Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.
Neuron. 2019 Jan 16;101(2):307-320.e6. doi: 10.1016/j.neuron.2018.11.021. Epub 2018 Dec 4.
Anhedonia is a core symptom of depression, but the underlying neurobiological mechanisms are unknown. Correlative neuroimaging studies implicate dysfunction within ventromedial prefrontal cortex, but the causal roles of specific subregions remain unidentified. We addressed these issues by combining intracerebral microinfusions with cardiovascular and behavioral monitoring in marmoset monkeys to show that over-activation of primate subgenual anterior cingulate cortex (sgACC, area 25) blunts appetitive anticipatory, but not consummatory, arousal, whereas manipulations of adjacent perigenual ACC (pgACC, area 32) have no effect. sgACC/25 over-activation also reduces the willingness to work for reward. F-FDG PET imaging reveals over-activation induced metabolic changes in circuits involved in reward processing and interoception. Ketamine treatment ameliorates the blunted anticipatory arousal and reverses associated metabolic changes. These results demonstrate a causal role for primate sgACC/25 over-activity in selective aspects of impaired reward processing translationally relevant to anhedonia, and ketamine's modulation of an affective network to exert its action.
快感缺失是抑郁症的核心症状，但潜在的神经生物学机制尚不清楚。相关的神经影像学研究表明，腹内侧前额叶皮层功能失调，但特定子区域的因果作用仍未确定。我们通过在狨猴中结合脑内微灌流与心血管和行为监测来解决这些问题，结果表明，灵长类动物前扣带皮层腹侧(subgenual anterior cingulate cortex, sgACC)的过度激活会削弱食欲的预期唤醒，但不会削弱食欲的满足唤醒，而相邻的扣带皮层旁回（perigenual ACC, pgACC）的操作则没有影响。sgACC/25 的过度激活也会降低获得奖励的意愿。F-FDG PET 成像显示，过度激活会引起与奖励处理和内脏感知相关的回路的代谢变化。氯胺酮治疗可以改善这种预期唤醒的减弱，并逆转相关的代谢变化。这些结果表明，灵长类动物 sgACC/25 的过度活跃在与快感缺失相关的受损奖励处理的选择性方面起着因果作用，而氯胺酮对情感网络的调节则发挥了其作用。
