Faculty Bibliography

Longitudinal imaging studies involve tracking changes in individuals by repeated image acquisition over time. The goal of these studies is to quantify biological shape variability within and across individuals, and also to distinguish between normal and disease populations. However, data variability is influenced by outside sources such as image acquisition, image calibration, human expert judgment, and limited robustness of segmentation and registration algorithms. In this paper, we propose a two-stage method for the statistical analysis of longitudinal shape. In the first stage, we estimate diffeomorphic shape trajectories for each individual that minimize inconsistencies in segmented shapes across time. This is followed by a longitudinal mixed-effects statistical model in the second stage for testing differences in shape trajectories between groups. We apply our method to a longitudinal database from PREDICT-HD and demonstrate our approach reduces unwanted variability for both shape and derived measures, such as volume. This leads to greater statistical power to distinguish differences in shape trajectory between healthy subjects and subjects with a genetic biomarker for Huntington's disease (HD).

The term prediction implies expected outcome in the future, often based on a model and statistical inference. Longitudinal imaging studies offer the possibility to model temporal change trajectories of anatomy across populations of subjects. In the spirit of subject-specific analysis, such normative models can then be used to compare data from new subjects to the norm and to study progression of disease or to predict outcome. This paper follows a statistical inference approach and presents a framework for prediction of future observations based on past measurements and population statistics. We describe prediction in the context of nonlinear mixed effects modeling (NLME) where the full reference population's statistics (estimated fixed effects, variance-covariance of random effects, variance of noise) is used along with the individual's available observations to predict its trajectory. The proposed methodology is generic in regard to application domains. Here, we demonstrate analysis of early infant brain maturation from longitudinal DTI with up to three time points. Growth as observed in DTI-derived scalar invariants is modeled with a parametric function, its parameters being input to NLME population modeling. Trajectories of new subject's data are estimated when using no observation, only the first or the first two time points. Leave-one-out experiments result in statistics on differences between actual and predicted observations. We also simulate a clinical scenario of prediction on multiple categories, where trajectories predicted from multiple models are classified based on maximum likelihood criteria.

Since 2005, an extensive literature documents individuals from several families afflicted with "Uner Tan Syndrome (UTS)," a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or "devolution." In support of this idea, individuals with "UTS" are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary "reversal," no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with "UTS", we found that these humans almost exclusively used lateral sequence-not diagonal sequence-quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the "devolution" hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.

The relations between attention-deficit hyperactivity disorder (ADHD) and motor skills are well documented, with research indicating both early and lifelong motor deficits in children with this disorder. Despite neuroanatomical and neurodevelopmental differences, which may predict differential rates of motor impairment between ADHD subtypes, evaluation of motor skill deficits in children with different presentations are limited in scope and equivocal in findings. The present investigation evaluated early motor development history and objectively measured motor skills in children with ADHD-Inattentive subtype (ADHD-I) and ADHD-Combined subtype (ADHD-C). One hundred and one children with ADHD-I (n = 53) and ADHD-C (n = 48) were included. Variables included Full-Scale IQ (FSIQ), history of motor delays, and utilization of early intervention services, as well as objectively measured motor impairment as assessed via tasks of fine-motor coordination. No between-group differences were found for FSIQ, but differences in age emerged, with the ADHD-I group being older. No differences in early motor delays were observed, though a considerably higher percentage of children with ADHD-C demonstrated early difficulties. Surprisingly, although children and adolescents with ADHD-C reported more frequent utilization of early intervention services, those with ADHD-I exhibited greater levels of current motor impairment on objective tasks. Given the over-representation of older children in the ADHD-I group, data were reanalyzed after excluding participants older than 10 years of age. Although the between-group differences were no longer significant, more than twice the number of parents of children with ADHD-C reported early motor delays, as compared with the ADHD-I group. Overall, children with ADHD-I were more likely to exhibit current objectively measured motor impairment, possibly due to later identification, less intervention, and/or different neurodevelopmental substrates underlying this disorder subtype.

Reviews the book, Reading Anna Freud by Nick Midgley (see record 2012-32286-000). Reading Anna Freud is less a work of criticism than a work of orientation, and doubly valuable as such. First, because of the Freud family fame, one sometimes presumes one knows more about them than one really does (indeed, a misplaced presumption of familiarity is at the core of so much of the popular contempt hurled Sigmund's way). Second, orienting yourself to Anna Freud is a way of orienting yourself to child mental health: from how we speak to children and the role of schools in a child's psychological health to developmental psychopathology and the consultation-liaison service. What comes through in Reading Anna Freud is that the core of Freud's success was not just patient, compassionate intellectualism, genes, or an ability to get published, but advocacy. Moreover, you do not need a degree or an internal review board to be an advocate. In fact, it is in this regard that she is most inspiring. Although the book provides a historical and personal orientation, it is intended as an orientation to Freud's intellectual contributions, and Midgely does an excellent job translating her work, some of it nearly a century old, into a language that is still alive, relevant, and enriching.

The future of the textbook as we know it is in doubt. Knowledge is being shuttled into the virtual world, where it is collaborative, linked, multimedia, and transnational. The iterative nature of knowledge never fit comfortably with textbooks. They have always been notoriously out of date by the time they roll off the press. Nevertheless, there remains something comforting in the textbook's authoritative heft, which is lost not only in the vapor-thin flicker of Web pages but also in the suspicion with which we approach anything online, knowing full well that the provenance is dubious. Sock puppetry is not just a children's craft anymore; it's a modern form of authorship. Of course, textbooks have value as a corpus of knowledge that is not constantly changing; as a way of studying a topic without being distracted by the rabbit holes of the Internet; and as a backup: all knowledge will not be lost in a blackout. What the future of the textbook means for expert knowledge is unclear. How can hardcover and paperback textbooks carve out a place in tomorrow's society? One answer may be to look back.

This article reviews the progression of a research program designed to develop, implement, and study the implementation of "achievable" evidence-based practices (EBPs) in schools. We review challenges encountered and ideas to overcome them to enhance this avenue of research. The article presents two federally funded randomized controlled trials involving comparison of a four-component targeted intervention (Quality Assessment and Improvement, Family Engagement and Empowerment, Modular Evidence-Based Practice, Implementation Support) versus a comparison intervention focused on personal wellness. In both studies, primary aims focused on changes in clinician attitudes and behavior, including the delivery of high-quality EBPs and secondary aims focused on student-level impacts. A number of challenges, many not reported in the literature, are reviewed, and ideas for overcoming them are presented. Given the reality that the majority of youth mental health services are delivered in schools and the potential of school mental health services to provide a continuum of mental health care from promotion to intervention, it is critical that the field consider and address the logistical and methodological challenges associated with implementing and studying EBP implementation by clinicians.