Thomas G. Brown, Ph.D., co-directeur de recherche / Objectifs : La capacité en matière de prise de décisions des récidivistes de conduite avec capacités affaiblies (CCA) semble les distinguer des non-contrevenants, particulièrement dans des situations ambiguës à haut risque, telles que la CCA. Cette étude exploratoire vise à vérifier l’hypothèse selon laquelle les récidivistes de CCA (R) auraient une moins bonne capacité de prise de décisions et une plus faible réponse de conductibilité électrodermale par anticipation à la tâche Iowa Gambling Task (IGT) que les non-contrevenants (C). Méthode : Vingt-trois récidivistes et 24 non-contrevenants ont été recrutés. Leur âge moyen (± É.T.) était 44.17(10.03) et 37.29 (10.60) ans respectivement. Les participants devaient être âgés de 18 ans ou plus, et avoir eu deux condamnations pour CCA ou plus pour le groupe R, et zéro CCA et un permis de conduire pour le groupe C. Les participants ont effectué I’IGT, une tâche neurocognitive de prise de décisions comprenant 100 sélections de cartes divisées en cinq blocs pour les analyses. On a comparé la performance du groupe R versus le groupe C à l’aide d’une ANOVA à mesures répétées [2 (groupe) x 5 (blocs)]. On a évalué la performance durant les blocs 1 & 2 (décisions dans l’ambiguïté) et blocs 3-5 (décisions sous haut risque) en utilisant des tests t post-hoc. Finalement, on a mesuré leur réponse de conductibilité électrodermale (RCEA) durant l’IGT. Résultats : L’ANOVA à mesures répétées des blocs 1 à 5 a révélé un effet significatif de l’interaction groupe par bloc, F(1,45)=5.28, p=.03, état carré =.11. Les tests t post hoc ont révélé une différence significative entre les groupes pour la combinaison des blocs 3 à 5, t(45) = 3.38, p = .002. Un effet d’interaction significatif a été détecté pour la RCEA des récidivistes de CCA versus celle des non-contrevenants, F(8,160)=2.33, p=.02, état carré =.10. Conclusion : Les récidivistes de CCA performent moins bien que les non-contrevenants à l’IGT. Ils persistent à prendre des décisions basées sur le potentiel de gains immédiats et négligent donc les risques de pertes. Ceci suggère qu’ils ont des déficits en matière de prise de décision, ce qui, en tant que groupe, les différencie des non-contrevenants. Une difficulté en matière de prise de décisions pourrait expliquer en partie le comportement impulsif fréquemment associé au récidivisme de CCA. Finalement, puisque les analyses de RCEA manquaient de puissance statistique, il est possible que de plus grands échantillons puissent permettre d’observer des différences entre les groupes de participants dans l’analyse de RCEA. / Objectives: Poor decision making in ambiguous high-risk situations, such as driving while impaired (DWI) by alcohol, may differentiate DWI recidivists from non-offenders. In this study, we test the hypothesis that DWI recidivists (R) will exhibit poorer decision-making performance on the Iowa Gambling Task (IGT), and in line with the Somatic Marker Hypothesis, weaker anticipatory somatic activation (using skin conductance response as index) than non-offenders (C, comparison group). Methods: DWI recidivists and non-DWI control drivers were recruited, [R (n=23) and C (n=24), mean ages (± SD) 44.17(10.03) and 37.29 (10.60) years respectively]. Participant selection criteria included ≥ 18 years old and ≥2 DWI convictions for group R and 0 DWI convictions lifetime and a driver’s license for group C. The participants performed the IGT, a decision-making neurocognitive task containing 100 card selection trials that we divided into 5 blocks for analyses. A 2 (group) x 5 (blocks) repeated measures ANOVA was used to compare group R performance on the IGT versus group C, followed by post hoc independent t-tests on aggregated blocks 1-2 (decision under ambiguity) & 3-5 (decision under high risk) to identify the source of group X block significant interactions. Two 3 (group) x 5 (blocks) repeated measures ANOVAs (for good decks and for bad decks) were used to compare the aSCR of groups C and R. Results: ANOVA repeated measures on blocks 1 to 5 produced a significant effect of group by block interaction F(1,45)=5.28, p=.03, partial ƞ2 =.11. Post hoc t-tests on aggregated blocks 3 to 5 were statistically significant, t(45) = 3.38, p = .002. A significant group x block interaction effect was found for good decks aSCR, F(8,160)=2.33, p=.02, partial ƞ2 =.10 . Conclusion: DWI recidivists performed more poorly than controls on the IGT, persistently making decisions based on potential immediate gains and neglecting associated loss risks and long-term outcome. This suggests they have reduced neurocognitive decision-making capacities distinguishable from the general population. While DWI recidivists’ behaviour appears as impulsive, these results suggest that their behaviour pattern involves decision-making difficulties. Larger sample sizes may be needed to detect a between-group effect in the aSCR analyses, as they were considerably underpowered.

<p>The Convolutional Neural Network (CNN) have shown a substantial improvement in the field of Machine Learning. But they do come with their own set of drawbacks. Capsule Networks have addressed the limitations of CNNs and have shown a great improvement by calculating the pose and transformation of the image. Deeper networks are more powerful than shallow networks but at the same time, more difficult to train. Residual Networks ease the training and have shown evidence that they can give good accuracy with considerable depth. Putting the best of Capsule Network and Residual Network together, we present Residual Capsule Network and 3-Level Residual Capsule Network, a framework that uses the best of Residual Networks and Capsule Networks. The conventional Convolutional layer in Capsule Network is replaced by skip connections like the Residual Networks to decrease the complexity of the Baseline Capsule Network and seven ensemble Capsule Network. We trained our models on MNIST and CIFAR-10 datasets and have seen a significant decrease in the number of parameters when compared to the Baseline models.</p>

INTRODUÇÃO. Embora esteja bem estabelecida a relação neuropatológica da síndrome de Down (SD) com a doença de Alzheimer (DA), os primeiros sintomas de demência na população com SD são considerados atípicos. Estudos indicam que os sintomas iniciais estão relacionados à disfunção comportamental que envolvem circuitos cerebrais fronto-subcorticais, como mudança de comportamento e disfunção executiva. O presente estudo teve como objetivo investigar fatores associados ao funcionamento do lobo frontal (disfunção executiva, desinibição e apatia) durante o declínio cognitivo e a DA em adultos com SD. MÉTODOS. 92 indivíduos com SD com idade acima de 30 anos foram alocados em três diferentes grupos diagnósticos (cognição estável, demência prodrômica e DA) por meio da avaliação com o instrumento Exame Cambridge para Transtornos Mentais em Adultos com Síndrome de Down e Deficiência Intelectual (CAMDEX-DS), previamente validado como parte da metodologia de trabalho. Os participantes foram avaliados com um protocolo de funções executivas desenvolvido para pessoas com deficiência intelectual por pesquisadores da Universidade de Cambridge e classificados para a presença de disfunção executiva, desinibição e apatia através da entrevista com um informante utilizando a Escala de Personalidade Frontal. Além disso, dados sobre características de comportamentos resultantes de disfunções frontais, memória e orientação foram analisados por meio do CAMDEX-DS em conjunto com uma amostra inglesa totalizando amostra combinada de 162 participantes com SD com mais de 30 anos e divididos em quatro grupos: cognição estável abaixo de 45 anos, cognição estável acima de 45 anos, demência prodrômica e DA. RESULTADOS. Os relatos de disfunção executiva, desinibição e apatia através da Escala de Personalidade Frontal foram correlacionados com o desempenho cognitivo dos participantes: quanto maior a disfunção comportamental nestas áreas, pior o desempenho cognitivo nas tarefas executivas. A desinibição e a disfunção executiva foram associadas aos diferentes diagnósticos. A probabilidade de ter DA aumentou com elevações nos escores da Escala de Personalidade Frontal (p <= 0,5). Na análise com o CAMDEX-DS, os sintomas frontais, assim como as queixas de memória e orientação, estavam presentes antes da evidência de declínio cognitivo. Diante do diagnóstico prodrômico e de DA, esses sintomas se agravaram. O impacto da deterioração cognitiva ocorreu em memória e orientação (odds ratio 35,07; P < 0,001) e disfunção executiva (odds ratio 7,16; P < 0,001) para o grupo prodrômico em relação à cognição estável; desinibição (odds ratio 3,54; P = 0,04) para DA em relação ao grupo prodrômico; e apatia (odds ratio 34,18; P < 0,001) para DA em relação à cognição estável. CONCLUSÃO. Disfunção executiva, desinibição e apatia estiveram presentes em indivíduos com SD e cognição estável. Estas medidas se agravam no declínio cognitivo inicial (prodrômico) e na DA nessa população e estão associados ao desempenho cognitivo em tarefas de funções executivas. Disfunções comportamentais devem ser levadas em consideração durante a avaliação clínica. Estudos futuros considerando a interseção entre neuropatologia, conectividade cerebral e expressão de comportamento podem agregar conhecimento sobre a base e a natureza dessas associações e servirem de base para a criação de estratégias preventivas eficazes / INTRODUCTION. Although a neuropathological correlation has been established between Down syndrome (DS) and Alzheimer\'s disease (AD), the early symptoms of dementia present atypically in the DS population. There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in DS, including changes in behaviour and executive dysfunction. The present study aimed to investigate factors associated with frontal lobe functioning (executive dysfunction, disinhibition and apathy) during cognitive decline and AD in adults with DS. METHODS. 92 individuals with DS aged over 30 years were evaluated and divided into three groups of diagnosis (stable cognition, prodromal dementia and AD) using the Cambridge Examination for Mental Disorders in Adults with Down Syndrome and others with Intellectual Disability (CAMDEX-DS), previously validated as part of our methodology. Participants were assessed with an executive function protocol developed for people with intellectual disabilities by researchers from University of Cambridge, and were rated for executive dysfunction, disinhibition and apathy by an informant using the Frontal Systems Behavior Scale (FrSBe). In addition, data on characteristics of frontal behaviour, memory and orientation were analysed through CAMDEX-DS in conjunction with an English sample totalling 162 participants with DS over 30 years old and divided into four groups: stable cognition under 45 years, stable cognition above 45 years, prodromal dementia and AD. RESULTS. Reports of executive dysfunction, disinhibition and apathy through FrSBe were correlated with participants\' cognitive performance: the higher the behavioural dysfunction in these areas, the worse the cognitive performance in executive tasks. Disinhibition and executive dysfunction were associated with diagnoses. The odds of having AD increased in parallel with increases in FrSBe scores (p <= 0.5). In the CAMDEX-DS analysis, amnestic and non-amnestic symptoms were found to be present before there was evidence of a cognitive decline. During the progression to dementia, those symptoms tended to worsen. Memory and orientation were poorer in the prodromal dementia group than in the stable cognition group (odds ratio 35.07, P < 0.001) as was executive function (odds ratio 7.16, P < 0.001). Disinhibition was greater in the AD group than in the prodromal dementia group (odds ratio 3.54, P = 0.04), and apathy was more pronounced in the AD group than in the stable cognition group (odds ratio 34.18; P < 0.001). CONCLUSION. Executive dysfunction, disinhibition and apathy were present in individuals with DS and stable cognition. These measures hasten the initial cognitive decline of AD and are related with cognitive performance in executive function tasks. Frontally mediated behaviour should be taken into consideration during the clinical evaluation of adults with DS. Future studies considering the intersection of neuropathology, brain connectivity, and behaviour may aggregate knowledge about the basis and nature of these associations, leading to the development of effective preventive strategies

INTRODUÇÃO. Embora esteja bem estabelecida a relação neuropatológica da síndrome de Down (SD) com a doença de Alzheimer (DA), os primeiros sintomas de demência na população com SD são considerados atípicos. Estudos indicam que os sintomas iniciais estão relacionados à disfunção comportamental que envolvem circuitos cerebrais fronto-subcorticais, como mudança de comportamento e disfunção executiva. O presente estudo teve como objetivo investigar fatores associados ao funcionamento do lobo frontal (disfunção executiva, desinibição e apatia) durante o declínio cognitivo e a DA em adultos com SD. MÉTODOS. 92 indivíduos com SD com idade acima de 30 anos foram alocados em três diferentes grupos diagnósticos (cognição estável, demência prodrômica e DA) por meio da avaliação com o instrumento Exame Cambridge para Transtornos Mentais em Adultos com Síndrome de Down e Deficiência Intelectual (CAMDEX-DS), previamente validado como parte da metodologia de trabalho. Os participantes foram avaliados com um protocolo de funções executivas desenvolvido para pessoas com deficiência intelectual por pesquisadores da Universidade de Cambridge e classificados para a presença de disfunção executiva, desinibição e apatia através da entrevista com um informante utilizando a Escala de Personalidade Frontal. Além disso, dados sobre características de comportamentos resultantes de disfunções frontais, memória e orientação foram analisados por meio do CAMDEX-DS em conjunto com uma amostra inglesa totalizando amostra combinada de 162 participantes com SD com mais de 30 anos e divididos em quatro grupos: cognição estável abaixo de 45 anos, cognição estável acima de 45 anos, demência prodrômica e DA. RESULTADOS. Os relatos de disfunção executiva, desinibição e apatia através da Escala de Personalidade Frontal foram correlacionados com o desempenho cognitivo dos participantes: quanto maior a disfunção comportamental nestas áreas, pior o desempenho cognitivo nas tarefas executivas. A desinibição e a disfunção executiva foram associadas aos diferentes diagnósticos. A probabilidade de ter DA aumentou com elevações nos escores da Escala de Personalidade Frontal (p <= 0,5). Na análise com o CAMDEX-DS, os sintomas frontais, assim como as queixas de memória e orientação, estavam presentes antes da evidência de declínio cognitivo. Diante do diagnóstico prodrômico e de DA, esses sintomas se agravaram. O impacto da deterioração cognitiva ocorreu em memória e orientação (odds ratio 35,07; P < 0,001) e disfunção executiva (odds ratio 7,16; P < 0,001) para o grupo prodrômico em relação à cognição estável; desinibição (odds ratio 3,54; P = 0,04) para DA em relação ao grupo prodrômico; e apatia (odds ratio 34,18; P < 0,001) para DA em relação à cognição estável. CONCLUSÃO. Disfunção executiva, desinibição e apatia estiveram presentes em indivíduos com SD e cognição estável. Estas medidas se agravam no declínio cognitivo inicial (prodrômico) e na DA nessa população e estão associados ao desempenho cognitivo em tarefas de funções executivas. Disfunções comportamentais devem ser levadas em consideração durante a avaliação clínica. Estudos futuros considerando a interseção entre neuropatologia, conectividade cerebral e expressão de comportamento podem agregar conhecimento sobre a base e a natureza dessas associações e servirem de base para a criação de estratégias preventivas eficazes / INTRODUCTION. Although a neuropathological correlation has been established between Down syndrome (DS) and Alzheimer\'s disease (AD), the early symptoms of dementia present atypically in the DS population. There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in DS, including changes in behaviour and executive dysfunction. The present study aimed to investigate factors associated with frontal lobe functioning (executive dysfunction, disinhibition and apathy) during cognitive decline and AD in adults with DS. METHODS. 92 individuals with DS aged over 30 years were evaluated and divided into three groups of diagnosis (stable cognition, prodromal dementia and AD) using the Cambridge Examination for Mental Disorders in Adults with Down Syndrome and others with Intellectual Disability (CAMDEX-DS), previously validated as part of our methodology. Participants were assessed with an executive function protocol developed for people with intellectual disabilities by researchers from University of Cambridge, and were rated for executive dysfunction, disinhibition and apathy by an informant using the Frontal Systems Behavior Scale (FrSBe). In addition, data on characteristics of frontal behaviour, memory and orientation were analysed through CAMDEX-DS in conjunction with an English sample totalling 162 participants with DS over 30 years old and divided into four groups: stable cognition under 45 years, stable cognition above 45 years, prodromal dementia and AD. RESULTS. Reports of executive dysfunction, disinhibition and apathy through FrSBe were correlated with participants\' cognitive performance: the higher the behavioural dysfunction in these areas, the worse the cognitive performance in executive tasks. Disinhibition and executive dysfunction were associated with diagnoses. The odds of having AD increased in parallel with increases in FrSBe scores (p <= 0.5). In the CAMDEX-DS analysis, amnestic and non-amnestic symptoms were found to be present before there was evidence of a cognitive decline. During the progression to dementia, those symptoms tended to worsen. Memory and orientation were poorer in the prodromal dementia group than in the stable cognition group (odds ratio 35.07, P < 0.001) as was executive function (odds ratio 7.16, P < 0.001). Disinhibition was greater in the AD group than in the prodromal dementia group (odds ratio 3.54, P = 0.04), and apathy was more pronounced in the AD group than in the stable cognition group (odds ratio 34.18; P < 0.001). CONCLUSION. Executive dysfunction, disinhibition and apathy were present in individuals with DS and stable cognition. These measures hasten the initial cognitive decline of AD and are related with cognitive performance in executive function tasks. Frontally mediated behaviour should be taken into consideration during the clinical evaluation of adults with DS. Future studies considering the intersection of neuropathology, brain connectivity, and behaviour may aggregate knowledge about the basis and nature of these associations, leading to the development of effective preventive strategies

Stress has emerged as one of the most important factors to consider in psychiatric diagnoses and has become a common reason for long-term sick leave (LTSL). Roughly 50% of LTSL due to psychiatric diseases are thought to be associated with work-related stress. The demarcation towards major depression is disputed, and no international consensus exists for how to diagnose and rehabilitate these individuals. The Swedish National Board of Health has suggested the term “exhaustion syndrome” to integrate these individuals into stress-related disorders. Prominent features of this syndrome are fatigue, sleeping disorders, and cognitive dysfunction. The cognitive dysfunction may be due to an interaction between personality features, environmental factors, the biological effects of stress hormones, and dysfunction in key brain areas, notably the hippocampus and prefrontal cortex. A consistent feature of chronic stress is activation of the cortisol, or hypothalamic-pituitary-adrenal, axis, which may be linked to cognitive dysfunction. Increased glucocorticoid levels, mainly cortisol in humans, are known to impair memory performance. The aim of this thesis was to investigate whether patients with exhaustion syndrome exhibit specific alterations in an extensive set of biological, psychological and immunological variables. Patients in Study 1 had significant cognitive impairment for specific tasks assumed to tap frontal lobe functioning. In Study 2 anxiety prone, worrying, pessimistic individuals with low executive drive and a persistent personality type were more likely to develop exhaustion syndrome. Decreased reactivity was found on the pituitary level after corticotropin releasing hormone (CRH) in exhaustion syndrome patients. The cortisol/adrenocorticotropic hormone response to CRH was slightly higher in patients compared to controls, indicating increased sensitivity at the adrenal cortex level. No differences were found in hippocampal volume. In Study 3, functional imaging revealed a different pattern of brain activation in working memory tests in patients with exhaustion syndrome compared to healthy individuals and patients with depression. In summary, our data suggests an intimate link between personality and wellbeing, cognitive performance and neuroendocrine dysfunction, in exhaustion syndrome. We thus find similarities with major depression but also distinct differences between the exhaustion syndrome and major depression.

Objectifs : La capacité en matière de prise de décisions des récidivistes de conduite avec capacités affaiblies (CCA) semble les distinguer des non-contrevenants, particulièrement dans des situations ambiguës à haut risque, telles que la CCA. Cette étude exploratoire vise à vérifier l’hypothèse selon laquelle les récidivistes de CCA (R) auraient une moins bonne capacité de prise de décisions et une plus faible réponse de conductibilité électrodermale par anticipation à la tâche Iowa Gambling Task (IGT) que les non-contrevenants (C). Méthode : Vingt-trois récidivistes et 24 non-contrevenants ont été recrutés. Leur âge moyen (± É.T.) était 44.17(10.03) et 37.29 (10.60) ans respectivement. Les participants devaient être âgés de 18 ans ou plus, et avoir eu deux condamnations pour CCA ou plus pour le groupe R, et zéro CCA et un permis de conduire pour le groupe C. Les participants ont effectué I’IGT, une tâche neurocognitive de prise de décisions comprenant 100 sélections de cartes divisées en cinq blocs pour les analyses. On a comparé la performance du groupe R versus le groupe C à l’aide d’une ANOVA à mesures répétées [2 (groupe) x 5 (blocs)]. On a évalué la performance durant les blocs 1 & 2 (décisions dans l’ambiguïté) et blocs 3-5 (décisions sous haut risque) en utilisant des tests t post-hoc. Finalement, on a mesuré leur réponse de conductibilité électrodermale (RCEA) durant l’IGT. Résultats : L’ANOVA à mesures répétées des blocs 1 à 5 a révélé un effet significatif de l’interaction groupe par bloc, F(1,45)=5.28, p=.03, état carré =.11. Les tests t post hoc ont révélé une différence significative entre les groupes pour la combinaison des blocs 3 à 5, t(45) = 3.38, p = .002. Un effet d’interaction significatif a été détecté pour la RCEA des récidivistes de CCA versus celle des non-contrevenants, F(8,160)=2.33, p=.02, état carré =.10. Conclusion : Les récidivistes de CCA performent moins bien que les non-contrevenants à l’IGT. Ils persistent à prendre des décisions basées sur le potentiel de gains immédiats et négligent donc les risques de pertes. Ceci suggère qu’ils ont des déficits en matière de prise de décision, ce qui, en tant que groupe, les différencie des non-contrevenants. Une difficulté en matière de prise de décisions pourrait expliquer en partie le comportement impulsif fréquemment associé au récidivisme de CCA. Finalement, puisque les analyses de RCEA manquaient de puissance statistique, il est possible que de plus grands échantillons puissent permettre d’observer des différences entre les groupes de participants dans l’analyse de RCEA. / Objectives: Poor decision making in ambiguous high-risk situations, such as driving while impaired (DWI) by alcohol, may differentiate DWI recidivists from non-offenders. In this study, we test the hypothesis that DWI recidivists (R) will exhibit poorer decision-making performance on the Iowa Gambling Task (IGT), and in line with the Somatic Marker Hypothesis, weaker anticipatory somatic activation (using skin conductance response as index) than non-offenders (C, comparison group). Methods: DWI recidivists and non-DWI control drivers were recruited, [R (n=23) and C (n=24), mean ages (± SD) 44.17(10.03) and 37.29 (10.60) years respectively]. Participant selection criteria included ≥ 18 years old and ≥2 DWI convictions for group R and 0 DWI convictions lifetime and a driver’s license for group C. The participants performed the IGT, a decision-making neurocognitive task containing 100 card selection trials that we divided into 5 blocks for analyses. A 2 (group) x 5 (blocks) repeated measures ANOVA was used to compare group R performance on the IGT versus group C, followed by post hoc independent t-tests on aggregated blocks 1-2 (decision under ambiguity) & 3-5 (decision under high risk) to identify the source of group X block significant interactions. Two 3 (group) x 5 (blocks) repeated measures ANOVAs (for good decks and for bad decks) were used to compare the aSCR of groups C and R. Results: ANOVA repeated measures on blocks 1 to 5 produced a significant effect of group by block interaction F(1,45)=5.28, p=.03, partial ƞ2 =.11. Post hoc t-tests on aggregated blocks 3 to 5 were statistically significant, t(45) = 3.38, p = .002. A significant group x block interaction effect was found for good decks aSCR, F(8,160)=2.33, p=.02, partial ƞ2 =.10 . Conclusion: DWI recidivists performed more poorly than controls on the IGT, persistently making decisions based on potential immediate gains and neglecting associated loss risks and long-term outcome. This suggests they have reduced neurocognitive decision-making capacities distinguishable from the general population. While DWI recidivists’ behaviour appears as impulsive, these results suggest that their behaviour pattern involves decision-making difficulties. Larger sample sizes may be needed to detect a between-group effect in the aSCR analyses, as they were considerably underpowered. / Thomas G. Brown, Ph.D., co-directeur de recherche

Rugby is a popular sport in South Africa, and has been played by young boys from as early as seven years old (South African Rugby Union [SARU], 2011). Despite various physical health benefits, it carries a high risk for injury, especially head injury, and consequently has a high incidence of concussion (Alexander, 2009; Laubscher, 2006; Shuttleworth-Edwards, Smith & Radloff, 2008). It is common for 12 to 13 per cent of adolescent rugby players to report mild traumatic brain injury or concussion per season (Laubscher, 2006; Shuttleworth-Edwards et al., 2008). The true incidence is however considered to be higher, even as high as 70.4% (Shuttleworth-Edwards et al., 2008). Concussion, otherwise known as mild traumatic brain injury (mTBI) is described as a traumatically induced alteration in mental status, or traumatically induced cerebral dysfunction (Kraus, McArthur, Silvermand & Jayaraman, 1996) which may, or may not involve loss of consciousness (Quality Standards Subcommittee, American Academy of Neurology [AAN], 1997). The nature of concussion has traditionally been considered to be transient, and symptoms are usually resolved within a few days or weeks (Kirkwood et al., 2008; Taylor et al., 2010). However, when concussions are not fully resolved prior to players returning to the game, they may be vulnerable to second impact syndrome. This syndrome causes herniation and brain oedema, which may result in death (Patel, 2005), as has been reported in South African press (Alexander, 2009; South African Press Association [SAPA], 2012). Even without second impact syndrome, repeated concussions may render the brain neurocognitively vulnerable, leading to an array of short- and long-term cognitive symptoms (Alexander, 2009; Shuttleworth-Edwards et al., 2008). Short-term problems include difficulties with attention, focus and concentration; following multi-step instruction, engaging in mental problem-solving; verbal expression, receiving and processing verbal and visual information; maintaining effective levels of mental and physical energy; controlling mood; suppressing impulsive behaviours; initiating and maintaining productive interpersonal relationships with peers; engaging in meaningful conversation and participating in group activities (Jantz & Coulter, 2007). Short-term cognitive impairments due to repeated concussion have also been found, and include amongst the former symptoms, also problems with delayed memory, learning, social functioning, and abstract thinking (Anderson, Brown, Newitt & Hoile, 2011; Laubscher, 2006). Long-term sequelae follow when children did not return to their baseline level of functioning after three months (Kirkwood et al., 2008; Taylor et al., 2010). Long-term sequelae include problems with memory, visuo-motor processing, executive functioning, learning and abstract thinking (Anderson, 2002; Anderson et al., 2010; Horton et al., 2010; Lezak et.al., 2004; Shuttleworth-Edwards & Radloff, 2008). As mTBI is traditionally thought to be of transient nature, researchers tend to investigate moderate to severe TBI, rather than mTBI (Alexander, 2009; Anderson et al., 2010; Patel, 2005). This could easily lead to important facts about mTBI being missed or not acknowledged. Nevertheless, recent investigations are uncovering facts about mTBI that could transform the way in which we understand mTBI, providing increasing evidence that mTBI is more serious than widely believed (Blakemore, 2012; Maxwell, 2011; Toleda et al., 2012). However, there remains a lack of research investigating mTBI from a single cause. Considering the above information, the current study provides unique information about mTBI. It specifically investigated the long-term effects of mTBI on adolescents from a homogenous cause, which makes results more comparable. The importance of this study is highlighted in the face of evidence for the long-term effects of multiple concussions, that were sustained during school rugby, on academic achievement (Alexander, 2009; Laubscher, 2006).In the light of grey areas in existing research, the aim of this current study was to investigate whether there is a significant difference in academic achievement within and between two groups of adolescents that had either played rugby and sustained multiple concussions, or had not played rugby nor sustained any concussions, when measured at four points in time over six years. A retrospective data-analysis was performed on matched, controlled, prospective longitudinal data, which was obtained from a study that evaluated the impact of repeated mTBI on the cognitive and academic functioning of early adolescent rugby players over time (Alexander, 2009). This study elaborates on a subset of the previous data, adding the gr. 12 results for academic aggregate scores, to the previously reported academic dataset. Participants were selected from Alexander‟s study (2009), and had either played rugby and obtained two or more concussions (Rugby/Concussed (RC- group); n=17), or did not play rugby nor sustained any concussions (Non-rugby/Non-concussed (NRC-group); n=13). Academic aggregate scores from baseline (gr. 7) through gr. 12 were analysed using quantitative statistical measures. A normal probability plot determined that the data was distributed normally. Descriptive statistics were reported, where after repeated measures ANOVA‟s were conducted to determine the statistical significance of differences in academic scores between and within the groups over time. These results indicated that the NRC-group displayed statistically significant increase in academic achievement over time (p = .000), whereas the RC-group did not display any significant differences, despite displaying a downwards trend in achievement. The difference between the two groups was measured at its highest in gr. 12 (p = .003), indicating that the NRC-group performed statistically significantly better than the RC-group over time. However, a Pearson‟s correlation test revealed that the estimated IQ (Vocabulary subscale of the WISC-III) (Wechsler, 1991) had a positive correlation on academic achievement [r(34) = .54, p < .05)]. To control for the effect that this correlation had on the academic results, an ANCOVA was conducted. This analysis indicated a statistically significant difference in academic achievement between the two groups in gr.12 (p = .004), with a large effect size (d = 1.41), implicating practical significance. Findings consequently confirmed our hypothesis. The significant increase in academic achievement observed within the NRC-group over time, is consistent with what could be expected if the brain is allowed to develop normally without disruption such as mTBI (Blakemore, 2012; Horton et al., 2010). The finding that the RC group did not display statistically significant intra-group differences in academic achievement when measured over time, but that academic achievement followed a downward trend, is difficult to substantiate in the literature. The few research studies on the effect of cumulative concussion on young athletes do not isolate academic achievement as a variable (Iverson et al., 2004; Shuttleworth-Edwards et al., 2008). Further research into intra-group differences in this specific area of enquiry and population group is therefore necessary. Normal cognitive and brain development, maintains that the brain develops in a posterior to anterior direction, and the prefrontal regions which are vulnerable to concussion, develop last (Anderson, 2010; Blakemore, 2012; Lezak, 2004). Whereas the primary motor and sensory areas and areas for receptive and expressive language are fully developed by the age of ten years, the prefrontal brain areas that are responsible for more complex and abstract thought repertoires only start maturing in early adolescence and this development continues up to the age of 24 and even into the early 30s (Toleda et al., 2012). Injury to the developing brain at this critical stage of maturation may adversely affect the development of cognitive skills, preventing the child from acquiring the effective cognitive strategies needed for normal academic functioning and adequate academic achievement after TBI (Horton et al., 2010). However, if there is no insult to the brain, cognitive functions are expected to develop normally as a result of synaptic pruning and increased white-matter volume in the prefrontal cortex (Blakemore, 2012), making it likely that the maturation of these abilities will lead to greater cognitive and academic ability (Blakemore & Choudhury, 2006), such as seen for the NRC-group in this study. Limitations for this study include a small sample size and the testing of only one variable. It is therefore recommended that future studies include more variables, and aim at creating a larger, randomized sample size, possibly providing a more representative pool of participants to study this phenomenon in South African context. It is also advised that future studies consider using neuropsychological measures to test cognitive functioning. As previous studies have indicated specific impairment in executive functioning after TBI, it may be worth researching the effect of concussion on executive functioning more thoroughly (Anderson, 2002; Anderson et al., 2010; Horton et al., 2010). Further it may be valuable to consider using functional MRI studies to broaden existing knowledge about the interaction between pathophysiology and cognitive functioning This study also highly recommends that schools and rugby clubs catering for child and adolescent players reconsider the importance of implementing proper return to play protocols after players obtain concussions. / Thesis (MA (Clinical Psychology))--North-West University, Potchefstroom Campus, 2013

Rugby is a popular sport in South Africa, and has been played by young boys from as early as seven years old (South African Rugby Union [SARU], 2011). Despite various physical health benefits, it carries a high risk for injury, especially head injury, and consequently has a high incidence of concussion (Alexander, 2009; Laubscher, 2006; Shuttleworth-Edwards, Smith & Radloff, 2008). It is common for 12 to 13 per cent of adolescent rugby players to report mild traumatic brain injury or concussion per season (Laubscher, 2006; Shuttleworth-Edwards et al., 2008). The true incidence is however considered to be higher, even as high as 70.4% (Shuttleworth-Edwards et al., 2008). Concussion, otherwise known as mild traumatic brain injury (mTBI) is described as a traumatically induced alteration in mental status, or traumatically induced cerebral dysfunction (Kraus, McArthur, Silvermand & Jayaraman, 1996) which may, or may not involve loss of consciousness (Quality Standards Subcommittee, American Academy of Neurology [AAN], 1997). The nature of concussion has traditionally been considered to be transient, and symptoms are usually resolved within a few days or weeks (Kirkwood et al., 2008; Taylor et al., 2010). However, when concussions are not fully resolved prior to players returning to the game, they may be vulnerable to second impact syndrome. This syndrome causes herniation and brain oedema, which may result in death (Patel, 2005), as has been reported in South African press (Alexander, 2009; South African Press Association [SAPA], 2012). Even without second impact syndrome, repeated concussions may render the brain neurocognitively vulnerable, leading to an array of short- and long-term cognitive symptoms (Alexander, 2009; Shuttleworth-Edwards et al., 2008). Short-term problems include difficulties with attention, focus and concentration; following multi-step instruction, engaging in mental problem-solving; verbal expression, receiving and processing verbal and visual information; maintaining effective levels of mental and physical energy; controlling mood; suppressing impulsive behaviours; initiating and maintaining productive interpersonal relationships with peers; engaging in meaningful conversation and participating in group activities (Jantz & Coulter, 2007). Short-term cognitive impairments due to repeated concussion have also been found, and include amongst the former symptoms, also problems with delayed memory, learning, social functioning, and abstract thinking (Anderson, Brown, Newitt & Hoile, 2011; Laubscher, 2006). Long-term sequelae follow when children did not return to their baseline level of functioning after three months (Kirkwood et al., 2008; Taylor et al., 2010). Long-term sequelae include problems with memory, visuo-motor processing, executive functioning, learning and abstract thinking (Anderson, 2002; Anderson et al., 2010; Horton et al., 2010; Lezak et.al., 2004; Shuttleworth-Edwards & Radloff, 2008). As mTBI is traditionally thought to be of transient nature, researchers tend to investigate moderate to severe TBI, rather than mTBI (Alexander, 2009; Anderson et al., 2010; Patel, 2005). This could easily lead to important facts about mTBI being missed or not acknowledged. Nevertheless, recent investigations are uncovering facts about mTBI that could transform the way in which we understand mTBI, providing increasing evidence that mTBI is more serious than widely believed (Blakemore, 2012; Maxwell, 2011; Toleda et al., 2012). However, there remains a lack of research investigating mTBI from a single cause. Considering the above information, the current study provides unique information about mTBI. It specifically investigated the long-term effects of mTBI on adolescents from a homogenous cause, which makes results more comparable. The importance of this study is highlighted in the face of evidence for the long-term effects of multiple concussions, that were sustained during school rugby, on academic achievement (Alexander, 2009; Laubscher, 2006).In the light of grey areas in existing research, the aim of this current study was to investigate whether there is a significant difference in academic achievement within and between two groups of adolescents that had either played rugby and sustained multiple concussions, or had not played rugby nor sustained any concussions, when measured at four points in time over six years. A retrospective data-analysis was performed on matched, controlled, prospective longitudinal data, which was obtained from a study that evaluated the impact of repeated mTBI on the cognitive and academic functioning of early adolescent rugby players over time (Alexander, 2009). This study elaborates on a subset of the previous data, adding the gr. 12 results for academic aggregate scores, to the previously reported academic dataset. Participants were selected from Alexander‟s study (2009), and had either played rugby and obtained two or more concussions (Rugby/Concussed (RC- group); n=17), or did not play rugby nor sustained any concussions (Non-rugby/Non-concussed (NRC-group); n=13). Academic aggregate scores from baseline (gr. 7) through gr. 12 were analysed using quantitative statistical measures. A normal probability plot determined that the data was distributed normally. Descriptive statistics were reported, where after repeated measures ANOVA‟s were conducted to determine the statistical significance of differences in academic scores between and within the groups over time. These results indicated that the NRC-group displayed statistically significant increase in academic achievement over time (p = .000), whereas the RC-group did not display any significant differences, despite displaying a downwards trend in achievement. The difference between the two groups was measured at its highest in gr. 12 (p = .003), indicating that the NRC-group performed statistically significantly better than the RC-group over time. However, a Pearson‟s correlation test revealed that the estimated IQ (Vocabulary subscale of the WISC-III) (Wechsler, 1991) had a positive correlation on academic achievement [r(34) = .54, p < .05)]. To control for the effect that this correlation had on the academic results, an ANCOVA was conducted. This analysis indicated a statistically significant difference in academic achievement between the two groups in gr.12 (p = .004), with a large effect size (d = 1.41), implicating practical significance. Findings consequently confirmed our hypothesis. The significant increase in academic achievement observed within the NRC-group over time, is consistent with what could be expected if the brain is allowed to develop normally without disruption such as mTBI (Blakemore, 2012; Horton et al., 2010). The finding that the RC group did not display statistically significant intra-group differences in academic achievement when measured over time, but that academic achievement followed a downward trend, is difficult to substantiate in the literature. The few research studies on the effect of cumulative concussion on young athletes do not isolate academic achievement as a variable (Iverson et al., 2004; Shuttleworth-Edwards et al., 2008). Further research into intra-group differences in this specific area of enquiry and population group is therefore necessary. Normal cognitive and brain development, maintains that the brain develops in a posterior to anterior direction, and the prefrontal regions which are vulnerable to concussion, develop last (Anderson, 2010; Blakemore, 2012; Lezak, 2004). Whereas the primary motor and sensory areas and areas for receptive and expressive language are fully developed by the age of ten years, the prefrontal brain areas that are responsible for more complex and abstract thought repertoires only start maturing in early adolescence and this development continues up to the age of 24 and even into the early 30s (Toleda et al., 2012). Injury to the developing brain at this critical stage of maturation may adversely affect the development of cognitive skills, preventing the child from acquiring the effective cognitive strategies needed for normal academic functioning and adequate academic achievement after TBI (Horton et al., 2010). However, if there is no insult to the brain, cognitive functions are expected to develop normally as a result of synaptic pruning and increased white-matter volume in the prefrontal cortex (Blakemore, 2012), making it likely that the maturation of these abilities will lead to greater cognitive and academic ability (Blakemore & Choudhury, 2006), such as seen for the NRC-group in this study. Limitations for this study include a small sample size and the testing of only one variable. It is therefore recommended that future studies include more variables, and aim at creating a larger, randomized sample size, possibly providing a more representative pool of participants to study this phenomenon in South African context. It is also advised that future studies consider using neuropsychological measures to test cognitive functioning. As previous studies have indicated specific impairment in executive functioning after TBI, it may be worth researching the effect of concussion on executive functioning more thoroughly (Anderson, 2002; Anderson et al., 2010; Horton et al., 2010). Further it may be valuable to consider using functional MRI studies to broaden existing knowledge about the interaction between pathophysiology and cognitive functioning This study also highly recommends that schools and rugby clubs catering for child and adolescent players reconsider the importance of implementing proper return to play protocols after players obtain concussions. / Thesis (MA (Clinical Psychology))--North-West University, Potchefstroom Campus, 2013

Abstract Children born preterm are prone to acute brain insults related to subsequent neurodevelopmental impairments. However, the role of specific biomarkers and perinatal clinical factors in the pathogenesis of brain injury and neurodevelopmental sequelae has remained poorly understood. The present study evaluated whether specific immunoproteins at birth predict the risk of intraventricular hemorrhage (IVH) and whether their receptors are localized at the bleeding site. We further investigated whether children who went on to develop cerebral palsy (CP) could be identified on the basis of blood immunoproteins collected during the perinatal period. The association between single nucleotide polymorphisms in the chemokine CCL18 gene and susceptibility to CP was also studied. Finally, we investigated the association of pre- and postnatal factors with cognitive outcomes in very preterm-born schoolchildren without impairments. The present study revealed that a low concentration of CCL18 in cord blood was an independent risk factor of IVH in very preterm infants. The CCL18 receptor, CCR3, was detectable in the periventricular area and in the neurons of the hippocampus in preterm infants already at 23 weeks of gestation. We also identified a cluster of cord blood cytokines that was associated with the risk of CP. In addition, inflammatory cytokine levels were associated with CP risk on days 1 and 7 after birth. The genetic study showed that both IVH and the CCL18 polymorphism independently and additively had an influence on CP susceptibility. Our study further demonstrated that schoolchildren born very preterm without CP or cognitive impairment had poorer performance in visuospatial–sensorimotor skills and in attention–executive functions than term-born children. Fetal growth restriction was an independent risk factor of compromised neurocognitive outcome in very preterm children predicting difficulties in language, memory and learning. In conclusion, specific cytokines and cytokine clusters serve as biomarkers of different pathways involved in damage to the brain structures and in the pathogenesis of CP. In addition, genetic factors can affect these processes. Further, fetal growth restriction and prematurity play important roles in neurocognitive development later in life. / Tiivistelmä Hyvin ennenaikaisina syntyneet lapset ovat alttiita akuuteille aivovaurioille sekä myöhemmin ilmeneville kehityshäiriöille. Eri välittäjäaineiden sekä raskaudenaikaisten ja syntymänjälkeisten kliinisten tekijöiden vaikutusta aivojen vaurioherkkyyteen sekä neurologiseen ja neurokognitiiviseen kehitykseen ei kuitenkaan ole tutkittu riittävästi. Tässä tutkimuksessa tarkasteltiin, ennustaako jokin napaverestä tutkituista sytokiineista aivoverenvuotoa hyvin ennenaikaisesti syntyneillä vastasyntyneillä. Lisäksi selvitettiin, onko sytokiinin spesifinen reseptori osoitettavissa vuotoherkällä alueella aivoissa. Tutkimme myös, ennustaako jokin napaveren immunoproteiini-profiilin komponentti CP-vamman syntyä joko itsenäisesti tai yhdessä muiden perinataalisten riskitekijöiden kanssa sekä lisääkö tietyn sytokiinin (CCL18) geneettinen vaihtelu CP-vamman riskiä hyvin ennenaikaisesti syntyneillä lapsilla. Lisäksi selvitimme, vaikuttavatko raskaudenaikaiset tekijät ja vastasyntyneisyyskauden sairaudet neurokognitiiviseen kehitykseen kouluiässä. Tämän tutkimuksen mukaan napaveren matala CCL18-kemokiinipitoisuus oli itsenäinen aivoverenvuodon riskitekijä. CCR3-reseptori, johon CCL18 sitoutuu, oli osoitettavissa sekä vuotoherkällä alueella että hermosoluissa 23. raskausviikon iästä lähtien. Havaitsimme myös, että tietyt napaveren sytokiiniryppäät ja yksittäisten tulehdusvastevälittäjäaineiden pitoisuudet 1. ja 7. elinpäivänä olivat yhteydessä CP-riskiin. Lisäksi havaitsimme yhteyden CCL18-kemokiinin geneettisen vaihtelun ja aivoverenvuodon sekä CP-vamman kehittymisen välillä. Tutkimuksemme mukaan hyvin ennenaikaisesti syntyneet koululaiset, joilla ei ollut CP- tai kehitysvammaa, suoriutuivat täysiaikaisina syntyneitä verrokkeja heikommin visuaalista hahmotusta ja sensomotoriikkaa sekä tarkkaavuutta ja toiminnanohjausta mittaavissa testeissä. Lisäksi havaitsimme sikiöaikaisen kasvuhäiriön ennustavan itsenäisesti heikkoa suoritusta kieltä, muistia ja oppimista testaavissa tehtävissä ennenaikaisesti syntyneillä lapsilla. Tietyt sytokiinit ja sytokiiniryppäät ovat yhteydessä aivovauriomekanismeihin. Nämä mekanismit saattavat yhdessä perinnöllisen alttiuden kanssa vaikuttaa myös CP-vamman syntyyn. Sikiöaikainen kasvuhäiriö ja ennenaikaisuus vaikuttavat lapsen myöhempään neurokognitiiviseen kehitykseen.

Abstract Leukemia treatment has been implicated to be responsible for a diversity of long-term adverse effects (Pui 2008), which can occur even years after diagnosis and can seriously impair survivors’ performance status and quality of life (Campbell et al. 2007, Zeltzer et al. 2008). The aim of the present work was to assess health-related quality of life in long-term survivors of acute lymphoblastic leukemia (ALL), and to find out whether vocational rehabilitation can promote the coping at work of young people who take part in a training intervention or help them find employment. Neuropsychological testing was performed on 64 survivors. Cranial irradiation had been administered to 44 of the survivors, while 20 survivors had been treated solely with chemotherapy. A control group consisted of 45 healthy young adults. We found that young adult survivors of childhood ALL treated with cranial irradiation had clear progressive deficits in their neurocognitive functioning at a mean of 20 years after diagnosis compared with healthy controls. Non-irradiated ALL survivors performed significantly better, but even they had statistically significant impairments in some of the neuropsychological test scores compared with the controls. Rand-36-Item health Survey (RAND-36) was used to assess subjective HRQoL, depressive symptoms were assessed with Beck Depression Inventory (BDI-21), and mental distress with General Health Questionnaire (GHQ-12) in 74 survivors of ALL. The control group consisted of 146 healthy young adults selected from local population registry. ALL survivors showed good HRQoL scores in comparison to the control group. Patients who had been treated for an ALL relapse and had received the most intensive chemo- and radiotherapy had significantly higher scores on mental health and vitality than the controls. Survivors of ALL report fewer depressive symptoms and equal mental well-being compared to healthy controls. Nine out of 63 survivors were selected for rehabilitation based on their occupation and psychosocial difficulties. The occupational rehabilitation course improved physical fitness and decreased overweight in long-term survivors of ALL, but impaired their HRQoL. Our findings support the idea that ALL survivors’ subjective experience of well-being is possibly affected by a repressive adaptive style. / Tiivistelmä Leukemiahoidoilla on todettu olevan pitkäaikaisvaikutuksia (Pui 2008), jotka voivat ilmetä jopa vuosia diagnoosin jälkeen heikentäen sairaudesta selvinneiden toimintakykyä ja elämänlaatua (Campbell et al. 2007, Zeltzer et al. 2008). Tämän tutkimuksen tavoitteena oli arvioida akuutista lymfaattisesta (ALL) leukemiasta selvinneiden terveyteen liittyvää elämänlaatua pitkällä aikavälillä sekä selvittää, voidaanko ammatillisen kuntoutuksen avulla edistää interventioon osallistuneiden työssä selviytymistä tai työllistymistä. Neuropsykologiseen tutkimukseen osallistui 64 ALL pitkäaikaisselviytyjää. Heistä 44 oli saanut pään alueen sädehoitoa ja 20 pelkästään solunsalpaajahoitoa. Verrokkiryhmässä oli 45 tervettä nuorta aikuista. Havaitsimme, että lapsuudessa pään alueen sädehoitoa saaneilla ALL-selviytyjillä oli verrokkeihin verrattuna selkeitä progressiivisia muutoksia neurokognitiivisessa toimintakyvyssä keskimäärin 20 vuotta diagnoosista. Ne, jotka eivät olleet saaneet sädehoitoa suoriutuivat huomattavasti paremmin, mutta heilläkin havaittiin tilastollisesti merkittäviä puutoksia joillakin neuropsykologisten testien osa-alueilla verrokkeihin verrattuna. 74 entisen ALL-potilaan terveyteen liittyvää elämänlaatua (HRQoL) mitattiin Rand-36 -mittarilla, masennusoireita Beckin masennustestillä (BDI-21) ja henkistä hyvinvointia General Health Questionnaire -mittarilla (GHQ-12). Verrokkiryhmäksi valittiin väestörekisteristä 146 tervettä nuorta aikuista. ALL-ryhmässä tutkittavien terveyteen liittyvää elämänlaatua mittaavat pisteet olivat hyvät verrokkiryhmään verrattuna. Ne potilaat, joita oli hoidettu leukemian uusiutumisen takia ja jotka olivat saaneet intensiivisintä solunsalpaaja- ja sädehoitoa saivat huomattavasti paremmat pisteet psyykkisen hyvinvoinnin ja vitaalisuuden osa-alueilla kuin verrokit. ALL -selviytyjät raportoivat vähemmän masennusoireita, ja he arvioivat psyykkinen hyvinvointinsa yhtä hyväksi kuin verrokit. Yhdeksän ALL pitkäaikaisselviytyjää osallistui heille suunnattuun ammatilliseen kuntoutusinterventioon. Ammatillinen kuntoutuskurssi paransi ALL -selviytyjien fyysistä suorituskykyä ja vähensi ylipainoa, mutta heikensi terveyteen liittyvää elämänlaatua. Tutkimustulokset tukevat ajatusta, että repressiivinen adaptaatio voi vaikuttaa lapsuusiän leukemiasta selvinneiden subjektiiviseen hyvinvoinnin kokemukseen.