Pre-stimulus neural activity predicts successful encoding of inter-item associations.

fMRI was employed to investigate the relationship between pre-stimulus neural activity and associative encoding of words and pictures in humans. While undergoing scanning, subjects studied randomly interleaved word or picture pairs. A pre-stimulus cue preceded the presentation of each study pair and signaled whether it would comprise words or pictures. Memory for the study pairs was later tested with an associative recognition test, which comprised word or picture pairs presented either in the same (intact) or a different (rearranged) pairing as at study, along with pairs of new items. The critical fMRI contrast was between study activity associated with pairs later correctly judged intact and pairs incorrectly judged as rearranged. A key question was whether material-selective pre-stimulus encoding effects could be identified which overlapped regions selectively activated by the respective study material. Picture-selective pre-stimulus effects were identified in bilateral fusiform and the intraparietal sulcus (IPS), whereas word-selective effects could not be identified. Material-invariant pre-stimulus subsequent memory effects were also identified in several neocortical regions as well as in the hippocampus. Whereas the loci of the neocortical effects suggest that they reflect the benefit to encoding that accrues from engagement of cognitive control processes, their magnitude was negatively correlated across subjects with associative recognition performance and positively related to false alarm rate. Conversely, the hippocampal effects also predicted unique variance in associative memory and were negatively related to hit rate. It is suggested that the neocortical pre-stimulus effects may reflect encoding processes that increase familiarity of single items, whereas the hippocampal pre-stimulus effects are proposed to reflect either the encoding of task-irrelevant features or the retrieval of task-relevant information associated with the pre-stimulus cues. Overall, the results provide evidence that pre-stimulus processes may be deleterious, rather than beneficial, to associative encoding.