Three generation families: Analysis of de novo variants in autism.

De novo variants (DNVs) analysis has proven to be a powerful approach to gene discovery in Autism Spectrum Disorder (ASD), which has not yet been shown in a Brazilian ASD cohort. The relevance of inherited rare variants has also been suggested, particularly in oligogenic models. We hypothesized that three-generation analyses of DNVs could provide new insights into the relevance of de novo and inherited variants across generations. To accomplish this goal, we performed whole-exome sequencing of 33 septet families composed of probands, parents, and grandparents (n = 231 individuals) and compared DNV rates (DNVr) between generations and those from two control cohorts. The DNVr in the probands (DNVr = 1.16) was marginally higher than in parents (DNVr = 0.60; p = 0.054), and in controls (DNVr = 0.68; p = 0.035, congenital heart disorder and DNVr = 0.70; p = 0.047, unaffected ASD siblings from Simons Simplex Collection). Moreover, most of the DNVs were found to have paternal origin in both generations (84.6%). Finally, we observed that 40% (6/15) of the DNVs in parents transmitted for probands are in ASD or ASD candidate genes, representing recently emerged risk variants to ASD in their families and suggest ZNF536, MSL2 and HDAC9 as ASD candidate genes. We did not observe an enrichment of risk variants nor sex bias of transmitted variants in the three generations, that can be due to sample size. These results further reinforce the relevance of de novo variants in ASD.

Copy number variations in a Brazilian cohort with autism spectrum disorders highlight the contribution of cell adhesion genes.

Prediction of pathogenicity of rare copy number variations (CNVs), a genomic alteration known to contribute to the etiology of autism spectrum disorder (ASD), represents a serious limitation to interpreting genetic tests, particularly for genetic counseling purposes. Chromosomal microarray analysis (CMA) was conducted in a unique collection of 144 Brazilian individuals with ASD of strong European and African ancestries. Rare CNVs were detected in 39 patients: 41 of unknown significance (VUS), four pathogenic and one likely pathogenic CNVs (clinical yield of 4.1%; 5/122). Based on gene content and recurrence in three large cohorts [a Brazilian neurodevelopmental disorder cohort, the autism MSSNG cohort, and the Canadian-based Centre for Applied Genomics microarray database], this work strengthened the pathogenicity of 14 genes (FAT1, CAMK4, BIRC6, DPP6, CSMD1, CTNNA3, CDH8/CDH11, CDH13, OR1C1, CNTN6, CNTNAP4, FGF2 and PTPRN2) within 14 CNVs. Notably, enrichment of cell adhesion proteins to ASD etiology was identified (p < 0.05), highlighting the importance of these gene families in the etiology of ASD.

Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport.

Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation.

Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort.

Large genomic databases of neurodevelopmental disorders (NDD) are helpful resources of genomic variations in complex and heterogeneous conditions, as Autism Spectrum Disorder (ASD). We evaluated the role of rare copy number variations (CNVs) and exonic de novo variants, in a molecularly unexplored Brazilian cohort of 30 ASD trios (n = 90), by performing a meta-analysis of our findings in more than 20,000 patients from NDD cohorts. We identified three pathogenic CNVs: two duplications on 1q21 and 17p13, and one deletion on 4q35. CNVs meta-analysis (n = 8,688 cases and n = 3,591 controls) confirmed 1q21 relevance by identifying duplications in other 16 ASD patients. Exome analysis led the identification of seven de novo variants in ASD genes (SFARI list): three loss-of-function pathogenic variants in CUL3, CACNA1H, and SHANK3; one missense pathogenic variant in KCNB1; and three deleterious missense variants in ATP10A, ANKS1B, and DOCK1. From the remaining 12 de novo variants in non-previous ASD genes, we prioritized PRPF8 and RBM14. Meta-analysis (n = 13,754 probands; n = 2,299 controls) identified six and two additional patients with validated de novo variants in PRPF8 and RBM14, respectively. By comparing the de novo variants with a previously established mutational rate model, PRPF8 showed nominal significance before multiple test correction (P = 0.039, P-value adjusted = 0.079, binomial test), suggesting its relevance to ASD. Approximately 60% of our patients presented comorbidities, and the diagnostic yield was estimated in 23% (7/30: three pathogenic CNVs and four pathogenic de novo variants). Our uncharacterized Brazilian cohort with tetra-hybrid ethnic composition was a valuable resource to validate and identify possible novel candidate loci. Autism Res 2020, 13: 199-206. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We believed that to study an unexplored autistic population, such as the Brazilian, could help to find novel genes for autism. In order to test this idea, with our limited budget, we compared candidate genes obtained from genomic analyses of 30 children and their parents, with those of more than 20,000 individuals from international studies. Happily, we identified a genetic cause in 23% of our patients and suggest a possible novel candidate gene for autism (PRPF8).

Actin cytoskeleton dynamics in stem cells from autistic individuals.

Several lines of indirect evidence, such as mutations or dysregulated expression of genes related to cytoskeleton, have suggested that cytoskeletal dynamics, a process essential for axons and dendrites development, is compromised in autism spectrum disorders (ASD). However, no study has yet examined whether cytoskeleton dynamics is functionally altered in cells from ASD patients. Here we investigated the regulation of actin cytoskeleton dynamics in stem cells from human exfoliated deciduous teeth (SHEDs) of 13 ASD patients and 8 control individuals by inducing actin filament depolymerization and then measuing their reconstruction upon activation of the RhoGTPases Rac, Cdc42 or RhoA. We observed that stem cells from seven ASD individuals (53%) presented altered dymanics of filament reconstruction, including a patient recently studied by our group whose iPSC-derived neuronal cells show shorten and less arborized neurites. We also report potentially pathogenic genetic variants that might be related to the alterations in actin repolymerization dynamics observed in some patient-derived cells. Our results suggest that, at least for a subgroup of ASD patients, the dynamics of actin polymerization is impaired, which might be ultimately leading to neuronal abnormalities.

Color Vision Losses in Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by impairments in social/communication abilities and restricted behaviors. The present study aims to examine color vision discrimination in ASD children and adolescents without intellectual disability. The participants were also subdivided in order to compare color vision thresholds of autistic participants and those who achieved diagnostic criteria for Asperger Syndrome (AS). Nine subjects with autism, 11 participants with AS and 36 typically developing children and adolescents participated in the study. Color vision was assessed by the Cambridge Color Test (CCT). The Trivector protocol was administered to determine color discrimination thresholds along the protan, deutan, and tritan color confusion lines. Data from ASD participants were compared to tolerance limits for 90% of the population with 90% probability obtained from controls thresholds. Of the 20 ASD individuals examined, 6 (30%) showed color vision losses. Elevated color discrimination thresholds were found in 3/9 participants with autism and in 3/11 AS participants. Diffuse and tritan deficits were found. Mechanisms for chromatic losses may be either at the retinal level and/or reflect reduced cortical integration.

Neurotoxic impact of mercury on the central nervous system evaluated by neuropsychological tests and on the autonomic nervous system evaluated by dynamic pupillometry.

Mercury vapor is highly toxic to the human body. The present study aimed to investigate the occurrence of neuropsychological dysfunction in former workers of fluorescent lamps factories that were exposed to mercury vapor (years after cessation of exposure), diagnosed with chronic mercurialism, and to investigate the effects of such exposure on the Autonomic Nervous System (ANS) using the non-invasive method of dynamic pupillometry. The exposed group and a control group matched by age and educational level were evaluated by the Beck Depression Inventory and with the computerized neuropsychological battery CANTABeclipse - subtests of working memory (Spatial Span), spatial memory (Spatial Recognition Memory), visual memory (Pattern Recognition Memory) and action planning (Stockings of Cambridge). The ANS was assessed by dynamic pupillometry, which provides information on the operation on both the sympathetic and parasympathetic functions. Depression scores were significantly higher among the former workers when compared with the control group. The exposed group also showed significantly worse performance in most of the cognitive functions assessed. In the dynamic pupillometry test, former workers showed significantly lower response than the control group in the sympathetic response parameter (time of 75% of pupillary recovery at 10cd/m2 luminance). Our study found indications that are suggestive of cognitive deficits and losses in sympathetic autonomic activity among patients occupationally exposed to mercury vapor.

Generalization of sensory auditory learning to top-down skills in a randomized controlled trial.

BACKGROUND: Research has shown that auditory training improves auditory sensory skills; however, it is unclear whether this improvement is transferred to top-down skills, such as memory, attention, and language, and whether it depends on group characteristics in regard to memory and attention skills. PURPOSE: The primary goal of this research was to investigate the generalization of learning from auditory sensory skills to top-down skills such as memory, attention, and language. We also aimed to compare whether this generalization process occurs in the same way among typically developing children and children with speech sound disorder. RESEARCH DESIGN: This study was a randomized controlled trial. STUDY SAMPLE: Typically developing 7- to 12-yr-old children and children with speech sound disorder were separated into four groups: a trained control group (TDT; n = 10, age 9.6 ± 2.0 yr), a nontrained control group (TDNT; n = 11, age 8.2 ± 1.6 yr), a trained study group (SSDT; n = 10, age 7.7 ± 1.2 yr), and a nontrained study group (SSDNT; n = 8, age 8.6 ± 1.2 yr). INTERVENTION: Both trained groups underwent a computerized, nonverbal auditory training that focused on frequency discrimination, ordering, and backward-masking tasks. The training consisted of twelve 45 min sessions, once a week, for a total of 9 hr of training, approximately. DATA COLLECTION AND ANALYSIS: Near-transfer (Gap-In-Noise [GIN] and Frequency Pattern Test) and far-transfer measures (auditory and visual sustained attention tests, phonological working memory and language tests) were applied before and after training. The results were analyzed using a 2 × 2 × 2 mixed-model analysis of variance with the group and training as the between-group variables and the period as the within-group variable. The significance threshold was p ≤ 0.05. RESULTS: There was a group × period × training interaction for GIN [F(1.35) = 7.18, p = 0.011], indicating a significant threshold reduction only for the TDT group (Tukey multiple comparisons). There was a significant group × period interaction [F(1.35) = 5.52, p = 0.025] and a training × period interaction for visual reaction time [F(1.35) = 4.20, p = 0.048], indicating improvement in the SSDT group and worsening in both nontrained groups. There was also a significant group × training × period interaction [F(1.35) = 4.27, p = 0.046] for the auditory false alarms, with a significant improvement after training only for the SSDT group. Analysis of variance also revealed that all groups exhibited approximately the same level of gains for all measures, except for GIN [F(3,38) = 4.261, p = 0.011] and visual response time [F(3.38) = 4.069, p = 0.014]. CONCLUSIONS: After training, the TDT group demonstrated a significant improvement for GIN and the SSDT exhibited the same for sustained attention, indicating learning generalization from an auditory sensory training to a top-down skill. For the other measures, all groups exhibited approximately the same level of gains, indicating the presence of a test-retest effect. Our findings also show that the memory span was not related to the learning generalization process given that the SSDT exhibited a more pronounced gain in attention skills after the sensory training.

Association between language development and auditory processing disorders.

INTRODUCTION: It is crucial to understand the complex processing of acoustic stimuli along the auditory pathway; comprehension of this complex processing can facilitate our understanding of the processes that underlie normal and altered human communication. AIM: To investigate the performance and lateralization effects on auditory processing assessment in children with specific language impairment (SLI), relating these findings to those obtained in children with auditory processing disorder (APD) and typical development (TD). MATERIAL AND METHODS: Prospective study. Seventy-five children, aged 6-12 years, were separated in three groups: 25 children with SLI, 25 children with APD, and 25 children with TD. All went through the following tests: speech-in-noise test, Dichotic Digit test and Pitch Pattern Sequencing test. RESULTS: The effects of lateralization were observed only in the SLI group, with the left ear presenting much lower scores than those presented to the right ear. The inter-group analysis has shown that in all tests children from APD and SLI groups had significantly poorer performance compared to TD group. Moreover, SLI group presented worse results than APD group. CONCLUSION: This study has shown, in children with SLI, an inefficient processing of essential sound components and an effect of lateralization. These findings may indicate that neural processes (required for auditory processing) are different between auditory processing and speech disorders.

Influence of memory, attention, IQ and age on auditory temporal processing tests: preliminary study.

PURPOSE: To investigate the existence of correlations between the performance of children in auditory temporal tests (Frequency Pattern and Gaps in Noise--GIN) and IQ, attention, memory and age measurements. METHOD: Fifteen typically developing individuals between the ages of 7 to 12 years and normal hearing participated in the study. Auditory temporal processing tests (GIN and Frequency Pattern), as well as a Memory test (Digit Span), Attention tests (auditory and visual modality) and intelligence tests (RAVEN test of Progressive Matrices) were applied. RESULTS: Significant and positive correlation between the Frequency Pattern test and age variable were found, which was considered good (p<0.01, 75.6%). There were no significant correlations between the GIN test and the variables tested. CONCLUSIONS: Auditory temporal skills seem to be influenced by different factors: while the performance in temporal ordering skill seems to be influenced by maturational processes, the performance in temporal resolution was not influenced by any of the aspects investigated.

Association between language development and auditory processing disorders / Associação entre transtornos no desenvolvimento de linguagem e processamento auditivo

INTRODUCTION: It is crucial to understand the complex processing of acoustic stimuli along the auditory pathway ;comprehension of this complex processing can facilitate our understanding of the processes that underlie normal and altered human communication. AIM: To investigate the performance and lateralization effects on auditory processing assessment in children with specific language impairment (SLI), relating these findings to those obtained in children with auditory processing disorder (APD) and typical development (TD). MATERIAL AND METHODS: Prospective study. Seventy-five children, aged 6-12 years, were separated in three groups: 25 children with SLI, 25 children with APD, and 25 children with TD. All went through the following tests: speech-in-noise test, Dichotic Digit test and Pitch Pattern Sequencing test. RESULTS: The effects of lateralization were observed only in the SLI group, with the left ear presenting much lower scores than those presented to the right ear. The inter-group analysis has shown that in all tests children from APD and SLI groups had significantly poorer performance compared to TD group. Moreover, SLI group presented worse results than APD group. CONCLUSION: This study has shown, in children with SLI, an inefficient processing of essential sound components and an effect of lateralization. These findings may indicate that neural processes (required for auditory processing) are different between auditory processing and speech disorders. .

INTRODUÇÃO: Entender como os estímulos acústicos são processados ao longo da via auditiva é fundamental para compreender os processos que subjazem à comunicação humana normal e alterada. OBJETIVO: Investigar o desempenho e efeitos de lateralidade na avaliação do processamento auditivo em crianças com distúrbio específico de linguagem (DEL), comparando os resultados obtidos aos encontrados em crianças com transtorno de processamento auditivo (TPA) e desenvolvimento típico (DT). MATERIAL E MÉTODO: Estudo Prospectivo. 75 crianças (6-12 anos), divididas em três grupos (25 crianças com DEL, 25 crianças com TPA e 25 crianças em DT), foram submetidas aos seguintes testes: Teste de Figura com Ruído, Teste Dicótico de Dígitos e Teste de Padrão de Frequência. RESULTADO: Os efeitos de lateralidade foram observados apenas no grupo DEL, sendo o desempenho na orelha esquerda inferior ao apresentado na orelha direita. Na comparação intergrupos, o desempenho dos grupos TPA e DEL foi significativamente inferior ao observado no grupo DT para todos os testes. Além disso, observamos nas crianças do grupo DEL um desempenho inferior às do grupo TPA. CONCLUSÃO: Este estudo constatou o processamento ineficiente de componentes cruciais de sons e o efeito de lateralidade em crianças com DEL. Esses achados evidenciam que os processos neurais que subjazem ao processamento auditivo são diferentes entre alterações de processamento auditivo e alterações de fala. .

Influence of memory, attention, IQ and age on auditory temporal processing tests: preliminary study / Influência da memória, atenção, QI e idade em testes de processamento auditivo temporal: estudo preliminar

PURPOSE: To investigate the existence of correlations between the performance of children in auditory temporal tests (Frequency Pattern and Gaps in Noise - GIN) and IQ, attention, memory and age measurements. METHOD: Fifteen typically developing individuals between the ages of 7 to 12 years and normal hearing participated in the study. Auditory temporal processing tests (GIN and Frequency Pattern), as well as a Memory test (Digit Span), Attention tests (auditory and visual modality) and intelligence tests (RAVEN test of Progressive Matrices) were applied. RESULTS: Significant and positive correlation between the Frequency Pattern test and age variable were found, which was considered good (p<0.01, 75.6%). There were no significant correlations between the GIN test and the variables tested. CONCLUSIONS: Auditory temporal skills seem to be influenced by different factors: while the performance in temporal ordering skill seems to be influenced by maturational processes, the performance in temporal resolution was not influenced by any of the aspects investigated. .

OBJETIVO: Investigar a existência de correlações entre o desempenho de crianças com desenvolvimento típico em testes temporais auditivos (Padrão de Frequência e Gaps in Noise - GIN) e medidas de memória, atenção, quociente intelectual e a idade. MÉTODO: Quinze participantes, com idades entre 7 e 12 anos, sem queixas envolvendo audição e desenvolvimento cognitivo, foram submetidos aos testes de processamento temporal auditivo (GIN e Padrão de Frequência), teste de Memória (Span de Dígitos), Atenção (auditiva e visual) e testes de inteligência (Matrizes Progressivas de Raven). RESULTADOS: Foram encontradas correlações significantes e positivas entre o teste Padrão de Frequência e a variável idade, sendo essa considerada boa (p<0,01, 75,6%). Não foram verificadas correlações significantes entre o teste GIN e as variáveis testadas. CONCLUSÃO: As habilidades temporais consideradas parecem ser influenciadas por diferentes fatores: enquanto a habilidade de ordenação temporal parece ser influenciada por processos maturacionais, o desempenho para a habilidade de resolução temporal não foi influenciado por nenhum dos aspectos investigados. .

Perfil comportamental e competência social de crianças e adolescentes com distrofia muscular de Duchenne / Behavior profile and social competence in children and adolescents with Duchenne muscular dystrophy

A distrofia muscular de Duchenne é uma doença genética caracterizada por enfraquecimento muscular progressivo e degeneração irreversível, acompanhados por danos sensoriais e neuropsicológicos. Os objetivos do estudo consistiram em avaliar o perfil comportamental de crianças/adolescentes com DMD e a influência do prejuízo motor, da idade no início do uso de cadeira de rodas e da idade no diagnóstico. Participaram 34 pacientes e 20 controles. Os pacientes formaram dois grupos conforme o quociente de inteligência (QI). Os pais responderam ao Inventário de Comportamentos da Infância e da Adolescência. Pacientes com DMD obtiveram escores mais baixos em Atividades e Sociabilidade (p < 0,01; ANCOVA). Os pacientes com QI < 80 apresentaram menores índices de Escolaridade. O prejuízo motor e as idades referentes à cadeira e ao diagnóstico correlacionaram-se com sintomas psiquiátricos/somáticos e problemas escolares. Os achados enfatizam a necessidade de programas educacionais acerca da doença como base para o desenvolvimento de estratégias de inclusão social.(AU)

Duchenne Muscular Dystrophy is a genetic disease characterized by progressive muscle weakness and degeneration, which are accompanied by sensory and neuropsychological losses. The aims of this study were to evaluate the behavior profile of DMD children and adolescents and examine the influence of motor impairment, age at start using a wheelchair, and age at diagnosis on behavioral characteristics. Thirty-five patients and 20 controls participated. DMD patients formed two different groups according to the intelligence quotient (IQ). Participants' parents completed the Child Behavior Checklist. DMD groups scored lower on the Activities and the Social scales. Patients with QI < 80 presented lower indices in the School scale (p < 0.01, ANCOVA). Motor impairment and age at start using a wheelchair and at diagnosis correlated with psychiatric/somatic symptoms and school problems. The findings highlight the need of educational programs concerning the disease as a basis for the development of social inclusion strategies.(AU)

Perfil comportamental e competência social de crianças e adolescentes com distrofia muscular de Duchenne / Behavior profile and social competence in children and adolescents with Duchenne muscular dystrophy

A distrofia muscular de Duchenne é uma doença genética caracterizada por enfraquecimento muscular progressivo e degeneração irreversível, acompanhados por danos sensoriais e neuropsicológicos. Os objetivos do estudo consistiram em avaliar o perfil comportamental de crianças/adolescentes com DMD e a influência do prejuízo motor, da idade no início do uso de cadeira de rodas e da idade no diagnóstico. Participaram 34 pacientes e 20 controles. Os pacientes formaram dois grupos conforme o quociente de inteligência (QI). Os pais responderam ao Inventário de Comportamentos da Infância e da Adolescência. Pacientes com DMD obtiveram escores mais baixos em Atividades e Sociabilidade (p < 0,01; ANCOVA). Os pacientes com QI < 80 apresentaram menores índices de Escolaridade. O prejuízo motor e as idades referentes à cadeira e ao diagnóstico correlacionaram-se com sintomas psiquiátricos/somáticos e problemas escolares. Os achados enfatizam a necessidade de programas educacionais acerca da doença como base para o desenvolvimento de estratégias de inclusão social.

Duchenne Muscular Dystrophy is a genetic disease characterized by progressive muscle weakness and degeneration, which are accompanied by sensory and neuropsychological losses. The aims of this study were to evaluate the behavior profile of DMD children and adolescents and examine the influence of motor impairment, age at start using a wheelchair, and age at diagnosis on behavioral characteristics. Thirty-five patients and 20 controls participated. DMD patients formed two different groups according to the intelligence quotient (IQ). Participants' parents completed the Child Behavior Checklist. DMD groups scored lower on the Activities and the Social scales. Patients with QI < 80 presented lower indices in the School scale (p < 0.01, ANCOVA). Motor impairment and age at start using a wheelchair and at diagnosis correlated with psychiatric/somatic symptoms and school problems. The findings highlight the need of educational programs concerning the disease as a basis for the development of social inclusion strategies.

Memory span measured by the spatial span tests of the Cambridge neuropsychological test automated battery in a group of Brazilian children and adolescents / Capacidade de memória medida por testes de retenção espacial da bateria neuropspicologica computadorizada de Cambridge em um grupo de crianças e adolescentes brasileiros

The neuropsychological tests of spatial span are designed to measure attention and working memory. The version of the spatial span test in the Cambridge Neuropsychological Test Automated Battery (CANTAB) evaluates these functions through the recall of sequences of spatial locations presented to the subject. Objective: The present study investigated how age, gender and educational level might affect the performance of the non-verbal system. Methods: A total of 60 children and adolescents aged 6 to 18 years were assessed (25 males and 35 females). Results: The results showed no gender differences in test performance. Children with six or more years of education showed better performance than children with less than three years of education. Older children had more schooling and thus were able to recall a greater number of items. Span length values proved similar to a previous large normative study which also employed the CANTAB Spatial Span (De Luca et al., 2003). Conclusion: The similarity in performance of the Brazilian children and adolescents studied and the group of Australian participants examined by the cited authors, despite the socio-cultural and economical differences, points to the suitability of the task for the assessment of attention and working memory in Brazilian children.

Testes neuropsicológicos de span visuoespacial são construídos para avaliar amplitude atencional e memória de trabalho. Na versão do teste de span visuoespacial da Cambridge Neuropsychological Test Automated Battery (CANTAB) essa avaliação é feita através de sequências de localização espacial. Objetivo: O presente estudo investiga como a idade, o sexo e a escolaridade podem afetar o desempenho nesse sistema não-verbal. Métodos: Foram avaliadas 60 crianças e adolescentes com idades entre 6 e 18 anos (25 meninos; 35 meninas). Resultados: Os resultados não mostraram diferenças no desempenho do teste entre os sexos. O grupo de crianças com seis ou mais anos de escolaridade foi melhor do que a de crianças menores de três anos de estudo. Nossos resultados sugerem que as crianças mais velhas e, portanto, com maior tempo de escolaridade conseguem se lembrar de um número maior de itens. Os valores de amplitude foram similares aos obtidos em um experimento normativo prévio amplo no qual foi utilizado o teste Spatial Span do CANTAB (De Luca et al., 2003). Conclusão: Estas concordâncias de desempenhos entre crianças e adolescentes brasileiros e o grupo de participantes australianos examinados pelos autores citados nos mostram que apesar das diferenças sócio-culturais e econômicas existentes, a tarefa é adequada para avaliação de atenção e memória de trabalho em crianças brasileiras.

Memory span measured by the spatial span tests of the Cambridge Neuropsychological Test Automated Battery in a group of Brazilian children and adolescents.

The neuropsychological tests of spatial span are designed to measure attention and working memory. The version of the spatial span test in the Cambridge Neuropsychological Test Automated Battery (CANTAB) evaluates these functions through the recall of sequences of spatial locations presented to the subject. OBJECTIVE: The present study investigated how age, gender and educational level might affect the performance of the non-verbal system. METHODS: A total of 60 children and adolescents aged 6 to 18 years were assessed (25 males and 35 females). RESULTS: The results showed no gender differences in test performance. Children with six or more years of education showed better performance than children with less than three years of education. Older children had more schooling and thus were able to recall a greater number of items. Span length values proved similar to a previous large normative study which also employed the CANTAB Spatial Span (De Luca et al., 2003). CONCLUSION: The similarity in performance of the Brazilian children and adolescents studied and the group of Australian participants examined by the cited authors, despite the socio-cultural and economical differences, points to the suitability of the task for the assessment of attention and working memory in Brazilian children.

Testes neuropsicológicos de span visuoespacial são construídos para avaliar amplitude atencional e memória de trabalho. Na versão do teste de span visuoespacial da Cambridge Neuropsychological Test Automated Battery (CANTAB) essa avaliação é feita através de sequências de localização espacial. OBJETIVO: O presente estudo investiga como a idade, o sexo e a escolaridade podem afetar o desempenho nesse sistema não-verbal. MÉTODOS: Foram avaliadas 60 crianças e adolescentes com idades entre 6 e 18 anos (25 meninos; 35 meninas). RESULTADOS: Os resultados não mostraram diferenças no desempenho do teste entre os sexos. O grupo de crianças com seis ou mais anos de escolaridade foi melhor do que a de crianças menores de três anos de estudo. Nossos resultados sugerem que as crianças mais velhas e, portanto, com maior tempo de escolaridade conseguem se lembrar de um número maior de itens. Os valores de amplitude foram similares aos obtidos em um experimento normativo prévio amplo no qual foi utilizado o teste Spatial Span do CANTAB (De Luca et al., 2003). CONCLUSÃO: Estas concordâncias de desempenhos entre crianças e adolescentes brasileiros e o grupo de participantes australianos examinados pelos autores citados nos mostram que apesar das diferenças sócio-culturais e econômicas existentes, a tarefa é adequada para avaliação de atenção e memória de trabalho em crianças brasileiras.

The use of the Cambridge Neuropsychological Test Automated Battery (CANTAB) in neuropsychological assessment: application in Brazilian research with control children and adults with neurological disorders

Computerized neuropsychological tests can be effective and have many benefits. This paper addresses these issues using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess Brazilian children and adults. Preliminary normative data for Brazilian children obtained in a series of CANTAB subtests are presented together with data from adults (controls) and samples of patients with multiple sclerosis and Duchenne muscular dystrophy. The results obtained in children confirmed the normative values reported for American children (Luciana & Nelson, 2002), indicating high applicability of the CANTAB battery for children in the evaluation of visual memory, working memory, planning, and set shifting. For multiple sclerosis patients, CANTAB revealed differences between the control and multiple sclerosis groups for all subtests employed, including visual memory, working memory, spatial memory, decision making, inhibitory control, and sustained attention. In children with Duchenne muscular dystrophy, the CANTAB tests revealed specific detriments in attention and memory. These results of the application of CANTAB in different patient groups indicate that the battery is appropriate for assessing several central nervous system diseases.(AU)

The use of the Cambridge Neuropsychological Test Automated Battery (CANTAB) in neuropsychological assessment: application in Brazilian research with control children and adults with neurological disorders

Computerized neuropsychological tests can be effective and have many benefits. This paper addresses these issues using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess Brazilian children and adults. Preliminary normative data for Brazilian children obtained in a series of CANTAB subtests are presented together with data from adults (controls) and samples of patients with multiple sclerosis and Duchenne muscular dystrophy. The results obtained in children confirmed the normative values reported for American children (Luciana & Nelson, 2002), indicating high applicability of the CANTAB battery for children in the evaluation of visual memory, working memory, planning, and set shifting. For multiple sclerosis patients, CANTAB revealed differences between the control and multiple sclerosis groups for all subtests employed, including visual memory, working memory, spatial memory, decision making, inhibitory control, and sustained attention. In children with Duchenne muscular dystrophy, the CANTAB tests revealed specific detriments in attention and memory. These results of the application of CANTAB in different patient groups indicate that the battery is appropriate for assessing several central nervous system diseases.

Preliminary findings on the effects of occupational exposure to mercury vapor below safety levels on visual and neuropsychological functions.

OBJECTIVE: To evaluate whether there are visual and neuropsychological decrements in workers with low exposure to Hg vapor. METHODS: Visual fields, contrast sensitivity, color vision, and neuropsychological functions were measured in 10 workers (32.5 +/- 8.5 years) chronically exposed to Hg vapor (4.3 +/- 2.8 years; urinary Hg concentration 22.3 +/- 9.3 microg/g creatinine). RESULTS: For the worst eyes, we found altered visual field thresholds, lower contrast sensitivity, and color discrimination compared with controls (P <0.05). There were no significant differences between Hg-exposed subjects and controls on neuropsychological tests. Nevertheless, duration of exposure was statistically correlated to verbal memory and depression scores. CONCLUSIONS: Chronic exposure to Hg vapor at currently accepted safety levels was found to be associated with visual losses but not with neuropsychological dysfunctions in the sample of workers studied.