高分辨率MRI描绘人脑丘脑到杏仁核的多条恐惧通路

研究做了什么

这项研究关注的是一个在动物实验中已有较多描述、但在人脑中尚未被系统描绘的问题：感觉信息能否不经大脑皮层，沿丘脑到杏仁核的短通路快速传递。研究团队由巴塞罗那大学的Emmanouela Kosteletou-Kassotaki领衔，招募了113名健康右利手志愿者，平均年龄24.5岁，其中65名女性。他们使用高分辨率弥散加权MRI，通过追踪脑组织中水分子的运动方向来估计神经纤维走向，再用纤维追踪技术重建丘脑若干核团与基底外侧杏仁核之间的可能通路。基底外侧杏仁核是恐惧学习中的关键区域。

研究设计还包含一次重复测量：其中24名参与者在平均约15天后接受了第二次扫描，用来检验这些通路能否在不同场次中被一致地重建。这一点对纤维追踪研究尤其重要，因为深部脑区纤维密集交叉，重建结果容易受方法影响。

哪些连接最稳定

结果显示，最可靠的连接集中在后部丘脑与基底外侧杏仁核之间。其中一条通路从下丘（中脑的听觉中枢）经内侧膝状体（丘脑中的听觉中继核）到达杏仁核，与啮齿类动物中已被详细记录的听觉恐惧通路相对应，这条通路几乎出现在所有参与者中。

另一组稳定连接涉及丘脑枕，一个与视觉注意和跨感官信息整合有关的结构。杏仁核与丘脑枕内侧、下侧和外侧部分的连接在全部113名参与者中都被重建，可重复性高，下侧丘脑枕尤其突出。相比之下，前部丘脑枕的连接稀疏且不一致；一条绕过内侧膝状体、直接从下丘到杏仁核的通路则无法被可靠重建。

内侧丘脑的背内侧核也显示出与基底外侧杏仁核的明显连接，重建出的纤维路径数量较多，可重复性中等偏高。但作者提醒，这条连接可能主要把信号从杏仁核传出，而不是传入杏仁核。丘脑中央旁的小型核团，尤其是束旁核和中央内侧核，也出现了连接，不过这些通路在个体之间以及两次扫描之间的差异更大。

不对称与分区

研究还观察到，不同丘脑区域倾向于连接基底外侧杏仁核的不同亚区，若干通路在左半球重建出的纤维路径多于右半球。作者对此保持谨慎，指出这种不对称可能部分反映方法学因素，而不能直接解读为大脑功能的左右差异。

整体来看，这些结果支持一个图景：人类拥有的不是一条单一的“低路”，而是多条从丘脑到杏仁核的直接通路。作者将其描述为为人脑多条直接丘脑—杏仁核通路提供了“统一的解剖学框架”。这些结构上的通路可能有助于快速传递感觉与情绪信号，从而支持灵活的防御反应，但这一功能推断并非本研究直接测量所得。

方法限制与解释边界

文章明确列出了弥散纤维追踪的技术局限。该方法可能在纤维交叉处错误地识别出并不存在的通路，也可能漏掉真实存在的通路，因此这些连接需要脑组织研究来确认。它也无法显示信号沿纤维传播的方向，提供的是结构信息而非实时脑功能。

因此，把上述通路与恐惧反应联系起来，主要依据的是动物研究中的对应发现，而不是在人类身上直接观察到的恐惧回路活动。研究样本为健康右利手年轻人，平均年龄约24.5岁，结果能否推广到其他年龄和人群，材料未作说明。这些限制并不否定解剖学发现的价值，但决定了它目前属于结构描述层面的证据，距离临床应用还有距离。

Researchers have mapped several direct routes between the human thalamus and amygdala that may help the brain respond rapidly to threatening information, according to a study published in NeuroImage. Connections involving the back of the thalamus were the most consistent, while others were weaker or harder to detect reliably.

Fear responses can begin quickly. When a person hears a sudden noise or sees a possible threat, the brain must evaluate the information and prepare the body to respond. Animal studies have identified short pathways that carry sensory information from the thalamus, a central relay station for incoming sensory signals, to the amygdala, a region involved in emotional learning and defensive responses.

These pathways have sometimes been described as “low roads” because they may transmit basic sensory information without first passing through the cerebral cortex, where more detailed analysis takes place. Although animal studies have characterized them, they had not been comprehensively mapped in the human brain.

Led by Emmanouela Kosteletou-Kassotaki of the University of Barcelona, the researchers studied 113 healthy right-handed volunteers (average age 24.5 years; 65 women).

The team used high-resolution diffusion-weighted MRI, a scanning method that estimates the direction of nerve fibers by tracking the movement of water through brain tissue. They then used tractography, a technique that reconstructs likely fiber pathways from these data, to map connections between several thalamic nuclei and the basolateral amygdala, a part of the amygdala central to fear learning. Their approach was designed to cope with the dense, crisscrossing fibers around these deep brain structures.

A smaller group of 24 participants underwent a second MRI scan about 15 days later on average. This allowed the researchers to examine whether the pathways could be reconstructed consistently across sessions.

The most reliable connections linked the posterior thalamus to the basolateral amygdala. One pathway ran from the inferior colliculus, an auditory hub in the midbrain, through the medial geniculate nucleus, a key auditory relay in the thalamus, to the amygdala, mirroring an auditory fear pathway well documented in rodents. This pathway was found in nearly all participants.

Connections between the amygdala and the medial, inferior and lateral portions of the pulvinar, a thalamic structure involved in visual attention and combining information across the senses, appeared in all 113 participants and were highly reproducible, particularly for the inferior pulvinar. By contrast, connections with the anterior pulvinar were sparse and inconsistent, and a direct route from the inferior colliculus to the amygdala that bypassed the medial geniculate nucleus could not be reliably reconstructed.

The mediodorsal nucleus, located in the medial thalamus, also showed a prominent connection with the basolateral amygdala, with a high number of reconstructed fiber paths and moderate-to-high reproducibility. The authors note, however, that this connection may mainly carry signals from the amygdala rather than to it.

Connections from intralaminar thalamic nuclei, a group of small nuclei near the center of the thalamus, were also identified, particularly from the parafascicular and central medial nuclei. However, these pathways varied more between people and between the first and second scans. This suggests that some connections are robust across people, while others may be weaker, more difficult to detect or more variable in their anatomy.

Different thalamic regions also tended to connect with different subregions of the basolateral amygdala, and several pathways showed more reconstructed fiber paths in the left hemisphere than in the right, although the authors caution that this asymmetry may partly reflect methodological factors. Overall, the results support the idea that humans possess several direct thalamus–amygdala pathways rather than one simple route. These pathways could help transmit sensory and emotional signals quickly, potentially supporting flexible defensive responses.

Kosteletou-Kassotaki and colleagues described the study as providing “a unifying anatomical framework for multiple direct thalamo-amygdala pathways in the human brain.”

Diffusion tractography has technical limitations that should be noted. It can mistakenly identify pathways that are not present or fail to detect pathways that are present, particularly where nerve fibers cross, so the connections will need to be confirmed with studies of brain tissue. The method also cannot show which direction signals travel and provides information about structure rather than real-time brain function, so the link to fear is inferred largely from animal research.

The study, “Mapping the subcortical pathways associated with fear in the human brain: multiple thalamo-amygdala connections revealed by high-resolution tractography,” was authored by Emmanouela Kosteletou-Kassotaki, Liu Mengxing, Martina T. Cinca-Tomás, Pedro M. Paz-Alonso and Judith Domínguez-Borràs.