Abnormalities of brain structure and lateralisation in schizophrenia

Researchers have proposed that schizophrenia is a disease related to abnormal cerebral lateralisation following findings of increased "schizophrenia-like" symptoms in left-hemisphere epileptics. Theories regarding abnormal brain structural asymmetries in schizophrenia suggest either ambiguous or extreme motor asymmetry. These theories are conceptually similar to ones proposed to explain non-right-handedness in normal subjects. In this thesis I objectively evaluate these hypotheses. Firstly, I critically survey the neuropsychological literature and find the evidence for lateralised cognitive deficit to be inconclusive. Next, a meta-analysis of studies reporting the finding of ventricular enlargement in schizophrenia is carried out and it is found that findings are highly influenced by methodological factors. A review of the literature concerning lateralised neuropathologies from brain imaging and postmortem studies similarly finds the evidence to be hindered by differences in experimental methodology. Furthermore, there is much disagreement between researchers regarding which asymmetries are empirically or theoretically meaningful. The next chapter concentrates exclusively with the experimental measurement of hand performance. The Annett pegboard, the Tapley and Bryden circle marking, and the Bishop square tracing tasks of hand performance are extended and used to test hand performance in normal subjects as a function of increasing task difficulty. Pursuit tracking is used to consider the Fourier spectrum and sub-components of relative hand performance. The differences between the hands on the conventional and tracking tasks are then subjected to factor analyses. Surprising results are obtained in which performance tasks show moderate-to-high internal reliability but correlate poorly with one another. Their relevance to handedness and motor research is then discussed. Schizophrenic hand preference is investigated in a meta-analytic assessment of studies reporting an increased incidence of non-dextral hand preference in schizophrenia. This is examined with respect to the definition and methods of measurement in these studies. Finally, the hand performance of schizophrenics is investigated. Testing hand performance, in conjunction with hand preference measures, allows for greater reliability in the evaluation of the notion of abnormal handedness in schizophrenia. Patients show poorer overall performance on all of the tasks, but show no significant differences in their degree of handedness as compared to normals. Conclusions are drawn that associations between abnormal handedness and disorders of brain structural asymmetry in schizophrenic patients are unlikely. Further implications for abnormalities of cerebral dominance and schizophrenia are considered

Interactive Exploration of Neuroanatomical Meta-Spaces

Large-archives of neuroimaging data present many opportunities for re-analysis and mining that can lead to new findings of use in basic research or in the characterization of clinical syndromes. However, interaction with such archives tends to be driven textually, based on subject or image volume meta-data, not the actual neuroanatomical morphology itself, for which the imaging was performed to measure. What is needed is a content-driven approach for examining not only the image content itself but to explore brains that are anatomically similar, and identifying patterns embedded within entire sets of neuroimaging data. With the aim of visual navigation of large- scale neurodatabases, we introduce the concept of brain meta-spaces. The meta-space encodes pair-wise dissimilarities between all individuals in a population and shows the relationships between brains as a navigable framework for exploration. We employ multidimensional scaling (MDS) to implement meta-space processing for a new coordinate system that distributes all data points (brain surfaces) in a common frame-of-reference, with anatomically similar brain data located near each other. To navigate within this derived meta-space, we have developed a fully interactive 3D visualization environment that allows users to examine hundreds of brains simultaneously, visualize clusters of brains with similar characteristics, zoom in on particular instances, and examine the surface topology of an individual brain's surface in detail. The visualization environment not only displays the dissimilarities between brains, but also renders complete surface representations of individual brain structures, allowing an instant 3D view of the anatomies, as well as their differences. The data processing is implemented in a grid-based setting using the LONI Pipeline workflow environment. Additionally users can specify a range of baseline brain atlas spaces as the underlying scale for comparative analyses. The novelty in our approach lies in the user ability to simultaneously view and interact with many brains at once but doing so in a vast meta-space that encodes (dis) similarity in morphometry. We believe that the concept of brain meta-spaces has important implications for the future of how users interact with large-scale archives of primary neuroimaging data

Resting-State Functional Connectivity in Autism Spectrum Disorders: A Review

Ongoing debate exists within the resting-state functional MRI (fMRI) literature over how intrinsic connectivity is altered in the autistic brain, with reports of general over-connectivity, under-connectivity, and/or a combination of both. Classifying autism using brain connectivity is complicated by the heterogeneous nature of the condition, allowing for the possibility of widely variable connectivity patterns among individuals with the disorder. Further differences in reported results may be attributable to the age and sex of participants included, designs of the resting-state scan, and to the analysis technique used to evaluate the data. This review systematically examines the resting-state fMRI autism literature to date and compares studies in an attempt to draw overall conclusions that are presently challenging. We also propose future direction for rs-fMRI use to categorize individuals with autism spectrum disorder, serve as a possible diagnostic tool, and best utilize data-sharing initiatives

Mapping Connectivity Damage in the Case of Phineas Gage

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a “tamping iron” was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25–36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized “average” brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient