Project Details
Description
PROJECT SUMMARY/ABSTRACT
Converging evidence has linked the habenula (Hb), a small epithalamic structure that inhibits dopaminergic
reward signaling, to a wide range of affective, motivational, and motor functions. Abnormalities in Hb circuitry are
increasingly implicated in psychiatric and behavioral disorders. In vivo Hb research has proceeded slowly,
however, due to technical constraints in magnetic resonance imaging (MRI) that make it difficult to define and
characterize this small region. Understanding of the Hb is especially limited in adolescence, a critical period
marked by rapid maturation of the reward system and, often, the first emergence of psychiatric disorders. To
address these gaps in basic and clinical neuroscience, our proposal leverages the unprecedented scale and
quality of high-resolution neuroimaging data available through the Adolescent Brain Cognitive Development
(ABCD) study to investigate the development of Hb function in early adolescence and its role in psychiatric illness
onset. The proposed research builds on extensive work by our group to develop and refine Hb imaging
methodology, including automated segmentation and a region of interest optimization approach that significantly
improves Hb fMRI sensitivity, and is supported by substantial data from our laboratory. In independent samples
of adult and adolescent healthy controls (HCs), we found a highly consistent pattern of positive Hb intrinsic
functional connectivity (iFC) with the dopaminergic ventral tegmental area (VTA), downstream nucleus
accumbens (NAc), and cortical salience network (SN), as well as negative Hb iFC throughout the default mode
network (DMN). Adults with high vs. low subclinical depression scores exhibited distinct iFC patterns with regions
associated with anxiety and depression, including the amygdala and insula. Moreover, adolescents with mood
and anxiety disorders had positive Hb iFC with the DMN, and this abnormal Hb-DMN iFC pattern was associated
with anxiety severity across both healthy and clinical adolescents, while hyperconnectivity with SN and other
expected Hb targets correlated with anhedonia. Building on our compelling findings to date, we propose to study
Hb function at Baseline and Year 2 ABCD neuroimaging timepoints in relation to normative (Aim 1) and clinical
(Aim 2) developmental trajectories. Subjects will comprise two cohorts of ~3000 adolescents each: clinical
subjects, with significant past or current mood and anxiety symptoms, and HCs, with no history of psychiatric
diagnoses or clinically significant symptoms. Study procedures will incorporate sophisticated preprocessing and
denoising, optimized subject-level Hb definition, neuroanatomically accurate cortical surface mapping, and
rigorous non-parametric statistics. Analyses will encompass both resting-state and task fMRI to characterize Hb
iFC and activation during specific reward, loss, and inhibitory control processes. We will examine both group
differences and associations with psychiatric symptom severity using hypothesis-driven as well as machine
learning approaches.
Status | Finished |
---|---|
Effective start/end date | 4/1/21 → 3/31/23 |
Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH: $210,000.00
- NATIONAL INSTITUTE OF MENTAL HEALTH: $252,000.00
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