Directional asymmetry in the volume of the human habenula


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.

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This work was supported by the National Commission for Scientific and Technological Research (FONDECYT 1020902, 1151029 and 3160486 to M.L.C, S.H. and P.A.G., respectively; FONDEF D11I1096 to S.H. and E.D.; Ring Initiative ACT1402 to M.L.C and S.H.; Fondap 15150012 to M.L.C.), and the Millennium Science Initiative (P09-015-F to M.L.C and S.H.). We are grateful to Iskra Signore and Steve Wilson for critical reading of the manuscript; Daniela Bravo and Nohema Contreras for help in histological sections, segmentation and volumetric reconstructions; Dr. Mario Celis from the Medical Legal Service and Dr. Laura Segovia from the Pathological Anatomy Unit at Barros Luco-Trudeau Hospital for help in collecting samples of human brains.

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Correspondence to Miguel L. Concha.

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The authors declare that they have no conflict of interest.

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P. Ahumada-Galleguillos and C. G. Lemus contributed equally.

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Ahumada-Galleguillos, P., Lemus, C.G., Díaz, E. et al. Directional asymmetry in the volume of the human habenula. Brain Struct Funct 222, 1087–1092 (2017) doi:10.1007/s00429-016-1231-z

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  • Habenula
  • Asymmetry
  • Volume
  • Shape
  • Gender
  • Humans