title: Characterization of the Statistical Signatures of Micro-Movements Underlying Natural Gait Patterns in Children with Phelan McDermid Syndrome: Towards Precision-Phenotyping of Behavior in ASD.
abstract: BACKGROUND
  There is a critical need for precision phenotyping across neurodevelopmental disorders, especially in individuals who receive a clinical diagnosis of autism spectrum disorder (ASD). Phelan-McDermid deletion syndrome (PMS) is one such example, as it has a high penetrance of ASD. At present, no biometric characterization of the behavioral phenotype within PMS exists.
  
  
  METHODS
  We introduce a data-type and statistical framework that permits the personalized profiling of naturalistic behaviors. Walking patterns were assessed in 30 participants (16 PMS, 3 idiopathic-ASD and 11 age- and sex-matched controls). Each individual's micro-movement signatures were recorded at 240 Hz. We empirically estimated the parameters of the continuous Gamma family of probability distributions and calculated their ranges. These estimated stochastic signatures were then mapped on the Gamma plane to obtain several statistical indexes for each child. To help visualize complex patterns across the cohort, we introduce new tools that enable the assessment of connectivity and modularity indexes across the peripheral network of rotational joints.
  
  
  RESULTS
  Typical walking signatures are absent in all children with PMS as well as in the children with idiopathic-ASD (iASD). Underlying these patterns are atypical leg rotational acceleration signatures that render participants with PMS unstable with rotations that are much faster than controls. The median values of the estimated Gamma parameters serve as a cutoff to automatically separate children with PMS 5-7 years old from adolescents with PMS 12-16 years old, the former displaying more randomness and larger noise. The fluctuations in the arm's motions during the walking also have atypical statistics that separate males from females in PMS and show higher rates of noise accumulation in idiopathic ASD (iASD) children. Despite high heterogeneity, all iASD children have excess noise, a narrow range of probability-distribution shapes across the body joints and a distinct joint network connectivity pattern. Both PMS and iASD have systemic issues with noise in micro-motions across the body with specific signatures for each child that, as a cohort, selectively deviates from controls.
  
  
  CONCLUSIONS
  We provide a new methodology for precision behavioral phenotyping with the potential to use micro-movement output noise as a natural classifier of neurodevelopmental disorders of known etiology. This approach may help us better understand idiopathic neurodevelopmental disorders and personalize the assessments of natural movements in these populations.
authors.affiliation: Department of Psychology, Computer Science, Rutgers Center for Cognitive Sciences and Computational Biomedicine Imaging and Modelling Center of Computer Science, Rutgers The State University of New Jersey New Brunswick, NJ, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Torres
authors.affiliation: Graduate Program in Neuroscience, Rutgers The State University of New Jersey New Brunswick, NJ, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Mathematics, Rutgers The State University of New Jersey New Brunswick, NJ, USA.
authors.forename: Sejal
authors.initials: S
authors.lastname: Mistry
authors.affiliation: Department of Psychology, Rutgers The State University of New Jersey New Brunswick, NJ, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Whyatt
authors.affiliation: Department of Computer Science, Rutgers The State University of New Jersey New Brunswick, NJ, USA.
authors.forename: Vilelmini
authors.initials: V
authors.lastname: Kalampratsidou
authors.affiliation: Psychiatry, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai New York, NY, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kolevzon
keywords: PMS; Phelan-McDermid syndrome; gait; gamma distribution; micro-movements; noise; precision phenotyping; stochastic signatures