Laterality and Sex Differences of Human Lateral Habenula Afferent and Efferent Fiber Tracts

IntroductionThe lateral habenula (LHb) is an epithalamic nucleus associated with negative valence and affective disorders. It receives input via the stria medullaris (SM) and sends output via the fasciculus retroflexus (FR). Here, we use tractography to reconstruct and characterize this pathway. MethodsMulti-shell human diffusion magnetic resonance imaging (dMRI) data was obtained from the human connectome project (HCP) (n = 20, 10 males) and from healthy controls (n = 10, 6 males) scanned at our institution. We generated LHb afferents and efferents using probabilistic tractography by selecting the pallidum as the seed region and the ventral tegmental area as the output target. ResultsWe were able to reconstruct the intended streamlines in all individuals from the HCP dataset and our dataset. Our technique also aided in identification of the LHb. In right-handed individuals, the streamlines were significantly more numerous in the left hemisphere (mean ratio 1.59 +/- 0.09, p = 0.04). In left-handed individuals, there was no hemispheric asymmetry on average (mean ratio 1.00 +/- 0.09, p = 1.0). Additionally, these streamlines were significantly more numerous in females than in males (619.9 +/- 159.7 vs. 225.9 +/- 66.03, p = 0.04). ConclusionWe developed a method to reconstruct the SM and FR without manual identification of the LHb. This technique enables targeting of these fiber tracts as well as the LHb. Furthermore, we have demonstrated that there are sex and hemispheric differences in streamline number. These findings may have therapeutic implications and warrant further investigation.

Automated summary

This study used tractography to reconstruct and characterize the lateral habenula (LHb) and found that in right-handed individuals, the streamlines were more numerous in the left hemisphere, while females had significantly more streamlines than males. These findings have potential therapeutic implications and warrant further investigation.