Faculty Bibliography
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395
A practical Alzheimer"™s disease classifier via brain imaging-based deep learning on 85,721 samples
Beyond detecting brain lesions or tumors, comparatively little success has been attained in identifying brain disorders such as Alzheimer"™s disease (AD), based on magnetic resonance imaging (MRI). Many machine learning algorithms to detect AD have been trained using limited training data, meaning they often generalize poorly when applied to scans from previously unseen scanners/populations. Therefore, we built a practical brain MRI-based AD diagnostic classifier using deep learning/transfer learning on a dataset of unprecedented size and diversity. A retrospective MRI dataset pooled from more than 217 sites/scanners constituted one of the largest brain MRI samples to date (85,721 scans from 50,876 participants) between January 2017 and August 2021. Next, a state-of-the-art deep convolutional neural network, Inception-ResNet-V2, was built as a sex classifier with high generalization capability. The sex classifier achieved 94.9% accuracy and served as a base model in transfer learning for the objective diagnosis of AD. After transfer learning, the model fine-tuned for AD classification achieved 90.9% accuracy in leave-sites-out cross-validation on the Alzheimer"™s Disease Neuroimaging Initiative (ADNI, 6,857 samples) dataset and 94.5%/93.6%/91.1% accuracy for direct tests on three unseen independent datasets (AIBL, 669 samples / MIRIAD, 644 samples / OASIS, 1,123 samples). When this AD classifier was tested on brain images from unseen mild cognitive impairment (MCI) patients, MCI patients who converted to AD were 3 times more likely to be predicted as AD than MCI patients who did not convert (65.2% vs. 20.6%). Predicted scores from the AD classifier showed significant correlations with illness severity. In sum, the proposed AD classifier offers a medical-grade marker that has potential to be integrated into AD diagnostic practice.
SCOPUS:85139957866
ISSN: 2196-1115
CID: 5350292
Journal of the American Academy of Child & Adolescent Psychiatry. 2022:61(11):1372-1384.DOI: 10.1016/j.jaac.2022.03.035
Cerebro-cerebellar Dysconnectivity in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
OBJECTIVE:Abnormal cerebellar development has been implicated in Attention-Deficit/Hyperactivity Disorder (ADHD), although cerebro-cerebellar functional connectivity (FC) has yet to be examined in ADHD. Our objective is to investigate the disturbed cerebro-cerebellar FC in children and adolescents with ADHD. METHOD/METHODS:We analyzed the dataset of 106 individuals with ADHD (68 children, 38 adolescents) and 62 healthy comparisons (34 children, 28 adolescents) from the publicly available ADHD-200 dataset. We identified seven cerebellar sub-regions based on cerebro-cerebellar FC and subsequently obtained the FC maps of cerebro-cerebellar networks. Main effects of ADHD and age and their interaction were examined using two-way analysis of variance. RESULTS:Compared to comparisons, ADHD showed higher cerebro-cerebellar FC in superior temporal gyrus within the somatomotor network. Interactions of diagnosis and age were identified in the supplementary motor area and postcentral gyrus within the somatomotor network and middle temporal gyrus within the ventral attention network. Follow-up Pearson correlation analysis revealed decreased cerebro-cerebellar FC in these regions with increasing age in comparisons, while the opposite pattern of increased cerebro-cerebellar FC occurred in ADHD. CONCLUSION/CONCLUSIONS:Increased cerebro-cerebellar FC in superior temporal gyrus within the somatomotor network could underlie impairments in cognitive control and somatic motor function in ADHD. In addition, increasing cerebro-cerebellar FC in older participants with ADHD suggests that enhanced cerebellar involvement may compensate for dysfunctions of the cerebral cortex in ADHD.
PMID: 35661770
ISSN: 1527-5418
CID: 5236272
Journal of the American Academy of Child & Adolescent Psychiatry. 2022:Conference:(The).DOI: 10.1016/j.jaac.2022.09.109
1.93 Testing Continued Effectiveness Through Multiple Modifications of an Empirically Supported Treatment for Organization, Time Management, and Planning Deficits in ADHD and Related Disorders [Meeting Abstract]
Objectives: Organizational skills training (OST) for youth with ADHD is an efficacious treatment that addresses impairments at home and in school. Modifications of OST were conducted to treat children with or without ADHD, to reduce treatment barriers, and to respond to changes in school demands during the COVID-19 pandemic.
Method(s): After an initial RCT documenting OST efficacy, 3 further studies involved: 1) an open replication of the original RCT confirming improvements in organization, time management, and planning (OTMP) in children diagnosed with ADHD (N = 15) using twice-weekly in-person visits; 2) a subsequent open trial investigating children with deficient organizational skills with or without ADHD and altering delivery to involve a combination of in-person and virtual meetings (N = 29); and 3) a third study with subjects with low OTMP skills who do not necessarily have ADHD, receive treatment with combined in-person and virtual delivery or, in response to COVID-19 restrictions, fully virtual delivery (N = 27, thus far), and, in response to remote school delivery, have altered OST content to fit varied school instruction demands (eg, use of electronic documents instead of papers) while adhering to the principles of OST. Change was measured on the Children's Organizational Skills Scales (COSS).
Result(s): 1) Improvements in OTMP skills (parent ratings d = 3.73; teacher ratings d = 1.12) in the first open study were comparable to the initial RCT findings. 2) In study 2, parents also reported substantial improvements (d = 3.04), and teachers reported large changes (d = 0.88) in pre-post comparisons. 3) In the ongoing RCT, subjects who received treatment immediately were reported to have large changes by parents (d = 2.17) and moderate changes by teachers (d = 0.47) when compared to waitlist controls.
Conclusion(s): Initial analyses indicate that OST leads to OTMP improvements in children struggling with disorganization with and without ADHD diagnosis. Improvements are found when treatment is delivered fully in-person, delivered in hybrid in-person and virtual meetings, or delivered fully virtually. OST could help children with or without ADHD improve behavioral and emotional adjustment at home and in school, when treatment delivery is modified to increase treatment availability, and when school demands are varied. ADHD, CBT, EBP
Copyright
Method(s): After an initial RCT documenting OST efficacy, 3 further studies involved: 1) an open replication of the original RCT confirming improvements in organization, time management, and planning (OTMP) in children diagnosed with ADHD (N = 15) using twice-weekly in-person visits; 2) a subsequent open trial investigating children with deficient organizational skills with or without ADHD and altering delivery to involve a combination of in-person and virtual meetings (N = 29); and 3) a third study with subjects with low OTMP skills who do not necessarily have ADHD, receive treatment with combined in-person and virtual delivery or, in response to COVID-19 restrictions, fully virtual delivery (N = 27, thus far), and, in response to remote school delivery, have altered OST content to fit varied school instruction demands (eg, use of electronic documents instead of papers) while adhering to the principles of OST. Change was measured on the Children's Organizational Skills Scales (COSS).
Result(s): 1) Improvements in OTMP skills (parent ratings d = 3.73; teacher ratings d = 1.12) in the first open study were comparable to the initial RCT findings. 2) In study 2, parents also reported substantial improvements (d = 3.04), and teachers reported large changes (d = 0.88) in pre-post comparisons. 3) In the ongoing RCT, subjects who received treatment immediately were reported to have large changes by parents (d = 2.17) and moderate changes by teachers (d = 0.47) when compared to waitlist controls.
Conclusion(s): Initial analyses indicate that OST leads to OTMP improvements in children struggling with disorganization with and without ADHD diagnosis. Improvements are found when treatment is delivered fully in-person, delivered in hybrid in-person and virtual meetings, or delivered fully virtually. OST could help children with or without ADHD improve behavioral and emotional adjustment at home and in school, when treatment delivery is modified to increase treatment availability, and when school demands are varied. ADHD, CBT, EBP
Copyright
EMBASE:2020631768
ISSN: 1527-5418
CID: 5511342
Virtual Ontogeny of Cortical Growth Preceding Mental Illness
BACKGROUND:Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS:Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS:Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS:Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
PMID: 35489875
ISSN: 1873-2402
CID: 5217792
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
