CA3 size predicts the precision of memory recall

Abstract

There is enduring interest in why some of us have clearer memories than others, given the substantial individual variation that exists in retrieval ability and the precision with which we can differentiate past experiences. Here we report novel evidence showing that variation in the size of human hippocampal subfield CA3 predicted the amount of neural interference between episodic memories within CA3, which in turn predicted how much retrieval confusion occurred between past memories. This effect was not apparent in other hippocampal subfields. This shows that subtle individual differences in subjective mnemonic experience can be accurately gauged from measurable variations in the anatomy and neural coding of hippocampal region CA3. Moreover, this mechanism may be relevant for understanding memory muddles in aging and pathological states.O ur memories often contain overlapping elements, because they tend to feature the same people and places that form the cornerstones of our lives. Nevertheless, we are generally able to recall many of these past experiences as distinct episodes, although we are not all equally adept at doing so. There is substantial individual variation in retrieval ability and the precision with which we can differentiate past events (1, 2). This is most acute as we age and in conditions such as dementia, where confusion about the past is often evident (2). There is keen interest, therefore, in elucidating the neural mechanisms that allow us to recollect numerous life experiences despite a high degree of intermemory similarity.We know little about how this is achieved in humans, but theoretical models propose that computations within hippocampal subfields facilitate the efficient storage and retrieval of similar memories (3-7). When we experience an event, pattern separation leads to the formation of a distinct neural representation within region CA3 (8-11). At retrieval, a previously stored memory representation within CA3 can be reactivated through the process of pattern completion (12, 13). However, when episodes are highly similar, the CA3 neuronal representations may not be completely distinct, leading to partial overlap (14). It is therefore not clear precisely what the limits of CA3 pattern separation might be. Here we directly tested the capacity of human CA3 to maintain distinct episodic representations in the presence of overlapping elements. We further investigated whether variation in this ability provides an explanatory account of individual differences in the precision of episodic memory retrieval. ResultsWe combined high-resolution functional MRI (14) (fMRI) with an ultra-high resolution structural MRI scanning protocol that permitted the separate identification of CA1, CA3, dentate gyrus (DG), and subiculum (15, 16). Stimuli were created by filming two brief action events against a green-screen background. Each event was then superimposed onto the same two spatial contexts, creating four movie clips that included every combination of the two events and the two contexts (17) (Fig...

Semantic representations in the temporal pole predict false memories

“…Given that we rely on shared semantic representation to communicate with one another, this individual variation is perhaps surprising. However, it does converge with other recent reports of individual differences in semantic (30) and episodic representation (38), and suggests that divergent personal experience is sufficient to create individually unique representations in higher-level semantic regions. This striking finding suggests that it will be important to further characterize both the shared and individually unique aspects of semantic cognition to better understand the nature of conceptual knowledge.…”

Attention promotes episodic encoding by stabilizing hippocampal representations

“…Computational models and animal electrophysiology have pointed to a prominent role for the DG in pattern separation, with CA3 contributing at moderate to low levels of event similarity (32). Recently, human neuroimaging studies have linked distinct hippocampal representations to better memory, both at encoding (37) and retrieval (46), with an emphasis on CA3 and/or DG (34,46,47).…”

“…We report results for these three subfield ROIs, as well as for a single hippocampal ROI collapsing across subfield labels. Moreover, motivated by computational theories and work with animal models, which highlight different roles for CA3 and DG in memory (32), as well as recent human neuroimaging studies that have examined these regions separately (33,34), we report supplemental exploratory analyses for separate CA2/3 and DG ROIs (Fig. S1).…”

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

“…Breakthroughs in highresolution functional magnetic resonance imaging (fMRI), in particular, have enabled localization of brain activity to hippocampal subfields, although it has been difficult to functionally separate the dentate gyrus and CA3 subfields with currently available methodologies (Lacy, Yassa, Stark, Muftuler, & Stark, 2011). However, behavioral tasks designed to approximate pattern separation and pattern completion have been shown to elicit the predicted pattern of activity in dentate gyrus and CA3/CA1 (Bakker, Kirwan, Miller, & Stark, 2008;Chadwick, Bonnici, & Maguire, 2014;Lacy, Yassa, Stark, Muftuler, & Stark, 2011;Tompary, Duncan, & Davachi, 2016). Indeed, Bakker et al (2008) used 3 Tesla (T) fMRI to scan healthy participants as they performed a modified recognition memory test.…”

“…Examination of discrimination and completion processes in individuals with selective lesions to hippocampal subfields is needed to infer causation in humans (Chadwick et al, 2014). Reports of discrimination deficits in patients with hippocampal lesions exist (Duff et al, 2012;Kirwan et al, 2012), but the lesions in these cases likely encompass other subfields and, in many cases, Hypotheses.…”