Sensitivity of the hippocampus to objective but not subjective episodic memory judgments.

We assessed whether neural activity in the hippocampus dissociates according to whether memory test items elicit a subjective sense of recollection or accurate retrieval of contextual information. We reanalyzed a previously acquired dataset from a study in which participants made both objective (source memory for spatial context) and subjective (Remember-Know) judgments for each test item. Results indicated that the hippocampus was exclusively sensitive to the amount of contextual information retrieved, such that accurate source memory judgments were associated with greater activity than inaccurate judgments, regardless of Remember/Know status. The findings add to the evidence that the hippocampus is insensitive to the subjective experience of recollection, but supports retrieval of contextual information.

The hippocampus is sensitive to the mismatch in novelty between items and their contexts.

In previous functional magnetic resonance imaging (fMRI) studies of continuous recognition memory it was reported that new items elicit greater hippocampal activity than old (repeated) items (hippocampal 'novelty' effects). Rather than reflecting recency differences between new and old items, hippocampal novelty effects may instead reflect the novelty of the association between test items and the experimental context, or a mismatch in the novelty of the test item and the context. The present continuous recognition study assessed these possibilities by manipulating item-context associations on a trial-by-trial basis. Each trial comprised the presentation of an object-word (context-item) pair. Repeated items were paired either with the same context as on their first presentation, a different but previously presented context, or a new context. The task was to judge whether each item was old or new, regardless of the study status of the associated context. We found no evidence that hippocampal novelty effects reflected either item and context recency, or the novelty of the item-context association. Rather, enhanced hippocampal activity was elicited when the novelty of the item and its context mismatched. These findings support the possibility that hippocampal novelty effects reflect, at least in part, the disjunction in novelty between test items and their contexts.

Dissociation of Recollection-Related Neural Activity in Ventral Lateral Parietal Cortex.

fMRI responses to recognition memory test items in two regions of ventral lateral parietal cortex-the angular gyrus and temporo-parietal junction (TPJ)-are enhanced when recognition is accompanied by recollection. According to the 'episodic buffer' hypothesis, ventral parietal recollection effects reflect processes involved in maintaining or representing recollected information. According to the 'attention to memory' hypothesis, however, the effects reflect attentional re-orienting to the products of recollection. The present experiment addressed the question whether these operations map on to the angular gyrus and TPJ, respectively. Subjects were scanned during a memory test that required a Remember/Know/New and a source memory judgment, allowing recollected items to be segregated by amount of contextual information recollected. Angular gyrus activity tracked amount of recollected information, whereas activity in the TPJ was enhanced for items endorsed as recollected, but was insensitive to amount of information recollected. Thus, the two regions likely support functionally dissociable processes.

Item memory, context memory and the hippocampus: fMRI evidence.

Dual-process models of recognition memory distinguish between the retrieval of qualitative information about a prior event (recollection), and judgments of prior occurrence based on an acontextual sense of familiarity. fMRI studies investigating the neural correlates of memory encoding and retrieval conducted within the dual-process framework have frequently reported findings consistent with the view that the hippocampus selectively supports recollection, and has little or no role in familiarity-based recognition. An alternative interpretation of these findings has been proposed, however, in which it is argued that the hippocampus supports the encoding and retrieval of 'strong' memories, regardless of whether the memories are recollection- or familiarity-based. Here, we describe the findings of eight fMRI studies from our laboratory: one study of source memory encoding, four studies of the retrieval of contextual information, and three studies of continuous recognition. Together, the findings support the proposal that hippocampal activity co-varies with the amount of contextual information about a study episode that is encoded or retrieved, and not with the strength of an undifferentiated memory signal.

Hippocampal activity during recognition memory co-varies with the accuracy and confidence of source memory judgments.

It has been proposed that the hippocampus selectively supports retrieval of contextual associations, but an alternative view holds that the hippocampus supports strong memories regardless of whether they contain contextual information. We employed a memory test that combined the 'Remember/Know' and source memory procedures, which allowed test items to be segregated both by memory strength (recognition accuracy) and, separately, by the quality of the contextual information that could be retrieved (indexed by the accuracy/confidence of a source memory judgment). As measured by fMRI, retrieval-related hippocampal activity tracked the quality of retrieved contextual information and not memory strength. These findings are consistent with the proposal that the hippocampus supports contextual recollection rather than recognition memory more generally.

Dissociation of the electrophysiological correlates of familiarity strength and item repetition.

Event-related potentials (ERPs) were employed to investigate the relationship between the familiarity strength of recognition memory test items (pictures of animate and inanimate objects) and a putative ERP correlate of familiarity, the mid-frontal 'old/new' effect. A modified Remember/Know task was used in which subjects endorsed items as 'remembered' if any detail of the study presentation could be retrieved and, if not, judged the old/new status of the item using a 4-point confidence scale ('confident old' to 'confident new'). Studied test items elicited a mid-frontal old/new effect that varied according to the rated familiarity of the eliciting item. Thus, prior findings that the mid-frontal effect is graded according to familiarity strength are not attributable to the confounding influence of study status, as has been suggested. ERPs elicited by studied and unstudied items that were rated equally familiar differed in the same latency range as that occupied by the mid-frontal old/new effect. Furthermore, the scalp topography of this repetition effect differed significantly from the topography of the mid-frontal effect. The findings suggest that ERPs elicited by recognition memory test items are modulated during the 300-500 ms latency range both by the familiarity strength of the item and, separately, by an implicit memory process that acts independently of the processes supporting familiarity-driven recognition judgments.

Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid.

Oxidative stress is implicated in the cognitive deterioration associated with normal aging as well as neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. We investigated the effect of ascorbic acid (vitamin C) on oxidative stress, cognition, and motor abilities in mice null for gulono-gamma-lactone oxidase (Gulo). Gulo-/- mice are unable to synthesize ascorbic acid and depend on dietary ascorbic acid for survival. Gulo-/- mice were given supplements that provided them either with ascorbic acid levels equal to- or slightly higher than wild-type mice (Gulo-sufficient), or lower than physiological levels (Gulo-low) that were just enough to prevent scurvy. Ascorbic acid is a major anti-oxidant in mice and any reduction in ascorbic acid level is therefore likely to result in increased oxidative stress. Ascorbic acid levels in the brain and liver were higher in Gulo-sufficient mice than in Gulo-low mice. F(4)-neuroprostanes were elevated in cortex and cerebellum in Gulo-low mice and in the cortex of Gulo-sufficient mice. All Gulo-/- mice were cognitively normal but had a strength and agility deficit that was worse in Gulo-low mice. This suggests that low levels of ascorbic acid and elevated oxidative stress as measured by F(4)-neuroprostanes alone are insufficient to impair memory in the knockouts but may be responsible for the exacerbated motor deficits in Gulo-low mice, and ascorbic acid may have a vital role in maintaining motor abilities.