Publications by authors named "David Pagliaccio"

57 Publications

Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project.

J Am Acad Child Adolesc Psychiatry 2021 May 6. Epub 2021 May 6.

Objective: Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cuts across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed-anxious youth.

Method: The Boston Adolescent Neuroimaging of Depression and Anxiety Human Connectome Project tested group differences regarding subcortical volume and nucleus accumbens activation during an incentive processing task among 14-17-year-old adolescents presenting with a primary depressive and/or anxiety disorder (n=129) or no lifetime history of mental disorders (n=64). Additionally, multimodal modeling examined predictors of depression and anxiety symptom change over a 6-month follow-up period.

Results: Our findings highlighted considerable convergence. Relative to healthy youth, depressed-anxious adolescents exhibited reduced nucleus accumbens volume and activation following reward receipt. These findings remained when removing all medicated participants (∼59% of depressed-anxious youth); subgroup analyses comparing anxious-only, depressed-anxious, and healthy youth also were largely consistent. Multimodal modeling showed that only structural alterations predicted depressive symptoms over time.

Conclusion: Multimodal findings highlight alterations within nucleus accumbens structure and function that characterize depressed-anxious adolescents. In the current hypothesis-driven analyses, only reduced nucleus accumbens volume, however, predicted depressive symptoms over time. An important next step will be to clarify why structural alterations impact reward-related processes and associated symptoms.
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http://dx.doi.org/10.1016/j.jaac.2021.04.014DOI Listing
May 2021

Prenatal environmental tobacco smoke exposure alters children's cognitive control circuitry: A preliminary study.

Environ Int 2021 May 6;155:106516. Epub 2021 May 6.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.

Background And Objectives: Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children's brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children's cognitive control circuitry and behavior.

Methods: Forty-one children (7-9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist.

Results: Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen's D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05).

Conclusions: Our findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren's neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.
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http://dx.doi.org/10.1016/j.envint.2021.106516DOI Listing
May 2021

Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability.

Cerebellum 2021 Apr 15. Epub 2021 Apr 15.

New York State Psychiatric Institute and Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Box 74 / Room 2403, New York, NY, 10032, USA.

Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting-state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contributes to social deficits. Twenty-seven children (12 with NVLD, 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnosis and greater social impairment was mediated by right inferior cerebellar peduncle FA. These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.
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http://dx.doi.org/10.1007/s12311-021-01265-4DOI Listing
April 2021

A quality control pipeline for probabilistic reconstruction of white-matter pathways.

J Neurosci Methods 2021 Apr 11;353:109099. Epub 2021 Feb 11.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, New York, NY, United States.

Background: One of the most well-validated tools for DTI data analysis is TRACULA, part of the FreeSurfer software. TRACULA automatically segments 18 major white matter (WM) tracts. Occasionally, tracts may be only partially reconstructed, thus requiring intervention to avoid biasing analyses. A majority of studies have not reported any quality control procedures and those that have tend to discard partially reconstructed tracts from group analyses if they cannot be salvaged during TRACULA reinitialization.

New Method: We propose a semi-automated method to improve the detection and recovery of incomplete WM tracts. We detail several steps to maximize the quality of preprocessed DTI data. The steps include: (1) a visual inspection of eddy current corrected diffusion weighted images and (2) an automated evaluation of color- encoded FA images; (3) assessment of the volume of each tract saved in the TRACULA output file; (4) re-processing of tracts with a volume smaller than a specified threshold; (5) minimal manual editing of the control points for tracts that remained partially reconstructed; and (6) final re-initiation of TRACULA.

Results: Our method can speed and improve quality control relative to tract-by-tract visual inspection and can recover data that otherwise would need to be excluded from analyses due to incomplete reconstruction.

Comparison With Existing Methods: To our knowledge, there are no publications proposing alternative methods for quality control and recovering of partially reconstructed tracts in the TRACULA environment.

Conclusions: Our method helps TRACULA users automatically access the quality of reconstructed WM tracts and semi-automatically recover those in-complete WM tracts.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006796PMC
April 2021

Frontoparietal and default mode network connectivity varies with age and intelligence.

Dev Cogn Neurosci 2021 Apr 27;48:100928. Epub 2021 Jan 27.

The Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, United States. Electronic address:

Background: Anticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ).

Methods: We utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7-25-year-olds (M = 15.80). Linear regression evaluated FP-DMN associations with IQ.

Results: We detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ.

Conclusions: FP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.
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http://dx.doi.org/10.1016/j.dcn.2021.100928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848769PMC
April 2021

Obsessive-Compulsive Symptoms Among Children in the Adolescent Brain and Cognitive Development Study: Clinical, Cognitive, and Brain Connectivity Correlates.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 04 6;6(4):399-409. Epub 2020 Nov 6.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.

Background: Childhood obsessive-compulsive symptoms (OCSs) are common and can be an early risk marker for obsessive-compulsive disorder. The Adolescent Brain and Cognitive Development (ABCD) Study provides a unique opportunity to characterize OCSs in a large normative sample of school-age children and to explore corticostriatal and task-control circuits implicated in pediatric obsessive-compulsive disorder.

Methods: The ABCD Study acquired data from 9- and 10-year-olds (N = 11,876). Linear mixed-effects models probed associations between OCSs (Child Behavior Checklist) and cognition (NIH Toolbox), brain structure (subcortical volume, cortical thickness), white matter (diffusion tensor imaging), and resting-state functional connectivity.

Results: OCS scores showed good psychometric properties and high prevalence, and they were related to familial/parental factors, including family conflict. Higher OCS scores related to better cognitive performance (β = .06, t = 6.28, p < .001, η= .01), particularly verbal, when controlling for attention-deficit/hyperactivity disorder, which related to worse performance. OCSs did not significantly relate to brain structure but did relate to lower superior corticostriatal tract fractional anisotropy (β = -.03, t = -3.07, p = .002, η= .02). Higher OCS scores were related to altered functional connectivity, including weaker connectivity within the dorsal attention network (β = -.04, t = -3.71, p < .001, η= .002) and weaker dorsal attention-default mode anticorrelation (β = .04, t = 3.94, p < .001, η = .002). Dorsal attention-default mode connectivity predicted OCS scores at 1 year (β = -.04, t = -2.23, p = .03, η = .03).

Conclusions: OCSs are common and may persist throughout childhood. Corticostriatal connectivity and attention network connectivity are likely mechanisms in the subclinical-to-clinical spectrum of OCSs. Understanding correlates and mechanisms of OCSs may elucidate their role in childhood psychiatric risk and suggest potential utility of neuroimaging, e.g., dorsal attention-default mode connectivity, for identifying children at increased risk for obsessive-compulsive disorder.
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http://dx.doi.org/10.1016/j.bpsc.2020.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035161PMC
April 2021

Network-based functional connectivity predicts response to exposure therapy in unmedicated adults with obsessive-compulsive disorder.

Neuropsychopharmacology 2021 04 14;46(5):1035-1044. Epub 2021 Jan 14.

Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 74, New York, NY, 10032, USA.

Obsessive-compulsive disorder (OCD) is associated with alterations in cortico-striato-thalamo-cortical brain networks, but some resting-state functional magnetic resonance imaging studies report more diffuse alterations in brain connectivity. Few studies have assessed functional connectivity within or between networks across the whole brain in unmedicated OCD patients or how patterns of connectivity predict response to exposure and ritual prevention (EX/RP) therapy, a first-line treatment for OCD. Herein, multiband resting-state functional MRI scans were collected from unmedicated, adult patients with OCD (n = 41) and healthy participants (n = 36); OCD patients were then offered twice weekly EX/RP (17 sessions). A whole-brain-network-based statistic approach was used to identify group differences in resting-state connectivity. We detected altered pre-treatment functional connectivity between task-positive regions in the temporal gyri (middle and superior) and regions of the cingulo-opercular and default networks in individuals with OCD. Signal extraction was performed using a reconstruction independent components analysis and isolated two independent subcomponents (IC1 and IC2) within this altered connectivity. In the OCD group, linear mixed-effects models tested whether IC1 or IC2 values predicted the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across EX/RP treatment. Lower (more different from controls) IC2 score significantly predicted greater symptom reduction with EX/RP (Bonferroni-corrected p = 0.002). Collectively, these findings suggest that an altered balance between task-positive and task-negative regions centered around temporal gyri may contribute to difficulty controlling intrusive thoughts or urges to perform ritualistic behaviors.
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http://dx.doi.org/10.1038/s41386-020-00929-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115173PMC
April 2021

Computational Modeling of Attentional Impairments in Disruptive Mood Dysregulation and Attention-Deficit/Hyperactivity Disorder.

J Am Acad Child Adolesc Psychiatry 2021 05 24;60(5):637-645. Epub 2020 Nov 24.

National Institute of Mental Health, Bethesda, Maryland.

Objective: Computational models provide information about cognitive components underlying behavior. When applied to psychopathology-relevant processes, they offer additional insight to observed differences in behavioral performance. Drift diffusion models have been successfully applied to investigate processing efficiency during binary choice tasks. Using these models, we examine the association between psychopathology (irritability and inattention/hyperactivity) and processing efficiency under different attentional demands.

Method: A total of 187 youths with attention-deficit/hyperactivity disorder (ADHD), disruptive mood dysregulation disorder (DMDD), both disorders, or no major psychopathology (age, mean ± SD, 13.09 ± 2.55 y, 34% female) completed an Eriksen Flanker task. Of these, 87 youths provided complete data on dimensional measures of the core symptom of DMDD (irritability) and those of ADHD (inattention and hyperactivity).

Results: In a categorical diagnosis-based analysis (n = 187), we found significant interactive effects among ADHD, DMDD, and task condition on processing efficiency, whereby changes in processing efficiency between conflict and nonconflict conditions were larger in youths without psychopathology compared with patients. Analysis of symptom severity (n = 87) across diagnoses similarly revealed an interaction between symptom dimensions and task condition on processing efficiency. Irritability moderated the magnitude of association between inattention symptoms and difference in processing efficiency between conflict and nonconflict conditions.

Conclusion: Adapting processing efficiency to cognitive demands may represent a shared cognitive endophenotype for both ADHD and DMDD. Highly irritable and/or inattentive youth may have difficulty adjusting processing efficiency to changing task demands, possibly reflecting impairments in cognitive flexibility.
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http://dx.doi.org/10.1016/j.jaac.2020.08.468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096646PMC
May 2021

Associations between Amygdala-Prefrontal Functional Connectivity and Age Depend on Neighborhood Socioeconomic Status.

Cereb Cortex Commun 2020 23;1(1):tgaa033. Epub 2020 Jul 23.

New York State Psychiatric Institute and Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Although severe early life stress has been shown to accelerate the development of frontolimbic resting-state functional connectivity (RSFC), less is known about the effects of socioeconomic disadvantage, a prolonged and multifaceted stressor. In a cross-sectional study of 127 participants aged 5-25, we examined whether lower neighborhood socioeconomic status (SES; measured by Area Deprivation Index and neighborhood poverty and educational attainment) was associated with prematurely reduced amygdala-ventromedial prefrontal cortex (vmPFC) RSFC. We further tested whether neighborhood SES was more predictive than household SES and whether SES effects on connectivity were associated with anxiety symptoms. We found reduced basolateral amygdala-vmPFC RSFC at earlier ages in participants from more disadvantaged neighborhoods; this effect was unique to neighborhood SES and absent for household SES. Furthermore, this reduced connectivity in more disadvantaged youth and increased connectivity in more advantaged youth were associated with less anxiety; children who deviated from the connectivity pattern associated with their neighborhood SES had more anxiety. These results demonstrate that neighborhood socioeconomic disadvantage is associated with accelerated maturation of amygdala-vmPFC RSFC and suggest that the pathophysiology of pediatric anxiety depends on a child's neighborhood socioeconomic characteristics. Our findings also underscore the importance of examining SES effects in studies of brain development.
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http://dx.doi.org/10.1093/texcom/tgaa033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503474PMC
July 2020

Emotional distractors and attentional control in anxious youth: eye tracking and fMRI data.

Cogn Emot 2021 Feb 21;35(1):110-128. Epub 2020 Sep 21.

Emotion and Development Branch, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.

Attentional control theory suggests that high cognitive demands impair the flexible deployment of attention control in anxious adults, particularly when paired with external threats. Extending this work to pediatric anxiety, we report two studies utilising eye tracking (Study 1) and functional magnetic resonance imaging (Study 2). Both studies use a visual search paradigm to examine anxiety-related differences in the impact of threat on attentional control at varying levels of task difficulty. In Study 1, youth ages 8-18 years ( = 109), completed the paradigm during eye tracking. Results indicated that youth with more severe anxiety took longer to fixate on and identify the target, specifically on difficult trials, compared to youth with less anxiety. However, no anxiety-related effects of emotional distraction (faces) emerged. In Study 2, a separate cohort of 8-18-year-olds ( = 72) completed a similar paradigm during fMRI. Behaviourally, youth with more severe anxiety were slower to respond on searches following non-threatening, compared to threatening, distractors, but this effect did not vary by task difficulty. The same interaction emerged in the neuroimaging analysis in the superior parietal lobule and precentral gyrus-more severe anxiety was associated with greater brain response following non-threatening distractors. Theoretical implications of these inconsistent findings are discussed.
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http://dx.doi.org/10.1080/02699931.2020.1816911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855043PMC
February 2021

Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability.

Hippocampus 2021 Jan 19;31(1):79-88. Epub 2020 Sep 19.

The Division of Child and Adolescent Psychiatry, Department of Psychiatry, The New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, New York, New York, USA.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.
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http://dx.doi.org/10.1002/hipo.23264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749072PMC
January 2021

Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability.

Hippocampus 2021 Jan 19;31(1):79-88. Epub 2020 Sep 19.

The Division of Child and Adolescent Psychiatry, Department of Psychiatry, The New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, New York, New York, USA.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.
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http://dx.doi.org/10.1002/hipo.23264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749072PMC
January 2021

Correction: Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Neuropsychopharmacology 2020 06;45(7):1241

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41386-020-0647-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411037PMC
June 2020

Spatial Network Connectivity and Spatial Reasoning Ability in Children with Nonverbal Learning Disability.

Sci Rep 2020 01 17;10(1):561. Epub 2020 Jan 17.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, 1051 Riverside Drive, New York, NY, 10032, USA.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7-15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.
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http://dx.doi.org/10.1038/s41598-019-56003-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969178PMC
January 2020

Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Neuropsychopharmacology 2020 06 17;45(7):1232-1240. Epub 2020 Jan 17.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12-16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.
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http://dx.doi.org/10.1038/s41386-020-0613-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235012PMC
June 2020

Prenatal exposure to polycyclic aromatic hydrocarbons modifies the effects of early life stress on attention and Thought Problems in late childhood.

J Child Psychol Psychiatry 2020 11 7;61(11):1253-1265. Epub 2020 Jan 7.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

Background: Risk for childhood psychopathology is complex and multifactorial, implicating direct and interacting effects of familial and environmental factors. The role of environmental neurotoxicants in psychiatric risk is of growing concern, including polycyclic aromatic hydrocarbons (PAH), common in air pollution. Prenatal PAH exposure is linked to adverse physical, behavioral, and cognitive outcomes as well as increasing psychiatric risk. It is unclear whether environmental exposures, like PAH, magnify the effects of exposure to early life stress (ELS), a critical risk factor for psychopathology. The current work aimed to test potential interactions between prenatal PAH exposure and psychosocial/socioeconomic stress on psychiatric symptoms in school-age children.

Methods: Data were from the Columbia Center for Children's Environmental Health Mothers and Newborns longitudinal birth cohort study. Prenatal PAH exposure was ascertained though air monitoring during pregnancy and maternal PAH-DNA adducts at delivery. Mothers reported on ELS (child age 5) and on child psychiatric symptoms across childhood (child age 5, 7, 9, and 11) using the Child Behavior Checklist (CBCL).

Results: Significant prenatal airborne PAH × ELS interactions (FDR-corrected) predicted CBCL Attention (β = 0.22, t(307) = 3.47, p < .001, p = .003) and Thought Problems T-scores (β = 0.21, t(307) = 3.29, p = .001, p = .004) at age 11 (n = 319). Relative to those with lower exposure, children with higher prenatal PAH exposure exhibited stronger positive associations between ELS and CBCL Attention and Thought Problem T-scores. This interaction was also significant examining convergent ADHD measures (Conners, DuPaul) and examining maternal PAH-DNA adducts (β = 0.29, t(261) = 2.48, p = .01; n = 273). A three-way interaction with assessment wave indicated that the PAH × ELS interaction on Attention Problems was stronger later in development (β = 0.03, t(1,601) = 2.19, p = .03; n = 477).

Conclusions: Prenatal exposure to PAH, a common neurotoxicant in air pollution, may magnify or sustain the effects of early life psychosocial/socioeconomic stress on psychiatric outcomes later in child development. This work highlights the critical role of air pollution exposure on child mental health.
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http://dx.doi.org/10.1111/jcpp.13189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338249PMC
November 2020

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

J Child Psychol Psychiatry 2020 12 31;61(12):1299-1308. Epub 2019 Dec 31.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

Background: Cognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD.

Methods: Twenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix.

Results: Thinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness.

Conclusions: The current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.
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http://dx.doi.org/10.1111/jcpp.13191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326644PMC
December 2020

Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary study.

Environ Int 2020 01 16;134:105212. Epub 2019 Nov 16.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N = 33). Maternal serum PBDE concentrations (∑PBDE) were measured at 12.2 ± 2.8 weeks gestation (mean ± SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between ∑PBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher ∑PBDE showed reduced GE of the RN; ∑PBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, ∑PBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between ∑PBDE concentrations and reading problems observed previously in older children.
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http://dx.doi.org/10.1016/j.envint.2019.105212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048018PMC
January 2020

Developmental pathways to social anxiety and irritability: The role of the ERN.

Dev Psychopathol 2020 08;32(3):897-907

Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD20892, USA.

Early behaviors that differentiate later biomarkers for psychopathology can guide preventive efforts while also facilitating pathophysiological research. We tested whether error-related negativity (ERN) moderates the link between early behavior and later psychopathology in two early childhood phenotypes: behavioral inhibition and irritability. From ages 2 to 7 years, children (n = 291) were assessed longitudinally for behavioral inhibition (BI) and irritability. Behavioral inhibition was assessed via maternal report and behavioral responses to novelty. Childhood irritability was assessed using the Child Behavior Checklist. At age 12, an electroencephalogram (EEG) was recorded while children performed a flanker task to measure ERN, a neural indicator of error monitoring. Clinical assessments of anxiety and irritability were conducted using questionnaires (i.e., Screen for Child Anxiety Related Disorders and Affective Reactivity Index) and clinical interviews. Error monitoring interacted with early BI and early irritability to predict later psychopathology. Among children with high BI, an enhanced ERN predicted greater social anxiety at age 12. In contrast, children with high childhood irritability and blunted ERN predicted greater irritability at age 12. This converges with previous work and provides novel insight into the specificity of pathways associated with psychopathology.
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http://dx.doi.org/10.1017/S0954579419001329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265174PMC
August 2020

Brain Volume Abnormalities in Youth at High Risk for Depression: Adolescent Brain and Cognitive Development Study.

J Am Acad Child Adolesc Psychiatry 2020 10 18;59(10):1178-1188. Epub 2019 Oct 18.

Columbia University, New York; New York State Psychiatric Institute, New York; Division of Clinical Developmental Neuroscience, Sackler Institute, New York. Electronic address:

Objective: Children of parents with depression are two to three times more likely to develop major depressive disorder than children without parental history; however, subcortical brain volume abnormalities characterizing major depressive disorder risk remain unclear. The Adolescent Brain and Cognitive Development (ABCD) Study provides an opportunity to identify subcortical differences associated with parental depressive history.

Method: Structural magnetic resonance data were acquired from 9- and 10-year-old children (N = 11,876; release 1.1, n = 4,521; release 2.0.1, n = 7,355). Approximately one-third of the children had a parental depressive history, providing sufficient power to test differences in subcortical brain volume between low- and high-risk youths. Children from release 1.1 were examined as a discovery sample, and we sought to replicate effects in release 2.0.1. Secondary analyses tested group differences in the prevalence of depressive disorders and clarified whether subcortical brain differences were present in youths with a lifetime depressive disorder history.

Results: Parental depressive history was related to smaller right putamen volume in the discovery (release 1.1; d = -0.10) and replication (release 2.0.1; d = -0.10) samples. However, in release 1.1, this effect was driven by maternal depressive history (d = -0.14), whereas in release 2.0.1, paternal depressive history showed a stronger relationship with putamen volume (d = -0.09). Furthermore, high-risk children exhibited a near twofold greater occurrence of depressive disorders relative to low-risk youths (maternal history odds ratio =1.99; paternal history odds ratio = 1.45), but youths with a lifetime depressive history did not exhibit significant subcortical abnormalities.

Conclusion: A parental depressive history was associated with smaller putamen volume, which may affect reward learning processes that confer increased risk for major depressive disorder.
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http://dx.doi.org/10.1016/j.jaac.2019.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165045PMC
October 2020

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder.

Proc Natl Acad Sci U S A 2019 10 23;116(41):20346-20353. Epub 2019 Sep 23.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY 10032.

Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD ( = 36) and healthy participants ( = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen's 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = -2.99; 43.61% of total effect; = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.
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http://dx.doi.org/10.1073/pnas.1909199116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789627PMC
October 2019

Efficacy and mechanisms underlying a gamified attention bias modification training in anxious youth: protocol for a randomized controlled trial.

BMC Psychiatry 2019 08 7;19(1):246. Epub 2019 Aug 7.

Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, 9000 Rockville Pike, MSC-2670, Building 15K, Bethesda, MD, 20892-2670, USA.

Background: Attention bias modification training (ABMT) and cognitive behavioral therapy (CBT) likely target different aspects of aberrant threat responses in anxiety disorders and may be combined to maximize therapeutic benefit. However, studies investigating the effect of ABMT in the context of CBT have yielded mixed results. Here, we propose an enhanced ABMT to target the attentional bias towards threat, in addition to classic CBT for anxiety disorders in youth. This enhanced ABMT integrates the modified dot-probe task used in previous studies, where a target is always presented at the previous location of the neutral and not the simultaneously presented threatening stimulus, with a visual search, where the targets are always presented distally of threatening distractors. These two training elements (modified dot-probe and visual search) are embedded in an engaging game to foster motivation and adherence. Our goal is to determine the efficacy of the enhanced ABMT in the context of CBT. Further, we aim to replicate two previous findings: (a) aberrant amygdala connectivity being the neurobiological correlate of the attentional bias towards threat at baseline; and (b) amygdala connectivity being a mediator of the ABMT effect. We will also explore moderators of treatment response (age, sex, depressive symptoms and irritability) on a behavioral and neuronal level.

Methods: One hundred and twenty youth (8-17 years old) with a primary anxiety disorder diagnosis all receive CBT and are randomized to nine weeks of either active or control ABMT and symptom improvement will be compared between the two study arms. We will also recruit 60 healthy comparison youth, who along with eligible anxious youth, will be assessed with the dot-probe task during fMRI (anxious youth: before and after training; healthy volunteers: second measurement twelve weeks after initial assessment).

Discussion: The present study will contribute to the literature by (1) potentially replicating that aberrant amygdala connectivity mediates the attentional bias towards threat in anxious youth; (2) determining the efficacy of enhanced ABMT; and (3) advancing our understanding of the mechanisms underlying ABMT.

Trial Registration: Clinicaltrials.gov: NCT03283930 Trial registration date: September 14th 2017. The trial registration took place retrospectively. Data acquisition started February 1st 2017.
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http://dx.doi.org/10.1186/s12888-019-2224-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686536PMC
August 2019

Cross-species convergence in pupillary response: understanding human anxiety via non-human primate amygdala lesion.

Soc Cogn Affect Neurosci 2019 08;14(6):591-599

Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

Few studies have used matched affective paradigms to compare humans and non-human primates. In monkeys with amygdala lesions and youth with anxiety disorders, we examined cross-species pupillary responses during a saccade-based, affective attentional capture task. Given evidence of enhanced amygdala function in anxiety, we hypothesized that opposite patterns would emerge in lesioned monkeys and anxious participants. A total of 53 unmedicated youths (27 anxious, 26 healthy) and 8 adult male rhesus monkeys (Macaca mulatta) completed matched behavioral paradigms. Four monkeys received bilateral excitotoxic amygdala lesions and four served as unoperated controls. Compared to healthy youth, anxious youth exhibited increased pupillary constriction in response to emotional and non-emotional distractors (F(1,48) = 6.28, P = 0.02, η2p = 0.12). Pupillary response was associated significantly with anxiety symptoms severity (F(1,48) = 5.59, P = 0.02, η2p = 0.10). As hypothesized, lesioned monkeys exhibited the opposite pattern i.e. decreased pupillary constriction in response to distractors, compared to unoperated control monkeys (F(1,32) = 24.22, P < 0.001, η2 = 0.33). Amygdala lesioned monkeys and youth with anxiety disorders show opposite patterns of pupil constriction in the context of an affective distractor task. Such findings suggest the presence of altered amygdala circuitry functioning in anxiety. Future lesion and human neuroimaging work might examine the way in which specific amygdala sub-nuclei and downstream circuits mediate these effects.
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http://dx.doi.org/10.1093/scan/nsz041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688453PMC
August 2019

Neural correlates of cognitive control deficits in children with reading disorder.

Brain Imaging Behav 2020 Oct;14(5):1531-1542

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, Unit 74. 10032, 1051 Riverside Drive, New York, NY, USA.

Reading disorder (RD) is characterized by deficient phonological processing, but children with RD also have cognitive control deficits, the neural correlates of which are not fully understood. We used fMRI to assess neural activity during the resolution of cognitive conflict on the Simon Spatial Incompatibility task and patterns of resting-state functional connectivity (RSFC) from task control (TC) regions in 7-12-year-old children with RD compared to their typically developing (TD) peers. Relative to TD children (n = 17), those with RD (n = 16) over-engaged a right superior/medial frontal cluster during the resolution of conflict (p = .05). Relative to TD children (n = 18), those with RD (n = 17) also showed reduced RSFC (voxel-wise p < .001; cluster-size p < .05, FDR corrected) from cingulo-opercular seeds to left hemisphere fronto-parietal and temporo-parietal reading-related regions, perhaps reflecting reduced organization of TC circuits and reduced integration with reading-related regions. Children with RD additionally showed reduced RSFC between fronto-parietal and default mode network regions. Follow-up analyses in a subset of children with both useable task and resting state data (RD = 13; TD = 17) revealed that greater conflict-related activation of the right frontal Simon task ROI associated with better word-reading, perhaps suggesting a compensatory role for this over-engagement. Connectivity from fronto-parietal seeds significantly associated with Simon task performance and word-reading accuracy in RD children. These findings suggest that altered functioning and connectivity of control circuits may contribute to cognitive control deficits in children with RD. Future studies should assess the utility of adding cognitive control training to reading remediation programs.
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http://dx.doi.org/10.1007/s11682-019-00083-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765445PMC
October 2020

Toward an Improved Understanding of Anhedonia.

JAMA Psychiatry 2019 06;76(6):571-573

Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts.

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http://dx.doi.org/10.1001/jamapsychiatry.2018.4600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817369PMC
June 2019

The Screen for Child Anxiety Related Emotional Disorders (SCARED): Informant Discrepancy, Measurement Invariance, and Test-Retest Reliability.

Child Psychiatry Hum Dev 2019 06;50(3):473-482

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, 10032, USA.

The Screen for Child Anxiety Related Emotional Disorders (SCARED) is a measure widely used to assess childhood anxiety based on parent and child report. However, while the SCARED is a reliable, valid, and sensitive measure to screen for pediatric anxiety disorders, informant discrepancy can pose clinical and research challenges. The present study assesses informant discrepancy, measurement invariance, test-retest reliability, and external validity of the SCARED in 1092 anxious and healthy parent-child dyads. Our findings indicate that discrepancy does not vary systematically by the various clinical, demographic, and familial variables examined. There was support for strict measurement invariance, strong test-retest reliability, and adequate external validity with a clinician-rated measure of anxiety. These findings further support the utility of the SCARED in clinical and research settings, but low parent-child agreement highlights the need for further investigation of factors contributing to SCARED informant discrepancy.
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http://dx.doi.org/10.1007/s10578-018-0854-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339086PMC
June 2019

Salience network connectivity and social processing in children with nonverbal learning disability or autism spectrum disorder.

Neuropsychology 2019 Jan 8;33(1):135-143. Epub 2018 Nov 8.

Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University Irving Medical Center.

Objective: Nonverbal learning disability (NVLD) is a putative neurodevelopmental disorder characterized by spatial processing deficits as well as social deficits similar to those characteristic of autism spectrum disorder (ASD). Nonetheless, NVLD may be a distinct disorder that is differentially associated with the functioning and connectivity of the salience (SN) and default mode (DMN) networks that support social processing. Thus, we sought to assess and compare connectivity across these networks in children with NVLD, ASD, and typically developing children.

Method: Resting-state fMRI data were examined in 17 children with NVLD, 17 children with ASD selected from the Autism Brain Imaging Data Exchange (ABIDE), and 40 TD children (20 from ABIDE). Average DMN and SN functional connectivity and pairwise region-to-region connectivity were compared across groups. Associations with social impairment and IQ were assessed.

Results: Children with NVLD showed reduced connectivity between SN regions (anterior insula to anterior cingulate and to rostral prefrontal cortex [rPFC]), whereas children with ASD showed greater connectivity between SN regions (supramarginal gyrus to rPFC) relative to the other groups. Both clinical groups showed higher levels of parent-reported social problems, which related to altered SN connectivity in the NVLD group. No differences were detected in overall average connectivity within or between networks.

Conclusions: The social deficits common across children with NVLD and ASD may derive from distinct alterations in connectivity within the SN. Such findings represent the first step toward identifying a neurobiological signature of NVLD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322976PMC
January 2019

Greater Response Interference to Pain Faces Under Low Perceptual Load Conditions in Adolescents With Impairing Pain: A Role for Poor Attention Control Mechanisms in Pain Disability?

J Pain 2019 04 29;20(4):453-461. Epub 2018 Oct 29.

Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, Maryland.

Persistent pain in young people in the community is common, but individuals vary in how much pain impacts daily life. Information-processing accounts of chronic pain partly attribute the fear and avoidance of pain, as well as associated interference, to a set of involuntary biases, including the preferential allocation of attention resources toward potential threats. Far less research has focused on the role of voluntary goal-directed attention control processes, the ability to flexibly direct attention toward and away from threats, in explaining pain-associated interference. Using a visual search task, we explored a poor attention control account of pain interference in young people with persistent pain from the community. One hundred and forty five young people aged 16 to 19 years were categorized into three groups: non-chronic pain (n = 68), low-interfering persistent pain (n = 40), and moderate- to high-interfering persistent pain (n = 22). We found that only adolescents with moderate-to high-interfering persistent pain but not the other two groups of adolescents were affected by a search task preceded by a pain face (compared to a neutral face), but this within-group difference emerged only under low perceptual load conditions. Because low perceptual load conditions are thought to require more strategic attention resources to suppress the interfering effects of pain face primes, our findings are consistent with a poor attention control account of pain interference in young people. Analyses further showed that these differences in task performance were not explained by confounding effects of anxiety. If replicated, these findings may have implications for understanding and managing the pain-associated disability in adolescents with chronic pain. PERSPECTIVE: Young people with moderately and highly interfering pain responded slower on an easy search task after seeing a pain face than after seeing a neutral face. If replicated, these findings could mean that boosting the ability to control attention toward and away from threatening cues is an effective strategy for managing interference from pain.
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http://dx.doi.org/10.1016/j.jpain.2018.10.005DOI Listing
April 2019

Temporally sensitive neural measures of inhibition in preschool children across a spectrum of irritability.

Dev Psychobiol 2019 03 17;61(2):216-227. Epub 2018 Oct 17.

Department of Medical Social Sciences, Northwestern University, Chicago, Illinois.

Irritability is a prominent feature of chronic mental disorders and a developmental marker of their early emergence. The most salient feature of irritability in early childhood is temper tantrums. While temper tantrums are normative in young children, they can be clinically concerning when they are dysregulated, very frequent, and/or occur in unexpected contexts. The present study uses behavioral and event-related brain potential (ERP) measures to characterize the relationship between irritability and neural markers of response inhibition in very young children. Forty-six children (ages 4-7 years) completed a go/no-go task under nonfrustrating and frustrating conditions. ERPs elicited by go and no-go stimuli were examined as a function of frustration condition and irritability, operationalized via the well-validated Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB). Higher Temper Loss scores were associated with larger N2 amplitudes and reduced no-go accuracy during frustration. This suggests that higher levels of irritability corresponded with increased conflict monitoring and poorer task performance during frustration. These findings add to a developing literature identifying the neurocognitive markers of varying levels of irritability in young children.
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http://dx.doi.org/10.1002/dev.21792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147937PMC
March 2019

Irritability Trajectories, Cortical Thickness, and Clinical Outcomes in a Sample Enriched for Preschool Depression.

J Am Acad Child Adolesc Psychiatry 2018 05 16;57(5):336-342.e6. Epub 2018 Mar 16.

Emotion and Development Branch, National Institute of Mental Health (NIMH), Bethesda, MD.

Objective: Cross-sectional, longitudinal, and genetic associations exist between irritability and depression. Prior studies have examined developmental trajectories of irritability, clinical outcomes, and associations with child and familial depression. However, studies have not integrated neurobiological measures. The present study examined developmental trajectories of irritability, clinical outcomes, and cortical structure among preschoolers oversampled for depressive symptoms.

Method: Beginning at 3 to 5 years old, a sample of 271 children enriched for early depressive symptoms were assessed longitudinally by clinical interview. Latent class mixture models identified trajectories of irritability severity. Risk factors, clinical outcomes, and cortical thickness were compared across trajectory classes. Cortical thickness measures were extracted from 3 waves of magnetic resonance imaging at 7 to 12 years of age.

Results: Three trajectory classes were identified among these youth: 53.50% of children exhibited elevated irritability during preschool that decreased longitudinally, 30.26% exhibited consistently low irritability, and 16.24% exhibited consistently elevated irritability. Compared with other classes, the elevated irritability class exhibited higher rates of maternal depression, early life adversity, later psychiatric diagnoses, and functional impairment. Further, elevated baseline irritability predicted later depression beyond adversity and personal and maternal depression history. The elevated irritability class exhibited a thicker cortex in the left superior frontal and temporal gyri and the right inferior parietal lobule.

Conclusion: Irritability manifested with specific developmental trajectories in this sample enriched for early depression. Persistently elevated irritability predicted poor psychiatric outcomes, higher risk for later depression, and decreased overall function later in development. Greater frontal, temporal, and parietal cortical thickness also was found, providing neural correlates of this risk trajectory.
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http://dx.doi.org/10.1016/j.jaac.2018.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932635PMC
May 2018