Faculty Bibliography

We propose a generic method for the statistical analysis of collections of anatomical shape complexes, namely sets of surfaces that were previously segmented and labeled in a group of subjects. The method estimates an anatomical model, the template complex, that is representative of the population under study. Its shape reflects anatomical invariants within the dataset. In addition, the method automatically places control points near the most variable parts of the template complex. Vectors attached to these points are parameters of deformations of the ambient 3D space. These deformations warp the template to each subject's complex in a way that preserves the organization of the anatomical structures. Multivariate statistical analysis is applied to these deformation parameters to test for group differences. Results of the statistical analysis are then expressed in terms of deformation patterns of the template complex, and can be visualized and interpreted. The user needs only to specify the topology of the template complex and the number of control points. The method then automatically estimates the shape of the template complex, the optimal position of control points and deformation parameters. The proposed approach is completely generic with respect to any type of application and well adapted to efficient use in clinical studies, in that it does not require point correspondence across surfaces and is robust to mesh imperfections such as holes, spikes, inconsistent orientation or irregular meshing. The approach is illustrated with a neuroimaging study of Down syndrome (DS). The results demonstrate that the complex of deep brain structures shows a statistically significant shape difference between control and DS subjects. The deformation-based modelingis able to classify subjects with very high specificity and sensitivity, thus showing important generalization capability even given a low sample size. We show that the results remain significant even if the number of control points, and hence the dimension of variables in the statistical model, are drastically reduced. The analysis may even suggest that parsimonious models have an increased statistical performance. The method has been implemented in the software Deformetrica, which is publicly available at www.deformetrica.org.

Although evidence supports the efficacy of early intervention for improving outcomes for children with autism spectrum disorder (ASD), the mechanisms underlying their effectiveness remain poorly understood. This paper reviews the research literature on the neural bases of the early core deficits in ASD and proposes three key features of early intervention related to the neural mechanisms that may contribute to its effectiveness in improving deficit areas. These features include (1) the early onset of intensive intervention which capitalizes on the experience-expectant plasticity of the immature brain, (2) the use of treatment strategies that address core deficits in social motivation through an emphasis on positive social engagement and arousal modulation, and (3) promotion of complex neural networks and connectivity through thematic, multi-sensory and multi-domain teaching approaches. Understanding the mechanisms of effective early intervention will enable us to identify common or foundational active ingredients for promoting optimal outcomes in children with ASD.

Studies on functional brain lateralization using functional magnetic resonance imaging (fMRI) have generally focused on lateralization of local brain regions. We analyzed lateralization of functional connectivity using resting-state fMRI (N=87, right handed) and mapped left- and right- lateralized networks. We divided 402 equally spaced regions of interest (ROI) covering the entire gray matter into 358 task-positive and 44 task-negative ROIs. Lateralized functional connections were obtained using k-means clustering analysis. The right-lateralized functional connections were between the occipital and inferior/middle frontal regions among other connections, whereas the left-lateralized functional connections were among fusiform gyrus, inferior frontal and inferior/superior parietal regions. Within the task-negative network, the left-lateralized connections were mainly between the precuneus and medial prefrontal regions. Specific brain regions exhibited different left- or right-lateralized connections with other regions which suggest the importance of reporting lateralized connections over lateralized seed regions. The mean lateralization indices of the left- and right-lateralized connections were correlated, suggesting that the lateralization of connectivity may result from complementary processes between the lateralized networks. The potential functions of the lateralized networks were discussed.

Previous neuroimaging studies of youth with bipolar disorder (BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n = 59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes. Whole brain analysis was used to identify clusters that showed differential activation to emotion vs. shapes across group. To assess pair-wise comparisons and potential confounders, mean activation data were extracted only from clusters within regions previously implicated in emotion regulation (including amygdala and ventral prefrontal regions). A cluster in the right inferior frontal gyrus (IFG) showed group differences to emotion vs. shapes (159 voxels, corrected p < .05). Within this cluster, U-BD youth showed decreased activation relative to HC (p = .007) and non-BD (p = .004) youth. M-BD also showed decreased activation in this cluster relative to HC and non-BD youth, but these differences were attenuated. Results were specific to negative emotions, and not found with happy faces. IFG findings were not explained by other medications (e.g. stimulants) or diagnoses. Compared to both HC and a non-BD sample, U-BD is associated with abnormally decreased right IFG activation to negative emotions.

The Strategies to Enhance Positive Parenting (STEPP) program, an enhanced behavioral parent training (BPT) intervention, was developed to improve engagement in and outcomes following treatment for single-mother families of school-age youth with attention-deficit/hyperactivity disorder (ADHD). A previous randomized clinical trial of the STEPP program demonstrated that the intervention resulted in statistically significant improvements at the group-level in child oppositional behavior, various areas of child impairment, parental stress, and parenting behavior, relative to a wait-list control condition and a traditional BPT group. Despite benefits at the group-level, little is known about outcomes at the individual-level of enhanced BPT relative to traditional BPT for various child- and parent-level outcomes. The current study compares the extent to which traditional BPT and the STEPP program result in reliable change and recovery across various child- and parent-level outcomes in a sample of 80, 5-12 year old youth with ADHD (70 % male). Analyses demonstrated the benefit of participating in either BPT treatment; and participation in the STEPP program compared to traditional BPT was associated with only minimal incremental clinical benefit. Results, as well as clinical and research implications for assessment and treatment of high-risk families of youth with ADHD enrolled in BPT are discussed.

OBJECTIVE: Project Training and Education for the Advancement of Children's Health (TEACH) provides training, consultation and referral support to build child and adolescent mental health (MH) expertise among primary care providers (PCPs). This study describes how TEACH engages PCP, how program components lead to changes in practice and how contextual factors influence sustainability. METHOD: Thirty PCPs randomly selected from 139 trained PCPs and 10 PCPs from 143 registered with TEACH but not yet trained completed semistructured interviews. PCP selection utilized purposeful sampling for region, rurality and specialty. Interviews were recorded, transcribed and analyzed using grounded theory. RESULTS: PCP participation was facilitated by perceived patient needs, lack of financial and logistic barriers and continuity of PCP-program relationships from training to ongoing consultation. Trained PCPs reported more confidence interacting with families about MH, assessing severity, prescribing medication and developing treatment plans. They were encouraged by satisfying interactions with MH specialists and positive feedback from families. Barriers included difficulties implementing screening, time constraints, competing demands, guarded expectations for patient outcomes and negative impressions of the MH system overall. CONCLUSIONS: Programs like TEACH can increase PCP confidence in MH care and promote increased MH treatment in primary care and through collaboration with specialists. Sustainability may depend on the PCP practice context and implementation support.

BACKGROUND:It has been well documented that, along with tonsillar herniation, Chiari Malformation Type I (CMI) is associated with smaller posterior cranial fossa (PCF) and altered cerebrospinal fluid (CSF) flow and tissue motion in the craniocervical junction. OBJECTIVE:This study assesses the relationship between PCF volumetry and CSF and tissue dynamics toward a combined imaging-based morphological-physiological characterization of CMI. Multivariate analysis is used to identify the subset of parameters that best discriminates CMI from a healthy cohort. METHODS:Eleven length and volumetric measures of PCF, including crowdedness and 4th ventricle volume, 4 measures of CSF and cord motion in the craniocervical junction, and 5 global intracranial measures, including intracranial compliance and pressure, were measured by magnetic resonance imaging (MRI) in 36 symptomatic CMI subjects (28 female, 37 ± 11 years) and 37 control subjects (24 female, 36 ± 12 years). The CMI group was further divided based on symptomatology into "typical" and "atypical" subgroups. RESULTS:Ten of the 20 morphologic and physiologic measures were significantly different between the CMI and the control cohorts. These parameters also had less variability and stronger significance in the typical CMI compared with the atypical. The measures with the most significance were clival and supraocciput lengths, PCF crowdedness, normalized PCF volume, 4th ventricle volume, maximal cord displacement (P < .001), and MR measure of intracranial pressure (P = .007). Multivariate testing identified cord displacement, PCF crowdedness, and normalized PCF as the strongest discriminator subset between CMI and controls. MR measure of intracranial pressure was higher in the typical CMI cohort compared with the atypical. CONCLUSION/CONCLUSIONS:The identified 10 complementing morphological and physiological measures provide a more complete and symptomatology-relevant characterization of CMI than tonsillar herniation alone.

Schizophrenia patients exhibit impairments in auditory-based social cognition, indicated by deficits in detection of prosody, such as affective prosody and basic pitch perception. However, little is known about the psychometric properties of behavioral tests used to assess these functions. The goal of this paper is to characterize the properties of prosody and pitch perception tasks and to investigate whether they can be shortened. The pitch perception test evaluated is a tone-matching task developed by Javitt and colleagues (J-TMT). The prosody test evaluated is the auditory emotion recognition task developed by Juslin and Laukka (JL-AER). The sample includes 124 schizophrenia patients (SZ) and 131 healthy controls (HC). Properties, including facility and discrimination, of each item were assessed. Effects of item characteristics (e.g., emotion) were also evaluated. Shortened versions of the tests are proposed based on facility, discrimination, and/or ability of item characteristics to discriminate between patients and controls. Test-retest reliability is high for patients and controls for both the original and short forms of the J-TMT and JL-AER. Thus, the original as well as short forms of the J-TMT and JL-AER are suggested for inclusion in clinical trials of social cognitive and perceptual treatments. The development of short forms further increases the utility of these auditory tasks in clinical trials and clinical practice. The large SZ vs. HC differences reported here also highlight the profound nature of auditory deficits and a need for remediation.

Background: Although ecstasy (MDMA) use is not as prevalent in the United States (US) as it was in the early 2000s, use remains popular among adolescents and young adults. Few recent studies have examined ecstasy use in national samples among those at particularly high risk for use-adolescents approaching adulthood. Research is needed to delineate sociodemographic correlates of use in this group. Methods: Data were examined from a nationally representative sample of high school seniors in the US (modal age = 18) from the Monitoring the Future study (years 2007-2012; weighted N = 26,504). Data from all cohorts were aggregated and correlates of recent (last 12-month) use of ecstasy were examined. Results: Roughly 4.4% of high school seniors reported use of ecstasy within the last year. Females and religious students were consistently at lower odds for use. Black and Hispanic students, and students residing with two parents, were at lower odds for ecstasy use, until controlling for other drug use. Odds of use were consistently increased for those residing in a city, students with weekly income of >$50 from a job, and students earning >$10 weekly from other sources. Lifetime use of alcohol, cigarettes, marijuana, and other illicit drugs each robustly increased odds of ecstasy use. Conclusion: Subgroups of high school seniors, defined by specific sociodemographic factors, and those who have used other drugs, are currently at high risk for ecstasy initiation and use. Since ecstasy is regaining popularity in the US, prevention efforts should consider these factors.