Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Psychology, Swansea University, Singleton Campus, Swansea, United Kingdom.
Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Psychology and Neuroscience, Duke University, Durham, NC, United States.
Cortex. 2021 Sep;142:62-73. doi: 10.1016/j.cortex.2021.05.013. Epub 2021 Jun 1.
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.
一些集中于人类神经影像学和动物研究表明，缰核神经元在预期非奖励结果时会发射，在预期奖励结果时会抑制其发射。缰核的这种规范功能在抑郁症中似乎被打乱了，这对氯胺酮的抗抑郁作用可能是至关重要的。然而，使用标准的 3T 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（7T）fMRI 技术，在十八名健康志愿者中进行了货币奖励延迟任务，重点研究了回避损失、货币损失和中性事件。我们评估了视野内（FOV）的神经激活情况，以及基于 ROI 的缰核特异性活动和广义的任务依赖性功能连接。整个 FOV 的结果表明，在货币损失和中性结果之间，以及在回避损失和中性结果之间存在显著的神经差异。缰核特异性分析显示，与其他结果相比，在回避损失期间双侧去激活。这项对回避损失期间缰核作用的首次研究表明，左侧缰核在区分回避损失和货币损失方面进一步发挥作用。与预期中性结果相比，当预期潜在损失时，右侧缰核与同侧海马体和扣带回下侧（涉及记忆和抑郁症发病机制的区域）之间的功能连接增强。我们的研究结果表明，与中性和货币损失相比，人类缰核对回避损失的结果反应最强，这表明缰核在奖励和厌恶处理中都有作用。这对于理解缰核功能在情绪和其他神经精神障碍中的发病机制，以及缰核靶向抗抑郁药（如氯胺酮）的作用机制具有重要意义。
