Subcortical brain connectivity at 7T

The habenula, a small, bilateral region posterior to the medial thalamus and dorsal to the posterior commissure, has been of interest in research on reward processing and goal-directed behavior. It receives input from the prefrontal cortex and several subcortical regions and projects to the serotonergic dorsal raphe nucleus, as well as the dopaminergic substantia nigra (SN). Despite the habenula’s critical involvement in reward processing and dopamine modulation, few neuroimaging studies have focused on this region. To address this discrepancy, we used complementary approaches to assess the whole brain functional connectivity of the habenula at rest and during task to uncover how this region may be differentially engaged across cognitive states.

We demonstrate in both rsFC and MACM analyses habenula’s functional interactions with the SN, consistent with a well-documented role in modulating dopaminergic signaling associated with reward prediction error (RPE), indicating this relationship is central to habenula function, regardless of cognitive state. Furthermore, the habenula is connected with the anterior cingulate cortex (ACC) both at rest and during various tasks, though habenula’s rsFC was largely ventral, and task-based MACM, doral. The habenula was connected with medial nodes of the default mode network at rest, but with key nodes of the salience network during tasks. Differential connectivity at rest and during task suggests context-specific functional roles of the habenula, potentially contributing to default mode processes at rest and likely providing RPE signaling to salience network regions during tasks.

Manuscripts

Presentations

• Results on NeuroVault
• GitHub Repository

Most investigation of hypothalamus connectivity is aimed at characterizing disease states, but understanding connectivity in healthy individuals contributes to knowledge of the general role of the hypothalamus. In this study, we used functional and structural imaging to develop a comprehensive model of healthy hypothalamic connectivity. To address this discrepancy, we used a multimodal approach to assess the whole brain functional connectivity of the human hypothalamus, integrating probabilistic tractography, resting-state functional connectivity (rsFC), and meta-analytic connectivity modeling (MACM)s.

Probabilistic tractography indicates direct hypothalamus connectivity with limbic and midline frontal regions. Regions functionally connected at rest include similar limbic and frontal clusters, and a large occipital cluster. Task-dependent connectivity extends to limbic clusters associated with all behavioral domains except action, inferior frontal clusters associated with emotion and cognition, and temporal clusters associated with all behaviors except action. Incorporating structural and functional connectivity informs the nature of connections between the hypothalamus and other regions, allowing us to distinguish regions directly connected with the hypothalamus from regions connected indirectly. Assessment of connections identifies patterns of behavioral integration; future research should investigate nodes of integration and functional segmentation.

Manuscripts

Presentations

This project was completed by my undergraduate research mentor, Jennifer Robinson, and used meta-analytic coactivation-based parcellation, in addition to resting-state functional and diffusion-weighted magnetic resonance imaging at 7T to delineate the functional topography of the hippocampus.

Manuscripts