Faculty Bibliography

The delay aversion hypothesis argues that the tendency for impulsive choice (preference for smaller sooner over larger later rewards) is motivated by the escape of negative affective states associated with delay. This model predicts that individuals with ADHD find the imposition of delay before an outcome or event especially aversive and its escape reinforcing. Consistent with this, fMRI studies show that ADHD is associated with amygdala hyper-sensitivity to cues of delay. However, evidence that delay escape is reinforcing is lacking. Here we extend fMRI research by using electrophysiological methods to study the reinforcing properties of delay-escape in ADHD. Thirty controls and 25 adolescents with ADHD aged 10-15 years performed the Escape Delay Incentive (EDI) task- in which pre-target cues indicated three conditions: i) CERTAIN DELAY: delay would follow a response irrespective of response speed ii) CONDITIONAL DELAY: delay would only follow if the response was too slow and iii) NO DELAY: delay would follow the response whatever the speed. We focused on the Contingent Negative Variation (CNV), a cue-evoked marker of motivated response preparation, across two time windows (CNV1 and CNV2). We took measures of parent, teacher and self-rated ADHD symptoms, task performance (RT) and self-rated delay aversion. We isolated CNV components and compared these between ADHD and controls. Adolescents with ADHD displayed a larger CNV2 to the CONDITIONAL DELAY than the CERTAIN DELAY cues compared to controls. However, this effect was not mirrored at the performance level and was unrelated to self-reported delay aversion. Our study provides the first ERP evidence that delay escape differentially reinforcers neural activation of attention preparation in ADHD cases. Future studies should examine the impact of varying cognitive load on task EDI performance.

Understanding of early brain changes has the potential to investigate imaging biomarkers for pre-symptomatic diagnosis and thus opportunity for optimal therapeutic intervention, for example in early diagnosis of infants at risk to autism or altered development of infants to drug exposure. In this paper, we propose a framework to analyze longitudinal changes of structural connectivity in the early developing infant brain by exploring underlying network components of brain structural connectivity and its changes with age. Structural connectivity is a non-negative sparse network. Projective non-negative matrix factorization (PNMF) offers benefits in sparsity and learning fewer parameters for non-negative sparse data. The number of matrix subcomponents was estimated by automatic relevance determination PNMF (ARDPNMF) for brain connectivity networks for the given data. We apply linear mixed effect modeling on the resulting loadings from ARDPNMF to model longitudinal network component changes over time. The proposed framework was validated on a synthetic example generated by known linear mixed effects on loadings of the known number of bases with different levels of additive noises. Feasibility of the framework on real data has been demonstrated by analysis of structural connectivity networks of high angular resonance diffusion imaging (HARDI) data from an ongoing neuroimaging study of autism. A total of 139 image data sets from high-risk and low-risk subjects acquired at multiple time points have been processed. Results demonstrate the feasibility of the framework to analyze connectivity network properties as a function of age and the potential to eventually explore differences associated with risk status

The aim of this study was to examine associations between maternal mentalization, interactive behavior, and child symptoms in families in which mothers suffer from interpersonal violence-related posttraumatic stress disorder (IPV-PTSD). Fifty-six mothers and children (aged 12-42 months) including mothers with a diagnosis of IPV-PTSD were studied. Mentalization was measured by the Parental Reflective Functioning (PRF) Scale. Interactive behavior during free-play was measured via the CARE-Index. Child symptoms were measured by the Infant-Toddler Social and Emotional Assessment (ITSEA). Data analyses included non-parametric correlations and multiple linear regression. Results showed that lower IPV-PTSD and higher Maternal Reflective Functioning (MRF) were related to greater maternal sensitivity. Lower MRF and greater controlling behavior were related to child dysregulation. MRF was found to be lower in the subgroup of IPV-PTSD when the child's father was the perpetrator of IPV. Both MRF and interactive behavior are thus likely to be important targets for intervention during sensitive periods of early social-emotional development.

BACKGROUND:Adverse childhood experiences (ACEs) is a significant public health and social welfare problem in low-and middle income countries (LMICs). However, most ACEs research is based on developed countries, and little is known about mechanisms of early ACEs on adulthood health and offspring's wellbeing for populations in LMICs. This area is needed to guide social welfare policy and intervention service planning. This study addresses these research gaps by examining patterns of ACEs and understanding the role of ACEs on adulthood health (i.e., physical, mental health, experience of underage pregnancy) and offspring's mental health in Kenya. The study was guided by an Integrated Family Stress and Adverse Childhood Experiences Mediation Framework. METHODS:Three hundred ninety four mothers from two informal communities in Kariobangi and Kangemi in Nairobi were included in this study. The Adverse Childhood Experiences International Questionnaire (ACE-IQ), the Kessler Psychological Distress Scale (K10), Overall Health and Quality of Life items, and Child Behavior Checklist were used to study research questions. Data was gathered through a one-time interview with mothers. Structural Equational Modeling (SEM) was applied for mediational mechanism testing. RESULTS:Among 13 ACE areas, most mothers experienced multiple adversity during their childhood (Mean (SD) = 4.93 (2.52)), with household member treated violently (75%) as the most common ACE. SEM results showedthat all domains of ACEs were associated with some aspects of maternal health, and all three domains of maternal health (maternal mental health, physical health, and adolescent pregnancy) were significantly associated with development of offspring's mental health problems. CONCLUSION/CONCLUSIONS:ACEs are highly prevalent in Kenyan informal settlements. Consistent with cross cultural literature on family stress model, maternal ACEs are robust predictors for poor child mental health. Preventive interventions for child mental health need to address maternal adverse childhood traumatic experiences as well as their current health in order to effectively promote child mental health.

Importance/UNASSIGNED:Prenatal exposure to certain medications has been hypothesized to influence the risk of autism spectrum disorders (ASD). However, the underlying effects on the neurotransmitter systems have not been comprehensively assessed. Objective/UNASSIGNED:To investigate the association of early-life interference with different neurotransmitter systems by prenatal medication exposure on the risk of ASD in offspring. Design, Setting, and Participants/UNASSIGNED:This case-control study included children born from January 1, 1997, through December 31, 2007, and followed up for ASD until January 26, 2015, within a single Israeli health maintenance organization. Using publicly available data, 55 groups of medications affecting neurotransmitter systems and prescribed to pregnant women in this sample were identified. Children prenatally exposed to medications were compared with nonexposed children. Data were analyzed from March 1, 2017, through June 20, 2018. Main Outcome and Measures/UNASSIGNED:Hazard ratios (HRs) and 95% CIs of ASD risk associated with exposure to medication groups using Cox proportional hazards regression, adjusted for the relevant confounders (eg, birth year, maternal age, maternal history of psychiatric and neurologic disorders, or maternal number of all medical diagnoses 1 year before pregnancy). Results/UNASSIGNED:The analytic sample consisted of 96 249 individuals (1405 cases; 94 844 controls; mean [SD] age at the end of follow-up, 11.6 [3.1] years; 48.8% female), including 1405 with ASD and 94 844 controls. Of 34 groups of medications, 5 showed nominally statistically significant association with ASD in fully adjusted models. Evidence of confounding effects of the number of maternal diagnoses on the association between offspring exposure to medication and ASD was found. Adjusting for this factor, lower estimates of ASD risk among children exposed to cannabinoid receptor agonists (HR, 0.72; 95% CI, 0.55-0.95; P = .02), muscarinic receptor 2 agonists (HR, 0.49; 95% CI, 0.24-0.98; P = .04), opioid receptor κ and ε agonists (HR, 0.67; 95% CI, 0.45-0.99; P = .045), or α2C-adrenergic receptor agonists (HR, 0.43; 95% CI, 0.19-0.96; P = .04) were observed. Exposure to antagonists of neuronal nicotinic acetylcholine receptor α was associated with higher estimates of ASD risk (HR, 12.94; 95% CI, 1.35-124.25; P = .03). Conclusions and Relevance/UNASSIGNED:Most of the medications affecting neurotransmitter systems in this sample had no association with the estimates of ASD risk. Replication and/or validation using experimental techniques are required.

While static functional connectivity (sFC) of resting state fMRI (rfMRI) measures the average functional connectivity (FC) over the entire rfMRI scan, dynamic FC (dFC) captures the temporal variations of FC at shorter time windows. Although numerous studies have implemented dFC analyses, only a few studies have investigated the reliability of dFC and this limits the biological interpretation of dFC. Here, we used a large cohort (N = 820) of subjects and four rfMRI scans from the Human Connectome Project to systematically explore the relationship between sFC, dFC and their test-retest reliabilities through intra-class correlation (ICC). dFC ICC was explored through the sliding window approach with three dFC statistics (standard deviation, ALFF, and excursion). Excursion demonstrated the highest dFC ICC and the highest age prediction accuracy. dFC ICC was generally higher at window sizes less than 40 s sFC and dFC were negatively correlated. Compared to sFC, dFC was less reliable. While sFC and sFC ICC were positively correlated, dFC and dFC ICC were negatively correlated, indicating that FC that was more dynamic was less reliable. Intra-network FCs in the frontal-parietal, default mode, sensorimotor and visual networks demonstrated high sFC and low dFC. Moreover, ICCs of both sFC and dFC in these regions were higher. The above results were consistent across two brain atlases and independent component analysis-based networks, multiple window sizes and all three dFC statistics. In summary, dFC is less reliable than sFC and additional experiments are required to better understand the neurophysiological relevance of dFC.

Hoarding disorder is characterized by difficulty parting with possessions and by clutter that impairs the functionality of living spaces. Cognitive behavioral therapy conducted by a therapist (individual or in a group) for hoarding symptoms has shown promise. For those who cannot afford or access the services of a therapist, one alternative is an evidence-based, highly structured, short-term, skills-based group using CBT principles but led by non-professional facilitators (the Buried in Treasures [BIT] Workshop). BIT has achieved improvement rates similar to those of psychologist-led CBT. Regardless of modality, however, clinically relevant symptoms remain after treatment, and new approaches to augment existing treatments are needed. Based on two recent studies - one reporting that personalized care and accountability made treatments more acceptable to individuals with hoarding disorder and another reporting that greater number of home sessions were associated with better clinical outcomes, we tested the feasibility and effectiveness of adding personalized, in-home uncluttering sessions to the final weeks of BIT. Participants (n = 5) had 15 sessions of BIT and up to 20 hours of in-home uncluttering. Reductions in hoarding symptoms, clutter, and impairment of daily activities were observed. Treatment response rate was comparable to rates in other BIT studies, with continued improvement in clutter level after in-home uncluttering sessions. This small study suggests that adding in-home uncluttering sessions to BIT is feasible and effective.