Stress modulates the engagement of multiple memory systems in classification learning.

Learning and memory are supported by anatomically and functionally distinct systems. Recent research suggests that stress may alter the contributions of multiple memory systems to learning, yet the underlying mechanism in the human brain remains completely unknown. Using event-related functional magnetic resonance imaging, we asked in the present experiment whether stress may modulate the engagement of hippocampus-based "declarative" and striatum-based "procedural" memory systems during classification learning in humans and what brain mechanisms are involved in this effect. We found that stress reduced declarative knowledge about the learning task and changed the used learning strategy from a single-cue-based declarative strategy to a multicue-based procedural strategy, whereas learning performance per se remained unaffected by stress. Neuroimaging revealed that hippocampal activity correlated positively with task performance in the control condition, whereas striatal activity correlated with performance in the stress condition. After stress, hippocampal activity was reduced and even negatively correlated with learning performance. These findings show for the first time that stress alters the engagement of multiple memory systems in the human brain. Stress impaired the hippocampus-dependent system and allowed the striatum to control behavior. The shift toward "procedural" learning after stress appears to rescue task performance, whereas attempts to engage the "declarative" system disrupt performance.