Data_Sheet_1_Laterality and Sex Differences of Human Lateral Habenula Afferent and Efferent Fiber Tracts.docx

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.

引言
外侧缰核（lateral habenula, LHb）是一种与负性效价及情感障碍相关的上丘脑核团。它通过髓纹（stria medullaris, SM）接收输入信号，并通过后屈束（fasciculus retroflexus, FR）传出信号。本研究采用纤维束追踪（tractography）技术对该神经通路进行重构与特征分析。

方法
本研究的多壳层人类扩散磁共振成像（diffusion magnetic resonance imaging, dMRI）数据来源于人类连接组计划（human connectome project, HCP）（n=20，其中男性10名）以及本机构扫描的健康对照人群（n=10，其中男性6名）。我们以苍白球（pallidum）作为种子区、腹侧被盖区（ventral tegmental area）作为输出靶点，采用概率性纤维束追踪（probabilistic tractography）技术生成外侧缰核的传入与传出神经纤维。

结果
我们成功在人类连接组计划数据集与本机构数据集中的所有受试者中重构出目标神经纤维束。本研究的技术还可辅助识别外侧缰核。在右利手受试者中，左侧半球的神经纤维束数量显著多于右侧半球（平均比值1.59±0.09，p=0.04）；而在左利手受试者中，半球间无显著不对称性（平均比值1.00±0.09，p=1.0）。此外，女性受试者的神经纤维束数量显著多于男性受试者（619.9±159.7 vs. 225.9±66.03，p=0.04）。

结论
本研究开发了一种无需手动识别外侧缰核即可重构髓纹与后屈束的方法。该技术可实现对上述神经纤维束及外侧缰核的精准靶向定位。此外，本研究证实神经纤维束数量存在性别与半球间差异。上述发现具有潜在的治疗价值，值得进一步开展相关研究。