No description available.

One of the consequences of traumatic brain injury is the postconcussion syndrome. The symptoms in this syndrome include headache, dizziness, poor memory, poor concentration, easy fatigue, drowsiness, irritability, sensitivity to light, sensitivity to noise, low alcohol tolerance, visual problems, auditory problems, nausea, vomiting, anxiety, and depression. Several factor analytic studies have shown that these symptoms load onto cognitive and noncognitive factors (Bohnen, Twijnstra, & Jolles, 1992). The aim of this study was to determine whether patients who report different symptoms also evidence differences in cognitive deficits, as indexed by reaction time. For this purpose 106 subjects (mean age 25.92 years; SD=6.05) of both sexes were tested on 8 reaction time tasks adapted from Shum, McFarland, Bain, and Humphreys (1990). There were 54 traumatic brain injury patients (mean age 26.40 years; SD=6.23) drawn from three Pretoria hospitals. They were heterogeneous with respect to diagnosis and severity of injury. For the controls (N=52), the mean age was 25.43 years (SD=5.88). The eight reaction time tasks constituted 4 task variables, each with 21evels. From these tasks, 36 reaction time indexes were derived. The indexes were classified into 4 groups, viz., reaction time (RT), movement time (MT), total reaction time (TT), and subtraction scores (SB, the difference between the 2 levels for each task variable). RT reflects the decision component and MT reflects the response execution component of reaction time. Partial correlation coefficients for all symptoms (p0,01) showed that some symptoms were most frequently associated with RT whilst others were most frequently associated with MT. On factor analysis with varimax rotation, symptoms loaded predominantly with SB scores. Symptoms also loaded with different task variablseuiggesting that they correlated with deficits on different stages of information processing. Taking into account possible methodological constraints that were discussed, these results confirm that different symptoms within the postconcussion syndrome correlate with different cognitive deficits. The correlations between symptoms and indices of reaction time are moderated by the characteristics of the symptoms (frequency & intensity), and the duration since injury. These findings have significance for understanding the aetiology of the postconcussion symptoms and for planning treatment. / Psychology / Ph. D. (Psychology)

The present study aimed at investigating the neuropsychological sequelae of transient ischaemic attacks. Transient ischaemic attacks are defined as those neurological disorders in which there is complete resolution of neurological symptoms within twenty·four hours. Transient ischaemic attacks may or may not reveal evidence of brain infarcts on imaging studies. In the present study, the neuropsychological sequelae of transient ischaemic attacks in the carotid circulation were investigated since, within the perspective of cognitive neuropsychology, it was assumed that localized changes in cognitive functions could be demonstrated.Since several psychological, medical and neurological factors are known to influence scores·on neuropsychological tests, regression analyses were performed to determine which factors contributed significantly to the variance of scores on neuropsychological tests in the transient ischaemic attack and control groups. Two transient ischaemic attack groups, each comprising forty left and forty right hemisphere involvement patients, were then compared with each other and with a control group of forty general medical patients. Stenosis of the carotid artery formed a significant predictor of test scores in the combined transient ischaemic attack group. When the groups were·analyzed independently, in the left transient ischaemic attack group stenosis predicted performance on the same tests reaching significance for the combined group, and for the Wisconsin Card Sorting Test (Perseverative Score). In the right transient ischaemic attack group, stenosis significantly predicted performance on Digits Forward, Backward and Total, the PASAT (2.4 seconds) and Trails B. On the other hand, education formed a significant predictor of performance on Digits Forward, Digits Backward and Digits Total and the PASAT (all levels) in the control group. Multivariate comparisons revealed that the left and right transient ischaemic attack groups performed worse than the controls on tests of attention, concentration and conceptual flexibi1ity. The left transient ischaemic attack group performed worse than the right transient ischaemic attack group on all tests of attention and concentration, but there was a significantly better performance of the former group on the Rey Auditory Verbal Learning Test (Trial 1), Block Designs and Verbal Fluency. The findings on the PASAT that left transient ischaemic attack patients performed significantly worse than the right hemisphere group ·were considered to be relatively unreported previously in the literature on transient ischaemic attacks. The findings obtained are discussed from a neurocognitive perspective of neuropsychological functioning in transient ischaemic attacks. / Psychology / Ph. D. (Psychology)

Introduction: After a brain injury there are often long term consequences impacting on QoL. However, this is a complex issue influenced by many factors. As someone recovers and adjusts it is likely that the way in which they evaluate QoL will also change. The theory of response shift suggests people will change the way they evaluate QoL in the face of changes in their life. The aim of this thesis is to investigate what influences a QoL judgement; examining the possibility of response shift. Methods: Quantitative and qualitative methods were used in 4 studies. These were a cross-sectional design utilising an individualised QoL measure (SEIQoL-DW); a longitudinal study utilising a ‘then-test’ approach; a cross-sectional questionnaire study; and a qualitative study using Interpretative Phenomenological Analysis. Study 1 (Ch.3) Results: Correlations between the QoL measures confirm the validity of the SEIQoL-DW; however, correlations were generally stronger for the simpler Hadorn Scale. There was little overall change in mean QoL when current and retrospective judgements were compared. There was evidence for a change in what areas of life were considered most important to QoL following injury. Study 2 (Ch.4) Results: Improvements in reported QoL between baseline and follow-up were small. A then-test indicates that any effect of response shift is small, and non-significant in the current research. There was also little evidence for reprioritisation or re-conceptualisation. Examination of other factors associated with QoL suggest that brain-injury specific factors (BIGI, RBANS) play a role in predicting QoL. Study 3 (Ch.5) Results: QoL was reported as worse post-injury on both Hadorn’s scale and the QOLIBRI-OS; a difference that was more pronounced on the QOLIBRI-OS. Differences were also reported in the importance of different areas of functioning. Change in QoL as measured by the QOLIBRI-OS was significantly influenced by disability as measured by the GOSE, emotional and informational support, and upwards social comparison. Optimism as measured by the LOT, but not upwards social comparison was a significant predictor of change on Hadorn’s scale; GOSE and emotional and informational support remain significant predictors. The GOSE, emotional and informational support, emotional coping styles and optimism were significant predictors of current QoL on the QOLIBRI-OS; and emotional and informational support and optimism were significant predictors of QoL on Hadorn’s scale. Little evidence was found to suggest that the factors proposed in Sprangers and Schwartz’s (1999) model of response shift have predicted relationships with QoL. Two candidate variables were studied: optimism and social support. However neither showed the predicted pattern of relationships. Nonetheless the study supports previous work indicating an influence of optimism and social support on QoL, and indicates that these warrant further study. There were systematic difference between current and retrospective ratings of importance of domains. The level of importance given to the areas of life defined by the QOLIBRI-OS is higher after injury than before, with the exception of “personal and social life” for which there is no significant difference. The areas of life chosen to reflect that which is measured by the GOSE (“work”, “close relationships”, and “social and leisure activities”) are rated as less important with the exception of “close relationships”. These findings provide further support for the idea that QoL domains are re-evaluated after brain injury. Study 4: This was an in depth qualitative investigation of the experience of recovery and adjustment following TBI. Semi-structured interviews and Interpretative Phenomenological Analysis (IPA) were used. Interviews were conducted with 4 men who were 3, 7, 12, and 18 years post injury. Main Outcome and Results: Themes emerging from the analysis were ‘Change: In Self and World’; ‘Reaching a point of realisation’; ‘Support’; ‘Adjusting to change/Coping with day to day life’; and ‘Participation, Goals and Focus’. These themes cover how participants felt both they and their lives had changed as a consequence of their injury; ways they went about coping and adjusting to changes; the importance of support; and the significance of social integration and participation in feeling satisfied with life. Summary and Conclusions: These studies provide evidence for response shift in different ways. There is little evidence for recalibration but there is some indication that reprioritization or reconceptualization may take place. Changes in how important different areas of life are before and after injury suggest that participants are changing the way they view and make evaluations of QoL. Factors identified as being important to QoL judgements were disability, social support (emotional and informational support identified in the questionnaire study and support in the IPA), upwards social comparison, and optimism. The IPA study suggests that functional outcome and participation are important after TBI; while also identifying ways of coping and providing an insight into the experience of recovery from brain injury. The different QoL measures used provides both evidence for their validity, but also evidence for the different conceptualisations of QoL that are measured by different instruments. The findings have implications both for understanding the QoL of the individual and for research on QoL after TBI.

No description available.

Quantitative electroencephalography (QEEG) was used in this study to describe cognitive processing, particularly brain locations used, during performance of the Wisconsin Card Sorting Test (WCST). The hypothesis was that significant cognitive functioning is not limited to the frontal lobes. Significant EEG activity was found in non-frontal areas as well as frontal areas.

Reitan and Wolfson's General Neuropsychological Deficit Scale and Left and Right Neuropsychological Deficit Scales were applied to Halstead-Reitan test data of individuals with psychotic or substance abuse disorders with and without a head injury.

The Embree/Butler scoring system served as criterion for ascertaining brain dysfunction on the protocols of 100 subjects--50 had been diagnosed by health professionals as having brain dysfunction, and 50 had been diagnosed as having no brain dysfunction. In comparing the hospital's diagnoses with those of the Embree/Butler method, the data strongly supported the hypothesis that the Embree/Butler scoring system did effectively discriminate (chi square of 77.99 < .01) between those with organic brain syndrome (or cerebral dysfunction) and those with psychiatric classification. A point-biserial correlation was used to distinguish the relationship between diagnosis and the score. A cutoff score of above 14 produced the least false-negative or false-positive evaluations.

Ependymin (EPN) is a goldfish brain neurotrophic factor (NTF) previously shown to function in a variety of cellular events related to long-term memory formation and neuronal regeneration. Because of these functions, EPN and other NTFs have potential applications for treating neuro-degenerative conditions, including stroke. In previous experiments, our lab in collaboration with Victor Shashoua of Ceremedix Inc (Boston, MA), designed short synthetic peptide CMX-8933 (a proteolytic cleavage product of EPN) and CMX-9236 (an EPN-Calmodulin combination peptide) that mimic the action of full-length EPN. In a rat stroke model, administration of these peptides i.v. significantly lowered brain ischemic volume (Shashoua et al., 2003). Because oxidative stress is one of the primary mediators of cell damage following a stroke, we hypothesized that NTFs, and in particular our therapeutic peptides, may act in part by reducing neuronal oxidative stress. Thus, the purpose of this thesis was to determine whether CMX-8933 and CMX-9236 increase the cellular titers of anti-oxidative enzymes. A hybridization array was used as a“hypothesis generator" to obtain candidates for further analysis. This approach applied to rat primary brain cortical cells treated with CMX-8933 identified superoxide dismutase (SOD) as strongly upregulated. SOD immunoblots on whole cell lysates, and RT-PCR on total cellular RNA, were used to confirm this observation. In time-course and dose-response experiments, treatment of rat primary cortical cultures with either peptide showed an optimal 8.5 fold (N = 5, p < 0.001) increase in SOD protein, while administration of CMX-8933 to murine neuroblastoma cells caused a 6.5 fold (N = 3, p = 0.001) increase in SOD mRNA levels. Previous work in other laboratories indicated that systemic (i.v.) administration of full-length NTFs allows only an inefficient delivery across the blood brain barrier (BBB). We hypothesized that our short synthetic peptides may cross the BBB more efficiently. Immunoblot analysis of brains and hearts excised from mice treated i.v. with various doses of CMX-8933 confirmed the elevated SOD titers (10 fold in brain, and 8 fold in heart, at a 6 mg/kg dose for 5 hr; N = 5, p < 0.001). Furthermore, we hypothesized that conjugation of CMX-8933 to BBB carrier DHA, a natural neuronal membrane fatty acid shown previously to enhance the delivery of dopamine to the brain (Shashoua and Hesse, 1996), might further enhance the NTF therapy. Delivery of DHA-8933 increased SOD expression by 3 fold (N = 4, p < 0.001) relative to non-conjugated CMX-8933. Recently, the use of special incubators that allow the culture of cells under low oxygen conditions (anoxia) has been used as an in vitro model for stroke. When we tested our peptides in this new in vitro model, surprisingly SOD was upregulated 3 fold (N = 3, p = 0.003) in rat primary cortical cells cultured for 24 hr under oxygen deprivation, compared to normoxic conditions. This implies that these rat cultures may have an endogenous cellular system for responding to oxygen stress, a finding worthy of further investigation. Treatment of anoxic cells with CMX-8933 increased SOD levels another 2.8 fold (N = 3, p < 0.001) compared to the levels for anoxia alone (for a total of 8.5 fold relative to normoxic cells). Altogether, the data from this thesis illustrate that small NTF EPN peptide mimetics increase the cellular titers of the mRNA and protein for the anti-oxidative enzyme SOD, which may be an important step in their known therapeutic benefits.

Multiple sclerosis (MS) is a prevalent and progressive autoimmune inflammatory disease affecting both white and gray matter and resulting in lesions and atrophy within the central nervous system (CNS) (Bermel & Bakshi, 2006; Confavreux & Vukusic, 2006; Cree, 2012; Friese, Schattling, & Fugger, 2014). Fine motor impairment, including manual motor speed and fine motor dexterity deficits, is common in MS patients (e.g., Benedict et al., 2011; Chipchase, Lincoln, & Radford, 2003). However, impairment does not progress uniformly across patients (Confavreux, Vukusic, Moreau, & Adeleine, 2000; Filippi & Rocca, 2011; Scalfari, Neuhaus, Daumer, DeLuca, & Muraro, 2013) and the association between disease burden and physical disability is moderate at best (Bermel & Bakshi, 2006; Filippi et al., 2013). Though the brain reserve hypothesis has helped to explain the clinico-pathologic dissociation between cognitive functioning and disease burden in MS patients (Sumowski et al., 2013; Sumowski et al., 2014a), there is no published literature on brain reserve and motor functioning in MS. Instead, only preliminary data have been presented on brain reserve and general physical disability (Sumowski et al., 2014b). As such, the purpose of this dissertation was to examine the protective effect of brain reserve, estimated via intracranial volume (ICV), on fine motor functioning in relapse-onset MS patients. A sample of 178 relapse-onset, right-handed MS patients underwent neuropsychological testing along with neurological examination, including magnetic resonance imaging (MRI). As part of the evaluation, patients were administered the Nine Hole Peg Test (NHPT; a measure of fine motor speed and dexterity) and the Finger Tapping Test (FTT; a measure of manual motor speed), which served as this study’s outcomes (i.e., dependent variables). Predictors (i.e., independent variables) included demographic variables (age, sex), disease variables (disease duration and disease phenotype, including relapsing-remitting MS (RRMS) or secondary-progressive MS (SPMS)), MRI estimates of disease burden (T2 lesion volume [T2LV], normalized brain volumes as measures of cerebral atrophy), and MRI-derived measures of ICV as an estimate of brain reserve. Results revealed that phenotype (r = .56, p < .001) significantly predicted performance on the NHPT, such that patients with SPMS did worse than patients with RRMS. Regarding disease burden, T2LV (r = .24, p = .001) and normalized gray matter volume (r = -.18, p = .019) predicted NHPT, with less disease burden associated with better performance. Greater ICV (r = -.21, p =.006) was also significantly associated with better performance on the NHPT. Next, phenotype (r = -.45, p < .001) predicted FTT with SPMS patients again performing worse than RRMS patients. Sex (r = .40, p < .001) was a significant predictor of FTT with men outperforming women, on average. For FTT, normalized gray matter volume (r = .36, p < .001) was the only measure of disease burden that predicted performance, with greater volume (i.e., less atrophy) associated with better performance. Similarly, greater ICV (r = .31, p < .001) significantly predicted better performance on the FTT. For both NHPT and FTT, interactions between measures of disease burden and ICV were not significant. As such, some evidence from this study was not consistent with the reserve hypothesis; however, this finding may be due to differences in the way brain reserve impacts motor outcomes (relative to cognitive outcomes). Nonetheless, as ICV was associated with better performance for both outcome measures, these findings provide partial support for the brain reserve hypothesis in fine motor functioning in MS. Therefore, findings from this study have real-life applications with regard to improved understanding of fine motor disability in MS and identification of patients at risk for upper extremity dysfunction, leading to the possibility of early intervention. Findings also have implications for informing clinical research in MS. Future research should examine the protective effect of brain reserve on fine motor functioning within larger cross-sectional samples (i.e., RRMS vs. SPMS), within primary-progressive MS (PPMS) patients, and when using additional measures of upper extremity disability (e.g., Grip Strength Test). Longitudinal research would also help to determine whether there is a moderating effect of brain reserve on fine motor disability progression as well as allow patients to serve as their own baseline, which would control for individual differences in motor functioning. Next, examining reserve in patients experiencing lesions and atrophy in specific brain regions underlying motor function (e.g., cerebellum and precentral gyrus) may help explain why interactions between disease burden and ICV were not significant within the present study. Finally, by testing the brain reserve hypothesis as it relates to fine motor functioning in non-clinical, healthy controls, it would be possible to determine whether the protective effect of reserve is present premorbidly.