Assessing atypical brain functional connectivity development : an approach based on generative adversarial networks

Generative Adversarial Networks (GANs) are promising analytical tools in machine learning applications. Characterizing atypical neurodevelopmental processes might be useful in establishing diagnostic and prognostic biomarkers of psychiatric disorders. In this article, we investigate the potential of GANs models combined with functional connectivity (FC) measures to build a predictive neurotypicality score 3-years after scanning. We used a ROI-to-ROI analysis of resting-state functional magnetic resonance imaging (fMRI) data from a community-based cohort of children and adolescents (377 neurotypical and 126 atypical participants). Models were trained on data from neurotypical participants, capturing their sample variability of FC. The discriminator subnetwork of each GAN model discriminated between the learned neurotypical functional connectivity pattern and atypical or unrelated patterns. Discriminator models were combined in ensembles, improving discrimination performance. Explanations for the model’s predictions are provided using the LIME (Local Interpretable Model-Agnostic) algorithm and local hubs are identified in light of these explanations. Our findings suggest this approach is a promising strategy to build potential biomarkers based on functional connectivity

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation

Connectome hubs at resting state in children and adolescents:reproducibility and psychopathological correlation

AbstractFunctional brain hubs are key integrative regions in brain networks. Recently, brain hubs identified through resting-state fMRI have emerged as interesting targets to increase understanding of the relationships between large-scale functional networks and psychopathology. However, few studies have directly addressed the replicability and consistency of the hub regions identified and their association with symptoms. Here, we used the eigenvector centrality (EVC) measure obtained from graph analysis of two large, independent population-based samples of children and adolescents (7–15 years old; total N=652; 341 subjects for site 1 and 311 for site 2) to evaluate the replicability of hub identification. Subsequently, we tested the association between replicable hub regions and psychiatric symptoms. We identified a set of hubs consisting of the anterior medial prefrontal cortex and inferior parietal lobule/intraparietal sulcus (IPL/IPS). Moreover, lower EVC values in the right IPS were associated with psychiatric symptoms in both samples. Thus, low centrality of the IPS was a replicable sign of potential vulnerability to mental disorders in children. The identification of critical and replicable hubs in functional cortical networks in children and adolescents can foster understanding of the mechanisms underlying mental disorders

Inference of neural activity time from BOLD effect in functional magnetic resonance imaging

A inferência do curso temporal da atividade neural a partir do efeito BOLD é um importante problema, ainda em aberto. A forma da curva BOLD não reflete diretamente as características temporais da atividade eletrofisiológica dos neurônios. Nessa tese, é introduzido o conceito de tempo de processamento neural (TPN) como um dos parâmetros do modelo biofísico da função de resposta hemodinâmica (HRF). O objetivo da introdução desse conceito é obter estimativas mais acuradas da duração da atividade neural a partir do efeito BOLD, que possui auto grau de nãolinearidade. Duas formas de estimar os parâmetros do modelo do efeito BOLD foram desenvolvidas. A validade e aplicabilidade do conceito de TPN e das rotinas de estimação foram avaliadas por simulações computacionais e análise de séries temporais experimentais. Os resultados das simulações e da aplicação foram comparados com medidas da forma da HRF. O experimento analisado consistiu em um paradigma de tomada de decisão na presença de distratores emocionais. Esperase que o TPN em áreas sensoriais primárias seja equivalente ao tempo de apresentação de estímulos. Por outro lado, o TPN em áreas relacionadas com a tomada de decisão deve ser menor que a duração dos estímulos. Além disso, o TPN deve depender da condição experimental em áreas relacionadas ao controle de distratores emocionais. Como predito, o valores estimados do TPN no giro fusiforme foram equivalentes à duração dos estímulos e o TPN no giro do cíngulo dorsal variou com a presença de distrator emocional. Observou-se ainda lateralidade do TPN no córtex pré-frontal dorsolateral. As medidas da forma da HRF obtidas por um método convencional não dectectaram as variações observadas no TPNThe extraction of information about neural activity dynamics related to the BOLD signal is a challenging task. The temporal evolution of the BOLD signal does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. We describe two routines to estimate the parameters of the HRF model. The face validity and applicability of the concept of NPT and the estimation procedures are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. We analysed an experiment based on a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas is approximately the stimulus presentation duration. On the other hand, the NPT in brain areas related to decisionmaking processes should be less than the stimulus duration. Moreover, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the estimated NPTs in the dorsolateral prefrontal cortex indicate functional laterality of this region. The analysis using standard measures of HRF did not detect the variations observed in our method (NPT

MSC Application

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Causal Relationships in Longitudinal Observational Data: An Integrative Modelling Approach

Much research in psychology relies on data from observational studies that traditionally do not allow for causal interpretation. However, a range of approaches in statistics and computational sciences have been developed to infer causality from correlational data. Based on conceptual and theoretical considerations on the integration of interventional and time-restrainment notions of causality, we set out to design and empirically test a new approach in order to identify potential causal factors in longitudinal correlational data. A principled and representative set of simulations and an illustrative application to identify early-life determinants of cognitive development in a large cohort study are presented. The simulation results illustrate the potential but also the limitations for discovering causal factors from observational data. In the illustrative application, plausible and reasonably well-established early life determinants of cognitive abilities in 5-year-old children were identified. Based on these results, we discuss the possibilities of using exploratory causal discovery in psychological research but also highlight its limits and potential misuses and misinterpretations

Determinants of Persistent PTSD in War-Exposed Children: Application of a New Causal Discovery and Inference Approach in Syrian Refugees

Objective: Identification of the most relevant factors leading to severe and persistent Post-Traumatic Stress Disorder (PTSD) presentation in refugee children is critical for prevention and treatment. Using causal inference tools for observational studies, we aimed to estimate the total putative causal effects of the most relevant factors for persistent and severe PTSD in Syrian refugee children living in Informal Tented Settlements (ITS) in Lebanon. Methods: A population-based prospective cohort study of Syrian refugee families living in ITS in Lebanon (BIOPATH study) was analysed. Families with children aged 8-16 years that had left Syria less than 4 years prior to recruitment were included. The first wave was conducted between October 2017 and January 2018. Follow-up data collection was conducted one year later (51.55 +/- 1.84 weeks). A subsample of 134 children was assessed with a structured clinical interview six months after the follow-up (27.02 +/- 7.16 weeks), between December 2018 and August 2019. Of the 2282 families approached in 77 selected settlements, 1600 (70.1%) agreed to participate. After one year, 1438 families were approached and data collected from 1009 families (62.8% re-participation rate). Data from 9 families were excluded during data cleaning. Ninety-eight variables across multiple domains (demographic, psychological, familial and community level) were measured using validated questionnaires and considered for a systematic causal discovery and inference method. Increased risk for severe and persistent PTSD based on symptom score was the primary outcome of interest. This outcome was validated a posteriori through structured clinical interviews in a subsample. Results: 1591 child-caregiver dyads were included (age = 11.44 +/- 2.44 years, 52.6% female) and 16.2% of children were at classified as at risk for severe and persistent PTSD (DSM-5 confirmed diagnoses in clinical interviews 6 months later 62.5% vs 34.5% in children with lower risk, p<.05; clinical severity score 4.5 vs 3.4, p<.01). In the systematic causal discovery and inference analysis, the level of war exposure (OR: 1.07, 95% CI: 1.03-1.11 , p<.01), peer violence victimisation (OR: 1.05 , 95% CI: 1.02-1.08, p<.05), neglect (OR: 1.11 , 95% CI: 1.05-1.17 , p<.01), maltreatment (OR: 1.04 , 95% CI: 1.02-1.07 , p<.05) and caregiver depression (OR: 1.04 , 95% CI: 1.01-1.17 , p<.05) predicted risk for persistent and severe PTSD. The quality of the concurrent refugee environment (OR: 0.55, 95% CI: 0.38-0.77, p<.01) was strongly negatively associated with severe and persistent PTSD presentations. Conclusion: Minimising violent re-victimization and exposure to daily stressors, and addressing caregiver mental health, might prevent the development of severe PTSD in refugee children

A systematic review of cultural adaptations of the Positive Affect and Negative Affect Schedule (PANAS)

Background: The Positive Affect and Negative Affect Schedule (PANAS) has been used worldwide as a valid and consistent instrument to investigate the bidimensional structure of affect. Researchers can adapt PANAS from English to other languages by developing a new scale or translating directly from the original. This review describes and evaluates the currently available PANAS translations according to instrument transcultural adaptation standards. We sought to improve the reliability and quality of transcultural investigations of the affective structure. Method: A systematic review based on Pubmed, NCBI, EMBASE, Web of Science, Scopus, EBSCO and Scielo was performed to identify PANAS-based new scale developments, translations and validation studies from 11th to 16th November 2020. Results: We detected 3 PANAS-based instruments developed in Japanese, Estonian and Portuguese (Portugal), 19 PANAS translations (Arabic; Chinese; French - 2; Hindi; Italian; Norwegian; Brazilian Portuguese; Romanian; Russian; Serbian; Spanish: Spain - 3, Mexico - 2, Argentina, Chile; Tunisian Arab), and 23 validation studies. According to our classification criterion (from A to G level of quality), no study reached the A level. Limitations: We included only manuscripts in English, Spanish, and Portuguese (PT and BR). Only three PANAS-based scale developments were found. Conclusions: Most transcultural adaptations of the PANAS show low compliance to adaptation standards. Based on the results of a systematic review of currently available instruments and their psychometric properties, we propose a guideline of procedures for future researchers aiming to translate and adapt scales

Abnormal functional resting-state networks in ADHD : graph theory and pattern recognition analysis of fMRI data

The framework of graph theory provides useful tools for investigating the neural substrates of neuropsychiatric disorders. Graph description measures may be useful as predictor variables in classification procedures. Here, we consider several centrality measures as predictor features in a classification algorithm to identify nodes of resting-state networks containing predictive information that can discriminate between typical developing children and patients with attention-deficit/hyperactivity disorder (ADHD). The prediction was based on a support vector machines classifier. The analyses were performed in a multisite and publicly available resting-state fMRI dataset of healthy children and ADHD patients: the ADHD-200 database. Network centrality measures contained little predictive information for the discrimination between ADHD patients and healthy subjects. However, the classification between inattentive and combined ADHD subtypes was more promising, achieving accuracies higher than 65% (balance between sensitivity and specificity) in some sites. Finally, brain regions were ranked according to the amount of discriminant information and the most relevant were mapped. As hypothesized, we found that brain regions in motor, frontoparietal, and default mode networks contained the most predictive information. We concluded that the functional connectivity estimations are strongly dependent on the sample characteristics. Thus different acquisition protocols and clinical heterogeneity decrease the predictive values of the graph descriptors

Development and psycholinguistic properties of the Brazilian-Portuguese Affect Scale (EAPB)

This study presents the development of the Brazilian-Portuguese Affect Scale based on the development procedures of the PANAS (Positive Affect and Negative Affect Schedule). We applied psycholinguistic and validity procedures to reduce an affective Brazilian lexicon with 404 words. The reduction was based on familiarity, state/trait categorization and semantic evaluations. A final list of 139 affective words was used in a synonym grouping task in a country-wide Brazilian sample (n = 1000; 594 women, 396 men, 2 transgender and 8 who did not inform; average age 29.9 [SD = 8.26]). An exploratory factor analysis revealed 13 factors, leading to two versions of the Brazilian-Portuguese Affect Scale (EAPB; 26 items and 65 items). The instrument is ready for investigations of its psychometric properties