No evidence of fast mapping in healthy adults using an implicit memory measure: failures to replicate the lexical competition results of Coutanche and Thompson-Schill (2014).

Fast mapping (FM) is a hypothetical, incidental learning process that allows rapid acquisition of new words. Using an implicit reaction time measure in a FM paradigm, Coutanche and Thompson-Schill (Coutanche, M. N., & Thompson-Schill, S. L. (2014). Fast mapping rapidly integrates information into existing memory networks. Journal of Experimental Psychology: General, 143(6), 2296-2303. https://doi.org/10.1037/xge0000020) showed evidence of lexical competition within 10 min of non-words being learned as names of unknown items, consistent with same-day lexicalisation. Here, Experiment 1 was a methodological replication (N = 28/group) that found no evidence of this RT competition effect. Instead, a post-hoc analysis suggested evidence of semantic priming. Experiment 2 (N = 60/group, online study, pre-registered on OSF) tested whether semantic priming remained when making the stimulus set fully counterbalanced. No evidence for either lexical competition nor semantic priming was detected. Experiment 3 (n = 64, online study, pre-registered on OSF) tested whether referent (a)typicality boosted lexical competition (Coutanche, M. N., & Koch, G. E. (2017). Variation across individuals and items determine learning outcomes from fast mapping. Neuropsychologia, 106, 187-193. https://doi.org/10.1016/j.neuropsychologia.2017.09.029), but again no evidence of lexical competition was observed, and Bayes Factors for the data combined across all three experiments supported the hypothesis that there is no effect of lexical competition under FM conditions. These results, together with our previous work, question whether fast mapping exists in healthy adults, at least using this specific FM paradigm.

Modified MRI Anonymization (De-Facing) for Improved MEG Coregistration.

Localising the sources of MEG/EEG signals often requires a structural MRI to create a head model, while ensuring reproducible scientific results requires sharing data and code. However, sharing structural MRI data often requires the face go be hidden to help protect the identity of the individuals concerned. While automated de-facing methods exist, they tend to remove the whole face, which can impair methods for coregistering the MRI data with the EEG/MEG data. We show that a new, automated de-facing method that retains the nose maintains good MRI-MEG/EEG coregistration. Importantly, behavioural data show that this "face-trimming" method does not increase levels of identification relative to a standard de-facing approach and has less effect on the automated segmentation and surface extraction sometimes used to create head models for MEG/EEG localisation. We suggest that this trimming approach could be employed for future sharing of structural MRI data, at least for those to be used in forward modelling (source reconstruction) of EEG/MEG data.

Functional Specialization of the Medial Temporal Lobes in Human Recognition Memory: Dissociating Effects of Hippocampal versus Parahippocampal Damage.

A central debate in the systems neuroscience of memory concerns whether different medial temporal lobe (MTL) structures support different processes in recognition memory. Using two recognition memory paradigms, we tested a rare patient (MH) with a perirhinal lesion that appeared to spare the hippocampus. Consistent with a similar previous case, MH showed impaired familiarity and preserved recollection. When compared with patients with hippocampal lesions appearing to spare perirhinal cortex, MH showed greater impairment on familiarity and less on recollection. Nevertheless, the hippocampal patients also showed impaired familiarity compared with healthy controls. However, when replacing this traditional categorization of patients with analyses relating memory performance to continuous measures of damage across patients, hippocampal volume uniquely predicted recollection, whereas parahippocampal, rather than perirhinal, volume uniquely predicted familiarity. We consider whether the familiarity impairment in MH and our patients with hippocampal lesions arises from "subthreshold" damage to parahippocampal cortex (PHC). Our data provide the most compelling neuropsychological support yet for dual-process models of recognition memory, whereby recollection and familiarity depend on different MTL structures, and may support a role for PHC in familiarity. Our study highlights the value of supplementing single-case studies with examinations of continuous brain-behavior relationships across larger patient groups.

Tau pathology in early Alzheimer's disease is linked to selective disruptions in neurophysiological network dynamics.

Understanding the role of Tau protein aggregation in the pathogenesis of Alzheimer's disease is critical for the development of new Tau-based therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography with [18F]AV-1451 PET scanning to quantify Tau-dependent network changes. Using a graph theoretical approach to brain connectivity, we quantified nodal measures of functional segregation, centrality, and the efficiency of information transfer and tested them against levels of [18F]AV-1451. Higher Tau burden in early Alzheimer's disease was associated with a shift away from the optimal small-world organization and a more fragmented network in the beta and gamma bands, whereby parieto-occipital areas were disconnected from the anterior parts of the network. Similarly, higher Tau burden was associated with decreases in both local and global efficiency, especially in the gamma band. The results support the translational development of neurophysiological "signatures" of Alzheimer's disease, to understand disease mechanisms in humans and facilitate experimental medicine studies.

Response to commentaries on our review of Fast Mapping in adults.

We thank all the commentators for their thoughts on our review of Fast Mapping (FM) in adults, where we questioned the evidence that FM is a distinct learning mechanism, and urged caution over the excitement generated by the original report of FM in adults with amnesia using the fast mapping paradigm (FMP) . While some commentators remain convinced that there is good evidence to support a FM process in adults, most reported a skepticism similar to ours. Here we respond to the main comments, and clarify some of the terms of debate.

Investigating Fast Mapping Task Components: No Evidence for the Role of Semantic Referent nor Semantic Inference in Healthy Adults.

Fast mapping (FM) is an incidental learning process that is hypothesized to allow rapid, cortical-based memory formation, independent of the normal, hippocampally dependent episodic memory system. It is believed to underlie the rapid vocabulary learning in infants that occurs separately from intentional memorisation strategies. Interest in adult FM learning was stimulated by a report in which adults with amnesia following hippocampal damage showed a normal ability to learn new object-name associations after an incidental FM task, despite their impaired memory under a conventional intentional memorization task. This remarkable finding has important implications for memory rehabilitation, and has led to a number of neuropsychological and neuroimaging studies in other patients and controls. Given this growing interest in adult FM, we conducted four behavioural experiments with healthy adults (N = 24 young or older adults in Experiments 1-3 using within-participant designs; N = 195 young adults in Experiment 4 using a between-participant design) that attempted to dissect which component(s) of the FM task are important for memory. Two key components of the FM task have been claimed to support FM learning: (1) provision of a known semantic referent and (2) requirement that the new association be inferred. Experiment 1 provided no evidence that removing the semantic referent impaired memory performance, while Experiment 2 provided no evidence that removing the semantic inference impaired performance. Experiment 3 was a replication of Experiment 2 with older participants, based on the hypothesis (from studies of amnesic individuals) that FM would be more effective following the hippocampal atrophy typical of increasing age, but again found no evidence that semantic inference is beneficial. Given potential concerns about contamination between tasks when each participant performed multiple variants of the FM task, we ran a final between-participant design in which each participant only ever did one condition. Despite 80% power and despite being able to detect better memory following intentional memorization in the explicit encoding (EE) control condition than in each of the FM conditions, we again found no evidence of differences between any FM conditions. We conclude that there is no evidence that the components hypothesized to be critical for FM are relevant to healthy adults.

Knowledge is power: Prior knowledge aids memory for both congruent and incongruent events, but in different ways.

Events that conform to our expectations, that is, are congruent with our world knowledge or schemas, are better remembered than unrelated events. Yet events that conflict with schemas can also be remembered better. We examined this apparent paradox in 4 experiments, in which schemas were established by training ordinal relationships between randomly paired objects, whereas event memory was tested for the number of objects on each trial. Better memory was found for both congruent and incongruent trials, relative to unrelated trials, producing memory performance that was a "U-shaped" function of congruency. The congruency advantage but not incongruency advantage was mediated by postencoding processes, whereas the incongruency advantage, but not congruency advantage, emerged even if the information probed by the memory test was irrelevant to the schema. Schemas therefore augment event memory in multiple ways, depending on the match between novel and existing information. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Little evidence for Fast Mapping (FM) in adults: A review and discussion.

Conventional memory theory proposes that the hippocampus is initially responsible for encoding new information, before this responsibility is gradually transferred to the neocortex. Therefore, a report in 2011 by Sharon et al. of hippocampal-independent learning in humans was notable. These authors reported normal learning of new object-name associations under a Fast Mapping (FM) procedure in adults with hippocampal damage, who were amnesic according to more conventional explicit memorisation procedures. FM is an incidental learning paradigm, inspired by vocabulary acquisition in children, which is hypothesised to allow rapid, cortical-based memory formation. In the years since the original report, there has been, understandably, a growing interest in adult FM, not only because of its theoretical importance, but also because of its potential to help rehabilitate individuals with memory problems. We review the FM literature in individuals with amnesia and in healthy adults, using both explicit and implicit memory measures. Contrary to other recent reviews, we conclude that the evidence for FM in adults is weak, and restraint is needed before assuming the phenomenon exists.

No effect of hippocampal lesions on stimulus-response bindings.

The hippocampus is believed to be important for rapid learning of arbitrary stimulus-response contingencies, or S-R bindings. In support of this, Schnyer et al. (2006) (Experiment 2) measured priming of reaction times (RTs) to categorise visual objects, and found that patients with medial temporal lobe damage, unlike healthy controls, failed to show evidence of reduced priming when response contingencies were reversed between initial and repeated categorisation of objects (a signature of S-R bindings). We ran a similar though extended object classification task on 6 patients who appear to have selective hippocampal lesions, together with 24 age-matched controls. Unlike Schnyer et al. (2006), we found that reversing response contingencies abolished priming in both controls and patients. Bayes Factors provided no reason to believe that response reversal had less effect on patients than controls. We therefore conclude that it is unlikely that the hippocampus is needed for S-R bindings.

Does prediction error drive one-shot declarative learning?

The role of prediction error (PE) in driving learning is well-established in fields such as classical and instrumental conditioning, reward learning and procedural memory; however, its role in human one-shot declarative encoding is less clear. According to one recent hypothesis, PE reflects the divergence between two probability distributions: one reflecting the prior probability (from previous experiences) and the other reflecting the sensory evidence (from the current experience). Assuming unimodal probability distributions, PE can be manipulated in three ways: (1) the distance between the mode of the prior and evidence, (2) the precision of the prior, and (3) the precision of the evidence. We tested these three manipulations across five experiments, in terms of peoples' ability to encode a single presentation of a scene-item pairing as a function of previous exposures to that scene and/or item. Memory was probed by presenting the scene together with three choices for the previously paired item, in which the two foil items were from other pairings within the same condition as the target item. In Experiment 1, we manipulated the evidence to be either consistent or inconsistent with prior expectations, predicting PE to be larger, and hence memory better, when the new pairing was inconsistent. In Experiments 2a-c, we manipulated the precision of the priors, predicting better memory for a new pairing when the (inconsistent) priors were more precise. In Experiment 3, we manipulated both visual noise and prior exposure for unfamiliar faces, before pairing them with scenes, predicting better memory when the sensory evidence was more precise. In all experiments, the PE hypotheses were supported. We discuss alternative explanations of individual experiments, and conclude the Predictive Interactive Multiple Memory Signals (PIMMS) framework provides the most parsimonious account of the full pattern of results.

Assumptions behind scoring source versus item memory: Effects of age, hippocampal lesions and mild memory problems.

Source monitoring paradigms have been used to separate: 1) the probability of recognising an item (Item memory) and 2) the probability of remembering the context in which that item was previously encountered (Source memory), conditional on it being recognised. Multinomial Processing Tree (MPT) models are an effective way to estimate these conditional probabilities. Moreover, MPTs make explicit the assumptions behind different ways to parameterise Item and Source memory. Using data from six independent groups across two different paradigms, we show that one would draw different conclusions about the effects of age, age-related memory problems and hippocampal lesions on Item and Source memory, depending on the use of: 1) standard accuracy calculation vs MPT analysis, and 2) two different MPT models. The MPT results were more consistent than standard accuracy calculations, and furnished additional parameters that can be interpreted in terms of, for example, false recollection or missed encoding. Moreover, a new MPT structure that allowed for separate memory representations (one for item information and one for item-plus-source information; the Source-Item model) fit the data better, and provided a different pattern of significant differences in parameters, than the more conventional MPT structure in which source information is a subset of item information (the Item-Source model). Nonetheless, there is no theory-neutral way of scoring data, and thus proper examination of the assumptions underlying the scoring of source monitoring paradigms is necessary before theoretical conclusions can be drawn.

The effects of hippocampal lesions on MRI measures of structural and functional connectivity.

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph-theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical "hub" in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey-matter volume that was consistent across patients, and the fornix was the only major white-matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default-mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default-mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbic-diencephalic structures and larger-scale networks. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

No evidence that 'fast-mapping' benefits novel learning in healthy Older adults.

Much evidence suggests that the Hippocampus is necessary for learning novel associations. Contrary to this, Sharon, Moscovitch, and Gilboa (2011) reported four amnesic patients with Hippocampal damage who maintained the capacity to learn novel object-name associations when trained with a 'fast-mapping' (FM) technique. This technique therefore potentially offers an alternative route for learning novel information in populations experiencing memory problems. We examined this potential in healthy ageing, by comparing 24 Older and 24 Young participants who completed a FM procedure very similar to Sharon et al. (2011). As expected, the Older group showed worse memory than the Young group under standard explicit encoding (EE) instructions. However, the Older group continued to show worse performance under the FM procedure, with no evidence that FM alleviated their memory deficit. Indeed, performance was worse for the FM than EE condition in both groups. Structural MRI scans confirmed reduced Hippocampal grey-matter volume in the Older group, which correlated with memory performance across both groups and both EE/FM conditions. We conclude FM does not help memory problems that occur with normal ageing, and discuss theoretical implications for memory theories.

Reversible information flow across the medial temporal lobe: the hippocampus links cortical modules during memory retrieval.

A simple cue can be sufficient to elicit vivid recollection of a past episode. Theoretical models suggest that upon perceiving such a cue, disparate episodic elements held in neocortex are retrieved through hippocampal pattern completion. We tested this fundamental assumption by applying functional magnetic resonance imaging (fMRI) while objects or scenes were used to cue participants' recall of previously paired scenes or objects, respectively. We first demonstrate functional segregation within the medial temporal lobe (MTL), showing domain specificity in perirhinal and parahippocampal cortices (for object-processing vs scene-processing, respectively), but domain generality in the hippocampus (retrieval of both stimulus types). Critically, using fMRI latency analysis and dynamic causal modeling, we go on to demonstrate functional integration between these MTL regions during successful memory retrieval, with reversible signal flow from the cue region to the target region via the hippocampus. This supports the claim that the human hippocampus provides the vital associative link that integrates information held in different parts of cortex.

My word! Interference from reading object names implies a role for competition during picture name retrieval.

A related word prime has been found to interfere with picture naming after unrelated intervening trials (word-to-picture interference). Recently, Stroop-type picture-word interference effects have been interpreted in terms of a postlexical response exclusion process rather than a competitive lexical selection process. An experiment is reported that examines whether word-to-picture effects could reflect response exclusion mechanisms and, more generally, strategic processing of the word prime. Forty-eight volunteer university students named aloud sequences of semantically related (and unrelated) word primes and picture targets, separated by two unrelated filler stimuli. On half of the trials, participants were asked to count backwards in threes from a random number presented immediately after naming the prime word. They were also given a surprise recall test at the end of the naming block. Results for naming times and errors indicated a main effect of relatedness; semantic interference effects were not dependent on the unfilled gap following the word prime trial and were also not tied to episodic recall of prime words. The data indicate that slowed picture naming times are more likely to emerge from processes intrinsic to word prime naming rather than controlled processing and do not readily fit the postlexical response exclusion account. The results are considered in relation to two recent accounts of interference over unrelated trials, which refer to some form of competition at, or prior to, lexical access.

The effect of macromolecular crowding on protein aggregation and amyloid fibril formation.

Macromolecular crowding is expected to have several significant effects on protein aggregation; the major effects will be those due to excluded volume and increased viscosity. In this report we summarize data demonstrating that macromolecular crowding may lead to a dramatic acceleration in the rate of protein aggregation and formation of amyloid fibrils, using the protein alpha-synuclein. The aggregation of alpha-synuclein has been implicated as a critical factor in development of Parkinson's disease. Various types of polymers, from neutral polyethylene glycols and polysaccharides (Ficolls, dextrans) to inert proteins, are shown to accelerate alpha-synuclein fibrillation. The stimulation of fibrillation increases with increasing length of polymer, as well as increasing polymer concentration. At lower polymer concentrations (typically up to approximately 100 mg/ml) the major effect is ascribed to excluded volume, whereas at higher polymer concentrations evidence of opposing viscosity effects become apparent. Pesticides and metals, which are linked to increased risk of Parkinson's disease by epidemiological studies, are shown to accelerate alpha-synuclein fibrillation under conditions of molecular crowding.

Accelerated alpha-synuclein fibrillation in crowded milieu.

Parkinson's disease is the second most common age-related neurodegenerative disease, resulting from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of alpha-synuclein has been implicated as a causative factor in the disease, and the process of fibril formation has been intensively studied in vitro with dilute protein solutions. However, the intracellular environment of proteins is crowded with other macromolecules, whose concentration can reach 400 g/l. To address this discrepancy, the effect of molecular crowding on alpha-synuclein fibrillation has being studied. The addition of high concentrations of different polymers (proteins, polysaccharides and polyethylene glycols) dramatically accelerated alpha-synuclein fibrillation in vitro. The magnitude of the accelerating effect depended on the nature of the polymer, its length and concentration. Our results suggest that the major factor responsible for the accelerated fibrillation under crowded conditions is the excluded volume.