This thesis explored the relationship between temporal lobe epilepsy and aggressive behavior. Prior studies have shown that temporal lobe epileptics display more aggressive behavior than do epileptics with other brain foci. This investigation explored the above mentioned relationship as it exists among the resident population of the New Castle State Hospital. Fifty-three temporal lobe subjects were identified and then matched with respect to age, sex, institutional environment, age of seizure onset, and medication. Frequency of aggressive acts was the dependent variable observed.Temporal lobe epileptics were observed tom differ from the non-temporal lobe epileptics in aggressive behavior. The non-temporal lobe epileptics were found to be significantly more self-aggressive (p<.05). Analysis of aggression towards objects or aggression toward other persons was not significant.

Temporal lobe epileptics often experience interictal (i.e., between-seizure) emotional disturbances such as fear and anxiety. Despite the problem that these disturbances present, little progress has been made in characterizing their nature and etiology because they are not amenable to experimental analysis in clinical populations. Accordingly, the general purpose of the experiments in this thesis was to demonstrate the potential of long-term amygdala kindling in rats as a model of the interictal hyperemotionality of temporal lobe epileptics. Seven experiments comprise this thesis. Experiments 1 and 2 established that longterm amygdala kindling (i.e., 100 stimulations) results in large and reliable increases in emotionality. In Experiment 1, the long-term amygdala-kindled rats displayed more resistance to capture from an open field and more open-arm activity on an elevated plus maze than did the sham-stimulated rats; in Experiment 2, the magnitude of this hyperemotionality was shown to be dependent on the number of amygdala stimulations that the rats received. Experiment 3 showed that kindling-induced hyperemotionality is enduring; the hyperemotionality present 1 day after the final stimulation did not decline significantly over the ensuing month although some amelioration of symptoms was observed. Experiment 4 established that kindling-induced hyperemotionality is not unique to amygdala stimulation. Although increases in emotionality were greatest in amygdalakindled rats, hippocampal-kindled, but not caudate-kindled, rats also displayed significant increases. Experiments 5 and 6 showed that kindling-induced hyperemotionality is fundamentally defensive in nature. In Experiment 5, amygdala-kindled rats displayed high levels of emotionality in an unfamiliar, but not in a familiar, situation; in Experiment 6, amygdala-kindled rats displayed more defensive, but less aggressive behaviour, in their interactions with other rats. Finally, Experiment 7 showed that 8-OH-DPAT binding to serotonin 5HT1A receptors is increased in the dentate gyrus of amygdala-kindled rats, but not in the amygdala, periaqueductal grey, perirhinal cortex, or CA1 or CA3 hippocampal subfields. Together, the results of these experiments establish the potential of long-term amygdala kindling as a useful animal model of interictal emotionality in temporal lobe epileptics.

Temporal lobe epileptics often experience interictal (i.e., between-seizure) emotional disturbances such as fear and anxiety. Despite the problem that these disturbances present, little progress has been made in characterizing their nature and etiology because they are not amenable to experimental analysis in clinical populations. Accordingly, the general purpose of the experiments in this thesis was to demonstrate the potential of long-term amygdala kindling in rats as a model of the interictal hyperemotionality of temporal lobe epileptics. Seven experiments comprise this thesis. Experiments 1 and 2 established that longterm amygdala kindling (i.e., 100 stimulations) results in large and reliable increases in emotionality. In Experiment 1, the long-term amygdala-kindled rats displayed more resistance to capture from an open field and more open-arm activity on an elevated plus maze than did the sham-stimulated rats; in Experiment 2, the magnitude of this hyperemotionality was shown to be dependent on the number of amygdala stimulations that the rats received. Experiment 3 showed that kindling-induced hyperemotionality is enduring; the hyperemotionality present 1 day after the final stimulation did not decline significantly over the ensuing month although some amelioration of symptoms was observed. Experiment 4 established that kindling-induced hyperemotionality is not unique to amygdala stimulation. Although increases in emotionality were greatest in amygdalakindled rats, hippocampal-kindled, but not caudate-kindled, rats also displayed significant increases. Experiments 5 and 6 showed that kindling-induced hyperemotionality is fundamentally defensive in nature. In Experiment 5, amygdala-kindled rats displayed high levels of emotionality in an unfamiliar, but not in a familiar, situation; in Experiment 6, amygdala-kindled rats displayed more defensive, but less aggressive behaviour, in their interactions with other rats. Finally, Experiment 7 showed that 8-OH-DPAT binding to serotonin 5HT1A receptors is increased in the dentate gyrus of amygdala-kindled rats, but not in the amygdala, periaqueductal grey, perirhinal cortex, or CA1 or CA3 hippocampal subfields. Together, the results of these experiments establish the potential of long-term amygdala kindling as a useful animal model of interictal emotionality in temporal lobe epileptics. / Arts, Faculty of / Psychology, Department of / Graduate

Verbal memory deficits are among the most prominent cognitive sequelae in individuals with left temporal lobe epilepsy (LTLE). However, relationships between verbal memory function and white matter integrity (WMI) in the left temporal lobe remain unclear. Current study aims included determining fractional anisotropy (FA) and mean diffusivity (MD) differences as an index of WMI between participants with left temporal lobe epilepsy (LTLE), participants with right TLE (RTLE), and controls, establishing group differences based on verbal memory function between TLE groups, and describing relationships between WMI and verbal memory function within TLE groups. Probabilistic tractography defined the left fornix (FRX), left uncinate fasciculus (UF), left parahippocampal cingulum (PHC), and a control region, the left corticospinal tract (CST), in 26 LTLE, 29 RTLE, and 20 control participants. The LTLE group demonstrated significantly lower fractional anisotropy (FA) along the PHC compared with controls. LTLE and RTLE groups did not differ significantly on measures of verbal memory until analyses were restricted to participants with left-lateralized language functioning. PHC FA was negatively correlated with semantic memory function in LTLE, but positively associated with episodic memory functioning in RTLE. Overall, findings highlight the PHC as vulnerable in LTLE, and differentially related to verbal memory functioning based on TLE group. Both findings are likely secondary to left-lateralized white matter disruption in LTLE. The current study also highlighted the importance of identifying homogenous groups to more clearly identify brain-behavior relationships. Current findings further define left-lateralized white matter alternations and related verbal memory deficits in TLE. Implications for these findings are presented in context with previous TLE literature, and future directions for further study are discussed.

No description available.

The Wechsler Memory Scale (WMS) is the most extensively used battery for memory assessment of adults. The third edition of the WMS (WMS-111) represents a substantial revision of previous versions. Accordingly, issues of validity of the revised instrument need to be addressed. The purpose of these studies was to contribute to the validation of the scale in the assessment of patients with temporal lobe epilepsy WE). An important role of the neuropsychological evaluation in TLE is to aid in the localization and lateralization of dysfunction. This is based on the premise that the temporal lobes are specialized for the acquisition of material-specific information, with dysfunction in the left and right mesial temporal regions being associated with verbal and nonverbal memory impairment, respectively. Since the WMS is utilized by the vast majority of epilepsy centres, evaluation of its meaning and utility in this population is essential. In Study 1, the utility of the WMS-I11 in detecting lateralized impairment was examined in a sample of patients with left (n = 55) or right (n = 47) TLE. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory-Visual Index discrepancy scores. The Auditory- Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction; however, the rarity of such scores limits their usefulness. ill In Study 2, five competing models specifying the factor structure underlying the WMS- 111 primarysubtest scores were evaluated in a large sample of patients with TLE (N = 254). Models specifying separate immediate and delayed constructs resulted in inadmissible parameter estimates and model specification error. There were negligible goodness-of-fit differences between a 3-factor model of working memory, auditory memory, and visual memory, and a nested- more parsimonious- 2-factor model of working memory and general memory. The results suggested that specifying a separate visual memory factor provided little advantage for this sample- an unexpected finding in a population with lateralized dysfunction, for which one might have predicted separate auditory and visual memory dimensions. These findings add to a growing literature which suggests that the WMS-I11 has little utility in detecting lateralized dysfunction in TLE. This has important implications for the preoperative assessment of epilepsy patients.

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.

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.

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

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)