CA3 size predicts the precision of memory recall

M. J. Chadwick, H. M. Bonnici, E. A. Maguire
2014 Proceedings of the National Academy of Sciences of the United States of America  
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
more » ... t 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. hippocampus | pattern separation | pattern completion | fMRI | decoding 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. Results We 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. 1) . Each participant viewed the four movies before scanning and then vividly recalled each one numerous times during fMRI. Because the four episodes completely overlapped with one another in terms of their constituent elements, any successful differentiation of the four memories from patterns of activation would suggest the presence of individual episodic memory traces (note that an alternative possibility based on the presence of separate event and spatial context components is considered and ruled out below). Using this paradigm we could also assess whether the recall of an episode led to the coactivation of overlapping episodes through CA3 pattern completion. Such a result would suggest that the episodic representations were not entirely distinct, but overlapped with one another owing to a partial failure of pattern separation. This design therefore allowed us to test for the presence of episodic information within CA3, as well as any possible overlap between the episodic representations. Data were analyzed using a model-based decoding approach (18-20) called multivariate Bayes (21-23) (MVB) in which a hierarchical Bayesian model is used to discover the pattern of voxels that best explains a given target variable from the experimental design (in this case, the activity profile associated with recalling a specific episodic memory). For each model, this voxel pattern was used to produce a predicted information time course, and model fit was assessed by correlating the predicted time course against the target variable. Statistical significance was assessed using a nonparametric permutation approach (24). This involved shuffling the memory labels, which provided a baseline level of information taking into account general retrieval processes, thereby ensuring that any significant results could only be due to the presence of information about each individual memory (Methods). We first assessed whether information about each of the four individual episodes was present within each of the four hippocampal subfields. Using a Bonferroni-corrected threshold of P < 0.0125, we found that only CA3 contained episodic information [t (14) = 3.34, P = 0.0049], whereas the other three subfields did not [CA1: t (14) = 2.02, P = 0.063; DG: t (14) = −0.53, P = 0.6; subiculum: t (14) = 2.09, P = 0.056]. This result is consistent with Significance How does the brain allow us to recall numerous life experiences despite there often being a high degree of similarity between memories? This is a key question in neuroscience. Moreover, there is also keen interest in understanding why some people are able to recall memories with greater clarity than other people. In this study, we identified a specific brain region, CA3, an area within a structure called the hippocampus, and a mechanism within it that helps to explain individual differences in recollection. These findings have relevance for all of us in elucidating memory muddles in general, in aging, and possibly also in conditions such as dementia, where confusion about the past is often evident. Author contributions: M.J.C. and E.A.M. designed research; M.J.C. performed research; H.M.B. contributed new reagents/analytic tools; M.J.C. and E.A.M. analyzed data; and M.J.C. and E.A.M. wrote the paper. The authors declare no conflict of interest.
doi:10.1073/pnas.1319641111 pmid:25002463 pmcid:PMC4115494 fatcat:lpkpxstws5d4lbnm6727guga6m