Objective: The Janssen Autism Knowledge Engine (JAKE®) is a clinical research outcomes assessment system developed to more sensitively measure treatment outcomes and identify subpopulations in autism spectrum disorder (ASD). Here we describe JAKE and present results from its digital phenotyping (My JAKE) and biosensor (JAKE Sense) components. Methods: An observational, non-interventional, prospective study of JAKE in children and adults with ASD was conducted at nine sites in the United States. Feedback on JAKE usability was obtained from caregivers. JAKE Sense included electroencephalography, eye tracking, electrocardiography, electrodermal activity, facial affect analysis, and actigraphy. Caregivers of individuals with ASD reported behaviors using My JAKE. Results from My JAKE and JAKE Sense were compared to traditional ASD symptom measures. Results: Individuals with ASD ( N = 144) and a cohort of typically developing (TD) individuals ( N = 41) participated in JAKE Sense. Most caregivers reported that overall use and utility of My JAKE was “easy” (69%, 74/108) or “very easy” (74%, 80/108). My JAKE could detect differences in ASD symptoms as measured by traditional methods. The majority of biosensors included in JAKE Sense captured sizable amounts of quality data (i.e., 93–100% of eye tracker, facial affect analysis, and electrocardiogram data was of good quality), demonstrated differences between TD and ASD individuals, and correlated with ASD symptom scales. No significant safety events were reported. Conclusions: My JAKE was viewed as easy or very easy to use by caregivers participating in research outside of a clinical study. My JAKE sensitively measured a broad range of ASD symptoms. JAKE Sense biosensors were well-tolerated. JAKE functioned well when used at clinical sites previously inexperienced with some of the technologies. Lessons from the study will optimize JAKE for use in clinical trials to assess ASD interventions. Additionally, because biosensors were able to detect features differentiating TD and ASD individuals, and also were correlated with standardized symptom scales, these measures could be explored as potential biomarkers for ASD and as endpoints in future clinical studies. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02668991 identifier: NCT02668991

Objective: The relationship between sleep (caregiver-reported and actigraphymeasured) and other caregiver-reported behaviors in children and adults with autism spectrum disorder (ASD) was examined, including the use of machine learning to identify sleep variables important in predicting anxiety in ASD.Methods: Caregivers of ASD (n = 144) and typically developing (TD) (n = 41) participants reported on sleep and other behaviors. ASD participants wore an actigraphy device at nighttime during an 8 or 10-week non-interventional study. Mean and variability of actigraphy measures for ASD participants in the week preceding midpoint and endpoint were calculated and compared with caregiver-reported and clinician-reported symptoms using a mixed effects model. An elastic-net model was developed to examine which sleep measures may drive prediction of anxiety.Results: Prevalence of caregiver-reported sleep difficulties in ASD was approximately 70% and correlated significantly (p < 0.05) with sleep efficiency measured by actigraphy. Mean and variability of actigraphy measures like sleep efficiency and number of awakenings were related significantly (p < 0.05) to ASD symptom severity, hyperactivity and anxiety. In the elastic net model, caregiver-reported sleep, and variability of sleep efficiency and awakenings were amongst the important predictors of anxiety. Conclusion:Caregivers report problems with sleep in the majority of children and adults with ASD. Reported problems and actigraphy measures of sleep, particularly variability,

Eye‐tracking studies have demonstrated that individuals with autism spectrum disorder sometimes show differences in attention and gaze patterns. This includes preference for certain nonsocial objects, heightened attention to detail, and more difficulty with attention shifting and disengagement, which may be associated with restricted and repetitive behaviors. This study utilized a visual exploration task and replicates findings of reduced number of objects explored and increased fixation duration on high autism interest objects in a large sample of individuals with autism spectrum disorder (n = 129, age 6–54 years) in comparison with a typically developing group. These findings correlated with parent‐reported repetitive behaviors. Additionally, we applied recurrent quantification analysis to enable identification of new eye‐tracking features, which accounted for temporal and spatial differences in viewing patterns. These new features were found to discriminate between autism spectrum disorder and typically developing groups and were correlated with parent‐reported repetitive behaviors. Original and novel eye‐tracking features identified by recurrent quantification analysis differed in their relationships to reported behaviors and were dependent on age. Trial Registration: NCT02299700. Autism Research 2018, 11: 1554–1566. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Using eye‐tracking technology and a visual exploration task, we showed that people with autism spectrum disorder (ASD) spend more time looking at particular kinds of objects, like trains and clocks, and look at fewer objects overall than people without ASD. Where people look and the order in which they look at objects were related to the restricted and repetitive behaviors reported by parents. Eye‐tracking may be a useful addition to parent reports for measuring changes in behavior in individuals with ASD.

Background: Reduction or differences in facial expression are a core diagnostic feature of autism spectrum disorder (ASD), yet evidence regarding the extent of this discrepancy is limited and inconsistent. Use of automated facial expression detection technology enables accurate and efficient tracking of facial expressions that has potential to identify individual response differences. Methods: Children and adults with ASD (N = 124) and typically developing (TD, N = 41) were shown short clips of "funny videos." Using automated facial analysis software, we investigated differences between ASD and TD groups and within the ASD group in evidence of facial action unit (AU) activation related to the expression of positive facial expression, in particular, a smile. Results: Individuals with ASD on average showed less evidence of facial AUs (AU12, AU6) relating to positive facial expression, compared to the TD group (p < .05, r = − 0.17). Using Gaussian mixture model for clustering, we identified two distinct distributions within the ASD group, which were then compared to the TD group. One subgroup (n = 35), termed "over-responsive," expressed more intense positive facial expressions in response to the videos than the TD group (p < .001, r = 0.31). The second subgroup (n = 89), ("under-responsive"), displayed fewer, less intense positive facial expressions in response to videos than the TD group (p < .001; r = − 0.36). The overresponsive subgroup differed from the under-responsive subgroup in age and caregiver-reported impulsivity (p < .05, r = 0.21). Reduced expression in the under-responsive, but not the over-responsive group, was related to caregiver-reported social withdrawal (p < .01, r = − 0.3). Limitations: This exploratory study does not account for multiple comparisons, and future work will have to ascertain the strength and reproducibility of all results. Reduced displays of positive facial expressions do not mean individuals with ASD do not experience positive emotions.