Pattern separation and pattern completion in Alzheimer's disease: Evidence of rapid forgetting in amnestic mild cognitive impairment

Abstract

Over the past four decades, the characterization of memory loss associated with Alzheimer's disease (AD) has been extensively debated. Recent iterations have focused on disordered encoding versus rapid forgetting. To address this issue, we used a behavioral pattern separation task to assess the ability of the hippocampus to create and maintain distinct and orthogonalized visual memory representations in patients with amnestic mild cognitive impairment (aMCI) and mild AD. We specifically used a lag-based continuous recognition paradigm to determine whether patients with aMCI and mild AD fail to encode visual memory representations or whether these patients properly encode representations that are rapidly forgotten. Consistent with the rapid forgetting hypothesis of AD, we found that patients with aMCI demonstrated decreasing pattern separation rates as the lag of interfering objects increased. In contrast, patients with AD demonstrated consistently poor pattern separation rates across three increasingly longer lags. We propose a continuum that reflects underlying hippocampal neuropathology whereby patients with aMCI are able to properly encode information into memory but rapidly lose these memory representations, and patients with AD, who have extensive hippocampal and parahippocampal damage, cannot properly encode information in distinct, orthogonal representations. Our results also revealed that whereas patients with aMCI demonstrated similar behavioral pattern completion rates to healthy older adults, patients with AD showed lower pattern completion rates when we corrected for response bias. Finally, these behavioral pattern separation and pattern completion results are discussed in terms of the dual process model of recognition memory.

Time manages interference in visual short-term memory

“…The comparisons of older adults, individuals with aMCI and with AD in the study of Ally et al (2013), which formed the basis for the present investigation, appeared to uncover a form of rapid interference-based forgetting. Individuals with aMCI and AD showed decreased pattern separation scores (BPS) with increasing 'lag'.…”

“…Although very interesting, the differing patterns of performance in pattern separation on the behavioural task demonstrated by Ally et al (2013) across normal ageing, aMCI and AD individuals must remain very tentative since their manipulation confounded two critical dimensions identified within theories of forgetting (Altmann & Gray, 2002): namely the temporal interval elapsing (that is, between encoding of an 'old' item into memory and its reintroduction later as a 'similar' item) and the number of intervening items occurring within this temporal interval. Time based forgetting in short term memory is well documented both in our own laboratory (McKeown, Holt, Delvenne, Smith & Griffiths, 2014;McKeown & Mercer, 2012;Mercer & McKeown, 2014) and elsewhere (Zhang & Luck, 2009), yet the underlying mechanisms of such decline in memory over time are fiercely debated (Altmann & Schunn, 2012;Waugh & Norman, 1965).…”

“…This is critical for the effective application of the BPS within the neuroscience and psychological literatures more broadly, beyond accounting for the outcomes in the specific populations employed by Ally et al (2013). We therefore recruited a young sample of adults of restricted age range, both to rule out extraneous ageand dementia-related factors (a younger sample is less likely to present with undetected neuropathology), and to allow for a more homogeneous group cognitively (older participants TIME MANAGES INTERFERENCE 8 become increasingly heterogeneous in this respect).…”

“…The task was adapted from Ally et al (2013) and arranged into 60-trial blocks, consisting of 20 single 'new' items, 10 'old' item pairs (an item presented and later presented again), and 10 'similar' item pairs (an item presented and a very similar item presented later). Throughout we use the words new, old and similar to refer both to our stimuli and to the response to those stimuli.…”

Pattern separation performance is decreased in patients with early multiple sclerosis

“…The bias towards pattern completion (i.e., incorrectly recognized a "similar" item as an "old" studied item) measured in PweMS appeared to be the counterpart of pattern separation impairment because these two processes work concurrently (Ally et al, 2013). Indeed, previous rodents and human studies have suggested that when dentate gyrus is unable to perform pattern separation, CA3 (and its connections to CA1) could balance this deficit by overwriting previous representations (Neunuebel & Knierim, 2014;.…”