Faculty Bibliography

Identify correlates of nicotine dependence [lifetime (l) and ongoing (o)] in adults with attention-deficit/hyperactivity disorder (ADHD) in childhood. We conducted a 33-year prospective follow-up of boys (mean age 8) with combined type ADHD (n = 135/207, 65% original sample). Correlates of nicotine dependence in adulthood were selected from characteristics obtained in childhood and adolescence. Among selected childhood features, only immature behavior was significantly related to nicotine dependence (OR(o) = 0.29, p = 0.02), indexing decreased risk. In contrast, several adolescent variables significantly correlated (p < 0.01) with nicotine dependence at mean age 41, including alcohol substance use disorder (SUD, OR(l) = 4.97), non-alcohol SUD (OR(o) = 4.33/OR(l) = 10.93), parental antisocial personality disorder (OR(l) = 4.42), parental SUD (OR(l) = 3.58), dropped out of school (OR(l) = 2.29), impulsivity (OR(o) = 1.53/OR(l) = 1.59), hyperactivity (OR(o) = 1.38), and number of antisocial behaviors (OR(o) = 1.10/OR(l) = 1.14). Results highlight the role of adolescent psychopathology in the development of nicotine dependence, motivating prospective longitudinal efforts to better define the developmental trajectories of risk and protection.

The use of movie-watching as an acquisition state for functional connectivity (FC) MRI has recently enabled multiple groups to obtain rich data sets in younger children with both substantial sample sizes and scan durations. Using naturalistic paradigms such as movies has also provided analytic flexibility for these developmental studies that extends beyond conventional resting state approaches. This review highlights the advantages and challenges of using movies for developmental neuroimaging and explores some of the methodological issues involved in designing pediatric studies with movies. Emerging themes from movie-watching studies are discussed, including an emphasis on intersubject correlations, developmental changes in network interactions under complex naturalistic conditions, and dynamic age-related changes in both sensory and higher-order network FC even in narrow age ranges. Converging evidence suggests an enhanced ability to identify brain-behavior correlations in children when using movie-watching data relative to both resting state and conventional tasks. Future directions and cautionary notes highlight the potential and the limitations of using movies to study FC in pediatric populations.

Background/UNASSIGNED:The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined. Methods/UNASSIGNED:) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined. Results/UNASSIGNED: > .05). Conclusion/UNASSIGNED:Decreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants.

OBJECTIVE: Children with NF1 display multiple structural and functional changes in the central nervous system, such as white matter alterations, and a unique profile of neuropsy-chological cognitive abnormalities. Assessment of resting state networks (RSNs) can reveal differences in the functional architecture of the developing brain in response to neurofibromin deficiency resulting from NF1 mutation. Here, we focused on resting-state functional connectivity between the subcortical striatum and cortical networks differentiated as primary (e.g., visual, somatomotor) versus association (e.g., ventral attention, default). MATERIAL-METHODS: Eighteen children with NF1 who had resting-state fMRI scans were group-matched (age, gender and head movement) with 18 typically developing children (TDC) from the ABIDE repository. Coherent slow fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional connectivity of cortical-subcortical structures. Assessment of RSNs was done using a previously established automated clustering algorithm. RESULTS: NF1 children demonstrated abnormal organization of association networks, particularly, deficient long-distance functional connectivity. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered, with NF1 children demonstrating diminished functional connectivity between striatum and the ventral attention network, as well as the posterior cingulate area, which is associated with the default network. By contrast, somatomotor functional connectivity with the striatum was increased. Functional connectivity of the visual network with the striatum did not differ in the NF1 group. CONCLUSION: These findings suggest that, much like in animal studies, the striatum plays a major role in NF1 cognitive pathogenesis. In addition, the "immature" pattern of deficient long distance functional connectivity suggests that NF1-associated myelin abnormalities may also play a significant role in the disrupted formation of RSNs

Cogmed Working Memory Training (CWMT), an online cognitive training program developed for children, is an increasingly popular non-pharmacological intervention for ADHD amongst all ages, despite limited supporting evidence. The initial objective of the present work was to examine the short- and long-term impacts of CWMT on brain function in adults with ADHD. However, during the conduct of our study, we experienced multiple levels of failures in recruitment and retention that signaled potential concerns about the suitability of CWMT for adults with ADHD. This perspective piece aims to describe the difficulties we encountered in the context of studies examining the efficacy of CWMT in comparable populations. We trace these difficulties to the limited tolerability of the current CWMT structure for adults with ADHD, and review similar limitations in the literature. We suggest that efficacy of CWMT in children may be due in large part to close monitoring and scaffolding provided by clinicians and caregivers. For CWMT to have viability for widespread use in adults, greater support and structure will be needed for users to improve the likelihood of adherence. We discuss implications and considerations for future efforts in both research and clinical practice.

A brain-computer-interface (BCI)-based attention training game system has shown promise for treating attention deficit/hyperactivity disorder (ADHD) children with inattentive symptoms. However, little is known about brain network organizational changes underlying behavior improvement following BCI-based training. To cover this gap, we aimed to examine the topological alterations of large-scale brain functional networks induced by the 8-week BCI-based attention intervention in ADHD boys using resting-state functional magnetic resonance imaging method. Compared to the non-intervention (ADHD-NI) group, the intervention group (ADHD-I) showed greater reduction of inattention symptoms accompanied with differential brain network reorganizations after training. Specifically, the ADHD-NI group had increased functional connectivity (FC) within the salience/ventral attention network (SVN) and increased FC between task-positive networks (including the SVN, dorsal attention (DAN), somatomotor, and executive control network) and subcortical regions; in contrast ADHD-I group did not have this pattern. In parallel, ADHD-I group had reduced degree centrality and clustering coefficient as well as increased closeness in task-positive and the default mode networks (prefrontal regions) after the training. More importantly, these reduced local functional processing mainly in the SVN were associated with less inattentive/internalizing problems after 8-week BCI-based intervention across ADHD patients. Our findings suggest that the BCI-based attention training facilitates behavioral improvement in ADHD children by reorganizing brain functional network from more regular to more random configurations, particularly renormalizing salience network processing. Future long-term longitudinal neuroimaging studies are needed to develop the BCI-based intervention approach to promote brain maturation in ADHD.

OBJECTIVE:Elevated response time intrasubject variability (RT-ISV) characterizes ADHD. Deficient emotional self-regulation (DESR), defined by summating Child Behavior Checklist Anxious/Depressed, Aggressive, and Attention subscale scores, has been associated with worse outcome in ADHD. To determine if DESR is differentially associated with elevated RT-ISV, we examined RT-ISV in children with ADHD with and without DESR and in typically developing children (TDC). METHOD/METHODS:We contrasted RT-ISV during a 6-min Eriksen Flanker Task in 31 children with ADHD without DESR, 34 with ADHD with DESR, and 65 TDC. RESULTS:Regardless of DESR, children with ADHD showed significantly greater RT-ISV than TDC ( p < .001). The ADHD subgroups, defined by presence or absence of DESR, did not differ from each other. CONCLUSION/CONCLUSIONS:Increased RT-ISV characterizes ADHD regardless of comorbid DESR. Alongside similar findings in children and adults with ADHD, these results suggest that RT-ISV is related to cognitive rather than emotional dysregulation in ADHD.

OBJECTIVE:Little is known of the factors that influence the course of childhood attention-deficit/hyperactivity disorder (ADHD). Objectives were to identify early features predictive of the adult outcome of children with ADHD. In the longest prospective follow-up to date of children with ADHD, predictors of multiple functional domains were examined: social, occupational, and overall adjustment and educational and occupational attainment. METHOD/METHODS:White boys (6-12 years, mean age 8 years) with ADHD (N = 135), selected to be free of conduct disorder, were assessed longitudinally through adulthood (mean age 41) by clinicians blinded to all previous characteristics. Predictors had been recorded in childhood and adolescence (mean age 18). RESULTS:Childhood IQ was positively associated with several outcomes: educational attainment, occupational rank, and social and occupational adjustment. Despite their low severity, conduct problems in childhood were negatively related to overall function, educational attainment, and occupational functioning. Two other childhood features that had positive associations with adult adjustment were socioeconomic status and reading ability, which predicted educational attainment. Of multiple adolescent characteristics, 4 were significant predictors: antisocial behaviors predicted poorer educational attainment; educational goals were related to better overall function; early job functioning had a positive relation with social functioning; and early social functioning was positively related to occupational functioning. CONCLUSION/CONCLUSIONS:Other than childhood IQ, which predicted better outcomes in several domains, there were no consistent prognosticators of adult function among children with ADHD. Providing additional supports to children with relatively lower IQ might improve the adult functional outcome of children with ADHD. However, predicting the course of children with ADHD remains a challenge.

Data sharing is increasingly recommended as a means of accelerating science by facilitating collaboration, transparency, and reproducibility. While few oppose data sharing philosophically, a range of barriers deter most researchers from implementing it in practice. To justify the significant effort required for sharing data, funding agencies, institutions, and investigators need clear evidence of benefit. Here, using the International Neuroimaging Data-sharing Initiative, we present a case study that provides direct evidence of the impact of open sharing on brain imaging data use and resulting peer-reviewed publications. We demonstrate that openly shared data can increase the scale of scientific studies conducted by data contributors, and can recruit scientists from a broader range of disciplines. These findings dispel the myth that scientific findings using shared data cannot be published in high-impact journals, suggest the transformative power of data sharing for accelerating science, and underscore the need for implementing data sharing universally.

Serotonin (5-HT) is one of the best-studied modulatory neurotransmitters with ubiquitous presynaptic release and postsynaptic reception. 5-HT has been implicated in a wide variety of brain functions, ranging from autonomic regulation, sensory perception, feeding and motor function to emotional regulation and cognition. The role of this neuromodulator in neuropsychiatric diseases is unquestionable with important neuropsychiatric medications, e.g., most antidepressants, targeting this system. Importantly, 5-HT modulates neurodevelopment and changes in its levels during development can have life-long consequences. In this mini-review, we highlight that exposure to both low and high serotonin levels during the perinatal period can lead to behavioral deficits in adulthood. We focus on three exogenous factors that can change 5-HT levels during the critical perinatal period: dietary tryptophan depletion, exposure to serotonin-selective-reuptake-inhibitors (SSRIs) and poor early life care. We discuss the effects of each of these on behavioral deficits in adulthood.