A critical role of the human hippocampus in an electrophysiological measure of implicit memory.

The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400 to 600 ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400 to 600 ms, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analyses were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors was systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that are beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures - but function in different physiological ways.

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.

Neurophysiological evidence for a recollection impairment in amnesia patients that leaves familiarity intact.

In several previous behavioral studies, we have identified a group of amnestic patients that, behaviorally, appear to exhibit severe deficits in recollection with relative preservation of familiarity-based recognition. However, these studies have relied exclusively on behavioral measures, rather than direct measures of physiology. Event-related potentials (ERPs) have been used to identify putative neural correlates of familiarity- and recollection-based recognition memory, but little work has been done to determine the extent to which these ERP correlates are spared in patients with relatively specific memory disorders. ERP studies of recognition in healthy subjects have indicated that recollection and familiarity are related to a parietal old-new effect characterized as a late positive component (LPC) and an earlier mid-frontal old-new effect referred to as an 'FN400', respectively. Here, we sought to determine the extent to which the putative ERP correlates of recollection and familiarity are intact or impaired in these patients. We recorded ERPs in three amnestic patients and six age matched controls while they made item recognition and source recognition judgments. The current patients were able to discriminate between old and new items fairly well, but showed nearly chance-level performance at source recognition. Moreover, whereas control subjects exhibited ERP correlates of memory that have been linked to recollection and familiarity, the patients only exhibited the mid-frontal FN400 ERP effect related to familiarity-based recognition. The results show that recollection can be severely impaired in amnesia even when familiarity-related processing is relatively spared, and they also provide further evidence that ERPs can be used to distinguish between neural correlates of familiarity and recollection.