Directional asymmetry in the volume of the human habenula

Abstract

Brain asymmetry is a conserved feature in vertebrates. The dorsal diencephalic habenular complex shows conspicuous structural and functional asymmetries in a wide range of species, yet it is unclear if this condition is also present in humans. Addressing this possibility becomes relevant in light of recent findings presenting the habenula as a novel target for therapeutic intervention of affective disorders through deep brain stimulation. Here we performed volumetric analyses in postmortem diencephalic samples of male and female individuals, and report for the first time, the presence of directional asymmetries in the volume of the human habenula. The habenular volume is larger on the left side in both genders, a feature that can be explained by an enlargement of the left lateral habenula compared to the right counterpart. In contrast, the volume of the medial habenula shows no left-right directional bias in either gender. It is remarkable that asymmetries involve the lateral habenula, which in humans is particularly enlarged compared to other vertebrates and plays relevant roles in aversive processing and aversively motivated learning. Our findings of structural asymmetries in the human habenula are consistent with recent observations of lateral bias in activation, metabolism and damage of the human habenula, highlighting a potential role of habenular laterality in contexts of health and illness.

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

“…In our study, we observed no significant differences between right and left habenula functional connectivity (see supplemental figures S4 and S5 for separate connectivity maps of left and right habenula). However, a significant volumetric difference was found, with the left habenula larger than the right, which replicates previous volumetric findings in humans (Ahumada-Galleguillos et al, 2016). One notes that this anatomical difference does not necessarily imply functional lateralization.…”

“…Following manual tracing of the habenula, the volumes of the left and right habenulae for each subject were computed separately. Because of reports of structural and functional laterality differences (Ahumada-Galleguillos et al, 2016; Bianco and Wilson, 2009; Hétu et al, 2016), left and right habenula volumes were compared using a paired t-test.…”

Nodal signalling and asymmetry of the nervous system

“…In craniates, the dorsal diencephalic epithalamic region is asymmetric in a wide range of species, including fishes (agnathans, chondrichthyans and teleosts), amphibians and amniotes (e.g. lizards, chick and rodents) (reviewed in [14]), and recent reports also extend this asymmetric feature to humans [15,16]. Asymmetries comprise the bilaterally paired habenular nuclei (Hb) and some midline components of the pineal complex, and show significant variations in morphology, and in the extent and sidedness of L-R differences among species [14,[17][18][19].…”

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

“…Segmentation of the human habenula in in vivo neuroimaging is challenging due to its small size (37.2/34.2 mm 3 (Ahumada‐Galleguillos et al, ) or 30.9/33.2 mm 3 (Ranft et al, ) for left/right habenula, respectively from postmortem histology in deceased subjects without reported cerebral illness or neuropathy) and its low anatomical contrast to the neighboring dorsomedial thalamus. A majority of previous in vivo human habenula volumetric studies have used manual contrast‐based (Carceller‐Sindreu et al, ; Savitz et al, ; Savitz et al, ) or geometric segmentation (Lawson, Drevets, & Roiser, ) on T1‐weighted (T1w) 3T MRI, while more recently, manual contrast‐based segmentation of the habenula from ultra‐high field (7T) T1 maps has also been reported (Schmidt et al, ).…”