The National Institute of Mental Health (NIMH) proposed the Research Domain Criteria (RDoC) initiative as an alternate way to organize research of mental illnesses, by looking at dimensions of functioning rather than being tied to categorical diagnoses. This paper briefly discusses the motivation for and organization of RDoC, and then explores the NIMH portfolio and recent work to monitor the utility and progress that RDoC has afforded developmental research. To examine how RDoC has influenced the NIMH developmental research portfolio over the last decade, we employed a natural language processing algorithm to identify the number of developmental science grants classified as incorporating an RDoC approach. Additional portfolio analyses examine temporal trends in funded RDoC‐relevant grants, publications and citations, and research training opportunities. Reflecting on how RDoC has influenced the focus of grant applications, we highlight examples from research on Attention‐Deficit Hyperactivity Disorder (ADHD), childhood irritability, and Autism Spectrum Disorder (ASD). Lastly, we consider how the dimensional and transdiagnostic approaches emphasized in RDoC have facilitated research on personalized intervention for heterogeneous disorders and preventive/early interventions targeting emergent or subthreshold psychopathology.
We examined whether modulation of functional connectivity by cognitive state differed between pre-adolescent children with Autism Spectrum Disorders (ASD) and age and IQ-matched control children. Children underwent functional magnetic resonance imaging (fMRI) during two states, a resting state followed by a sustained attention task. A voxel-wise method was used to characterize functional connectivity at two levels, local (within a voxel's 14 mm neighborhood) and distant (outside of the voxel's 14 mm neighborhood to the rest of the brain) and regions exhibiting Group × State interaction were identified for both types of connectivity maps. Distant functional connectivity of regions in the left frontal lobe (dorsolateral [BA 11, 10]; supplementary motor area extending into dorsal anterior cingulate [BA 32/8]; and premotor [BA 6, 8, 9]), right parietal lobe (paracentral lobule [BA 6]; angular gyrus [BA 39/40]), and left posterior middle temporal cortex (BA 19/39) showed a Group × State interaction such that relative to the resting state, connectivity reduced (i.e., became focal) in control children but increased (i.e., became diffuse) in ASD children during the task state. Higher state-related increase in distant connectivity of left frontal and right angular gyrus predicted worse inattention in ASD children. Two graph theory measures (global efficiency and modularity) were also sensitive to Group × State differences, with the magnitude of state-related change predicting inattention in the ASD children. Our results indicate that as ASD children transition from an unconstrained to a sustained attentional state, functional connectivity of frontal and parietal regions with the rest of the brain becomes more widespread in a manner that may be maladaptive as it was associated with attention problems in everyday life.
Studies suggest that the affective response is impaired in both schizophrenia and adolescent offspring of schizophrenia patients. Adolescent offspring of patients are developmentally vulnerable to impairments in several domains, including affective responding, yet the bases of these impairments and their relation to neuronal responses within the limbic system are poorly understood. The amygdala is the central region devoted to the processing of emotional valence and its sub-nuclei including the baso-lateral and centro-medial are organized in a relative hierarchy of affective processing. Outputs from the centro-medial nucleus converge on regions involved in the autonomous regulation of behavior, and outputs from the basolateral nucleus modulate the response of reward processing regions. Here using fMRI we assessed the intra-amygdala response to positive, negative, and neutral valenced faces in a group of controls (with no family history of psychosis) and offspring of schizophrenia parents (n=44 subjects in total). Subjects performed an affective continuous performance task during which they continually appraised whether the affect signaled by a face on a given trial was the same or different from the previous trial (regardless of facial identity). Relative to controls, offspring showed reduced activity in the left centro-medial nucleus to positively (but not negatively or neutral) valenced faces. These results were independent of behavioral/cognitive performance (equal across groups) suggesting that an impaired affective substrate in the intra-amygdala response may lie at the core of deficits of social behavior that have been documented in this population.
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