Significant heterogeneity in structural asymmetry of the habenula in the human brain: A systematic review and meta‐analysis

Understanding the evolutionarily conserved feature of functional laterality in the habenula has been attracting attention due to its potential role in human cognition and neuropsychiatric disorders. Deciphering the structure of the human habenula remains to be challenging, which resulted in inconsistent findings for brain disorders. Here, we present a large-scale meta-analysis of the left-right differences in the habenular volume in the human brain to provide a clearer picture of the habenular asymmetry. We searched PubMed, Web of Science, and Google Scholar for articles that reported volume data of the bilateral habenula in the human brain, and assessed the left-right differences. We also assessed the potential effects of several moderating variables including the mean age of the participants, magnetic field strengths of the scanners and different disorders by using meta-regression and subgroup analysis. In total 52 datasets (N = 1427) were identified and showed significant heterogeneity in the left-right differences and the unilateral volume per se. Moderator analyses suggested that such heterogeneity was mainly due to different MRI scanners and segmentation approaches used. While inversed asymmetry patterns were suggested in patients with depression (leftward) and schizophrenia (rightward), no significant disorder-related differences relative to healthy controls were found in either the left-right asymmetry or the unilateral volume. This study provides useful data for future studies of brain imaging and methodological developments related to precision habenula measurements, and also helps to further understand potential roles of the habenula in various disorders.