Novelty Enhancements in Memory Are Dependent on Lateral Prefrontal Cortex

Physiological evidence indicates that several brain regions, including the medial temporal lobes and prefrontal cortex (PFC), are involved in processing events that are novel or distinctive in their immediate context. However, behavioral studies that investigate whether these regions are critical for producing stimulus novelty advantages in memory are limited. For example, evidence from an animal lesion study indicated that the PFC is involved in stimulus novelty effects, but this has not been examined in humans. In the current study, we used a von Restorff novelty paradigm to test a large cohort of lateral PFC patients (n = 16). We found that patients with lateral PFC damage were impaired in recollection- and familiarity-based recognition, and they did not exhibit a normal memory advantage for novel compared with non-novel items. These results provide neuropsychological evidence supporting a key role for the lateral PFC in producing stimulus novelty advantages in memory.