Faculty Bibliography

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

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: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.

Is covert visuospatial attention-selective processing of information in the absence of eye movements-preserved in adults with attention-deficit/hyperactivity disorder (ADHD)? Previous findings are inconclusive due to inconsistent terminology and suboptimal methodology. To settle this question, we used well-established spatial cueing protocols to investigate the perceptual effects of voluntary and involuntary attention on an orientation discrimination task for a group of adults with ADHD and their neurotypical age-matched and gender-matched controls. In both groups, voluntary attention significantly improved accuracy and decreased reaction times at the relevant location, but impaired accuracy and slowed reaction times at irrelevant locations, relative to a distributed attention condition. Likewise, involuntary attention improved accuracy and speeded responses. Critically, the magnitudes of all these orienting and reorienting attention effects were indistinguishable between groups. Thus, these counterintuitive findings indicate that spatial covert attention remains functionally intact in adults with 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.

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.

Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p < .05- threshold free-cluster enhancement-family-wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto-parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age.

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.