A Machine Learning Approach to Reveal the NeuroPhenotypes of Autisms

This work was partly supported by the MINECO Under the TEC2015-64718-R Project, the Salvador de Madariaga Mobility Grants 2017 and the Consejería de Economía, Innovación, Ciencia y Empleo (Junta de Andalucía, Spain) under the Excellence Project P11-TIC-7103. The study was conducted in association with the National Institute for Health Research Collaborations for Leadership in Applied Health Research and Care (NIHR CLAHRC) East of England (EoE). The Project was supported by the UK Medical Research Council (Grant No. GO 400061) and European Autism Interventions — a Multicentre Study for Developing New Medications (EU-AIMS); EU-AIMS has received support from the Innovative Medicines Initiative Joint Undertaking Under Grant Agreement No. 115300, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. During the period of this work, M-CL was supported by the OBrien Scholars Program in the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children, Toronto, the Academic Scholar Award from the Department of Psychiatry, University of Toronto, the Slaight Family Child and Youth Mental Health Innovation Fund, CAMH Foundation, and the Ontario Brain Institute via the Province of Ontario Neurodevelopmental Disorders (POND) Network; MVL was supported by the British Academy, Jesus College Cambridge, Wellcome Trust, and an ERC Starting Grant (ERC-2017-STG; 755816); SB-C was supported by the Autism Research Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health, UK.Although much research has been undertaken, the spatial patterns, developmental course, and sexual dimorphism of brain structure associated with autism remains enigmatic. One of the difficulties in investigating differences between the sexes in autism is the small sample sizes of available imaging datasets with mixed sex. Thus, the majority of the investigations have involved male samples, with females somewhat overlooked. This paper deploys machine learning on partial least squares feature extraction to reveal differences in regional brain structure between individuals with autism and typically developing participants. A four-class classification problem (sex and condition) is specified, with theoretical restrictions based on the evaluation of a novel upper bound in the resubstitution estimate. These conditions were imposed on the classifier complexity and feature space dimension to assure generalizable results from the training set to test samples. Accuracies above 80% on gray and white matter tissues estimated from voxel-based morphometry (VBM) features are obtained in a sample of equal-sized high-functioning male and female adults with and without autism (N=120, n=30/group). The proposed learning machine revealed how autism is modulated by biological sex using a low-dimensional feature space extracted from VBM. In addition, a spatial overlap analysis on reference maps partially corroborated predictions of the “extreme male brain” theory of autism, in sexual dimorphic areas.This work was partly supported by the MINECO Under the TEC2015-64718-R Project, the Salvador de Madariaga Mobility Grants 2017 and the Consejería de Economía, Innovación, Ciencia y Empleo (Junta de Andalucía, Spain) under the Excellence Project P11-TIC-7103The Project was supported by the UK Medical Research Council (Grant No. GO 400061) and European Autism Interventions — a Multicentre Study for Developing New Medications (EU-AIMS)EU-AIMS has received support from the Innovative Medicines Initiative Joint Undertaking Under Grant Agreement No. 115300MVL was supported by the British Academy, Jesus College Cambridge, Wellcome Trust, and an ERC Starting Grant (ERC-2017-STG; 755816

A Machine Learning Approach to Reveal the NeuroPhenotypes of Autisms.

Although much research has been undertaken, the spatial patterns, developmental course, and sexual dimorphism of brain structure associated with autism remains enigmatic. One of the difficulties in investigating differences between the sexes in autism is the small sample sizes of available imaging datasets with mixed sex. Thus, the majority of the investigations have involved male samples, with females somewhat overlooked. This paper deploys machine learning on partial least squares feature extraction to reveal differences in regional brain structure between individuals with autism and typically developing participants. A four-class classification problem (sex and condition) is specified, with theoretical restrictions based on the evaluation of a novel upper bound in the resubstitution estimate. These conditions were imposed on the classifier complexity and feature space dimension to assure generalizable results from the training set to test samples. Accuracies above 80% on gray and white matter tissues estimated from voxel-based morphometry (VBM) features are obtained in a sample of equal-sized high-functioning male and female adults with and without autism (N = 120, n = 30/group). The proposed learning machine revealed how autism is modulated by biological sex using a low-dimensional feature space extracted from VBM. In addition, a spatial overlap analysis on reference maps partially corroborated predictions of the "extreme male brain" theory of autism, in sexual dimorphic areas.This work was partly supported by the MINECO under the TEC2015-64718-R project, the Salvador de Madariaga Mobility Grants 2017 and the Consejer´ıa de Econom´ıa, Innovaci´on, Ciencia y Empleo (Junta de Andaluc´ıa, Spain) under the Excellence Project P11-TIC-7103. The study was conducted in association with the National Institute for Health Research Collaborations for Leadership in Applied Health Research and Care (NIHR CLAHRC) East of England (EoE). The project was supported by the UK Medical Research Council (grant number GO 400061) and European Autism Interventions—a Multicentre Study for Developing New Medications (EU-AIMS); EU-AIMS has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n◦ 115300, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007 - 2013) and EFPIA companies’ in-kind contribution. During the period of this work M-CL was supported by the O’Brien Scholars Program in the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children, Toronto, the Academic Scholar Award from the Department of Psychiatry, University of Toronto, the Slaight Family Child and Youth Mental Health Innovation Fund, CAMH Foundation, and the Ontario Brain Institute via the Province of Ontario Neurodevelopmental Disorders (POND) Network; MVL was supported by the British Academy, Jesus College Cambridge,Wellcome Trust, and an ERC Starting Grant (ERC-2017- STG; 755816); SB-C was supported by the Autism Research Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health, U

Behavioral Activity Recognition Based on Gaze Ethograms

Noninvasive behavior observation techniques allow more natural human behavior assessment experiments with higher ecological validity. We propose the use of gaze ethograms in the context of user interaction with a computer display to characterize the user's behavioral activity. A gaze ethogram is a time sequence of the screen regions the user is looking at. It can be used for the behavioral modeling of the user. Given a rough partition of the display space, we are able to extract gaze ethograms that allow discrimination of three common user behavioral activities: reading a text, viewing a video clip, and writing a text. A gaze tracking system is used to build the gaze ethogram. User behavioral activity is modeled by a classifier of gaze ethograms able to recognize the user activity after training. Conventional commercial gaze tracking for research in the neurosciences and psychology science are expensive and intrusive, sometimes impose wearing uncomfortable appliances. For the purposes of our behavioral research, we have developed an open source gaze tracking system that runs on conventional laptop computers using their low quality cameras. Some of the gaze tracking pipeline elements have been borrowed from the open source community. However, we have developed innovative solutions to some of the key issues that arise in the gaze tracker. Specifically, we have proposed texture-based eye features that are quite robust to low quality images. These features are the input for a classifier predicting the screen target area, the user is looking at. We report comparative results of several classifier architectures carried out in order to select the classifier to be used to extract the gaze ethograms for our behavioral research. We perform another classifier selection at the level of ethogram classification. Finally, we report encouraging results of user behavioral activity recognition experiments carried out over an inhouse dataset.This work has been supported by FEDER funds through MINECO project TIN2017-85827-P. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 777720. Additional support comes from grant IT1284-19 of the Basque Country Government

Impact of Machine Learning Pipeline Choices in Autism Prediction from Functional Connectivity Data

Autism Spectrum Disorder (ASD) is a largely prevalent neurodevelopmental condition with a big social and economical impact affecting the entire life of families. There is an intense search for biomarkers that can be assessed as early as possible in order to initiate treatment and preparation of the family to deal with the challenges imposed by the condition. Brain imaging biomarkers have special interest. Specifically, functional connectivity data extracted from resting state functional magnetic resonance imaging (rs-fMRI) should allow to detect brain connectivity alterations. Machine learning pipelines encompass the estimation of the functional connectivity matrix from brain parcellations, feature extraction, and building classification models for ASD prediction. The works reported in the literature are very heterogeneous from the computational and methodological point of view. In this paper, we carry out a comprehensive computational exploration of the impact of the choices involved while building these machine learning pipelines. Specifically, we consider six brain parcellation definitions, five methods for functional connectivity matrix construction, six feature extraction/selection approaches, and nine classifier building algorithms. We report the prediction performance sensitivity to each of these choices, as well as the best results that are comparable with the state of the art.This work has been partially supported by theFEDER funds through MINECO project TIN2017-85827-P. This project has received funding from theEuropean Union’s Horizon 2020 research and inno-vation program under the Marie Sklodowska-Curiegrant agreement No 77772

Sleep and Daytime Functioning in Children on the Fetal Alcohol and Autism Spectrums

Autism and Fetal Alcohol Spectrum Disorders (FASD) are neurodevelopmental conditions that affect at least 3% of the school aged population. Both have serious secondary sequelae including anxiety and depression, problems with concentration in class, learning new concepts through relevant curriculums, and social communication. Sleep is crucial to healthy neurodevelopment. It is not just a period of rest, but a time when the brain is highly active. During sleep, the brain consolidates newly acquired information, organises memory, and can lay the basis for emotional memory. Within Autism and FASD (as well as in many other developmental and psychological conditions), sleep quality and quantity remain much lower than the average and necessary amount. It is not known why this is, but research suggests that there is a complex and bidirectional relationship between sleep and development. This relationship may be part of the compromise of atypical development. This thesis links sleep with a number of daytime outcomes in children with Autism and FASD. According to the research carried out as part of this thesis, sleep is connected to anxiety, behaviours such as aggression and withdrawal, cognitive aspects such attention and working memory, as well as social and environmental factors. This is apparent not only in children in the neurodevelopmental categories, but in typically developing children too. This research also finds that children with Autism and FASD experience more sleep problems than typically developing children. It is therefore proposed here that sleep health interventions should be strongly considered as part of the therapeutic practice for children with Autism and FASD