published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Paediatrics / Master / Master of Philosophy

Brain damage in the first week of life is behaviorally and anatomically devastating for a rat. I investigated the use of pre- and/or postnatal experience as interventions that might improve the outcomes in rats with postnatal day 4 (P4) frontal cortex lesions. Prenatal maternal tactile stimulation or maternal complex housing facilitated recovery in P4 lesion animals and produced changes in brain organization. Post-lesion tactile stimulation also was found to be beneficial possibly via experience dependent changes in FGF-2 expression. Levels of FGF-2 were increased in both skin and brain after tactile stimulation and correlated with behavioral and anatomical changes. Direct post-lesion administration of FGF-2 had similar effects. These results are the first demonstration that prenatal experience can be prophylactic for postnatal brain injury and that behavioral experience can act on brain organization via enhanced trophic factor expression originating in skin. / xxi, 221 leaves : ill. ; 28 cm.

The time course of peri-infarct diaschisis following a focal ischemic infarct and the effects of delayed rehabilitation on behavioral and functional recovery were examined. Intracortical microstimulation (ICMS) was used to derive topographical maps of forelimb representations within the rat motor cortex and ischemia was induced via bipolar coagulation of surface vasculature. At one hour there was a dramatic expansion of reprentations in control but not ischemic animals. A significant loss of forelimb representations within peri-infarct dysfunction indicates the need for immediate administration of therapeutic interventions following an ischemic event. These results indicate that the timing of rehabilitation does not effect functional and behavioral recovery but does support the need for rehabilitative interventions of facilitate these types of recovery. / 132 leaves : ill. ; 28 cm.

Mild head injury or concussion accounts for as many as 90% of all traumatic brain injuries and can sometime result in long-lasting and disabling post-concussion symptoms (PCS), even in the absence of detectable structural damage to the brain by morphological imaging. To date, the nature of persistent PCS following mild head injury remains poorly understood as objective and scientifically valid diagnostic tools are practically absent. This, in turn, likely accounts for missed diagnoses, prevents accurate assessment of the severity of the injury and creates difficulties for achieving proper patient management. / This dissertation describes 4 functional magnetic resonance imaging (fMRI) studies designed to establish whether there is a pathological basis to persistent PCS following cerebral concussion in male athletes. Study 1 was intended to evaluate the feasibility of using fMRI to detect changes in brain activation following concussion. The results showed that concussed athletes displayed reduced prefrontal activities compared to a healthy control group when performing a working memory task. In Study 2, we examined the relationship between self-reported PCS and the pattern of brain activity measured by fMRI. The severity of self-reported PCS was found to be associated with blood oxygen level dependent (BOLD) activation patterns in the region of interest: the higher the PCS score the lower the BOLD signal. In Study 3, we used serial fMRI approach to investigate brain activation pattern in the course of injury recovery. The results showed that symptom resolution was accompanied by a return to normal BOLD response patterns. Study 4 was designed to investigate the nature of depression, a common PCS, following concussion. Concussed athletes with depression showed less activation in the dorsolateral prefrontal cortex, and attenuated deactivation in the medial prefrontal region, consistent with functional neuroimaging findings in major depression. Again, depression severity correlated with the strength of the fMRI signal in the region of interests. / Taken together, these results demonstrate the value of functional MRI in the evaluation of cerebral concussion, and provide evidence of an underlying pathology in persistent PCS following concussion.

Alexandria Luria's approach to neuropsychological assessment and his theory of brain functioning have been exploited in order to develop a neuropsychological evaluation procedure for children which incorporates a conceptualization of brain-behaviour development. Luria's Neuropsychological Investigation for adults was administered to intact children aged eight to 14 years in order to ascertain which tasks were beyond their capabilities. These were then adapted or deleted. The adapted version of the protocol was then administered to a second group of intact children to determine that the proposed adaptations were appropriate. This process was guided by the results of a statistical analysis which revealed significant findings with respect to age, socioeconomic status, and task performance. A model of brain-behaviour development and interpretive protocol were devised. Together these provide a conceptual and interpretive framework for the battery. Developmental trends which emerged whilst developing Luria's Neuropsychological Investigation for Children (LNI-C) were consistent with the progressive development of successively more complex forms of information processing as depicted in this model. They were also in keeping with prominent developmental theories such as those of Piaget and Vygotsky. These trends revealed that children made most mistakes on adult LNI tasks involving abstract reasoning, the simultaneous synthesis of data, and complex goal-directed behaviour - all of which apparently reflect tertiary cortical zone functioning. Fewer mistakes were related to a lack of training and inability to process the same quantity of information as adults - difficulties which seemed related to secondary zone functioning. None of the mistakes made appeared to reflect subcortical or primary zone functioning. The LNI-C was applied to brain-damaged children who had had a CT scan in order to demonstrate its application and the hypothetico-deductive process of interpreting findings using the concepts of syndrome analysis and double dissociation. The LNI-C findings were consistent with the general pattern of symptoms Luria described for different brain disorders and lesion localities in children, although additional insight into the nature of the sequelae present was gained in each case. In early brain damage, the most frequent disturbances were a disruption in the role played by executive functions and the ability to process data simultaneously - both of which are associated with the tertiary zones of the brain. Furthermore, these disturbances appeared to be important factors underlying disturbances to language and educationally acquired skills. The qualitative, process-orientated nature of the LNI-C proved effective for identifying the factors underlying disturbances described in paramedical reports. These seemed to be the linchpins on which retraining should focus. It was argued that the CT scan was limited in its ability to identify the type of diffuse and/or multifocal brain pathology frequently found in children. The usefulness of the model of brain-behaviour ontogeny and interpretive protocol for diagnosis, understanding and predicting the developmental consequences of childhood brain pathology was demonstrated on the basis of nine brain disorders. Finally, areas of future research were highlighted by the study. / Thesis (Ph.D.)-University of Natal, Durban, 1989.

No description available.

The present study attempts to further define the neuropsychological characteristics associated with mild, moderate, and severe closed head injuries (CHI). The Dean-Woodcock Neuropsychological Assessment System (D-WNAS), a new neuropsychological battery, was administered to 119 CHI patients. The scores of the cognitive portion of the D-WNAS were then analyzed via cluster analysis in an attempt to further delineate neuropsychological impairment into more specific classifications occurring within types of brain trauma.Results suggested that the cognitive portion of the D-WNAS was effective in separating 4 subtypes within CHI, which are best interpreted as "profiles" or characteristics associated with "levels" of impairment. These levels of impairment were characterized by distinctly different subtest profiles, and were labeled as mild/high functioning, mild, moderate, and severe. The highest performing group, mild/high functioning, showed no neuropsychological deficits. The most severely impaired group was characterized by many deficits in short-term memory, visual stimuli, new learning, processing speed, visual-spatial abilities, abstract reasoning, attention/concentration, and remote memory tasks. A multivariate analysis showed that educational level was significant in differentiating between the subtypes and suggested that, depending on the severity of injury, educational level might also protect individuals from obtaining a poorer prognosis.From this investigation, the cognitive portion of the D-WNAS appears to offer valuable utility in identifying CHI patients and in further classifying their varied neuropsychological characteristics. Implications for diagnosing and differentiating between different levels or profiles of CHI was discussed. / Department of Educational Psychology

This thesis investigates the reading and writing of two patients with brain injuries due to cerebro-vascular accidents. Background tests show both patients to be moderately anomic and to have severe impairments in reading and writing nonwords. Investigations of the locus of impairment in AN's nonword reading showed her to have normal orthographic analysis capabilities but impairments in converting single and multiple graphemes into phonemes and in phonemic blending. The central issue studied was the role of lexical but non-semantic processes in reading aloud, writing to dictation and copying. For this purpose a "familiar nonword" paradigm was developed in which the patients learned to read or write a small set of nonwords either with or without any associated semantics. Both AN and AM were able to learn to read nonwords to which no meanings were attached but they could still not read novel nonwords. Both patients were unable to report any meanings for the familiar nonwords when they read them and there was no evidence that learning to read them improved their sub-lexical processing abilities. These results are evidence for a direct lexical route from print to sound that is dedicated to processing whole familiar words. It was also shown with AN that if nonwords are given meanings then learning is faster than if they are not given meanings. Experiments designed to test the hypothesis that nonwords are read by analogy to words found no support for it. Both patients have severe impairments in writing novel nonwords to dictation. As they can repeat spoken nonwords after they have failed to write them, this is not due to a short-term memory impairment. Despite their nonword writing impairments, both patients were able to write to dictation the meaningless nonwords that they had previously learned to read at the first attempt, and AN did so one month after learning to read them. Neither patient however, could write novel nonwords made by reordering the letters of the familiar nonwords. Furthermore, the familiar nonwords used spellings that are of a priori low probability. The familiar nonwords must therefore have been written using lexical knowledge. Tests of semantic association showed that the familiar nonwords evoked no semantic information that the patients could report. Function words dictated to AN evoked little semantic information but she wrote them to dictation significantly better than nonwords made by reordering their letters. These results are evidence for a direct lexical route for writing to dictation. Copying was studied both with and without a five second delay between presentation and response. AN was better at delayed copying of meaningless but familiar nonwords than she was at copying novel nonwords. She was also better at delayed copying of six-letter, bi-syllabic nonwords that she had been trained to copy than she was at copying novel nonwords made by recombining the first and second halves of the familiar nonwords such that these halves retained their positions from the parent nonwords. AN was better at copying function words than nonwords made by reordering their letters. She was also better at copying function words than she was at reading or writing them to dictation. These results are evidence for a direct lexical route for copying. AN and AM were both able to write to dictation nonwords that they had never heard or written before but with which they had been made visually familiar during a visual discrimination task. They must have used lexical knowledge to do so because the spellings used were of a priori very low probability. The creation of lexical orthographic information which can be retrieved from novel auditory input raises difficulties for current models and various possible interpretations are discussed. Finally, some of the possible implications of the re-learning abilities shown by these patients, for rehabilitation procedures are discussed briefly.

The overall aim of this thesis was to characterize single-channel aEEG/EEG, recorded during the first postnatal days in preterm infants, in relation to brain function and two-year outcome. Study I investigated if aEEG/EEG was associated with neonatal brain injury, inflammation and outcome in 16 very preterm (VPT) infants. The interburst interval (IBI) was prolonged, and aEEG amplitudes were lower in infants with brain injury, and in infants developing handicap. Cord blood TNF-α correlated with IBI. Study II investigated inter-rater agreement of visual burst detection, as compared to automated burst detection based on a non-linear energy operator (NLEO) in an EEG data set from 12 extremely preterm (EPT) and 6 VPT infants. The sensitivity of the NLEO was 64 % and 69 % (EPT and VPT infants, respectively) and the specificity 96 % and 88 %. The algorithm was then modified to further improve the accuracy. Study III investigated if arterial carbon dioxide and plasma glucose is associated with EEG continuity. In 247 sets of samples (PaCO2, plasma glucose, IBI) from 32 EPT infants there was a positive association between PaCO2 and IBI; higher PaCO2 was associated with longer IBI. Corrected for carbon dioxide, plasma glucose had a U-shaped association with IBI in infants with good outcome. Study IV investigated the predictive value of aEEG/EEG in 41 EPT and 8 VPT infants. All VPT infants had good outcome. Predictors of outcome in EPT infants included presence or absence of burst-suppression, continuous activity and cyclicity, median IBI and interburst%. Seizures were associated with neonatal brain damage but not with outcome. Improved preterm brain monitoring may in the future be used for early identification of infants at high risk of brain damage and adverse outcome, which may have implications for direction of care and for early intervention.