the distribution of the internal magnetic field throughout the head is position dependent resulting in an interaction between distortion and head motion. Therefore, a single field map may not be sufficient to correct for the distortions throughout a whole fMRI time series. In this paper we present a quantitative evaluation of image distortion correction for fMRI at 2T. We assess (i) methods for the acquisition and calculation of field maps, (ii) the effect of image distortion correction on the coregistration between anatomical and functional images, and (iii) the interaction between distortion and head motion, assessing the feasibility of using field maps to reduce this effect. We propose that field maps with acceptable noise levels can be generated easily using a dual echo-time EPI sequence and demonstrate the importance of distortion correction for anatomical coregistration, even for small distortions. Using a dual echo-time series to generate a unique field map at each time point, we characterize the interaction between head motion and geometric distortion. However, we suggest that the variance between successively measured field maps introduces additional unwanted variance in the voxel time-series and is therefore not adequate to correct for time-varying distortions.

Algorithms↗

Automatic differentiation of anatomical patterns in the human brain: validation with studies of degenerative dementias.

We compared voxel-based morphometry (VBM) with independent accurate region-of-interest (ROI) measurements of temporal lobe structures in order to validate the usefulness of this fully automated and unbiased technique in Alzheimer's disease (AD) and semantic dementia (SD). In AD, ROI analyses appear more sensitive to volume loss in the amygdalae, whereas VBM analyses appear more sensitive to right middle temporal gyrus and regional hippocampal volume loss. In SD, ROI analyses appear more sensitive to left middle and inferior temporal gyrus volume loss, whereas VBM appears more sensitive to regional hippocampal volume loss. In addition the significance of volume reductions was generally less in VBM owing to more stringent corrections for multiple comparisons. In conclusion, the automated technique detects a general trend of atrophy similar to that of expertly labeled ROI measurements in AD and SD, although there are discrepancies in the ranking of severity and in the significance of volume reductions that are more marked in AD.

Alzheimer Disease↗

Functional magnetic resonance imaging technology and traumatic brain injury rehabilitation: guidelines for methodological and conceptual pitfalls.

OBJECTIVES: To illuminate the current methodological and conceptual pitfalls inherent in conducting functional magnetic resonance imaging (fMRI) research with individuals who have sustained traumatic brain injury (TBI) and to discuss appropriate remedies. The aim is describe fMRI research, its limitations, and how to best use this technology to examine TBI. DISCUSSION: The topics discussed in this article include issues regarding signal detection, brain activation measurement, head movement, and sources of signal artifact. Issues surrounding data interpretation and the importance of analyzing the brain as a connected neural network is also discussed. Finally, problems with spatial normalization when examining individuals with TBI are reviewed. CONCLUSIONS: To date, there is a scarcity of research applying fMRI technology to the study of TBI. However, because it is a noninvasive procedure with high availability in hospital settings across the country, the next decade of TBI research will likely include a proliferation of this form of investigation. At this time, much work is needed to better understand how to optimally use this technology to examine the effects of TBI on behavior. For fMRI to enhance TBI research it will be imperative to establish valid research protocols and reliable methods of data interpretation.

Brain Injuries↗