Posttraumatic stress disorder (PTSD) is associated with significant functional impairments and disruptions in cognitive functioning. Functional recovery and remediation of cognitive difficulties are oft over-looked treatment targets in this population, despite their significant contribution to the burden of PTSD to the individual and to society. Existing literature suggests that functional impairment and cognitive dysfunction may not respond to first-line treatments for PTSD. Thus, the focus of this thesis was to examine symptom dimensions associated with cognitive dysfunction and functional impairment among individuals with PTSD, and to investigate a novel approach to cognitive remediation, Goal Management Training (GMT), in this population. Study one in this thesis is a review in which we identified a strong relation between dissociative symptoms and neuropsychological functioning, transdiagnostically and among individuals with PTSD. The hypothesis that dissociative symptoms would be strongly related to functional impairment among individuals with PTSD was explored in study two. We found that dissociative symptoms mediated the relation between PTSD symptoms and functional impairment among a sample of military members, veterans, and first responders with PTSD. Study three identified that emotion regulation difficulties and dissociative symptoms most strongly predicted functional impairment among civilians with PTSD and high rates of exposure to childhood abuse and neglect. In study four we investigated the effectiveness of a cognitive training program, Goal Management Training (GMT), in improving cognitive functioning, clinical symptoms, and functional impairment among inpatients with PTSD. Participation in GMT was associated with improved cognitive functioning and increased ability to engage in goal directed behaviours when highly emotional. This thesis highlights the importance of assessing emotion regulation difficulties and dissociative symptoms in order to target functional impairment and cognitive dysfunction among individuals with PTSD. Moreover, it provides evidence for a potential treatment approach to ameliorate these difficulties. / Thesis / Doctor of Philosophy (PhD) / Posttraumatic stress disorder (PTSD) is a mental health condition that develops after exposure to a traumatic event. It is associated with reduced functioning in important areas of life, including social relationships, work performance, and self-care. PTSD is also associated with reduced cognitive functioning in areas such as memory, planning, and organization. This thesis focuses on examining variables that may be related to these difficulties, including specific symptoms such as difficulty managing emotions and difficulties remaining in the present moment (dissociation). We also investigate a treatment program, Goal Management Training (GMT), aimed at teaching skills to improve cognitive and daily functioning. By understanding what contributes to cognitive functioning and functional difficulties in individuals with PTSD and by providing evidence for a treatment that can improve these difficulties, we hope to improve the lives of individuals with PTSD.

Mild traumatic brain injury (mTBI) is a common and often inconspicuous wound that is frequently associated with chronic low-grade symptoms and cognitive dysfunction. Previous evidence suggests that daily blue wavelength light therapy may be effective at reducing fatigue and improving sleep in patients recovering from mTBI. However, the effects of light therapy on recovering brain structure remain unexplored. In this study, we analyzed white matter diffusion properties, including generalized fractional anisotropy, and the quantity of water diffusion in isotropic (i.e., isotropic diffusion) and anisotropic fashion (i.e., quantitative anisotropy, QA) for fibers crossing 11 brain areas known to be significantly affected following mTBI. Specifically, we investigated how 6 weeks of daily morning blue light exposure therapy (compared to an amber-light placebo condition) impacted changes in white matter diffusion in individuals with mTBI. We observed a significant impact of the blue light treatment (relative to the placebo) on the amount of water diffusion (QA) for multiple brain areas, including the corpus callosum, anterior corona radiata, and thalamus. Moreover, many of these changes were associated with improvements in sleep latency and delayed memory. These findings suggest that blue wavelength light exposure may serve as one of the potential non-pharmacological treatments for facilitating structural and functional recovery following mTBI; they also support the use of QA as a reliable neuro-biomarker for mTBI therapies.

Heterogeneity in the profile of HIV-associated neuropsychological disorder (HAND) may obscure understanding of its etiology and prognosis. Despite longstanding acknowledgement of this heterogeneity, HAND diagnostic approaches such as the Frascati criteria characterize neuropsychological function based on the level of impairment, without regard to the pattern of strengths and weaknesses. Attention to these patterns may enhance etiologic and prognostic specificity. We used latent class analysis (LCA) to identify relatively homogeneous subtypes of neurocognitive function in adults with well-treated HIV infection. We compared the diagnostic agreement of latent classes and Frascati categories, as well as their associations with demographics, HIV markers and antiretroviral factors, comorbid medical and psychiatric conditions, and everyday functioning. LCA identified four classes, whose cognitive profiles are depicted in Figure 1: cognitively intact, mild-to-moderate motor/speed impairment, mild-to-moderate memory/visuoconstruction impairment, and moderate mixed impairment. Latent classes and Frascati categories demonstrated good agreement in the overall classification of impaired cognition but more disagreement regarding subtypes of impairment. Both latent classes and Frascati categories demonstrated unique associations with etiologic factors and significant associations with functional outcomes. However, only latent classes, not Frascati categories, were associated with HIV variables. Additionally, functional difficulties were significantly elevated in the motor impairment class but not the memory impairment class despite similar levels of cognitive impairment in the two groups. Findings support the utility of a diagnostic approach that accounts for both the level and pattern of neurocognitive impairment. Future research should examine the neuropathological mechanisms, longitudinal trajectories, and treatments of empirically identified HAND subtypes. / Psychology

The aim of this doctoral thesis was to study neuropsychological function in relation to structural and functional brain changes in Alzheimer´s disease (AD). In the first study relations between hippocampal volume, neuropsychological function and limbic-hypothalamic-pituitary-adrenal (LHPA) axis disturbances in AD were investigated with magnetic resonance imaging (MRI). Reduced hippocampal CA1 volume and suppressed cortisol levels in combination, best predicted the variation in neuropsychological performance. The conclusion was that reduced hippocampal volume and LHPA axis disturbances are associated to level of cognitive function in AD. The second study focused on whether patients with early AD showed an altered regional cerebral blood flow (rCBF) pattern compared to control persons, correlation between performance on memory tests and rCBF in sub-lobar volumes of the brain were investigated. The rCBF was measured with single photon emission computed tomography (SPECT). AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus compared to controls. The diagnostic sensitivity and specificity for AD was high in temporoparietal regions. AD-patients had significantly lower performance on semantic and, in particular, episodic memory-tests compared to the controls, and their performance on several episodic tests correlated with rCBF in parietal and temporal regions including left hippocampus, which suggest that abnormalities in the rCBF pattern underlie impaired episodic memory functioning in AD. The conclusion was that an observer-independent analyzing method for SPECT with sub-lobar volumes VOI´s is promising in the diagnosis of AD. In a third study possible differences in memory-related functional brain activation between persons with high versus low risk for AD were examined with functional magnetic resonance imaging (fMRI). The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences. During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal and hippocampal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. The conclusion was that patterns of prefrontal brain activity related to episodic memory differed between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease. In a final study SPECT was used to map patterns of rCBF in an activated state (an episodic encoding task) and in a rest condition in persons with mild AD and in healthy elderly control persons. A reduction of rCBF in temporoparietal regions that was more pronounced in mild AD in the activated encoding task was observed. The conclusion was that there are rCBF differences between mild AD patients and healthy controls in temporoparietal regions, and the temporoparietal reduction is more pronounced during activation than during rest which might be important in the early diagnosis of AD. Taken together, these findings show that level of neuropsychological function, notably episodic memory, can be systematically related to functional disturbances in the LHPA axis and to the function of temporoparietal and prefrontal brain regions in AD patients. These changes are detectable in patients with risk for AD and in an early phase of AD which suggests that the obtained results might be important for early diagnosis of AD.

The aim of this doctoral thesis was to study the influence of memory, pain, age and education on the regional cerebral blood flow (rCBF), i.e. brain function, in early Alzheimer's disease (AD) and in chronic neck pain patients in comparison to healthy controls and in healthy elderly per se. This was done by optimizing single photon emission computed tomography (SPECT) as a method to study rCBF with the tracer Technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and by matching all image data to a brain atlas before evaluation. The rCBF-SPECT was evaluated and developed to obtain higher diagnostic accuracy in AD and in chronic neck pain patients it was used to study basic pain related cerebral processes in chronic pain of different origin. A new semimanual registration method, based on fiducial marker, suitable for investigations with low spatial resolution was developed. The method was used to reconstruct images with an improved attenuation and scatter correction by using an attenuation-map calculated from the patients' previously acquired CT images. The influence of age and education on rCBF was evaluated with statistical parametric mapping, SPM in healthy elderly. The main findings were age related changes in rCBF in regions close to interlobar and interhemispheric space but not in regions typically affected in early AD, except for the medial temporal lobe. The theory of a 'cognitive reserve' in individuals with a longer education was supported with findings in the lateral temporal lobe, a region related to semantic memory, and in the frontal lobe. A cross-sectional study of chronic neck pain patients showed extensive rCBF changes in coping related regions in a non-traumatic pain patients compared to both healthy and a pain group with a traumatic origin, i.e. whiplash syndrome. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. This suggests different pain mechanisms in these groups. The AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus. These changes were associated to episodic memory performance, and especially to face recognition. The diagnostic sensitivity for AD was high. The face recognition test (episodic memory) was used in AD patients to improve the sensitivity of method, i.e. memory-provoked rCBF-SPECT (MP-SPECT). The results were compared to healthy controls and the reductions of rCBF in temporoparietal regions were more pronounced in mild AD during provocation. Memory provocation increased the sensitivity of AD-related rCBF changes at group level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might then be of help to set diagnosis earlier. In conclusion rCBF in temporoparietal regions are associated to an impaired episodic memory in early AD. Changes in these regions do not have a strong connection to chronological age. The diagnostic sensitivity of rCBF-SPECT in AD is high and there is a potentially higher sensitivity if memory provoked investigations are used. The findings in this thesis have given an increased knowledge of underlying cerebral pain processing in non-traumatic and traumatic (whiplash) neck pain. Preliminary results supporting the theory of 'cognitive reserve' by showing a correlation between long education and preserved rCBF was found in healthy elderly.

A presente pesquisa centra-se no estudo das relações entre memória de curto prazo, memória de trabalho, velocidade de processamento, processamento visuoespacial, funções executivas, atenção seletiva e alternada e desempenho matemático, uma vez que essas relações podem esclarecer as diferenças entre os alunos na aprendizagem da matemática. O trabalho teve como objeto de observação crianças da 2ª série do ensino fundamental. Consiste em um estudo com base correlacional e comparativa. A amostra desta pesquisa é composta por 40 alunos, com idade entre 8 e 9 anos. A investigação envolvendo o funcionamento neuropsicológico e o desempenho cognitivo na aprendizagem matemática é relevante, pois para desenvolver habilidades de cálculo matemático é fundamental que o aluno tenha construído o conceito de número e esta construção está vinculada ao desenvolvimento das funções neuropsicológicas. O desempenho matemático é avaliado através da Prova de Aritmética de Capovilla, Montiel e Capovilla (2007) e as funções neuropsicológicas, através de quatro subtestes da Escala Wechsler WISCIII, que são: Memória de Curto Prazo – teste de Dígitos de Ordem Direta; Memória de Trabalho – Dígitos de Ordem Inversa; Velocidade de Processamento - Procurar Símbolos e Códigos; Percepção Visuoespacial – teste de Cubos. A Função Executiva é avaliada através do Teste das Trilhas de Montiel e Capovilla (2007) e a Atenção, através do Teste de Atenção por Cancelamento de Montiel e Capovilla (2007). Observa-se uma correlação significativa entre Desempenho Matemático e Memória de Curto Prazo, Velocidade de Processamento, Função Executiva e Atenção. Neste estudo, não se encontrou uma correlação estatisticamente significativa entre as funções Memória de Trabalho e Processamento Visuoespacial. / This paper approaches the relationship amongst neuropsychological functions –Short Term Memory (STM), Working Memory (WM), Speed Processing (SP), Visual Spatial Perception (VSP), Executive Functions (EF), Attention (A) and Math Performance (MP) in 2nd grade children at a public Elementary School from Porto Alegre. It is a comparative and correlation study. The sample of this research is composed for 40 pupils with are between 8 and 9 years. Research involving neuropsychological functioning and cognitive performance in mathematics is pertinent, for it is essential that the student build the notion of number in order to develop mathematical skills and such construction relies on the expansion of neuropsychological functions. The mathematical performance is measured by the Arthmetic Test of Capovilla, Montiel and Capovilla (2007) and the neuropsychological functions are verified by subtests Wechsler WIS CIII; Short Term Memory is assessed by the Digits in Direct Order, while the Working Memory is established by the Digits in Reverse Order. The speed processing is assessed through the use of Find Symbols and Codes activities, and spatial perception is confirmed by the utilization of cubes. The Executive Function is assessed by the Trail Making of Montiel and Capovilla (2007) and attention is assessed by the Attention Test for Cancellation of Montiel and Capovilla (2007). There is a momentous correlation amid math performance and Short-Term Memory, speed processing, executive function and attention. This study one did not mett, however, the establishment of a statistically significant correlation between the Working Memory functions and the Visual Spatial Processing.

A presente pesquisa centra-se no estudo das relações entre memória de curto prazo, memória de trabalho, velocidade de processamento, processamento visuoespacial, funções executivas, atenção seletiva e alternada e desempenho matemático, uma vez que essas relações podem esclarecer as diferenças entre os alunos na aprendizagem da matemática. O trabalho teve como objeto de observação crianças da 2ª série do ensino fundamental. Consiste em um estudo com base correlacional e comparativa. A amostra desta pesquisa é composta por 40 alunos, com idade entre 8 e 9 anos. A investigação envolvendo o funcionamento neuropsicológico e o desempenho cognitivo na aprendizagem matemática é relevante, pois para desenvolver habilidades de cálculo matemático é fundamental que o aluno tenha construído o conceito de número e esta construção está vinculada ao desenvolvimento das funções neuropsicológicas. O desempenho matemático é avaliado através da Prova de Aritmética de Capovilla, Montiel e Capovilla (2007) e as funções neuropsicológicas, através de quatro subtestes da Escala Wechsler WISCIII, que são: Memória de Curto Prazo – teste de Dígitos de Ordem Direta; Memória de Trabalho – Dígitos de Ordem Inversa; Velocidade de Processamento - Procurar Símbolos e Códigos; Percepção Visuoespacial – teste de Cubos. A Função Executiva é avaliada através do Teste das Trilhas de Montiel e Capovilla (2007) e a Atenção, através do Teste de Atenção por Cancelamento de Montiel e Capovilla (2007). Observa-se uma correlação significativa entre Desempenho Matemático e Memória de Curto Prazo, Velocidade de Processamento, Função Executiva e Atenção. Neste estudo, não se encontrou uma correlação estatisticamente significativa entre as funções Memória de Trabalho e Processamento Visuoespacial. / This paper approaches the relationship amongst neuropsychological functions –Short Term Memory (STM), Working Memory (WM), Speed Processing (SP), Visual Spatial Perception (VSP), Executive Functions (EF), Attention (A) and Math Performance (MP) in 2nd grade children at a public Elementary School from Porto Alegre. It is a comparative and correlation study. The sample of this research is composed for 40 pupils with are between 8 and 9 years. Research involving neuropsychological functioning and cognitive performance in mathematics is pertinent, for it is essential that the student build the notion of number in order to develop mathematical skills and such construction relies on the expansion of neuropsychological functions. The mathematical performance is measured by the Arthmetic Test of Capovilla, Montiel and Capovilla (2007) and the neuropsychological functions are verified by subtests Wechsler WIS CIII; Short Term Memory is assessed by the Digits in Direct Order, while the Working Memory is established by the Digits in Reverse Order. The speed processing is assessed through the use of Find Symbols and Codes activities, and spatial perception is confirmed by the utilization of cubes. The Executive Function is assessed by the Trail Making of Montiel and Capovilla (2007) and attention is assessed by the Attention Test for Cancellation of Montiel and Capovilla (2007). There is a momentous correlation amid math performance and Short-Term Memory, speed processing, executive function and attention. This study one did not mett, however, the establishment of a statistically significant correlation between the Working Memory functions and the Visual Spatial Processing.

A presente pesquisa centra-se no estudo das relações entre memória de curto prazo, memória de trabalho, velocidade de processamento, processamento visuoespacial, funções executivas, atenção seletiva e alternada e desempenho matemático, uma vez que essas relações podem esclarecer as diferenças entre os alunos na aprendizagem da matemática. O trabalho teve como objeto de observação crianças da 2ª série do ensino fundamental. Consiste em um estudo com base correlacional e comparativa. A amostra desta pesquisa é composta por 40 alunos, com idade entre 8 e 9 anos. A investigação envolvendo o funcionamento neuropsicológico e o desempenho cognitivo na aprendizagem matemática é relevante, pois para desenvolver habilidades de cálculo matemático é fundamental que o aluno tenha construído o conceito de número e esta construção está vinculada ao desenvolvimento das funções neuropsicológicas. O desempenho matemático é avaliado através da Prova de Aritmética de Capovilla, Montiel e Capovilla (2007) e as funções neuropsicológicas, através de quatro subtestes da Escala Wechsler WISCIII, que são: Memória de Curto Prazo – teste de Dígitos de Ordem Direta; Memória de Trabalho – Dígitos de Ordem Inversa; Velocidade de Processamento - Procurar Símbolos e Códigos; Percepção Visuoespacial – teste de Cubos. A Função Executiva é avaliada através do Teste das Trilhas de Montiel e Capovilla (2007) e a Atenção, através do Teste de Atenção por Cancelamento de Montiel e Capovilla (2007). Observa-se uma correlação significativa entre Desempenho Matemático e Memória de Curto Prazo, Velocidade de Processamento, Função Executiva e Atenção. Neste estudo, não se encontrou uma correlação estatisticamente significativa entre as funções Memória de Trabalho e Processamento Visuoespacial. / This paper approaches the relationship amongst neuropsychological functions –Short Term Memory (STM), Working Memory (WM), Speed Processing (SP), Visual Spatial Perception (VSP), Executive Functions (EF), Attention (A) and Math Performance (MP) in 2nd grade children at a public Elementary School from Porto Alegre. It is a comparative and correlation study. The sample of this research is composed for 40 pupils with are between 8 and 9 years. Research involving neuropsychological functioning and cognitive performance in mathematics is pertinent, for it is essential that the student build the notion of number in order to develop mathematical skills and such construction relies on the expansion of neuropsychological functions. The mathematical performance is measured by the Arthmetic Test of Capovilla, Montiel and Capovilla (2007) and the neuropsychological functions are verified by subtests Wechsler WIS CIII; Short Term Memory is assessed by the Digits in Direct Order, while the Working Memory is established by the Digits in Reverse Order. The speed processing is assessed through the use of Find Symbols and Codes activities, and spatial perception is confirmed by the utilization of cubes. The Executive Function is assessed by the Trail Making of Montiel and Capovilla (2007) and attention is assessed by the Attention Test for Cancellation of Montiel and Capovilla (2007). There is a momentous correlation amid math performance and Short-Term Memory, speed processing, executive function and attention. This study one did not mett, however, the establishment of a statistically significant correlation between the Working Memory functions and the Visual Spatial Processing.