Mismatch negativity as a marker of auditory pattern separation.

To what extent does incidental encoding of auditory stimuli influence subsequent episodic memory for the same stimuli? We examined whether the mismatch negativity (MMN), an event-related potential generated by auditory change detection, is correlated with participants' ability to discriminate those stimuli (i.e. targets) from highly similar lures and from dissimilar foils. We measured the MMN in 30 young adults (18-32 years, 18 females) using a passive auditory oddball task with standard and deviant 5-tone sequences differing in pitch contour. After exposure, all participants completed an incidental memory test for old targets, lures, and foils. As expected, participants at test exhibited high sensitivity in recognizing target items relative to foils and lower sensitivity in recognizing target items relative to lures. Notably, we found a significant correlation between MMN amplitude and lure discrimination, but not foil discrimination. Our investigation shows that our capacity to discriminate sensory inputs at encoding, as measured by the MMN, translates into precision in memory for those inputs.

Dentate Gyrus Integrity Is Necessary for Behavioral Pattern Separation But Not Statistical Learning.

Pattern separation, the creation of distinct representations of similar inputs, and statistical learning, the rapid extraction of regularities across multiple inputs, have both been linked to hippocampal processing. It has been proposed that there may be functional differentiation within the hippocampus, such that the trisynaptic pathway (entorhinal cortex > dentate gyrus > CA3 > CA1) supports pattern separation, whereas the monosynaptic pathway (entorhinal cortex > CA1) supports statistical learning. To test this hypothesis, we investigated the behavioral expression of these two processes in B. L., an individual with highly selective bilateral lesions in the dentate gyrus that presumably disrupt the trisynaptic pathway. We tested pattern separation with two novel auditory versions of the continuous mnemonic similarity task, requiring the discrimination of similar environmental sounds and trisyllabic words. For statistical learning, participants were exposed to a continuous speech stream made up of repeating trisyllabic words. They were then tested implicitly through a RT-based task and explicitly through a rating task and a forced-choice recognition task. B. L. showed significant deficits in pattern separation on the mnemonic similarity tasks and on the explicit rating measure of statistical learning. In contrast, B. L. showed intact statistical learning on the implicit measure and the familiarity-based forced-choice recognition measure. Together, these results suggest that dentate gyrus integrity is critical for high-precision discrimination of similar inputs, but not the implicit expression of statistical regularities in behavior. Our findings offer unique new support for the view that pattern separation and statistical learning rely on distinct neural mechanisms.

A Cost-Benefit Analysis of a Group Memory Intervention for Healthy Older Adults with Memory Concerns.

This study examines whether memory intervention programs can mitigate health care costs. Research suggests these programs translate to a decreased intention of older adults who are worried about age-normal memory changes to seek traditional outlets for medical/psychiatric help. We employed a cost-benefit analysis approach to analyze the effectiveness of a memory intervention program within Ontario. We leveraged estimates of decreased intentionality to seek physician care following a community-based memory intervention with physician billing profiles to calculate the potential cost savings to the province's health care system. The intervention studied was found to reduce provincial health care spending by $6,094 per program group. This amount exceeds $121.25 in direct costs per attendee associated with administering five program sessions. This analysis justifies further research on how community-based memory and aging programs can offer low-cost solutions to help individuals cope with subjective memory complaints and assist the health care system in prioritizing care for aging patients.

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

Our day-to-day experiences are often similar to one another, occurring in the same place at the same time of day, with common people and objects, and with a shared purpose. Humans have an episodic memory to represent unique, personal events that are rich in detail [1]. For this to occur, at least two basic neural mechanisms are required: one to orthogonalize or "separate" overlapping input patterns at encoding and another to reinstate or "complete" memories from partial cues at retrieval [2-6]. To what extent do these purported "pattern separation" and "pattern completion" mechanisms rely on distinct subfields of the hippocampus [6]? Computational models [4-6] and lesion and genetic studies in rodents [7-12] largely point to the dentate gyrus as responsible for pattern separation and the CA3 and CA1 subfields for pattern completion (but see [13-16]). In high-resolution fMRI studies of humans, behavioral discrimination and completion tasks designed to approximate pattern separation and pattern completion, respectively, elicit the predicted pattern of activity in the dentate gyrus and CA3/CA1 [17-21]. Likewise, impaired behavioral discrimination has been demonstrated in individuals with hippocampal lesions [22, 23], but the lesions most likely encompass other subfields. Examination of these processes in individuals with selective lesions to hippocampal subfields is needed to infer causation [19]. Here, we report the rare case of BL, a 54-year-old man with bilateral ischemic lesions to the hippocampus [24] primarily affecting the dentate gyrus. Studying BL provides the unique opportunity to directly evaluate theories of hippocampal function that assign the dentate gyrus a specific role in discriminating old from new memories.