Faculty Bibliography

BACKGROUND: Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area might clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood. METHODS: Children were assessed for BI at multiple age points from infancy through age seven. On the basis of a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (n = 44). Participants completed an event-related functional magnetic resonance imaging attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews. RESULTS: The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms. CONCLUSIONS: Behavioral inhibition during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology.

The lateral entorhinal cortex (LEC) receives direct input from olfactory bulb mitral cells and piriform cortical pyramidal cells and is the gateway for olfactory input to the hippocampus. However, the LEC also projects back to the piriform cortex and olfactory bulb. Activity in the LEC is shaped by input from the perirhinal cortices, hippocampus, and amygdala, and thus could provide a rich contextual modulation of cortical odor processing. The present study further explored LEC feedback to anterior piriform cortex by examining how LEC top-down input modulates anterior piriform cortex odor evoked activity in rats. Retrograde viral tracing confirmed rich LEC projections to both the olfactory bulb and piriform cortices. In anesthetized rats, reversible lesions of the ipsilateral LEC increased anterior piriform cortical single-unit spontaneous activity. In awake animals performing an odor discrimination task, unilateral LEC reversible lesions enhanced ipsilateral piriform cortical local field potential oscillations during odor sampling, with minimal impact on contralateral activity. Bilateral LEC reversible lesions impaired discrimination performance on a well learned, difficult odor discrimination task, but had no impact on a well learned simple odor discrimination task. The simple discrimination task was impaired by bilateral reversible lesions of the anterior piriform cortex. Given the known function of LEC in working memory and multisensory integration, these results suggest it may serve as a powerful top-down modulator of olfactory cortical function and odor perception. Furthermore, the results provide potential insight into how neuropathology in the entorhinal cortex could contribute to early olfactory deficits seen in Alzheimer's disease.

BACKGROUND:Recent guidelines suggest lowering the target blood pressure for patients with chronic kidney disease, although the strength of evidence for this suggestion has been uncertain. We sought to assess the renal and cardiovascular effects of intensive blood pressure lowering in people with chronic kidney disease. METHODS:We performed a systematic review and meta-analysis of all relevant reports published between 1950 and July 2011 identified in a search of MEDLINE, Embase and the Cochrane Library. We included randomized trials that assigned patients with chronic kidney disease to different target blood pressure levels and reported kidney failure or cardiovascular events. Two reviewers independently identified relevant articles and extracted data. RESULTS:We identified 11 trials providing information on 9287 patients with chronic kidney disease and 1264 kidney failure events (defined as either a composite of doubling of serum creatinine level and 50% decline in glomerular filtration rate, or end-stage kidney disease). Compared with standard regimens, a more intensive blood pressure-lowering strategy reduced the risk of the composite outcome (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.68-0.98) and end-stage kidney disease (HR 0.79, 95% CI 0.67-0.93). Subgroup analysis showed effect modification by baseline proteinuria (p = 0.006) and markers of trial quality. Intensive blood pressure lowering reduced the risk of kidney failure (HR 0.73, 95% CI 0.62-0.86), but not in patients without proteinuria at baseline (HR 1.12, 95% CI 0.67-1.87). There was no clear effect on the risk of cardiovascular events or death. INTERPRETATION/CONCLUSIONS:Intensive blood pressure lowering appears to provide protection against kidney failure events in patients with chronic kidney disease, particularly among those with proteinuria. More data are required to determine the effects of such a strategy among patients without proteinuria.

The default mode network (DMN) is characterised by coherent very low frequency (VLF) neural oscillations in the resting brain. The attenuation of this activity has been demonstrated following the transition from rest to performance of a broad range of cognitive goal-directed tasks. Whether the activity of resting state VLF oscillations is attenuated during non-cognitive goal-directed tasks such as waiting for rewarding outcomes is not known. This study examined the VLF EEG power from resting to performance of attention demanding task and two types of goal-directed waiting tasks. The association between the attenuation of VLF EEG power and Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms was examined. Direct current EEG (DC-EEG) data were collected from 32 healthy young adults (half high and half low ADHD symptom scorers) during (i) a rest state, (ii) while performing a cognitive demanding reaction time task (2CRT), and (iii) while undertaking each of two different goal-directed waiting conditions: "forced-to-wait (FW)" and "choose-to-wait (CW)" tasks. The spatial distribution of VLF EEG power across scalp was similar to that seen in previous resting VLF EEG studies. Significant rest-to-task attenuation of VLF EEG power occurred during the 2CRT and the CW task, but not during the FW task. The association between self-ratings of ADHD symptoms and waiting-induced attenuation was not significant. This study suggests VLF EEG power attenuation that occurs following rest-to-task transition is not simply determined by changes in cognitive load. The goal-directed nature of a task, its motivated nature and/or the involvement of effortful attention may also contribute. Future studies should explore the attenuation of resting state VLF oscillations during waiting and impulsive choice.

Functional connectomics is one of the most rapidly expanding areas of neuroimaging research. Yet, concerns remain regarding the use of resting-state fMRI (R-fMRI) to characterize inter-individual variation in the functional connectome. In particular, recent findings that "micro" head movements can introduce artifactual inter-individual and group-related differences in R-fMRI metrics have raised concerns. Here, we first build on prior demonstrations of regional variation in the magnitude of framewise displacements associated with a given head movement, by providing a comprehensive voxel-based examination of the impact of motion on the BOLD signal (i.e., motion-BOLD relationships). Positive motion-BOLD relationships were detected in primary and supplementary motor areas, particularly in low motion datasets. Negative motion-BOLD relationships were most prominent in prefrontal regions, and expanded throughout the brain in high motion datasets (e.g., children). Scrubbing of volumes with FD>0.2 effectively removed negative but not positive correlations; these findings suggest that positive relationships may reflect neural origins of motion while negative relationships are likely to originate from motion artifact. We also examined the ability of motion correction strategies to eliminate artifactual differences related to motion among individuals and between groups for a broad array of voxel-wise R-fMRI metrics. Residual relationships between motion and the examined R-fMRI metrics remained for all correction approaches, underscoring the need to covary motion effects at the group-level. Notably, global signal regression reduced relationships between motion and inter-individual differences in correlation-based R-fMRI metrics; Z-standardization (mean-centering and variance normalization) of subject-level maps for R-fMRI metrics prior to group-level analyses demonstrated similar advantages. Finally, our test-retest (TRT) analyses revealed significant motion effects on TRT reliability for R-fMRI metrics. Generally, motion compromised reliability of R-fMRI metrics, with the exception of those based on frequency characteristics - particularly, amplitude of low frequency fluctuations (ALFF). The implications of our findings for decision-making regarding the assessment and correction of motion are discussed, as are insights into potential differences among volume-based metrics of motion.

BACKGROUND: Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology. METHODS: Non-substance abusing youth (N=19; mean age=12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N=18; mean age=11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation. RESULTS: High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group. CONCLUSIONS: These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence.

OBJECTIVE: This study sought to describe reasons for disengagement from services and practical guidelines to enhance engagement among individuals with serious mental illness and high need for treatment. METHODS: Qualitative interviews were conducted with 56 individuals with serious mental illness and 25 providers recruited from a larger project that used administrative data to identify individuals with serious mental illness who had disengaged from care. Individuals with serious mental illness and providers described reasons for disengagement and effective provider engagement strategies. RESULTS: Individuals with serious mental illness and providers differed in reported reasons for disengagement. Reasons reported by individuals with serious mental illness included services that were not relevant to their needs, inability to trust providers, and a belief that they were not ill. Providers cited lack of insight, stigma, and language and cultural barriers as common reasons for disengagement. Strategies for increasing engagement were grouped into a framework of acceptable, accessible, and available services. Acceptable services reflect a partnership model that fosters support and instills hope; accessible services minimize barriers related to transportation and intake procedures; and available services address recovery needs in addition to treatment of general medical and psychiatric problems. CONCLUSIONS: Individuals with serious mental illness and providers often do not agree on reasons for seeking care. The framework of acceptable, accessible, and available services identifies opportunities for providers to adjust practices and maximize engagement in services among individuals with serious mental illness who are in high need of treatment.

The current diagnostic criteria do not allow co-diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). As a result, there has been little research on how these two disorders co-occur in the ASD population. The current study aimed to extend the literature in this area by examining comorbid rates in three different diagnostic groups (ASD, ADHD, and comorbid ASD+ADHD) using the Autism Spectrum Disorders-Comorbidity for Children (ASD-CC). Children with comorbid ASD and ADHD evinced higher rates of comorbid symptoms than children with ASD or ADHD alone. Additionally, children with comorbid ASD and ADHD endorsed more severe comorbid symptoms. Implications regarding these findings are discussed.

Latino children in urban contexts marked by poverty are at high risk of being exposed to violence and developing posttraumatic stress disorder (PTSD). Nonetheless, there is great variability in individual responses to violence exposure. This study examines risk for developing re-experiencing, avoidance, and arousal symptoms of PTSD as a function of individual differences in behavioral inhibition and exposure to community violence. Participants were 148 Latino students (M age =11.43 years, SD = 0.69; 55 % girls) living in an area marked by poverty and crime. Children completed self-report measures of behavioral inhibition and posttraumatic stress symptoms during a baseline assessment. During a follow-up interview 6 months later, children completed self-report measures of exposure to community violence since the baseline assessment and posttraumatic stress symptoms. Structural equation models revealed that behavioral inhibition at baseline was positively associated with PTSD avoidance and arousal symptoms at follow-up, after controlling for symptoms at baseline. Furthermore, behavioral inhibition moderated the association between violence exposure and symptoms such that violence was more strongly associated with the development of PTSD avoidance symptoms as behavioral inhibition increased. Results suggest that individual differences in behavioral inhibition contribute to risk for specific PTSD symptoms and are important for understanding variation in responses to trauma exposure. By examining diathesis--stress models within a disorder, we may be better able to elucidate the etiology of a disorder and translate this improved understanding into personalized intervention approaches that maximize effectiveness.

Abstract Background: Poor sleep, common during pregnancy, is associated with negative health risks. The study aimed to identify predictors of clinically significant insomnia among pregnant Latinas. Methods: A total of 1289 pregnant Latinas recruited from obstetric clinics completed the Insomnia Severity Index (ISI) and questions about demographics and sleep. Results: Clinically significant insomnia (ISI>/=10) was present among 17% of participants. Significant correlates of clinically significant insomnia were higher scores on the Edinburgh Postnatal Depression Scale (EPDS) after removing the sleep item (47% of women with EPDS>/=9 and 9% with EPDS<9), completing measures in English (rather than Spanish: 26% versus 13%), and income but not pregnancy week, age, highest education level, or marital status. The highest percentage of clinically significant insomnia (59%) was experienced by women with EPDS>/=9 who completed measures in English. The lowest percentage of clinically significant insomnia (6.2%) was experienced by women with EPDS<9 who completed measures in Spanish. Conclusions: In this sample of low-income, mostly Spanish-speaking pregnant Latinas, rates of clinically significant insomnia appear to be higher than rates among nonpregnant Latinas. Rates of clinically significant insomnia are particularly high among Latinas with elevated depressive symptom severity, a known risk for insomnia. Acculturation, as indicated by completing measures in English, may be another risk specific to Latinas, possibly owing to loss of some ethnicity-specific protective factors (e.g., social support, strong family ties, and group identity). It will be important to directly test this explanation in future research.