Temporal lobe epilepsy (TLE) is a common form of intractable epilepsy that can be treated with surgical resection of the epileptogenic medial temporal lobe tissue, specifically the hippocampus. This resection can lead to a variable degree of memory deficit and considerable research has been directed at identifying predictors of these deficits. This thesis explores the relationship between structural predictors and functional predictors in TLE. I looked at fMRI activation asymmetry produced by a scene encoding task as well as volume asymmetry ratios within the hippocampus and the relationship of these predictors to memory performance in patients with TLE. Mediation analysis was performed according to Baron and Kenny (1986) and showed that fMRI activation asymmetry mediated the relationship between volume asymmetry and memory asymmetry in patients with TLE. This suggests that activation asymmetry may be a preferred variable for assessing functional adequacy in the medial temporal region.

The multidimensional nature of the frontal lobes serves to organize and coordinate brain functioning, playing a central and pervasive role in human cognition. The organizational and strategic nature of frontal lobe functioning affects memory processes by enhancing the organization of to-be-remembered information. Among the specific memory systems presumed to be based on anterior cerebral structures is the temporal organization of memory. An essential component of memory that involves temporal organization is sequential ordering. The acquisition of abilities thought to be mediated by the frontal lobes, including sequential memory, unfolds throughout childhood, serving to condition patterns of behavior for the rest of the brain. Development of the frontal regions of the brain is known to continue through late adolescence and into early adulthood, in contrast to the earlier maturation of other cortical regions. The purpose of the present study was to evaluate the development of sequential memory and to compare such findings to what currently is known regarding the development of frontal lobe functioning. Through an analysis of the previously collected standardization data of the Test of Memory and Learning (TOMAL; Reynolds & Bigler, 1994), a developmental function depicting the maturational process of sequential memory was derived. This model was then compared to an overall representative model of frontal lobe functioning. Results indicated a staging of development that begins in early childhood with the maturation of sequential memory continuing, although at a decreased rate, into early adolescence. The greatest period of development in sequential memory was evident between 5 and 8 years of age. The rate of development then decreased, and a continued deceleration of maturation continued throughout the age span examined. Gender was not found to be a significant predictor of developmental performance on sequential memory tasks. The results of the present study are consistent with previous findings that have suggested that the development of frontal functions occurs in a step-wise fashion with greatest period of development in frontal lobe functioning occurring at the 6- and 8-year old levels, with more moderate effects between the ages of 9 and 12 and performance approximating adult levels during adolescence.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 145-158).

Underling neuronal loss and subsequent hippocampal sclerosis, as reflected by hippocampal atrophy on structural magnetic resonance (MR) imaging, are the dominant findings in the patient with mesial temporal lobe epilepsy (MTLE). Yet, prolongation of T2 relaxation time has also been reported as an early marker for MTLE, but it is a rather insensitive marker. Typical age-related atrophy often constitutes a significant confounding factor, and atrophy often represents a late sign in hippocampal sclerosis. In this connection, there is an urge for a sensitive independent predictor for the early detection of MTLE. T1rho MR imaging provides a distinct contrast mechanism in tissue characteristics. It is sensitive to physio-chemical processes and has been tested successfully in Alzheimer’s disease, Parkinson’s disease and certain brain tumors. Therefore, it is possible to depict early biochemical change in patients with MTLE by means of measuring the changes in T1rho relaxation time. T1rho relaxation time is not affected by age-related atrophic changes and thus can be used as an independent marker. In this preliminary study, we aimed to assess the feasibility of T2 relaxometry and T1rho MR imaging in identification of the atrophied zones in patients with MTLE. Seven patients with unilateral MTLE and fourteen normal subjects were recruited. Three-dimensional T1-weighted imaging, axial T2 relaxometry and T1rho imaging were performed on a 3T MR scanner. Hippocampal head, hippocampal body, hippocampal tail and amygdala were contoured on the axial T2-weighted images and then co-registered onto T2 relaxometry and T1rho images. A combination of visual and quantitative volumetric assessment was used as the primary end outcome. For T2 relaxometry and T1rho imaging, their respective relaxation times together with the corresponding right-left asymmetric ratios were calculated for subsequent analysis. Abnormal right-left asymmetric ratio is defined as a deviation of 2SD from the mean of the Z-score. In the lateralizing epileptogenic zones, T1rho yielded an overall accuracy of 92.9% (sensitivity 100%, specificity 60%), while T2 relaxometry yielded an overall accuracy of 71.4% (sensitivity 65.2%, specificity 100%) only. T1rho imaging is thus superior to T2 relaxometry (P = 0.036, by chi-square test). To conclude, the present study indicated that T1rho is feasible and potentially useful to serve as a non-invasive imaging tool in the detection of lateralization of the epileptogenic zone in patients with MTLE. It can also facilitate prompt diagnosis and longitudinal disease monitoring. In addition, the generation of associated color-coded parametric map can provide an easy mean for direct visual analysis. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

The moth Manduca sexta has been a common model for the study of the insect olfactory systems. The neuronal architecture in the antennal lobes (ALs) of insects and in the olfactory lobes of vertebrates is similar in structure and development. In Manduca, as in other olfactory systems, sensory receptor neurons send axons into the AL where they form synapses with local interneurons (LNs) and projection neurons (PNs) within the structural units of glomeruli. Here, I present the morphological development of one type of interneuron, the uniglomerular projection neuron (uPN), in normal AL development and in AL development in the absence of olfactory receptor neurons (ORNs). Using fluorescent-dye labeling of uPNs and confocal microscopy, my results show that in the absence of ORNs, uPN dendritic arborization is uncharacteristic of that in normally developing ALs, reinforcing the concept that afferent input guides the development of architecture in sensory areas of the brain.

Traumatic brain injury (TBI) is a leading cause of disability globally. Cognitive deficits represent the primary source of on-going disability in this population, yet the mechanisms of these deficits remain poorly understood. Here functional and diffusion-weighted imaging techniques were employed to characterize the mechanisms of neurofunctional change following TBI and their relationship to cognitive function. TBI subjects who had sustained moderate to severe brain injury, demonstrated good functional and neuropsychological recovery, and screened positive for diffuse axonal injury but negative for focal brain lesions were recruited for the project. TBI subjects and matched controls underwent structural, diffusion-weighted and functional MRI. The functional scanning paradigm consisted of a complex working memory task with both load and executive control manipulations. Study one demonstrated augmented functional engagement for TBI subjects relative to healthy controls associated with executive control processing but not maintenance operations within working memory. In study two, multivariate neuroimaging analyses demonstrated that activity within a network of bilateral prefrontal cortex (PFC) and posterior parietal regions was compensatory for task performance in the TBI sample. Functional connectivity analyses revealed that a common network of bilateral PFC regions was active in both groups during working memory performance, although this activity was behaviourally relevant at lower levels of task demand in TBI subjects relative to healthy controls. In study three, diffusion-imaging was used to characterize the impact of diffuse white matter pathology on these neurofunctional changes. Unexpectedly, decreased white matter integrity was not correlated with working memory performance following TBI. However, markers of white matter pathology did inversely correlate with the compensatory functional changes observed previously. These results implicate diffuse white matter pathology as a primary mechanism of functional brain change following TBI. Moreover, reactive neurofunctional changes appear to mediate the impact of diffuse injury following brain trauma, suggesting new avenues for neurorehabilitation in this population.

Traumatic brain injury (TBI) is a leading cause of disability globally. Cognitive deficits represent the primary source of on-going disability in this population, yet the mechanisms of these deficits remain poorly understood. Here functional and diffusion-weighted imaging techniques were employed to characterize the mechanisms of neurofunctional change following TBI and their relationship to cognitive function. TBI subjects who had sustained moderate to severe brain injury, demonstrated good functional and neuropsychological recovery, and screened positive for diffuse axonal injury but negative for focal brain lesions were recruited for the project. TBI subjects and matched controls underwent structural, diffusion-weighted and functional MRI. The functional scanning paradigm consisted of a complex working memory task with both load and executive control manipulations. Study one demonstrated augmented functional engagement for TBI subjects relative to healthy controls associated with executive control processing but not maintenance operations within working memory. In study two, multivariate neuroimaging analyses demonstrated that activity within a network of bilateral prefrontal cortex (PFC) and posterior parietal regions was compensatory for task performance in the TBI sample. Functional connectivity analyses revealed that a common network of bilateral PFC regions was active in both groups during working memory performance, although this activity was behaviourally relevant at lower levels of task demand in TBI subjects relative to healthy controls. In study three, diffusion-imaging was used to characterize the impact of diffuse white matter pathology on these neurofunctional changes. Unexpectedly, decreased white matter integrity was not correlated with working memory performance following TBI. However, markers of white matter pathology did inversely correlate with the compensatory functional changes observed previously. These results implicate diffuse white matter pathology as a primary mechanism of functional brain change following TBI. Moreover, reactive neurofunctional changes appear to mediate the impact of diffuse injury following brain trauma, suggesting new avenues for neurorehabilitation in this population.

Through the use of chronic experimental animal models, the majority of in vitro investigations of temporal lobe epilepsy have demonstrated enhanced network activity within the subdivisions of the hippocampal formation. However, clinical evidence in combination with in vivo and in vitro studies indicates that structures external to the hippocampus contribute to the genesis of seizure activity. To address the effects of limbic network excitation, I have utilized combined hippocampal---entorhinal cortex brain slices from pilocarpine-treated rats that display chronic seizures. / My investigations have focused upon three structures, the subiculum, entorhinal cortex and the insular cortex. The experiments in the pilocarpine-treated subiculum demonstrated increased network excitability that was attributed to a more positive GABAA receptor mediated inhibitory post-synaptic potential (IPSP) reversal point coupled with a reduced IPSP peak conductance. Utilizing RT-PCR analysis and immunohistochemical staining we observed a decline in K+-Cl- cotransporter mRNA expression and a reduced number of parvalbumin-positive, presumptive inhibitory interneurons. My second project assessed the network hyperexcitability in layer V of the lateral entorhinal cortex. This is the first study to report spontaneous bursting, in the absence of epileptogenic agents, in the epileptic entorhinal cortex. We attributed this level of network excitation to reduced GABAA receptor mediated inhibition and increased synaptic sprouting. In the final project, we extended our slice preparation to include the insular cortex, a structure external to the temporal lobe. Our investigations identified a mechanism of NMDA receptor dependent synaptic bursting that masked GABA A receptor mediated conductances.

An impression which has dominated both the clinical setting and research literature is that patients with temporal lobe epilepsy (TLE) not infrequently issue "bitter" complaints about their memory function. This observation has rarely been subjected to investigation, based as it is, on the implicit assumption that TLE subjects are "entitled" to a memory disturbance given the involvement of a critical memory structure (i.e, hippocampus) in the pathogenesis of the disorder. While it is almost axiomatic that clinicians become aware of memory difficulties because of the subjective complaints issued by patients, there is growing awareness that the relationship between complaint and objective memory disturbance is a complex and often counterintuitive one. This is particularly true of many patients with TLE who while complaining about their memory function often do so in the presence of objectively normal interictal memory function. / This thesis addressed the question: Why do patients with TLE complain about their memory? It was premised on the notion that memory self-report is not a unidimensional construct explicable in terms of an underlying memory dysfunction alone, but the perception and expression of memory may arise from seemingly disparate sources. The principal objective of the thesis was to systematically and comprehensively investigate the complaint in TLE, and to derive an understanding of the variables which contribute to the perception and expression of poor memory in members of this population. The variables selected for investigation emerged from a detailed review of the literature and can be grouped into five broad conceptual domains: demographic, epileptological, psychological, cognitive, and metacognitive. (For complete abstract open document)

Thesis (M.Sc.)(Psych.)--University of Melbourne, Dept. of Behavioural Sciences, 2006. / Typescript. Includes bibliographical references (leaves 132-148).