Faculty Bibliography
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411
Exploring self-generated thoughts in a resting state with natural language processing
The present study seeks to examine individuals' stream of thought in real time. Specifically, we asked participants to speak their thoughts freely out loud during a typical resting-state condition. We first examined the feasibility and reliability of the method and found that the oral reporting method did not significantly change the frequency or content characteristics of self-generated thoughts; moreover, its test-retest reliability was high. Based on methodological feasibility, we combined natural language processing (NLP) with the Bidirectional Encoder Representation from Transformers (BERT) model to directly quantify thought content. We analyzed the divergence of self-generated thought content and expressions of sadness and empirically verified the validity and behavioral significance of the metrics calculated by BERT. Furthermore, we found that reflection and brooding could be differentiated by detecting the divergence of self-generated thought content and expressions of sadness, thus deepening our understanding of rumination and depression and providing a way to distinguish adaptive from maladaptive rumination. Finally, this study provides a new framework to examine self-generated thoughts in a resting state with NLP, extending research on the continuous content of instant self-generated thoughts with applicability to resting-state functional brain imaging.
PMID: 34647279
ISSN: 1554-3528
CID: 5068022
A longitudinal resource for studying connectome development and its psychiatric associations during childhood
Most psychiatric disorders are chronic, associated with high levels of disability and distress, and present during pediatric development. Scientific innovation increasingly allows researchers to probe brain-behavior relationships in the developing human. As a result, ambitions to (1) establish normative pediatric brain development trajectories akin to growth curves, (2) characterize reliable metrics for distinguishing illness, and (3) develop clinically useful tools to assist in the diagnosis and management of mental health and learning disorders have gained significant momentum. To this end, the NKI-Rockland Sample initiative was created to probe lifespan development as a large-scale multimodal dataset. The NKI-Rockland Sample Longitudinal Discovery of Brain Development Trajectories substudy (N = 369) is a 24- to 30-month multi-cohort longitudinal pediatric investigation (ages 6.0-17.0 at enrollment) carried out in a community-ascertained sample. Data include psychiatric diagnostic, medical, behavioral, and cognitive phenotyping, as well as multimodal brain imaging (resting fMRI, diffusion MRI, morphometric MRI, arterial spin labeling), genetics, and actigraphy. Herein, we present the rationale, design, and implementation of the Longitudinal Discovery of Brain Development Trajectories protocol.
PMCID:9197863
PMID: 35701428
ISSN: 2052-4463
CID: 5277832
Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder
The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.
PMCID:9170720
PMID: 35668086
ISSN: 2158-3188
CID: 5277702
Investigating Motor Preparation in Autism Spectrum Disorder With and Without Attention Deficit/Hyperactivity Disorder
This study investigated motor preparation and action-consequence prediction using the lateralized readiness potential (LRP). Motor impairments are common in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. Alterations in predictive processes may impact motor planning. Whether motor planning deficits are characteristic of ASD broadly or magnified in the context of co-morbid ADHD is unclear. ASD children with (ASD + ADHD; n = 12) and without (ASD - ADHD; n = 9) comorbid ADHD and typical controls (n = 29) performed voluntary motor actions that either did or did not result in auditory consequences. ASD - ADHD children demonstrated LRP enhancement when their action produced an effect while ASD + ADHD children had attenuated responses regardless of action-effect pairings. Findings suggest influence of ADHD comorbidity on motor preparation and prediction in ASD.
PMID: 34160725
ISSN: 1573-3432
CID: 4965562
[Skeptical review of the state of neuroimaging in attention deficit hyperactivity disorder]
Attention-deficit/hyperactivity disorder (ADHD) has been the focus of magnetic resonance imaging studies for more than 30 years, with more than 2200 articles listed in PubMed. Nevertheless, the brain substrates of ADHD remain poorly understood. This reflects the crisis of replicability across nearly all scientific endeavors, deriving from factors such as small sample sizes combined with a proliferation in analytical approaches, yielding high rates of false positive results. The field of molecular genetics confronted this by adopting open and immediate sharing of raw data and insistence on rigorous corrections for multiple comparisons. These strategies are yielding more robust genetic findings, albeit with much smaller effect sizes than before. This brief review focuses on two recent consortium efforts, i.e., the international Enhancing Neuro-Imaging Genetics through Meta-Analysis (ENIGMA), and the U.S. Adolescent Behavior & Cognitive Developm ent Study (ABCD). Both embrace the culture of open science, and are beginning to yield credible findings, despite being limited initially to cross-sectional analyses. As the field continues to mature, these and other ongoing longitudinal large-scale studies are poised to transform our understanding of the pathophysiology of ADHD to bring closer the day when neuroimaging can contribute to clinical utility.
PMID: 35171804
ISSN: 1669-9106
CID: 5175662
Trends in ASD Pharmacological Research: An Analysis of ClinicalTrials.gov
Despite decades of research, both understanding and availability of pharmacological interventions for autistic people are limited. We examined characteristics of pharmacological trials on ClinicalTrials.gov (N = 235) to elucidate trends, identify gaps, and suggest future research directions. We observed that trials predominantly sampled school-aged children and adolescents and focused largely on core autism symptoms, neglecting younger children and adults as well as associated symptom domains often identified by stakeholders as treatment priorities. A variety of intervention agents were trialed, with nearly 60% appearing in just one study. Notably, in line with previous research, there was little consistency in outcome measures used, with the majority (58.9%) used in only one trial. Innovation in research strategies is urgently needed; potential directions for such changes are discussed.
SCOPUS:85122512584
ISSN: 2195-7177
CID: 5145062
Greater male than female variability in regional brain structure across the lifespan
For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
PMID: 33044802
ISSN: 1097-0193
CID: 4632482
Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years
Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
PMID: 33595143
ISSN: 1097-0193
CID: 4799902
Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years
Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
PMID: 33570244
ISSN: 1097-0193
CID: 4799802
Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure
Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.
PMID: 32420680
ISSN: 1097-0193
CID: 4446612
