Resting state connectivity of the human habenula at ultra-high field

Abstract

The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7 Tesla fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network.

Reproducibility of myelin content‐based human habenula segmentation at 3 Tesla

“…Recently, we developed an objective semi‐automated human habenula segmentation scheme based on myelin content from the ratio of T1w and T2‐weighted (T2w) images at 3T (Kim et al, ) in order to improve the time‐consuming and operator‐dependent manual habenula segmentation processes and enable efficient and reproducible habenula volumetric analysis in large cohorts. Using our method, we have shown group‐wise habenula center‐of‐gravity in the MNI space consistent with the geometric segmentation method of the habenula (i.e., Lawson's method), primarily aimed to objectively locate the habenula as seed regions in functional MRI (Furman & Gotlib, ; Hétu et al, ; Lawson et al, ; Lawson et al, ; Torrisi et al, ) or diffusion MRI (Shelton et al, ) applications.…”

“…The mean habenula volumes measured by manual contrast‐based segmentation at 3T were 18.8/16.4 mm 3 (Savitz et al, ), 19.5/17.9 mm 3 (Savitz et al, ), left/right habenula respectively, and 43.0 mm 3 (Carceller‐Sindreu et al, ), bilateral, while those from 7T T1 map were 17.6/17.3 mm 3 (Schmidt et al, ), left/right habenula respectively in healthy controls. Using the geometric segmentation (i.e., Lawson's method), the habenula volumes from 3T were 27.9/28.0 mm 3 (Hétu et al, ), 28.3/28.7 mm 3 (Furman & Gotlib, ), 29.4/29.3 mm 3 (Lawson et al, ), left/right habenula respectively, and 22.3 mm 3 (Lawson et al, ) per hemisphere, while those from 7T (0.7 mm isotropic resolution MPRAGE) were 18.8/14.9 mm 3 (Torrisi et al, ), left/right habenula respectively. Assessing the accuracy of in vivo habenula segmentation would require a carefully planned cadaver MRI, ex vivo MRI, and histology from the same brain, which is beyond the scope of this study.…”

“…We caution against misusing Lawson's method to assess human habenula anatomical laterality (Bianco & Wilson, ), as suggested by Concha's group (Ahumada‐Galleguillos et al, ). Lawson's method has been successfully used for objectively localizing the habenula seed regions in functional MRI (Furman & Gotlib, ; Hétu et al, ; Lawson et al, ; Torrisi et al, ) or diffusion MRI (Shelton et al, ) applications, which our myelin content‐based habenula segmentation method provides a reproducible and efficient alternative (Ely et al, ).…”

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

“…Continued improvements in equipment hardware and continued development of open-source toolboxes [82] will increase the more widespread adoption of physiological noise reduction. These limitations may be at least partially circumvented utilizing higher resolution imaging techniques achieved at 7T [83] or at 3T [44,47] yielding voxel resolution in the 1mm-2mm isotropic range as well as enhanced preprocessing for physiological noise reduction. Second, we acknowledge the functional specialization of the medial and lateral subdivisions of the habenula identified in preclinical work such that medial aspects possessing higher densities of nAChRs have been primarily linked with aversive responses to high nicotine doses [38,39] and the lateral habenula having been primarily linked with reward processing, aversive stimuli, and emotions [70].…”

For Value or for Worth? Part 2: A Neuroeconomical Thought-Action-Mood-Space Modulated by (Un-)Certainty as Sign- or Goal-tracking

“…The latest review on STs [148] points also to the lateral habenulae (LHb) [149][150][151], and thereby, see below, also to mast cells (MCs), as a part of the food-cue-induced "motive circuit", and its rapid adaptions. Within a larger network [152] they help in attributing salience [153] to the point, that the LHb drives the VTA and SNr during RPE [154].…”