A avaliação neuropsicológica é instrumento auxiliar para lateralização em epilepsia temporal (ET). Desempenho comprometido em memória verbal (MV) e não verbal (MNV) sugeririam, respectivamente, disfunção no sistema de memória do hemisfério dominante e não dominante. Não há consenso sobre a capacidade lateralizatória da avaliação de memória em pacientes com epilepsia. Estudou-se o poder lateralizatório da avaliação neuropsicológica em testes de memória verbal e não verbal em ET secundária a esclerose mesial temporal (EMT) unilateral. Comparamos o desempenho em memória verbal (RAVLT e o Memória Lógica) e não verbal (RVDLT e a figura complexa de Rey) em 87 pacientes destros com EMT (44 direita, 43 esquerda) e 42 controles. Pacientes e controles tinham escolaridade>8 anos, QI>70, sem comorbidades. Pacientes com EMTE tiveram desempenho rebaixado comparado a controles e EMTD em evocação livre e tardia do RAVLT. EMTE e EMTD tiveram desempenho rebaixado em relação a controles em evocação livre e tardia em Memória Lógica. EMTD tiveram desempenho rebaixado em relação a controles em evocação tardia da figura complexa de Rey. Observou-se baixa prevalência de dificuldade em ambos tipos de memória em ambos os grupos. Quando considerado acometimento de específico de MV observou-se associação com EMTE, com baixa sensibilidade, médio valor preditivo positivo (VPP) e alta especificidade. Quando considerado acometimento específico de MNV observou-se associação com EMTD, com baixa sensibilidade e altos valor preditivo positivo (VPP) e especificidade. O poder lateralizatório da testagem neuropsicológica de memória em EMT é observado, em apenas uma parcela de pacientes com EMT unilateral / Neuropsychological testing is a standard tool in the evaluation of patients with epilepsy. It allows assessment of performance in various cognitive domains, and is used as a lateralizing tool for seizure focus localization. Poor performance in verbal memory (VM) test is believed to indicate a dominant hemisphere focus. Poor performance in nonverbal memory (NVM) tests would localize the focus to the nondominant hemisphere. There still is a paucity of evidence of the ability of neuropsychological testing to predict seizure focus lateralization. We studied the lateralizing ability of neuropsychological testing of VM and NVM in a sample of 87 right handed patients with epilepsy secondary to unilateral mesial sclerosis (MTS) (44 right R, 43 left - L) and 42 controls (C), with an IQ>70, eight or more years of schooling, without comorbidities. LMTS patients performed significantly worse than controls in free and delayed recall of RAVLT items. L and RMTS performed worse than controls in immediate and delayed recall of the Logical Memory stories. RMTS performed worse than controls in delayed recall of the Complex Rey Figure. Our findings showed a low prevalence of VM and NVM impairment in both groups, an association between specific VM deficit and LMTS, with fair PPV and good specificity, and low sensibility. Selective NVM impairment was associated with RMTS, with good PPV and specificity for RMTS, and low sensibility. The lateralizing power of neuropsychological testing is noted only in a minority of patients with specific selective patterns of VM and NVM impairment

Introdução: a descrição tradicional da Esclerose Múltipla (EM) enfatiza ser esta uma doença desmielinizante inflamatória acometendo a substância branca (SB) do sistema nervoso central. Porém, nas últimas décadas vêm sendo acumuladas evidências de acometimento da substância cinzenta (SC), tanto em estudos anátomo-patológicos como de imagem quantitativa de ressonância magnética (IRM-q). Este comprometimento da SC é mais evidente na fase crônica progressiva da doença, onde a atrofia predomina, sendo as alterações cognitivas entendidas como algo restrito a esta fase. No entanto, como foi provada a existência de dano axonal precoce na EM, nós hipotetizamos que existe comprometimento de funções superiores detectáveis por exames neuropsicológicos mesmo em pacientes com déficit mínimo. Objetivo: testar a hipótese de que existem alterações cognitivas precoces na EM mesmo com disabilidade mínima e dano tecidual discreto. Método: foram avaliados com bateria neuropsicológica extensiva e exames de IRM-q pormenorizados 17 indivíduos (6 homens e 11 mulheres) com EM recorrente remitente (RR), com diagnóstico clinicamente definido e comprovado por imagem de acordo com os critérios de McDonald. O tempo de doença foi igual ou inferior a cinco anos, contados a partir do diagnóstico e com disabilidade mínima (EDSS menor que 3). Um grupo controle de 17 voluntários normais pareados foi avaliado para comparação. Resultados: os pacientes apresentaram disfunção de funções superiores estatisticamente significantes que incluíram dificuldades de atenção, memória, velocidade de processamento de informação, habilidades visuoespaciais, planejamento, abstração verbal, raciocínio numérico, flexibilidade mental, controle inibitório, compreensão verbal e escores de QI (tanto de QI geral, quanto de QI de execução e verbal). Apresentaram-se preservados com relação aos controles: a capacidade de nomeação, a velocidade de processamento motor e o raciocínio lógico. Na IRM-q houve alterações significativas discretas, compatíveis com a fase inicial da doença. Conclusão: nossos achados sugerem que existe déficit cognitivo precoce na EMRR, mesmo quando a debilidade é incipiente ou ausente. / Introduction: the traditional description of Multiple Sclerosis (MS) emphasizes that this is an inflammatory demyelinating disease affecting the white matter (WM) of the central nervous system. However, in recent decades has been accumulated evidence of involvement of gray matter (GM), both in anatomical and pathological studies as a quantitative magnetic resonance imaging (MRI-q). This impairment of the GM is more evident in chronic progressive disease, where atrophy predominates, and cognitive changes seen as something restricted to this phase. However, as has proven the existence of early axonal damage in MS, we hypothesized that there is impairment of higher functions detectable by neuropsychological tests, even in patients with minimal deficit. Objective: to test the hypothesis that there are early cognitive changes in MS even with disabled with minimal tissue damage and discreet. Methods: we evaluated extensive neuropsychological and MRI scans q-detailed 17 subjects (6 men and 11 women) with relapsing remitting (RR), defined clinically diagnosed and confirmed by the image according to the McDonald criteria. Disease duration was equal to or less than five years, starting from the diagnosis and disabled with minimal (EDSS less than 3). A control group of 17 matched normal volunteers were evaluated for comparison. Results: patients showed impairment of higher functions were statistically significant, which included attention deficit, memory, speed of information processing, visuospatial abilities, planning, verbal abstraction, numerical reasoning, mental flexibility, inhibitory control, verbal comprehension and IQ scores (both IQ general, the implementation of IQ and verbal). Presented are preserved with respect to controls: the ability of appointment, the speed of motor processing and logical reasoning. In MRI-q discrete significant changes consistent with early disease was finding. Conclusion: our findings suggest that cognitive deficits exist in early RR-MS, even when the disability is weak or absent.

Orientador: Benito Pereira Damasceno, Fernando Cendes / Tese (doutorado) - Universidade Estadual de Campinas - Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T09:38:00Z (GMT). No. of bitstreams: 1 Balthazar_MarcioLuizFigueredo_D.pdf: 11095820 bytes, checksum: 868237eff7c956adc28757f2870b225d (MD5) Previous issue date: 2008 / Resumo: A organização cerebral da memória léxico-semântica, assim como suas alterações em pacientes com doença de Alzheimer (DA) leve e Comprometimento Cognitivo Leve amnéstico (CCLa) não são completamente conhecidas. Neste estudo, avaliamos o desempenho de pacientes com DA leve, CCLa e idosos normais em testes léxico-semânticos como o Teste de Nomeação de Boston (TNB), Teste de Similaridades do CAMCOG e Fluência Verbal (FV) para categoria animais, além de outros domínios cognitivos. Aprofundamos o estudo do desempenho dos pacientes no TNB avaliando: 1) se houve benefício com o uso de pistas semânticas e fonêmicas, após erros espontâneos de nomeação e 2) o padrão de erros de nomeação espontâneos (classificados como semânticos, fonológicos, por omissão e por paragnosia visual); e subclassificando os erros semânticos de forma hierárquica (erros superordenados, coordenados e circunlóquios). Avaliamos também os padrões de atrofia cerebral desses pacientes em relação a controles por meio de métodos de neuroimagem estrutural por Ressonância Magnética: volumetria hipocampal e Morfometria Baseada em Voxels (RM-MBV). Ainda, correlacionamos o desempenho dos pacientes no Teste de Aprendizado Auditivo Verbal de Rey (TAAVR) com o volume hipocampal e o padrão de erros espontâneos gerais e semânticos no TNB com a densidade de substância cinzenta em todo o cérebro por RM-MBV. Os pacientes com CCLa tiveram desempenho inferior aos controles no teste de FV para animais, enquanto que os pacientes com DA leve tiveram desempenho inferior ao grupo CCLa e controles em todos os testes léxico-semânticos. Porém, após utilizarem pista fonêmica, os pacientes com DA leve tiveram desempenho em nomeação de figuras proporcionalmente semelhante aos controles e CCLa. Também, os três grupos tiveram padrão de erros espontâneos gerais e semânticos qualitativamente iguais, embora quantitativamente tenha havido maior número de erros no grupo DA leve, seguido por CCLa e controles, respectivamente. Quanto ao exames de neuroimagem estrutural, houve um continuum no volume hipocampal, porém sem diferença estatística significante entre DA leve e CCLa. Houve correlação significativa entre o volume hipocampal e o item de evocação tardia do TAAVR, considerando os três grupos em conjunto; quanto à RM-MBV, os pacientes com DA leve apresentaram mais áreas com maior grau de atrofia de substância cinzenta que CCLa e controles; o grupo CCLa apresentou atrofia principalmente em giros parahipocampais e tálamos, quando comparados aos controles. Em relação à substância branca, o grupo DA leve apresentou atrofia em região periventricular, corpo caloso e em áreas próximas a córtices associativos. Não houve áreas de atrofia de substância branca no grupo CCLa em relação aos controles. Encontramos diversas áreas em que houve correlação significativa entre os erros espontâneos de nomeação e a densidade de substância cinzenta, considerando os três grupos juntos. Notadamente, as regiões temporais mediais e tálamos correlacionaram-se com todos os subtipos de erros; as regiões anteriores dos lobos temporais, principalmente os giros superior e inferior, correlacionaram-se com erros coordenados e circunlóquios; os giros frontais superiores (o esquerdo mais que o direito) correlacionaram-se com erros superordenados, e os inferiores, com erros tipo circunlóquios. Discutimos o possível papel de cada uma dessas áreas nos processos mentais léxicosemânticos e sua contribuição para o entendimento de como esse tipo de memória está organizada no cérebro humano. / Abstract: Cerebral organization of lexical-semantic memory, as well as its disruption in mild Alzheimer's disease (AD) and in amnestic Mild Cognitive Impairment (aMCI) is not fully understood. In this study, we evaluated the performance of mild AD, aMCI and normal aging subjects in lexical-semantic tests: Boston Naming Test (BNT), CAMCOG's Similarities item, Verbal Fluency (VF) for animals' category and others cognitive domains. We detailed their performance on BNT by evaluating: 1) if they needed or were benefited by semantic and phonemic cues and 2) the pattern of general errors (classified as semantic errors, visual paragnosia, phonological errors, and omission errors). The semantic errors were further subcategorized into three subclasses (coordinate, superordinate, and circumlocutory). We also evaluated the pattern of brain atrophy in aMCI and mild AD patients by using structural neuroimaging methods: hippocampal volumetry (HV) and Voxel-based morphometry (VBM). We correlated HV with subjects' performance on Rey Auditory Verbal Learning Test (RAVLT) delayed recall item, and the pattern of spontaneous and semantic errors on BNT with grey matter density, by using VBM. aMCI subjects performed worse than controls on VF for animals' category, while mild AD performed worse than aMCI and controls in all lexical-semantic tests. However, after phonemic cues, mild AD subjects performed similar to aMCI and control subjects. They also had the same qualitative pattern of spontaneous and semantic errors, although quantitatively, AD patients committed the most errors, controls committed the fewest errors, and aMCI subjects showed an intermediate performance. Concerning structural neuroimaging, the three groups also presented a continuum pattern in HV, although there were no statistically differences between aMCI and AD HV. RAVLT delayed recall item was significantly related to HV, considering the three groups together. In relation to VBM analysis, mild AD patients had more areas with more grey matter atrophy than aMCI and control subjects. aMCI showed more atrophy mainly in parahippocampal gyri and thalami, when compared with control subjects. Considering white matter, mild AD group showed atrophy in periventricular regions, corpus callosum and areas adjacent to associative cortices. There was not white matter atrophy in aMCI patients in comparison with controls subjects. We found several areas with significant correlations between spontaneous naming errors on BNT and grey matter density, considering the three groups together. Medial temporal structures and thalami were correlated with all subtypes of errors; anterior temporal regions, mainly superior and inferior temporal gyri, were related with coordinate and circumlocutory errors; superior frontal gyri (left more than right) were related with superordinate errors, while inferior frontal gyri (left more than right) were related to circumlocutory errors. We discussed the possible role of each of these areas in the lexical-semantic mental processes, and their contribution to the understanding of cerebral organization of semantic memory. / Doutorado / Neurologia / Doutor em Ciências Médicas

D.Litt. et. Phil. / Head injury is the major cause of death for individuals under 35 years old in the United States of America, and a similar picture exists in South Africa. A major cause of traumatic brain injury is motor vehicle accidents. In addition, the advances in modem medical technology increase the chances for survival, for example, sophisticated medical diagnostic techniques such as computerised tomography (CT), and magnetic resonance imaging (MRI). Advances in emergency trauma and neurosurgical procedures have also increased the number of survivors following a head injury. The symptoms resulting from head injury include disturbed physical, cognitive, psychological and behavioural functioning. Long-term management of these symptoms is usually required. A body of evidence exists that demonstrates the value of rehabilitation during the first year of recovery from traumatic brain injury. Head injury cases often result in litigation in that the injured person may be entitled to compensation for the injuries sustained. Considerable forensic debate exists around the issue of whether the victim's symptoms are attributable to organic brain damage, or whether they reflect a pre-existing functional psychological state of psychiatric illness, or personality disorder. Further still, the individual may be 'malingering' or faking postconcussion symptoms of headache, dizziness, fatigue, memory deficit, impaired concentration, irritability, anxiety, insomnia, concern about bodily functions, and hypersensitivity to light and noise. Alternatively, a common diagnosis is traumatic neurosis with a psychogenic basis, and in the context of litigation is referred to as "compensation neurosis". Specifically, the issue of contention revolves around concussion, and mild or minor head injuries. This study proposed that both neuropathophysiological and psychosocial symptoms occur in the event of a traumatic brain injury. This view supports the traditional model that pain or the sequelae of head injury are not affected by compensation. Therefore, the objective of the study was that follow-up assessment after compensation pay-outs should produce similar results to the assessment results obtained during the litigation process. The hypotheses of the study were essentially confirmed. The neuropsychological error scores produced in the assessments during litigation, and two-to-four years after the completion of litigation were similar. However, similar to other studies, variations were evident. Four exceptions were demonstrated in that significant improvement was evident with regard to shotterm verbal memory delayed recall for paragraphs, and for immediate recall (without and after interference) in verbal memory for a word list. These improvements therefore pertain to verbal memory. The fourth improvement occurred with respect to manual dexterity and visual-motor work speed, although the improvement may be peripheral or primary (neurological). Further findings included that no gender differences were evident in the neuropsychological posttest scores. It was confirmed that individuals with a good Glasgow Outcome Scale rating showed less posttraumatic amnesia, a shorter time since injury, less additional injuries, and a lower compensation sum. It was also supported that individuals with a good Glasgow Outcome Scale rating showed less impairment on neuropsychological indices. However, an exception was that individuals with a moderate Glasgow Outcome Scale rating showed improvement on the neuropsychological index measuring immediate concentration, visual scanning, and visual-motor work speed. The qualitative data or psychosocial measures of severity and outcome produced a similar picture that the majority of subjects maintained their pretest status although some exceptions were evident. Within the medico-legal domain it was shown that, in general, concordance of severity was high amongst the medical experts for the plaintiffs and the defendents. However, their prognoses were indicated to be less accurate, and whilst their consistency in documenting diagnoses in the reports of the subjects was adequate, they were found to be inconsistent in documenting severity ratings and prognoses. It was suggested that improvements may be attributed to neurophysiological differences, non-participation in a rehabilitation programme, the interference and delay of rehabilitation, increased psychological reactions associated with litigation, and mechanisms of secondary gain which may by attributed to the other players, such as the family, the attorneys, the medical experts, among others, and not only to the individual or victim.

Abstract Many adults with schizophrenia have cognitive deficits, and many children who go on to develop schizophrenia as adults have subtle sub-clinical signs of early developmental deviance. However, the relationship between early markers of neurodevelopment and later neurocognition remains unclear. The present thesis principally investigates infant neurodevelopment, adolescent scholastic function and adult cognition in the Northern Finland 1966 Birth Cohort (n = 12,058). Proxy markers of neurocognition – developmental milestones and school performance – were collected prospectively. Individuals who went on to develop schizophrenia were identified. School performance in pre-schizophrenic individuals was assessed by teacher ratings (n = 100). Cognition in subjects with schizophrenia was assessed at age 33–35 (n = 61). A representative sample of the general population at risk was studied as a comparison group (school assessments n = 9351; neurocognitive assessment n = 104). The schizophrenia group achieved neuromotor milestones later (p < 0.0001) and performed worse than the control group on all cognitive measures (p < 0.0025). In pooled analyses there were associations between infant motor development and adult cognition in executive function (p = 0.006), verbal learning (p = 0.007) and visuospatial working memory (p = 0.02), (earlier development was linked to better adult cognition) but not in visual object learning. The pattern of associations between development and adult cognition was broadly similar in schizophrenia and the general population, whereas associations between development and adolescent scholastic function were stronger in schizophrenia than in controls (p < 0.05). A complementary neuropsychological case study of spontaneous clinical and cognitive improvement in chronic schizophrenia is also presented, showing that cognitive deficits in schizophrenia do not always represent a static encephalopathy, but can be subject to marked improvement. The possibility of using knowledge about premorbid features to help predict and prevent schizophrenia is also critically reviewed, using the school setting as a practical example. It is concluded that many obstacles remain before knowledge about premorbid features can be translated to preventative interventions. Overall, the results of these investigations are consistent with the hypothesis that in schizophrenia, mild infant motor developmental delay, adolescent scholastic performance and cognitive deficits may be age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome. / Tiivistelmä Skitsofreniaa sairastavilla aikuisilla on kognitiivisten toimintojen puutoksia. Kognitiivisia (tiedon prosessoinnin) toimintoja ovat esimerkiksi tarkkaavaisuus, huomiokyky, oppiminen, muisti, asioiden suunnittelu ja ongelmanratkaisu. Monilla lapsilla, jotka sairastuvat aikuisiällä skitsofreniaan, on vähäisiä, kliinisesti merkityksettömiä varhaisen kehityksen poikkeamia tai hitautta. Varhaisen kehityksen ja myöhemmän kognition yhteys on toistaiseksi epäselvä. Tämä tutkimus selvittää varhaisen hermostonkehityksen, nuoruusiän koulunkäynnin ja aikuisiän kognition yhteyttä Pohjois-Suomen 1966 syntymäkohortissa (N = 12 058). Tiedot hermoston tietotoimintoja kuvaavista muuttujista (varhainen kehitys ja koulumenestys) kerättiin prospektiivisesti, samoin tieto skitsofreniaan sairastumisesta. Opettajat arvioivat tutkittavien (n = 100) koulumenestystä ennen sairastumista. Skitsofreniaa sairastavien kognitiivinen suorituskyky arvioitiin 33–35 vuoden iässä (n = 61). Vertailuryhmänä käytettiin edustavaa otosta yleisväestöstä (koulumenestys n = 9351; kognitiivinen suorituskyky n = 104). Skitsofreniaryhmä saavutti motoriset kehityskynnykset (kuten seisomaan ja kävelemään oppiminen) keskimäärin merkittävästi myöhemmin ja suoriutui huonommin kuin kontrolliryhmä kaikissa kognitiivisen suorituskyvyn mittauksissa. Lisäksi varhaisen motorisen kehityksen ja aikuisiän kognitiivisen suorituskyvyn välillä havaittiin yhteys. Erityisesti varhainen motorinen kehitys ennusti hyvää toiminnanohjausta, verbaalista oppimista ja visuospatiaalista työmuistia. Vastaavaa yhteyttä ei havaittu visuaalisen oppimisen alueella. Varhaisen kehityksen ja aikuisiän kognitiivisten toimintojen yhteys oli samantyyppinen sekä skitsofreniassa että yleisväestössä, kun taas varhaisen kehityksen ja nuoruusiän koulumenetyksen yhteys oli vahvempi skitsofreniaan sairastuneilla kuin verrokkihenkilöillä. Yhtenä osatyönä esitetään tapausselostus, jossa kaksi kroonista skitsofreniaa sairastavaa henkilöä toipui spontaanisti sekä kliinisesti ja kognitiivisesti. Tapausselostus osoittaa, että skitsofreniaan liittyvä kognitiivisen tason lasku ei välttämättä heijasta pysyvää aivojen toiminnantason laskua, vaan tila voi huomattavasti korjaantua. Tutkimuksen osana on myös katsaus siitä, missä määrin on mahdollista ennustaa skitsofreniaa sairautta edeltävien piirteiden ja koulussa tehtyjen havaintojen perusteella. Katsauksen valossa on ilmeistä, että on edelleen hyvin vaikea hyödyntää sairautta edeltäviä piirteitä tulevan sairauden ennustamisessa ja etenkin ehkäisyssä. Yhteenvetona voidaan todeta tämän tutkimuksen keskeisten tulosten tukevan hypoteesia, jonka mukaan skitsofreniaan myöhemmin sairastuneilla havaittu lievä varhaisen motorisen kehityksen viive, heikko nuoruusiän koulumenestys ja kognitiivisen tason lasku heijastanevat ikäsidonnaista keskushermoston kehitysprosessia ja voivat olla osa samasta pitkittäisestä oirekokonaisuudesta.

Comprendre le fonctionnement cognitif d’un patient et les répercussions de ses troubles constituent un enjeu majeur de la rééducation neuropsychologique. Chez le sujet jeune, la réalisation de cette rééducation amène à s’interroger sur les possibilités et les stratégies d’amélioration cognitive dans le cadre développemental. Ces interrogations sont à la base de ce travail doctoral qui examine la validité cognitive, les références au corpus théorique et les stratégies rééducatives prototypiques à développer dans les troubles du neurodéveloppement et plus particulièrement dans le Trouble du Déficit de l’Attention/Hyperactivité (TDAH). Ces travaux de recherche visent ainsi à élaborer et à évaluer différentes techniques de rééducation dans le trouble de l’inhibition, déficit considéré comme central selon Barkley dans son modèle relatif au TDAH. Par une étude contrôlée, randomisée et incluant 38 enfants âgés de 9 à 13 ans porteurs d’un TDAH, ces travaux s’attachent à examiner les effets et les critères opérants d’un protocole de rééducation combinant une double approche cognitive se référant aux modèles du traitement de l’information. Les résultats et les perspectives de recherches issus de ce travail s’inscrivent in fine dans une structuration du champ de la rééducation cognitive chez l’enfant / Understanding a patient's cognitive functioning and the impact of the disorder is a major challenge in neuropsychological rehabilitation. The rehabilitation of young patients raises questions on the prospects and strategies for cognitive enhancement in the context of development. The doctoral research presented here, which examines cognitive validity, theoretical references and prototypic rehabilitation strategies that need to be developed for neurodevelopmental disorders and, more specifically, attention deficit hyperactivity disorder (ADHD), is based on these questions. These research studies aim to develop and assess several rehabilitation techniques for impaired inhibition, which is a central deficit in Barkley's model of ADHD. Building upon a controlled, randomised study of 38 children aged 9 to 13 years with ADHD, this research looks at the effects and operative criteria of a rehabilitation protocol using a dual cognitive approach that draws upon models of information processing. Finally, the results and prospects for future research fall within the context of structuring the field of cognitive rehabilitation in children

Bipolar disorder (BD) and major depressive disorder (MDD) are characterised by a fundamental disturbance of mood, with strong support for overlapping causal pathways. Structural brain and neurocognitive abnormalities have been associated with mood disorders, but it is unknown whether these reflect early adverse effects predisposing to mood disorders or emerge as a consequence of illness onset. The Bipolar Family Study is well-suited to examine the origin of structural brain and neuropsychological abnormalities in mood disorders further. The volumes of subcortical brain regions, cortical thickness and surface area measures of frontal and temporal regions of interest and neuropsychological performance over a two-year time interval was compared at baseline and longitudinally between three groups: young individuals at high risk of mood disorders who subsequently developed MDD during the follow-up period (HR-MDD), individuals at high risk of mood disorders who remained well (HR-well), and healthy control subjects (HC). The longitudinal analysis of cortical thickness revealed significant group effects for the right parahippocampal and right fusiform gyrus. Cortical thickness in both of these brain regions across the two time points was reduced in both high-risk groups relative to controls, with the HR-MDD group displaying a thinner parahippocampus gyrus than the HR-well group. Moreover, a significant interaction effect was observed for the left inferior frontal and left precentral gyrus. The HR-well subjects had progressive thickness reductions in these brain regions relative to controls, while the HR-MDD group showed cortical thickening of these areas. Finally, longitudinal analyses of neuropsychological performance revealed a significant group effect for long delay verbal memory and extradimensional set-shifting performance. Reduced neurocognitive performance during both tasks across the two time points was found in the HR-well group relative to controls, with the HR-MDD group displaying decreased extradimensional set-shifting abilities as compared to the HC group only. These findings indicate, that reduced left parahippocampal and fusiform thickness constitute a familial trait marker for vulnerability to mood disorders and may thus form potential neuroanatomic endophenotypes. Particularly strong thickness reductions of the parahippocampal gyrus appear be linked to an onset of MDD. Moreover, progressive thickness reductions in the left inferior frontal and precentral gyrus in early adulthood form a familial trait marker for vulnerability to mood disorders, potentially reflecting early neurodegenerative processes. By contrast, an absence of cortical thinning of these brain regions in early adulthood appears to be linked to the onset of MDD, potentially reflecting a lack or delay of normal synaptic pruning processes. Reduced long delay verbal memory and extradimensional set-shifting performance across time constitute a familial trait marker for vulnerability to mood disorders, likely representing disturbances of normal brain development predisposing to illness. These findings advance our understanding of the origin of structural brain and neurocognitive abnormalities in mood disorders.

Ph.D. / Epilepsy is a multidimensional disorder that extends beyond the medical implications to impact nearly every aspect of the person's life, as well as the lives of the people in the surrounding environment. Intractable epilepsy has a poor prognosis with possible worsening of seizures and cognitive decline over time. Anterior temporal lobe surgery for epilepsy provides an opportunity for the alleviation of seizures; however there are potential risks, to memory in particular. Research on surgery outcome thus far has evaluated outcome from a linear paradigm and has studied impact of surgery on isolated areas of function, the results derived from this have been largely inconsistent. So far, there has been very little research that focuses on the person as a whole, and as yet there has been no integrated approach to studying surgical outcome. The aim of the current study was therefore to investigate the impact of anterior temporal lobe surgery, specifically the symptomatic and functional surgical outcomes, in an integrated and holistic manner. This was done in accordance with the paradigm of complex systems theory as a critique of the previous literature in this field, and to gain a more holistic understanding of surgical outcome. A combination of methodologies was employed in order to achieve this. The sample consisted of male (n=10) and female (n=24) patients with intractable epilepsy undergoing left-sided (n=13) and right-sided (n=21) temporal lobe surgery at the Milpark Hospital Johannesburg between the ages of 14 and 58 (mean = 39 years), over a period of seven years. A pretest-posttest design was employed to obtain quantitative data (n=34). Post surgical assessments were conducted up to seven years post surgery (mean=3.6 years). Pre and post surgery assessment included neurocognitive functioning, particularly memory and language functions, by means of the Rey Complex Figure Test, Wechsler Memory Scale-Ill, and Controlled Oral Word Association Test; as well as emotional functioning, particularly depression and anxiety, by means of the Beck Depression lnventory-11 and Beck Anxiety lnventory-11. The quantitative data was subjected to statistical analysis of the sample as a whole, as well as gender and side of surgery comparisons, and included tests of normality of distribution of the data; the paired samples t-test; the independent samples t-test; the Wilcoxon Signed Ranks test; the Mann-Whitney U test; and the Wilks' Lambda test. A semi-structured interview was also conducted (n=30) in order to obtain qualitative data on the functional (psychosocial) aspects of outcome. The interview included an assessment of postoperative seizure outcome; changes in daily activity functions; the client's report on positive and negative outcomes of surgery; quality of life changes and satisfaction with surgery. The qualitative data was analysed using the methods of open coding and axial coding. The results for neuropsychological function reflected known lateralization effects with memory showing auditory-verbal memory deficits after left-sided surgery; and visual (figural) memory deficits after right-sided surgery. Gender differences reflected known neuropsychological differences with female superiority in verbal fluency and a male advantage on visual-spatial tasks. Importantly, there was no relationship between neuropsychological deficit and decrements in daily activity functions, emotional functioning or quality of life. This indicates little impact of neuropsychological deficit post surgery and may be an indication of the effectiveness of the preoperative screening procedures. The results for emotional functioning showed a statistically significant improvement in the 'moderate/severe' depression and anxiety groups from pre to post surgery. This indicates a substantial improvement in both depression and anxiety for this severity group. The qualitative results showed that surgery rendered 74% of the sample seizure free, 15% showing worthwhile improvement, and 11% no change or worse seizures. Seizure outcome however did not determine quality of life changes, even those with some improvement or no change still reported an improvement in quality of life post surgically. The functional outcomes showed little postoperative change in daily activity functions (driving, occupational functioning and marital status) but still a reported improvement in quality of life. There were far more reports on perceived positive than negative outcomes. The most positive benefit of surgery, as reported by participants, was that of increased feelings of control, decreased helplessness, and less anxiety and worry of having seizures. The overwhelming majority of participants reported improved quality of life (90%) and satisfaction with surgery (93%).

The aim of the study was to produce preliminary normative indications for the Trail Making Test and the Stroop Test, administered in English, on a non-clinical sample of black, Xhosa-speaking, unskilled individuals (N = 33), with an educational level of 11 – 12 years, in two age categories (18 –29 and 30 – 40 years). The sample was equally distributed for gender and level of education. Participants, who were required to have a basic proficiency in English, were from traditionally black township schools with relatively disadvantaged quality of education. Within-sample age and gender effects were investigated. There were no significant age effects on the Trail Making Test, whereas there was one significant difference between age groups on the Stroop Test with respect to the Color-Word task, and a result that strongly approached significance on the Word task, with the younger group performing better than the older group. There were no significant gender effects on the Trail Making Test, whereas there was one significant difference between genders on the Stroop Test with respect to the Word task, and a result that approached significance on the Color task, with females performing better than males. Normative indications for both measures were compared to available normative data on western populations with higher levels and more advantaged quality of education. This comparison revealed consistently poorer performances for both the Trail Making Test and the Stroop Test, confirming the need for localised normative datasets to facilitate accurate neuropsychological diagnoses on culturally disadvantaged individuals.

This study investigated the effect of cognitive factors on competency to stand trial. Previous researchers have investigated how psychological variables --such as psychosis and intelligence--contribute to incompetency. Although several researchers have established that intelligence contributes to incompetency, very few have investigated the role of specific cognitive abilities within the realm of intelligence. This study investigated the performance of 55 defendants referred for competency restoration on neuropsychological measures. Specifically, competent defendants and incompetent defendants were compared on several measures assessing functioning in seven cognitive domains. Competent defendants performed significantly better than incompetent defendants on measures of verbal comprehension, social judgment, verbal memory, and executive functioning. Competent and incompetent defendants did not differ on attention, visual spatial skills, or nonverbal memory.