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OBJECTIVE: Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. METHODS: Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Resting-state positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. RESULTS: Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). CONCLUSION: Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients.

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Objective: Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. Methods: Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Resting-state positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. Results: Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). Conclusion: Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients.

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The deposition of amyloid plaques is considered one of the main microscopic features of Alzheimer's disease (AD). Since plaque formation can precede extensive neurodegeneration and it is the main clinical manifestation of AD, it constitutes a relevant target for new treatment and diagnostic approaches. Micro-Raman spectroscopy, a label-free technique, is an accurate method for amyloid plaque identification and characterization. Here, we present a high spatial resolution micro-Raman hyperspectral study in transgenic APPswePS1ΔE9 mouse brains, showing details of AD tissue biochemical and histological changes without staining. First we used stimulated micro-Raman scattering to identify the lipid-rich halo surrounding the amyloid plaque, and then proceeded with spontaneous (conventional) micro-Raman spectral mapping, which shows a cholesterol and sphingomyelin lipid-rich halo structure around dense-core amyloid plaques. The detailed images of this lipid halo relate morphologically well with dystrophic neurites surrounding plaques. Principal Component Analysis (PCA) of the micro-Raman hyperspectral data indicates the feasibility of the optical biomarkers of AD progression with the potential for discriminating transgenic groups of young adult mice (6-month-old) from older ones (12-month-old). Frequency-specific PCA suggests that plaque-related neurodegeneration is the predominant change captured by Raman spectroscopy, and the main differences are highlighted by vibrational modes associated with cholesterol located majorly in the lipid halo.

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Given the long subclinical stage of Alzheimer's disease (AD), the study of biomarkers is relevant both for early diagnosis and the fundamental understanding of the pathophysiology of AD. Biomarkers provided by Amyloid-ß (Aß) plaques have led to an increasing interest in characterizing this hallmark of AD due to its promising potential. In this work, we characterize Aß plaques by label-free multimodal imaging: we combine two-photon excitation autofluorescence (TPEA), second harmonic generation (SHG), spontaneous Raman scattering (SpRS), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS) to describe and compare high-resolution images of Aß plaques in brain tissues of an AD mouse model. Comparing single-laser techniques images, we discuss the origin of the SHG, which can be used to locate the plaque core reliably. We study both the core and the halo with vibrational microscopy and compare SpRS and SRS microscopies for different frequencies. We also combine SpRS spectroscopy with SRS microscopy and present two core biomarkers unexplored with SRS microscopy: phenylalanine and amide B. We provide high-resolution SRS images with the spatial distribution of these biomarkers in the plaque and compared them with images of the amide I distribution. The obtained spatial correlation corroborates the feasibility of these biomarkers in the study of Aß plaques. Furthermore, since amide B enables rapid imaging, we discuss its potential as a novel fingerprint for diagnostic applications.

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ABSTRACT Objective: To investigate the psychometric properties of the short or multimodal treatment study version of the Swanson, Nolan, and Pelham, Version IV (SNAP-IV) scale, which measures attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms. Methods: Participants were 765 parents of children from 4 to 16 years old (641 non-attention-deficit/hyperactivity disorder and 124 attention-deficit/hyperactivity disorder children) from Belo Horizonte, Brazil, who reported sociodemographic characteristics and answered the SNAP-IV. Parents of the clinical sample also underwent the K-SADS-PL interview. Results: Age was significantly associated with SNAP-IV hyperactivity-impulsivity problems (r = −0.14), but not with inattention or oppositional defiant disorder. Sex was a significant influence on attention-deficit/hyperactivity disorder and oppositional defiant disorder severity (all p < 0.001), with boys showing higher scores in the full sample, but not within the attention-deficit/hyperactivity disorder group. Exploratory and confirmatory factor analysis supports a three-factor structure of the SNAP-IV scale. Moderate-to-strong correlations were found between SNAP-IV and K-SADS-PL measures. All SNAP-IV scales showed very high internal consistency coefficients (all above 0.91). SNAP-IV inattention scores were the most predictive of attention-deficit/hyperactivity disorder diagnosis (AUC: 0.877 for the averaging rating method and the raw sum method, and 0.874 for the symptom presence/absence method). Conclusion: The parent SNAP-IV showed good psychometric properties in a Brazilian school and clinical sample.

RESUMO Objetivo: Investigar as propriedades psicométricas da versão curta ou MTA da escala Swanson, Nolan e Pelham, versão IV (SNAP-IV), que mede os sintomas do transtorno de déficit de atenção/hiperatividade e transtorno desafiador de oposição. Métodos: Os participantes incluíram 765 pais de crianças de 4 a 16 anos (641 crianças sem transtorno de déficit de atenção/hiperatividade e 124 com transtorno de déficit de atenção/hiperatividade) de Belo Horizonte, Brasil, que relataram características sociodemográficas e responderam o SNAP-IV. Os pais da amostra clínica também foram submetidos à entrevista com K-SADS-PL. Resultados: A idade foi significativamente associada aos problemas de hiperatividade-impulsividade no SNAP-IV (r = −0,14), mas não à desatenção ou aos transtornos desafiadores de oposição. O sexo foi uma influência significativa na gravidade do transtorno de déficit de atenção/hiperatividade e transtorno desafiador de oposição (todos os p < 0,001), os meninos apresentaram escores mais altos na amostra completa, mas não no grupo de transtorno de déficit de atenção/hiperatividade. A análise fatorial exploratória e confirmatória apoia uma estrutura de três fatores da escala SNAP-IV. Foram encontradas correlações moderadas a fortes entre as medidas dos instrumentos SNAP-IV e K-SADS-PL. Todas as escalas do SNAP-IV mostraram coeficientes de consistência interna muito altos (todos acima de 0,91). Os escores de desatenção do SNAP-IV foram os mais preditivos do diagnóstico de transtorno de déficit de atenção/hiperatividade (AUC - área sob a curva ROC: 0,877 para o método de classificação da média e o método da soma bruta e 0,874 para o método de presença ou ausência de sintomas). Conclusão: A avaliação do SNAP-IV pelos pais apresentou boas propriedades psicométricas em uma escola brasileira e amostra clínica.

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The global prevalence of Alzheimer's disease (AD) points to endemic levels, especially considering the increase of average life expectancy worldwide. AD diagnosis based on early biomarkers and better knowledge of related pathophysiology are both crucial in the search for medical interventions that are able to modify AD progression. In this study we used unsupervised spectral unmixing statistical techniques to identify the vibrational spectral signature of amyloid ß aggregation in neural tissues, as early biomarkers of AD in an animal model. We analyzed spectral images composed of a total of 55 051 Raman spectra obtained from the frontal cortex and hippocampus of five bitransgenic APPswePS1ΔE9 mice, and colocalized amyloid ß plaques by other fluorescence techniques. The Raman signatures provided a multifrequency fingerprint consistent with the results of synthesized amyloid ß fibrils. The fingerprint obtained from unmixed analysis in neural tissues is shown to provide a detailed image of amyloid plaques in the brain, with the potential to be used as biomarkers for non-invasive early diagnosis and pathophysiology studies in AD on the retina.

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Spinal cord injury results in locomotor impairment attributable to the formation of an inhibitory fibrous scar, which prevents axonal regeneration after trauma. The scarcity of knowledge about the molecular and cellular mechanisms involved in scar formation after spinal cord lesion impede the design of effective therapies. Recent studies, by using state-of-the-art technologies, including genetic tracking and blockage of pericytes in combination with optogenetics, reveal that pericyte blockage facilitates axonal regeneration and neuronal integration into the local neural circuitry. Strikingly, a pericyte subset is essential during scarring after spinal cord injury, and its arrest results in motor performance improvement. The arising knowledge from current research will contribute to novel approaches to develop therapies for spinal cord injury. We review novel advances in our understanding of pericyte biology in the spinal cord.

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In mammals, new neurons can be generated from neural stem cells in specific regions of the adult brain. Neural stem cells are characterized by their abilities to differentiate into all neural lineages and to self-renew. The specific microenvironments regulating neural stem cells, commonly referred to as neurogenic niches, comprise multiple cell populations whose precise contributions are under active current exploration. Understanding the cross-talk between neural stem cells and their niche components is essential for the development of therapies against neurological disorders in which neural stem cells function is altered. In this review, we describe and discuss recent studies that identified novel components in the neural stem cell niche. These discoveries bring new concepts to the field. Here, we evaluate these recent advances that change our understanding of the neural stem cell niche heterogeneity and its influence on neural stem cell function.

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OBJECTIVE: To investigate the psychometric properties of the short or multimodal treatment study version of the Swanson, Nolan, and Pelham, Version IV (SNAP-IV) scale, which measures attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms. METHODS: Participants were 765 parents of children from 4 to 16 years old (641 non-attention-deficit/hyperactivity disorder and 124 attention-deficit/hyperactivity disorder children) from Belo Horizonte, Brazil, who reported sociodemographic characteristics and answered the SNAP-IV. Parents of the clinical sample also underwent the K-SADS-PL interview. RESULTS: Age was significantly associated with SNAP-IV hyperactivity-impulsivity problems (r=-0.14), but not with inattention or oppositional defiant disorder. Sex was a significant influence on attention-deficit/hyperactivity disorder and oppositional defiant disorder severity (all p<0.001), with boys showing higher scores in the full sample, but not within the attention-deficit/hyperactivity disorder group. Exploratory and confirmatory factor analysis supports a three-factor structure of the SNAP-IV scale. Moderate-to-strong correlations were found between SNAP-IV and K-SADS-PL measures. All SNAP-IV scales showed very high internal consistency coefficients (all above 0.91). SNAP-IV inattention scores were the most predictive of attention-deficit/hyperactivity disorder diagnosis (AUC: 0.877 for the averaging rating method and the raw sum method, and 0.874 for the symptom presence/absence method). CONCLUSION: The parent SNAP-IV showed good psychometric properties in a Brazilian school and clinical sample.

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Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using state-of-the-art technologies, including two-photon microscopy in combination with sophisticated Cre/loxP in vivo tracing techniques, a novel role of pericytes was revealed in vascular remodeling in the adult brain. Strikingly, after pericyte ablation, neighboring pericytes expand their processes and prevent vascular dilatation. This new knowledge provides insights into pericyte plasticity in the adult brain.

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Objective: Cognitive failures are simple mistakes in routine activities, such as forgetting commitments and experiencing difficulty concentrating. The Cognitive Failures Questionnaire (CFQ) was designed to assess the frequency of these errors in everyday life. Although widely used in psychiatry and psychology, both in clinical and research settings, it has not been adapted for use in Brazil. Our objective was to perform cross-cultural adaptation of the CFQ for the Brazilian reality and assess its validity and reliability. Methods: The original version of the CFQ was translated into Brazilian Portuguese by two independent researchers, analyzed by a multidisciplinary board of experts, and back-translated into English. The final version was administered to 225 adults. Validity was assessed by correlation with the Self Reporting Questionnaire-20 (SRQ-20) and the Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale (ASRS-18). Reliability was analyzed by calculating internal consistency and test-retest stability. Results: The adapted version of the CFQ showed significant correlations with SRQ-20 (r = -0.311), ASRS-18 inattention (r = 0.696), and hyperactivity/impulsivity (r = 0.405) scores. Reliability analysis suggests high internal consistency (0.906) and temporal stability (0.813). Conclusion: The Brazilian Portuguese version of the CFQ showed moderate correlations with other measures of mental health, as well as adequate reliability.

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BACKGROUND: HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals. METHODOLOGY: This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF). PRINCIPAL FINDINGS: 18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model. CONCLUSIONS: 18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP. SIGNIFICANCE: Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.

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The cerebellum plays major role in motor coordination and learning. It contains half of the neurons in the brain. Thus, deciphering the mechanisms by which cerebellar neurons are generated is essential to understand the cerebellar functions and the pathologies associated with it. In a recent study, Wojcinski et al. (2017) by using in vivo Cre/loxP technologies reveal that Nestin-expressing progenitors repopulated the external granular cell layer after injury. Depletion of postnatal external granular cell layer is not sufficient to induce motor behavior defects in adults, as the cerebellum recovers these neurons. Strikingly, Nestin-expressing progenitors differentiate into granule cell precursors and mature granule neurons after ablation of perinatal external granular layer, either by irradiation or by genetic ablation. This work identified a novel role of Nestin-expressing progenitors in the cerebellar microenvironment during development, and revealed that extracellular signals can convert specified progenitors into multipotent stem cells. Here, we discuss the findings from this study, and evaluate recent advances in our understanding of the cerebellar neurogenesis.

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OBJECTIVE: Cognitive failures are simple mistakes in routine activities, such as forgetting commitments and experiencing difficulty concentrating. The Cognitive Failures Questionnaire (CFQ) was designed to assess the frequency of these errors in everyday life. Although widely used in psychiatry and psychology, both in clinical and research settings, it has not been adapted for use in Brazil. Our objective was to perform cross-cultural adaptation of the CFQ for the Brazilian reality and assess its validity and reliability. METHODS: The original version of the CFQ was translated into Brazilian Portuguese by two independent researchers, analyzed by a multidisciplinary board of experts, and back-translated into English. The final version was administered to 225 adults. Validity was assessed by correlation with the Self Reporting Questionnaire-20 (SRQ-20) and the Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale (ASRS-18). Reliability was analyzed by calculating internal consistency and test-retest stability. RESULTS: The adapted version of the CFQ showed significant correlations with SRQ-20 (r = -0.311), ASRS-18 inattention (r = 0.696), and hyperactivity/impulsivity (r = 0.405) scores. Reliability analysis suggests high internal consistency (0.906) and temporal stability (0.813). CONCLUSION: The Brazilian Portuguese version of the CFQ showed moderate correlations with other measures of mental health, as well as adequate reliability.

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The Grooved Pegboard Test, in its standard use, has well-documented utility. However, a revised methodology needs further study, leading us to investigate whether duration of eye fixation could predict performance on different task conditions of the Grooved Pegboard Test (place and remove pegs) with the preferred and nonpreferred hands. Fifty-two right-handed undergraduate students (33 male and 19 female), with a mean age of 22.22 (±3.57) years, performed the Grooved Pegboard Test. SensoMotoric eye-tracking glasses with a binocular time resolution of 30 Hz were used to measure eye fixation. The videos were recorded in iView software, and data were analyzed using BeGaze software. The number and duration of eye fixations were statistically different with preferred and nonpreferred hands and also differed across tasks. Simple linear regression showed eye fixation duration to predict movement time in the place task (preferred hand: R2 = 31%; nonpreferred hand: R2 = 41%) and in the remove task (preferred hand: R2 = 11%; nonpreferred hand: R2 = 25%). Thus, duration of eye fixation during the Grooved Pegboard Test differentially predicted performance with each hand and on preferred and different subtests of this instrument.

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