Faculty Bibliography

It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.

The human brain is highly dynamic, supporting a remarkable range of cognitive abilities that emerge over the course of development. While flexible and dynamic coordination between neural systems is firmly established for children, our understanding of brain functional organization in early life has been built largely on the implicit assumption that functional connectivity (FC) is static. Understanding the nature of dynamic neural interactions during development is a critical issue for cognitive neuroscience, with implications for neurodevelopmental pathologies that involve anomalies in brain connectivity. In this work, FC dynamics of neurocognitive networks in a sample of 146 youth from varied sociodemographic backgrounds were delineated. Independent component analysis, sliding time window correlation, and k-means clustering were applied to resting-state fMRI data. Results revealed six dynamic FC states that re-occur over time and that complement, but significantly extend, measures of static FC. Moreover, the occurrence and amount of time spent in specific FC states are related to the content of self-generated thought during the scan. Additionally, some connections are more variable over time than are others, including those between inferior parietal lobe and precuneus. These regions contribute to multiple networks and likely play a role in adaptive processes in childhood. Age-related increases in temporal variability of FC among neurocognitive networks were also found. Taken together, these findings lay the groundwork for understanding how variation in the developing chronnectome is related to risk for neurodevelopmental disorders. Understanding how brain systems reconfigure with development should provide insight into the ontogeny of complex, flexible cognitive processes. Hum Brain Mapp 38:97-108, 2017. © 2016 Wiley Periodicals, Inc.

Traumatic experiences early in life predispose animals and humans to later cognitive-behavioral, emotional, and somatic problems. In humans, traumatic experiences are strong predictors of psychiatric illness. A growing body of research has emphasized alterations in neurological structure and function that underscore phenotypic changes following trauma. However, results are mixed and imprecise. We argue that future translation of neurological findings to clinical practice will require: (1) discovery of neurobehavioral associations within a longitudinal context, (2) dissociation of trauma types and of trauma versus chronic stress, and (3) better localization of neural sequelae considerate of the fine resolution of neural circuitry. We provide a brief overview of early brain development and highlight the role of longitudinal research in unearthing brain-behavior relations in youth. We relay an emergent framework in which dissociable trauma types are hypothesized to impact distinct, rationally informed neural systems. In line with this, we discuss the long-standing challenge of separating effects of chronic stress and trauma, as these are often intertwined. We bring to light inconsistencies in localization of neural correlates of trauma, emphasizing results in medial prefrontal regions. We assert that more precise spatial brain localization will help to advance prevailing models of trauma pathways and inform future research.

BACKGROUND:Preclinical data suggest that early life stress has detrimental effects on the brain's dopaminergic system, particularly the mesocorticolimbic pathway. Altered dopamine function is thought to contribute to the development of stress-related pathologies; yet, little is known about the impact of early stress on dopamine systems during childhood and adolescence, when stress-related disorders frequently emerge. Here, we evaluate the impact of early threat exposure (violence, abuse) on functional connectivity of putative dopaminergic midbrain regions, the ventral tegmental area (VTA) and substantia nigra (SN), giving rise to mesocorticolimbic and nigrostriatal pathways, respectively. METHODS:Resting-state functional magnetic resonance imaging scans were completed in 43 trauma-exposed and 43 matched comparison youth (ages 7-17). Functional connectivity of the VTA and SN were compared between groups. RESULTS:The trauma group demonstrated lower functional connectivity between the VTA and hippocampus. No group differences in SN connectivity were observed. Across all participants, there were age-related decreases in connectivity of both VTA and SN with the hippocampus, suggesting that age-related attenuations in VTA-hippocampal circuitry may be exacerbated in trauma-exposed youth. Higher levels of anxiety symptomology were associated with reduced SN-nucleus accumbens connectivity. CONCLUSIONS:Prior research suggests that VTA-hippocampal circuitry is critical for the gating of new information into long-term memory. Lower connectivity in this circuitry suggests a novel mechanism that may serve to adaptively prevent the overwriting of a previously stored trauma memory, but at the same time contribute to the broad range of cognitive and emotional difficulties linked to early stress exposure.

States are restructuring health care delivery with a focus on cost savings and care quality. Building on lessons learned from the first statewide roll-out of the NY State Managing and Adapting Practice (MAP) program, we targeted adaptations to the MAP trainings with the goal of addressing key factors related to clinician dropout. We describe these adaptations made to MAP version 2, using Damschroder et al.'s (2009) theoretical model of the consolidated Framework for Implementation Research (CFIR). our adaptations were connected with each of the five domains: intervention characteristics, outer setting (incentives and cost), inner setting (leadership/champions), characteristics of the individuals, and the process of training implementation (planning, engaging, executing, and reflecting and evaluating. Next, we compared dropout rates between MAP version 1 (v1) and MAP version 2 (v2). Because the structural adaptations aimed to increase retention rate by targeting factors hypothesized to be associated with empirically derived predictors of dropout, we expected that the dropout rate would be significantly lower in MAP v2. We then examined associations of clinician sociodemographic characteristics, clinical characteristics, and attitudes with dropout. Although older participant age was significantly associated with dropout in MAP v1, we hypothesized that participant age will not be a significant predictor of dropout in MAP v2 because MAP v2 adaptations focused on age-related factors. However, we expected clinic region, which is immutable, to remain a significant predictor of dropout.

Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta-analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity.

BACKGROUND:The purpose of this study was to determine whether the cost of readmissions after primary total hip and knee arthroplasty (THA and TKA) has decreased since the introduction of health care reform legislation and what patient, clinical, and hospital factors drive such costs. METHODS:The 100% Medicare inpatient dataset was used to identify 1,654,602 primary THA and TKA procedures between 2010 and 2014. The per-patient cost of readmissions was evaluated in general linear models in which the year of surgery and patient, clinical, and hospital factors were treated as covariates in separate models for THA and TKA. RESULTS:The year-to-year risk of 90-day readmission was reduced by 2% and 4% (P < .001) for THA and TKA, respectively. By contrast, the cost of readmissions did not change significantly over time. The 5 most important variables associated with the cost of 90-day THA readmissions (in rank order) were the nature of the readmission (ie, due to medical or procedure-related reasons), the length of stay, hospital's teaching status, discharge disposition, and hospital's overall total joint arthroplasty volume. The top 5 factors associated with the cost of 90-day TKA readmissions were (in rank order) the length of stay, hospital's teaching status, discharge disposition, patient's gender, and age. CONCLUSION/CONCLUSIONS:Although readmission rates declined slightly, the results of this study do not support the hypothesis that readmission costs have decreased since the introduction of health care reform legislation. Instead, we found that clinical and hospital factors were among the most important cost drivers.

In a randomized clinical trial (RCT), it is often of interest not only to estimate the effect of various treatments on the outcome, but also to determine whether any patient characteristic has a different relationship with the outcome, depending on treatment. In regression models for the outcome, if there is a non-zero interaction between treatment and a predictor, that predictor is called an "effect modifier". Identification of such effect modifiers is crucial as we move towards precision medicine, that is, optimizing individual treatment assignment based on patient measurements assessed when presenting for treatment. In most settings, there will be several baseline predictor variables that could potentially modify the treatment effects. This article proposes optimal methods of constructing a composite variable (defined as a linear combination of pre-treatment patient characteristics) in order to generate an effect modifier in an RCT setting. Several criteria are considered for generating effect modifiers and their performance is studied via simulations. An example from a RCT is provided for illustration.

Leikauf, J. E., & Solanto, M. V. (2016). Sluggish Cognitive Tempo, Internalizing Symptoms, and Executive Function in Adults With ADHD. Journal of Attention Disorders. Advance online publication. doi: 10.1177/1087054716659361.