Four types of novelty-familiarity responses in associative recognition memory of humans

Animal studies show that, like inferior temporal neurons, dorsolateral prefrontal and parietal neurons often respond more strongly to individual novel than to individual familiar stimuli. It is currently unclear whether the novelty preference of prefrontal and parietal neurons extends to associative memory. We used electromagnetic recordings (MEG/EEG) and functional magnetic resonance imaging in two groups of healthy young adults to identify neural populations outside the inferior temporal cortex that exhibit associative novelty (stronger responses for new than for old configurations of two familiar items), and to distinguish them from associative familiarity (stronger responses for old than for new configurations of two familiar items). Subjects were required to learn and were later tested for associations based on the spatial configurations of two stimuli (a face and a tool). At test, learned (old) and rearranged (new) spatial stimulus configurations had to be discriminated. This recognition memory test could only be solved through the associative relationship between individual items because all component items of the stimulus configurations were equally familiar. In both imaging modalities, right dorsolateral prefrontal cortex and right parietal cortex showed an associative novelty response, whereas the right superior temporal cortex showed an associative familiarity response. With EEG/MEG only, the right extrastriate cortex showed an early associative familiarity and a late associative novelty response, whereas the opposite pattern emerged in bilateral frontopolar cortex. Thus, through a multimodal approach, it was possible to identify four types of associative novelty/familiarity responses outside the inferior temporal cortex.