Characterization of executive function dimensions across pediatric psychiatric disorders
Characterization of executive function dimensions across pediatric psychiatric disorders
批准号:
9471432
负责人:
LAUREN KENWORTHY
金额:
$38.55万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-19 至 2021-04-30
关键词:
13 year oldAccountingAddressAmygdaloid structureAnxiety DisordersArousalAttention deficit hyperactivity disorderBackBehaviorBehavior TherapyBehavioralBrainCategoriesChildChild Behavior ChecklistChildhoodClassificationClinicClinicalCommunitiesComorbidityCorpus striatum structureDataDetectionDiagnosisDiagnosticDimensionsDiseaseDisruptive Behavior DisorderDorsalEmotionalEquipment and supply inventoriesExecutive DysfunctionFactor AnalysisFailureFunctional Magnetic Resonance ImagingGenerationsGilles de la Tourette syndromeGoalsHeterogeneityHyperactive behaviorImpairmentImpulsive BehaviorImpulsivityInterventionLateralLearning DisabilitiesLifeLinkMachine LearningMeasuresMediatingMedicalMedical centerMental disordersMethodsMood DisordersNatureNeurobiologyNeuropsychologyOutcomeOutpatientsParentsParietalPathway interactionsPatient Self-ReportPatternPhenotypePopulationProcessPropertyPsychiatric DiagnosisQuality of lifeReportingResearch Domain CriteriaRestRiskServicesShort-Term MemorySymptomsSystemTestingThinkingTic disorderTrainingWorkassociated symptomautism spectrum disorderbaseclinical practiceclinically significantcognitive controlcognitive systemcohortcomparison groupdimensional analysisdisease classificationemotion regulationexecutive functionfallsflexibilitygraph theoryinattentionneural circuitnovelpersonalized approachrecruitresponseskillssocialsuccessteachertreatment effect
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
The proposal responds to RFA-MH-16-510 by focusing on the domain of “Cognitive Systems” and constructs
“cognitive control” and “working memory” and integrating units of analysis “brain circuit” and “behavior”. These
constructs are subsumed under executive function (EF), the ability to voluntarily constrain thoughts and actions
in the service of goals. Among pediatric psychiatric categories, EF deficits define Attention Deficit Hyperactivity
Disorder (ADHD) and are comorbid with a variety disorders, including Autism Spectrum Disorders, disruptive
behavior disorders, mood and anxiety disorders, Tourette's/tics, and learning disabilities. Across these
disorders, EF deficits limit adaptive functioning and success of behavioral intervention. Ameliorating EF
deficits is a challenge, however, because current EF nosology falls short of capturing heterogeneity
within and across disorders. The primary challenge then is identifying the dimensions of EF that
capture the specific nature of impairment across disorders. Most past approaches utilize dimension-
reducing methods that are sensitive to shared variance, but exclude unique variance. Here, we address
this challenge through novel data-driven generation of behavioral profile-based EF dimensions derived from
graph theory community-detection (following [1, 2]), applied to common clinical parent-report measures (ADHD
Rating scale, inattention, hyperactivity/impulsivity, 8 Behavior Rating Inventory of Executive Function
subdomains, Child Behavior Checklist internalizing, and externalizing). Community-detection applied to N=322
(8-13 yrs; IQ>70; no “medical” diagnosis) presenting at Children's National Medical Center neuropsychology
clinics identified three EF profiles distinguished by deficits and relative strengths: 1) poor working memory;
good flexibility and inhibition; 2) poor inhibition; good working memory; 3) poor flexibility and emotion
regulation; good working memory. We will recruit from this growing cohort to examine: Aim 1 – seek
replication by testing a new larger cohort with support vector machine classification trained on
preliminary data. Aim 2 - characterize functional networks distinguishing the 3 profiles, by group
comparison and dimensional analysis. Task-based functional connectivity will test hypothesis about specific
circuits distinguishing the novel EF dimensions using fMRI during: 1) N-back working memory; 2) Response
inhibition; and 3) Adaptive socio-emotional cognitive control. Task-free resting-state fMRI will test hypothesis
about large-scale network interaction differences between EF dimensions. Aim 3 - test the hypothesis that
the novel EF dimensions are associated with specific domains of adaptive function, mediated by
specific functional networks. Results will: 1) provide neurobiologically validated EF dimensions for re-
conceptualizing pediatric psychiatric nosology, and 2) identify treatment targets and increase precision in
measuring treatment effects – i.e., who should receive what treatment and how to best measure response and
outcome, both of which are essential to the success of a personalized approach to clinical practice.
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依托单位:
海外基金