A literature review of the schizophrenia brain electrophysiology was undertaken with specific emphasis placed on the topographical distribution of evoked potentials (EPs). The outcomes of this review suggests that schizophrenia brain electrophysiology, demonstrate some differences, but with a variability reflective of the symptom heterogeneity. The literature associated with the use of attentional tasks while recording EPs, tended to demonstrate some consistency. The methodological issues associated with the EEG and EP recordings may also account for this variability. An evoked potential technique, which has been demonstrated to be sensitive to the changes in cognitive processes associated with attention, is the Steady State Probe Topography (SSPT) technique. The SSPT is a combination of both the Steady State Visual Evoked Potential (SSVEP) and the Probe-ERP paradigm. This technique allows the SSVEP to be measured continuously, is relatively insensitive to artifact, and can display the topographic distribution of the SSVEP measures during the attentional task. The technique employs the use of a sixty-four channel EEG recording system. This consists of a multichannel electrode helmet; multichannel amplifier/filter, task presentation computer and a computer controlled data acquisition system. Software was also developed to analyse the recorded brain electrical activity to produce the SSVEP magnitude and phase versus time series for each electrode site. The topographic distribution of the SSVEP measures associated with specific events during attentional tasks could also be displayed. At the time of the pilot study, this technique had not been applied previously to the study of schizophrenia and therefore warranted further study. Two separate studies are reported; an investigative pilot study and a chronic group study. The pilot SSVEP and schizophrenia study was designed to examine the changes in the SSVEP and its topography, during the performance of a number of attentional or activation tasks to examine the possibility of hypofrontality. The tasks selected for the study were those previously used for the examination of hypofrontality with metabolic imaging techniques; the Continuous Performance Task (CPT) and the Wisconsin Card Sort (WCS). The SSVEP was elicited by a superimposed 13Hz flicker on the visual field, while subjects performed computerised versions of the neuropsychological tasks. Topographical maps of the SSVEP magnitude distribution were then interpolated and displayed as an animated sequence synchronised with particular events occurring during the tasks. In comparison to the male control group, male schizophrenic patients exhibited differences in the SSVEP topography for all tasks, possibly reflecting the deficits in behavioural indices. Overall, the findings indicated that the technique demonstrated some merit for further examination of frontal SSVEP topography in schizophrenia. In a larger study of twenty chronic schizophrenia patients, the frontal topographical distribution of the SSVEP was examined. The earlier pilot study finding of reduced frontal SSVEP amplitude was replicated. The issue of hypofrontality in schizophrenia was applied as a possible interpretation.

"December 2003" / Includes bibliographical references (leaves 106-128) / xii, 128 leaves : ill., plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine and The Hanson Institute, 2004

abstract / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

Lymphocytes play a key role in the mammalian immune system and migrate around the body interacting with both soluble factors and tissues in their role of detecting and eliminating disease causing pathogens. These interactions are mediated by the molecules expressed at the cell surface of the leukocyte which have become a popular paradigm for the study of intercellular communication. Proteins which belong to the immunoglobulin superfamily (IgSF) are the most abundant of these cell surface molecules and one of these (OX-2) is the major focus of this thesis. The OX-2 glycoprotein is expressed in both the neuronal and lymphoid compartments of rats and has no known function. However, a highly avid OX-2 binding reagent was previously shown to specifically interact with a cell surface receptor expressed by macrophages. A monoclonal antibody, MRC OX-102, which bound rat macrophages and blocked the binding of OX-2 was raised and used to molecularly identify the receptor on the macrophage by a combination of protein purification and PCR-based strategies. The rat OX-2 receptor (OX-2R) was identified as a novel member of the IgSF and had a close evolutionary relationship to the OX-2 protein itself. The two glycoproteins interacted with an affinity of 2.5μM and K_off 0.8 sec^-1, values typical of interactions between cell surface proteins. A mouse form of the OX-2 receptor was also cloned. The cytoplasmic region of the OX-2R contained conserved tyrosine residues which were shown to be phosphorylated upon pervanadate treatment of macrophages. Preliminary distribution data suggest that the receptor is restricted to cells of myeloid origin and the functional consequences of the interaction are discussed. A monoclonal antibody, MRC OX-104, was raised to the human OX-2 protein to initiate the translation of this work from rodent models to humans. OX-2 showed highly conserved patterns of expression between the two species.

Psychiatric disorders and cognitive impairment are increasingly being described in patients with vestibular pathology. Yet frameworks that describe the link between emotion, memory and the vestibular system have yet to reach maturity, partly because studies have not yet provided detailed accounts of behavioral changes in experimental animals, or in man. One of the goals of this thesis was to use experimental psychology to define changes in memory and emotional behaviour in rats given bilateral vestibular deafferentation (BVD, n=18) or sham surgery (Sham, n=17). In an elevated-plus maze task, BVD rats made up to 166% greater open arm entries and spent up to 42% more time in the open arms compared to Sham rats. In an elevated-T maze task, BVD rats failed to develop a normal learned inhibition response to open space. In an open field maze BVD rats consistently showed 50-60% greater movement velocity, spent on average 35% more time in the inner most aversive part of the arena, and failed to show the normal boundary-seeking behaviour (thigmotaxis) typical of untreated or Sham rats. In a social interaction test BVD rats spent up to 34% less time engaged in social contact compared to Sham rats. In a hyponeophagia test, BVD rats� latency to eat was 70% greater than Sham rats at 3-weeks post-op., however this difference disappeared at 3- and 5-months. These findings suggest that BVD treatment may in some cases disrupt normal behavioral inhibition. Memory performance was also affected. In a T-maze task BVD rats achieved 40-60% correct arm entries, compared to 90-100% for Sham controls. In a foraging task carried out in darkness, BVD rats� initial homing angle was random, homing paths were ~70% longer, and reference memory errors were ~56% greater compared to Sham rats. To elucidate possible neurochemical substrates for these behavioral changes, western blot assays on monoamine proteins were carried out on tissue from a naïve set of rats (BVD n=6; Sham n=6). In BVD rats, serotonin transporter protein expression was 39% lower in CA1 hippocampus and 27% lower in the forebrain region, despite forebrain tryptophan hydroxylase expression being 34% upregulated. Tyrosine hydroxylase expression in the forebrain region was 27% lower in BVD rats. Proteins related to synaptogenesis were also investigated. In the dentate gyrus SNAP-25 was 37% upregulated in BVD rats, while in area CA2/3 of the hippocampus neurofilament-L was 13% upregulated. Forebrain and entorhinal cortex drebrin expression was 28% and 38% downregulated in BVD rats. Neurofilament-L was also 31% downregulated in the forebrain region of BVD rats. To test whether any of these behavioral or biochemical changes may have been attributable to chronic physiological stress, a corticosterone assay was carried out at the conclusion of behavioral testing; however, the no significant between treatment differences were found. In conclusion, vestibular information appears to be needed for the acquisition of spatial and reference memory as well as the normal expression of emotional behaviour. The neurochemical changes described herein point toward possible substrates for these behaviors, however their full significance has yet to be determined.

Bibliography: leaves 193-200. / ix, 200 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Argues that pain or discomfort so widely experienced in "normal" populations cannot, in all cases, have a pathological basis and that, therefore, there must be a non pathological cause. As well, a possible aetiology is suggested for other activity-related conditions which have not yet received generally accepted explanations such as Fibromyalgia. / Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery, RAH, 1996

In vertebrates the brain superimposes control on fundamental processes such as reproduction and growth. Neuropeptides secreted from the brain initiate a cascade of events that affect these processes. In this thesis three neuropeptides are examined to determine their structures and patterns in the context of vertebrate evolution. Reproduction in vertebrates is controlled by the neuropeptide gonadotropin-releasing hormone, GnRH, a decapeptide belonging to a peptide family of twelve known members. One common theme in vertebrates is that there is usually more than one form of GnRH in the brain of a single species; often each form of GnRH has a separate location in the brain and therefore, an implied distinct function. In this thesis, the brain of Siberian sturgeon, Acipenser gueldenstaedti, initially was examined for GnRH using reversed-phase high performance liquid chromatography, HPLC, and radioimmunoassay, RIA, with specific antisera and was shown to contain mammalian (m)GnRH by chemical sequence analysis and by accurate determination of the molecular mass. In addition, another form of GnRH, termed chicken (c)GnRH-II, was found in the sturgeon brain. This is the first report to show that the primary structure of GnRH is identical in an evolutionarily-ancient fish and in mammals including humans. Further, the second form of GnRH, cGnRH-11, was identified for the first time in the brain of adult stumptail monkeys (Macaca speciosa) as well as in adult and fetal rhesus monkey (Macaca mulatta) brains. This study implies that at least two forms of GnRH are found in the brain of most vertebrate species including mammals. In cartilaginous fish that evolved earlier than sturgeon, the same HPLC and RIA methods were used to demonstrate that regions of the brain and pituitary of skate. Raja canebensis, also contained cGnRH-II but dogfish (df)GnRH rather than mGnRH. By the same criteria, teleost fish like whitefish (Prosopium williamsoni), platyfish (Xiphophorus maculatus), green swordtail (Xiphophorus hellerei) and sablefish (Anoplomia fimbria) were shown to have cGnRH-II and salmon (s)GnRH, as well as one or two more immunoreactive variants of GnRH with novel or seabream (sb)GnRH-like properties, within their brain. The identity of at least three types of immunoreactive GnRH molecules in the brain of these fish species suggests that three forms of GnRH in the brain is an early condition in teleost evolution. Ancestral sturgeon emerged at a branch point between the bony fish lineage and the tetrapod lineage and therefore, it is useful to compare the neuropeptide structures found in their brain with those both in fish and more evolutionarily-advanced vertebrates. Several tetrapod species were examined to determine if the forms of GnRH found in the sturgeon brain had been retained in their evolution. In contrasts to studies in our laboratory and by others showing that most amphibians, reptiles and birds contain two forms of GnRH, the present research shows that the brain of the green anole lizard, Anolis carolinensis, contained only cGnRH-II within its brain. In addition, my HPLC and RIA studies showed that only mGnRH was present in the brain of guinea pig, hamster and rat suggesting that there are some species which function with only one form of GnRH in their brain. Also, there were no distinguishable forms of GnRH in a human placenta, demonstrating that the type(s) of GnRH might be tissue-specific. Two neuropeptides associated with growth also were isolated from the sturgeon brain. A cDNA encoding growth hormone-releasing factor, GRF, and pituitary adenylate cyclase-activating polypeptide, PACAP, was isolated and sequenced using the polymerase chain reaction, PCR, and other molecular biology methods. In contrast to mammals where GRF and PACAP are encoded on separate genes, in sturgeon, GRF and PACAP are encoded in tandem on a single mRNA. In this thesis, I establish the structure of GnRH, GRF, and PACAP in sturgeon, a species that evolved near a critical branching point between bony fish and tetrapods. These structures are used as a focal point for comparison to those of other vertebrates. This comparative evolutionary approach is an important step toward understanding the evolution of these important neuropeptides as well as enhancing our knowledge of general principles in the endocrine systems controlling reproduction and growth. / Graduate

yes / Identifying and explaining the pathophysiology of sepsis, as well as the importance of monitoring for indicators of patient deterioration in sepsis.