A number of convergent human neuroimaging and animal studies suggest that habenula neurons fire in anticipation of non-rewarding outcomes, and suppress their firing in anticipation of rewarding outcomes. This normative function of the habenula appears disrupted in depression, and may be critical to the anti-depressant effects of ketamine. However, studying habenula functionality in humans using standard 3 T MRI is inherently limited by its small size. We employed ultra-high field (7 T) fMRI to investigate habenular activity in eighteen healthy volunteers during a Monetary Incentive Delay Task, focussing on loss avoidance, monetary loss and neutral events. We assessed neural activation in the field of view (FOV) in addition to ROI-based habenula-specific activity and generalized task-dependent functional connectivity. Whole FOV results indicated substantial neural differences between monetary loss and neutral outcomes, as well as between loss avoidance and neutral outcomes. Habenula-specific analyses showed bilateral deactivation during loss avoidance, compared to other outcomes. This first investigation into the habenula's role during loss avoidance revealed that the left habenula further differentiated between loss avoidance and monetary loss. Functional connectivity between the right habenula and the ipsilateral hippocampus and subcallosal cingulate (regions implicated in memory and depression pathophysiology) was enhanced when anticipating potential losses compared to anticipating neutral outcomes. Our findings suggest that the human habenula responds most strongly to outcomes of loss avoidance when compared to neutral and monetary losses, suggesting a role for the habenula in both reward and aversive processing. This has critical relevance to understanding the pathophysiology of habenula function in mood and other neuropsychiatric disorders, as well as the mechanism of action of habenula-targeting antidepressants such as ketamine.

许多融合的人类神经影像学和动物研究表明，缰核神经元在预期无回报结果时会放电，并在预期有回报结果时抑制它们的放电。缰核的这种正常功能在抑郁症中似乎被破坏，并且可能对氯胺酮的抗抑郁作用至关重要。然而，使用标准 3 T MRI 研究人类缰核的功能在本质上受到其体积小的限制。我们采用超高场 (7 T) fMRI 调查 18 名健康志愿者在货币激励延迟任务期间的缰核活动，重点关注损失避免、货币损失和中性事件。除了基于 ROI 的缰核特异性活动和广义的任务相关功能连接之外，我们还评估了视野 (FOV) 中的神经激活。整个 FOV 结果表明，金钱损失和中性结果之间以及损失避免和中性结果之间存在显着的神经差异。与其他结果相比，缰核特异性分析显示在避免损失期间双侧失活。对缰核在避免损失过程中的作用的首次调查表明，左侧缰核进一步区分了损失避免和金钱损失。与预期中性结果相比，在预期潜在损失时，右侧缰核与同侧海马体和胼胝体扣带回（涉及记忆和抑郁症病理生理学的区域）之间的功能连接得到增强。我们的研究结果表明，与中性损失和金钱损失相比，人类缰核对避免损失的结果反应最强烈，暗示缰核在奖励和厌恶处理中的作用。这对于理解缰核在情绪和其他神经精神疾病中的功能的病理生理学以及以缰核为靶点的抗抑郁药（如氯胺酮）的作用机制具有重要意义。