Faculty Bibliography

Meta-analysis of neuroimaging results has proven to be a popular and valuable method to study human brain functions. A number of studies have used meta-analysis to parcellate distinct brain regions. A popular way to perform meta-analysis is typically based on the reported activation coordinates from a number of published papers. However, in addition to the coordinates associated with the different brain regions, the text itself contains considerably amount of additional information. This textual information has been largely ignored in meta-analyses where it may be useful for simultaneously parcellating brain regions and studying their characteristics. By leveraging recent advances in document clustering techniques, we introduce an approach to parcellate the brain into meaningful regions primarily based on the text features present in a document from a large number of studies. This new method is called MAPBOT (Meta-Analytic Parcellation Based On Text). Here, we first describe how the method works and then the application case of understanding the sub-divisions of the thalamus. The thalamus was chosen because of the substantial body of research that has been reported studying this functional and structural structure for both healthy and clinical populations. However, MAPBOT is a general-purpose method that is applicable to parcellating any region(s) of the brain. The present study demonstrates the powerful utility of using text information from neuroimaging studies to parcellate brain regions.

Naturalistic viewing paradigms such as movies have been shown to reduce participant head motion and improve arousal during fMRI scanning relative to task-free rest, and have been used to study both functional connectivity and stimulus-evoked BOLD-signal changes. These task-based hemodynamic changes are synchronized across subjects and involve large areas of the cortex, and it is unclear whether individual differences in functional connectivity are enhanced or diminished under such naturalistic conditions. This work first aims to characterize variability in BOLD-signal based functional connectivity (FC) across 2 distinct movie conditions and eyes-open rest (n=31 healthy adults, 2 scan sessions each). We found that movies have higher within- and between-subject correlations in cluster-wise FC relative to rest. The anatomical distribution of inter-individual variability was similar across conditions, with higher variability occurring at the lateral prefrontal lobes and temporoparietal junctions. Second, we used an unsupervised test-retest matching algorithm that identifies individual subjects from within a group based on FC patterns, quantifying the accuracy of the algorithm across the three conditions. The movies and resting state all enabled identification of individual subjects based on FC matrices, with accuracies between 61 and 100%. Overall, pairings involving movies outperformed rest, and the social, faster-paced movie attained 100% accuracy. When the parcellation resolution, scan duration, and number of edges used were increased, accuracies improved across conditions, and the pattern of movies>rest was preserved. These results suggest that using dynamic stimuli such as movies enhances the detection of FC patterns that are unique at the individual level.

OBJECTIVE:To test explanations for the underrecognition of female ADHD by examining differences in adult ratings of boys and girls matched for levels of directly observed ADHD behaviors. METHOD/METHODS:In a secondary analysis of a population-based sample, 3- to 4-year-olds ( n = 153, 79 male) and 8- to 9-year-olds ( n = 144, 75 male) were grouped according to levels of directly observed ADHD behaviors (low/moderate/high). Groups were then compared with parent/teacher ADHD ratings. RESULTS:There were no sex differences in levels of directly observed ADHD behaviors within groups. For preschoolers, parents' ratings of males, but not females, significantly increased across groups-mirroring levels of observed behaviors. For older children, both parent and teacher mean ratings were significantly higher for males than females across groups. CONCLUSION/CONCLUSIONS:Identified differences in adult ratings of males and females matched for directly observed behaviors may contribute to understanding the substantial ADHD underrecognition in females.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. METHODS: This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. RESULTS: Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. CONCLUSIONS: These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

OBJECTIVE: To determine optimal percent reduction and raw score cutoffs on the parent- and child-report Screen for Child Anxiety Related Emotional Disorders (SCARED) for predicting treatment response and remission among youth with anxiety disorders. METHOD: Data were obtained from youth (N = 438; 7-17 years old) who completed treatment in the Child/Adolescent Anxiety Multimodal treatment Study, a multisite, randomized clinical trial that examined the relative efficacy of medication (sertraline), cognitive-behavioral therapy (Coping Cat), their combination, and pill placebo for the treatment of separation anxiety disorder, generalized anxiety disorder, and social phobia. The parent- and youth-report SCARED were administered at pre- and posttreatment. Quality receiver operating characteristic methods evaluated the performance of various SCARED percent reduction and absolute cutoff scores in predicting treatment response and remission, as defined by posttreatment ratings on the Clinical Global Impression scales and the Anxiety Disorders Interview Schedule. RESULTS: Reductions of 55% on the SCARED-Parent and 50% on the SCARED-Youth optimally predicted treatment response. Posttreatment absolute raw scores of 10 (SCARED-Parent) and 12 (SCARED-Youth) optimally predicted remission in the total sample, although separate SCARED-Parent cutoffs for children (12-13) and adolescents (9) showed greatest quality of efficiency. Each cutoff significantly predicted response and remission at 6-month follow-up. CONCLUSION: Results serve as guidelines for operationalizing treatment response and remission on the SCARED, which could help clinicians systematically monitor treatment outcomes of youth with anxiety disorders in a cost- and time-efficient manner. Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov/; NCT00052078.

This study focused on social support and its association with child developmental outcomes, indirectly through parenting practices, in families of 4-5 year old Latino children. Data were collected from mothers and teachers of 610 Mexican American (MA) and Dominican American (DA) children. Mothers reported on perceived social support, parenting practices and children's problem and adaptive behavior functioning at home, and teachers reported on mothers' parent involvement and children's problem and adaptive behavior functioning in the classroom. Results showed that support received from family was higher than support received from school networks for both ethnic groups. Moreover, familial support was associated with child behavior, mediated by positive parenting practices, whereas support from school networks was not associated with child outcomes. During early childhood, social support from family members may be an important protective factor that can promote positive behavioral functioning among Latino children.

Objective/UNASSIGNED:To identify factors associated with early initiation and achievement of therapeutic hypothermia (TH) in newborns with hypoxic-ischemic encephalopathy (HIE). Methods/UNASSIGNED:Retrospective cohort study of newborns who received TH according to National Institute of Child Health and Human Development (NICHD) criteria in two academic level 3 Neonatal Intensive Care Units (NICU) between 2009 and 2013. All infants were transported by a neonatal transport team (NNTT). Multivariate linear regression including who initiated cooling and degree of resuscitation in the model was performed. Results/UNASSIGNED:Two hundred and seven infants were included. Waiting for advice from a tertiary care NICU was independently associated with a 50 minute delay in the median time of initiation of TH. The need for extensive resuscitation (cardiopulmonary resuscitation [CPR] or epinephrine) was independently associated with a reduction of 43 minutes in the median time to reach target core temperature. Log-transformed time to initiation of TH was associated with time to reach target core temperature (P<0.001). A doubling of time to initiation of TH corresponds to a 24% (95% CI 18% to 30%) increase in median time to reach target core temperature. Conclusions/UNASSIGNED:Initiating passive cooling at the referring centre, before transfer, is critical to faster achievement of target core temperature in asphyxiated infants. Greater outreach education and development of clinical care pathways are needed to improve optimal delivery of TH to enhance outcome.