Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
J Neurosci. 2012 Sep 19;32(38):13164-76. doi: 10.1523/JNEUROSCI.1210-12.2012.
Current theories of classical conditioning assume that learning depends on the predictive relationship between events, not just on their temporal contiguity. Here we employ the classic experiment substantiating this reasoning-the blocking paradigm-in combination with functional magnetic resonance imaging (fMRI) to investigate whether human amygdala responses in aversive learning conform to these assumptions. In accordance with blocking, we demonstrate that significantly stronger behavioral and amygdala responses are evoked by conditioned stimuli that are predictive of the unconditioned stimulus than by conditioned stimuli that have received the same pairing with the unconditioned stimulus, yet have no predictive value. When studying the development of this effect, we not only observed that it was related to the strength of previous conditioned responses, but also that predictive compared with nonpredictive conditioned stimuli received more overt attention, as measured by fMRI-concurrent eye tracking, and that this went along with enhanced amygdala responses. We furthermore observed that prefrontal regions play a role in the development of the blocking effect: ventromedial prefrontal cortex (subgenual anterior cingulate) only exhibited responses when conditioned stimuli had to be established as nonpredictive for an outcome, whereas dorsolateral prefrontal cortex also showed responses when conditioned stimuli had to be established as predictive. Most importantly, dorsolateral prefrontal cortex connectivity to amygdala flexibly switched between positive and negative coupling, depending on the requirements posed by predictive relationships. Together, our findings highlight the role of predictive value in explaining amygdala responses and identify mechanisms that shape these responses in human fear conditioning.
当前的经典条件作用理论假设，学习取决于事件之间的预测关系，而不仅仅是它们的时间连续性。在这里，我们采用经典实验证明了这一推理，即阻断范式，结合功能磁共振成像（fMRI）来研究人类杏仁核在厌恶学习中的反应是否符合这些假设。与阻断相一致，我们证明，与已经与无条件刺激配对但没有预测价值的条件刺激相比，对有预测价值的条件刺激的行为和杏仁核反应要强得多。在研究这种效应的发展时，我们不仅观察到它与先前条件反应的强度有关，而且与预测性相比，非预测性的条件刺激会受到更多的显性注意，这可以通过 fMRI 与眼动追踪同时测量来证明，并且这伴随着杏仁核反应的增强。我们还观察到，前额叶区域在阻断效应的发展中起着作用：腹内侧前额叶皮层（前扣带回的下侧）仅在条件刺激必须被确定为对结果没有预测性时才表现出反应，而背外侧前额叶皮层也在条件刺激必须被确定为有预测性时表现出反应。最重要的是，背外侧前额叶皮层与杏仁核的连接根据预测关系的要求，灵活地在正耦合和负耦合之间切换。总之，我们的发现强调了预测价值在解释杏仁核反应中的作用，并确定了在人类恐惧条件作用中塑造这些反应的机制。
