The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents—a radical departure from commonly used deep brain stimulation protocols—is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

When learning from direct experience, neurons in the primate brain have been shown to encode a teaching signal used by algorithms in artificial intelligence: the reward prediction error (PE)—the difference between how rewarding an event is, and how rewarding it was expected to be. However, in humans and other species learning often takes place by observing other individuals. Here, we show that, when humans observe other players in a card game, neurons in their rostral anterior cingulate cortex (rACC) encode both the expected value of an observed choice, and the PE after the outcome was revealed. Notably, during the same task neurons recorded in the amygdala (AMY) and the rostromedial prefrontal cortex (rmPFC) do not exhibit this type of encoding. Our results suggest that humans learn by observing others, at least in part through the encoding of observational PEs in single neurons in the rACC.