Detection of Children/Youth With Fetal Alcohol Spectrum Disorder Through Eye Movement, Psychometric, and Neuroimaging Data

Abstract

Background: Fetal alcohol spectrum disorders (FASD) is one of the most common causes of developmental disabilities and neurobehavioral deficits. Despite the high-prevalence of FASD, the current diagnostic process is challenging and time- and money- consuming, with underreported profiles of the neurocognitive and neurobehavioral impairments because of limited clinical capacity. We assessed children/youth with FASD from a multimodal perspective and developed a high-performing, low-cost screening protocol using a machine learning framework. Methods and Findings: Participants with FASD and age-matched typically developing controls completed up to six assessments, including saccadic eye movement tasks (prosaccade, antisaccade, and memory-guided saccade), free viewing of videos, psychometric tests, and neuroimaging of the corpus callosum. We comparatively investigated new machine learning methods applied to these data, toward the acquisition of a quantitative signature of the neurodevelopmental deficits, and the development of an objective, high-throughput screening tool to identify children/youth with FASD. Our method provides a comprehensive profile of distinct measures in domains including sensorimotor and visuospatial control, visual perception, attention, inhibition, working memory, academic functions, and brain structure. We also showed that a combination of four to six assessments yields the best FASD vs. control classification accuracy; however, this protocol is expensive and time consuming. We conducted a cost/benefit analysis of the six assessments and developed a high-performing, low-cost screening protocol based on a subset of eye movement and psychometric tests that approached the best result under a range of constraints (time, cost, participant age, required administration, and access to neuroimaging facility). Using insights from the theory of value of information, we proposed an optimal annual screening procedure for children at risk of FASD. Conclusions: We developed a high-capacity, low-cost screening procedure under constrains, with high expected monetary benefit, substantial impact of the referral and diagnostic process, and expected maximized long-term benefits to the tested individuals and to society. This annual screening procedure for children/youth at risk of FASD can be easily and widely deployed for early identification, potentially leading to earlier intervention and treatment. This is crucial for neurodevelopmental disorders, to mitigate the severity of the disorder and/or frequency of secondary comorbidities.

Keywords: DTI; early screening; eye movements; fetal alcohol spectrum disorder (FASD); psychometrics.

Figures

Figure 1

Illustration of experimental methods and classification procedure. (A) Prosaccade task. (B) Antisaccade task. (C) Memory-guided saccade task. (D) Inhibition subtests of psychometric tests (see Supplementary Material for test description) (E) DTI. (F) Natural viewing task. (G) SVM-RFE. (H) Attentional eye traces and Tiled CNN.

Figure 2

Classification results. (A) Classification accuracies and evaluations on single assessments. Top: train (cross validation) and test accuracies of each assessment. Bottom: evaluations of different assessments. (B) Classification accuracy on all assessments. Left: classification accuracy and the chance level. Right: the confusion matrix. (C) Classification results of pairwise assessments. The first three light-colored bars show accuracies of the top pairs. The forth shows the highest accuracy without psychometric tests.

Figure 3

Multilinear regression results. (A) Ratio (in percentage) of significant features of one assessment predicted by another. (B) r2 of predicting the differentiation probability of one assessment from another.

Figure 4

Screening procedure. The participant is first assessed by the ProSac and Natural viewing tasks, with an accuracy of 78.26% for estimating the risk of being FASD. For older children/youth, the addition of the AntiSac task and/or short battery of psychometric tests adds to the classification accuracy, adding greater confidence that at-risk children/youth are not missed. The confusion matrices are also shown.

Figure 5

Model structure for cost evaluation of the screening procedure. CS, screening cost; rD, detection rate; rFA, false alarm rate; rTN, true negative rate; rM, miss rate; pF, priori probability of having FASD; CD, clinical diagnostic cost; G, gain; L, loss.