Mechanisms involved in the assessment of cumulative long-term familiarity of object concepts: An ERP study

We investigated the sensitivity of ERP components implicated in recognition memory to degree of experimentally controlled and lifetime cumulative exposures during explicit memory judgements. A parietally distributed ERP component spanning both the FN400/N400 and the LPC time windows tracked both types of judgements. This effect appears to be an LPC effect with an early onset, and differs from previously reported effects of repetition linked to implicit memory. Based on recent evidence, we interpreted it as response-related evidence accumulation processes that are in line with both single-process models and continuous dual-process models. We also observed more positive ERPs in the left ROIs for frequency judgements as compared to lifetime familiarity judgements. This effect could be linked to encoding differences in the perirhinal cortex. Our findings provided new evidence concerning the memory of cumulative exposures, and demonstrated the possibility of studying certain aspects of lifetime cumulative familiarity in a laboratory environment

Feeling-of-knowing experiences breed curiosity

A central tenet in theoretical work on metacognition is that retrieval experiences during memory search can exert control over behaviour. States of curiosity, which reflect motivational tendencies to seek out information, may play a critical role in this control function. We conducted two experiments to address this idea, focusing on links between feeling-of knowing (FOK) experiences, memory-search duration, and subsequent information-seeking behaviour. We administered an episodic FOK paradigm that probed memory for previously studied face-name pairs, and subsequently provided an opportunity to select limited pairs for restudy. This set-up allowed us to test whether current search duration and subsequent restudy choices are biased towards items with high FOK ratings. Results revealed a positive relationship between FOK ratings and the response times of these judgements. We observed a similar positive relationship between FOK ratings and subsequent item selection for restudy. Moreover, experimental manipulations of FOK ratings based on familiarity of the face cues also had parallel effects. Our findings suggest that metacognitive experiences during unsuccessful retrieval from episodic memory can induce states of curiosity that shape behaviour beyond the immediate retrieval context. Curiosity may act as a bond to ensure that memory gaps identified through unsuccessful retrieval adaptively guide future learning

Late positive complex in event-related potentials tracks memory signals when they are decision relevant.

The Late Positive Complex (LPC) is an Event-Related Potential (ERP) consistently observed in recognition-memory paradigms. In the present study, we investigated whether the LPC tracks the strength of multiple types of memory signals, and whether it does so in a decision dependent manner. For this purpose, we employed judgements of cumulative lifetime exposure to object concepts, and judgements of cumulative recent exposure (i.e., frequency judgements) in a study-test paradigm. A comparison of ERP signatures in relation to degree of prior exposure across the two memory tasks and the study phase revealed that the LPC tracks both types of memory signals, but only when they are relevant to the decision at hand. Another ERP component previously implicated in recognition memory, the FN400, showed a distinct pattern of activity across conditions that differed from the LPC; it tracked only recent exposure in a decision-dependent manner. Another similar ERP component typically linked to conceptual processing in past work, the N400, was sensitive to degree of recent and lifetime exposure, but it did not track them in a decision dependent manner. Finally, source localization analyses pointed to a potential source of the LPC in left ventral lateral parietal cortex, which also showed the decision-dependent effect. The current findings highlight the role of decision making in ERP markers of prior exposure in tasks other than those typically used in studies of recognition memory, and provides an initial link between the LPC and the previously suggested role of ventral lateral parietal cortex in memory judgements

Neural correlates of familiarity across time scales and their involvement in explicit memory decisions

Familiarity is a type of memory signal that can support recognition of prior occurrences without retrieval of associated contextual information. It is typically probed with respect to recent laboratory exposure in recognition-memory studies involving human participants. This line of work has revealed several neural correlates including event-related potentials (ERPs) and blood-oxygenation-level-dependent (BOLD) activity in several regions. However, few studies have examined familiarity accumulated outside of laboratory settings through lifetime experience. Hence, it is currently unclear whether similar neural correlates are involved. The fluency-attribution framework decomposes familiarity judgement into automatic and decision-related processes. Since recent and lifetime familiarity are phenomenologically and experimentally dissociable for meaningful stimuli, another question is whether certain neural correlates track both types of familiarity regardless of task relevance --- as a marker of automaticity, and whether they can be distinguished from other neural correlates that are decision-related. To answer these questions, I conducted an ERP and an fMRI study using a common paradigm in which degree of recent and lifetime familiarity could be compared in both task-relevant and -irrelevant conditions. In Chapter 2, I focused on ERP (FN400/N400 and LPC) responses and found that the LPC tracked both lifetime and recent familiarity when they were relevant to the task, while the N400 tracked both types of familiarity regardless of task relevance. The FN400 was sensitive only to task-relevant recent familiarity. In Chapter 3, I focused on BOLD activity in PrC and found that the left PrC tracked both types of familiarity regardless of task-relevance, while a set of frontoparietal regions tracked only task-relevant familiarity. In Chapter 4, I attempted to further delineate the decision-related neural correlates in familiarity judgement by combining the fMRI data collected in Chapter 3 with drift-diffusion modelling (DDM). A model comparison procedure showed that familiarity effects in medial frontal regions were most strongly involved in decision-making, followed by PrC, then by medial parietal regions. Overall, these results revealed temporally (ERP) and spatially (fMRI) distinct neural correlates corresponding to the automatic and decision-related processes in both recent and lifetime familiarity judgement. Furthermore, a hierarchy exists among the decision-related neural correlates

Global matching and fluency attribution in familiarity assessment

Copyright © Cambridge University Press 2020. In the integrative memory model proposed by Bastin et al.familiarity is thought to arise from attribution of fluency signals. We suggest that, from a computational and anatomical perspective, this conceptualization converges with a global-matching account of familiarity assessment. We also argue that consideration of global matching and evidence accumulation in decision making could help further our understanding of the proposed attribution system

Deficits in recent but not lifetime familiarity in amnestic mild cognitive impairment.

People with amnestic mild cognitive impairment (aMCI) repeat questions, seemingly without any sense of familiarity (i.e., recognition of prior occurrence without recollection of episodic context). Accumulation of neurofibrillary tau in preclinical Alzheimer\u27s disease begins in perirhinal cortex, a medial temporal lobe region linked to familiarity. Both observations would predict impaired familiarity assessment in aMCI; however, the extant evidence is mixed. To reveal familiarity impairments, it may be necessary to minimize the influence of recollection. In the current study, older adults with aMCI and healthy controls were administered two tasks on which a well-characterized patient (NB) with selective familiarity impairments due to surgical left temporal lobe excision sparing the hippocampus showed abnormal performance: frequency judgments for words exposed to in a recent study phase and judgments of cumulative lifetime familiarity for object concepts denoted by words. We also administered a process dissociation procedure (PDP) task that previously revealed spared familiarity in aMCI. We predicted that familiarity would be spared in aMCI on the PDP task, but impaired when assessed by frequency judgments for recent laboratory exposures and lifetime familiarity judgments. Familiarity was spared on the PDP task, but was impaired when probed with frequency judgments for recently exposed words in aMCI. Lifetime familiarity was also not impaired in aMCI. These results highlight the benefits of studying familiarity under conditions that minimize recollection and the value of frequency judgments in revealing familiarity deficits, and suggest that perirhinal cortex may not be necessary for accessing familiarity accumulated over a lifetime of experience

Endoplasmic reticulum stress mediates nickel chloride-induced epithelial‑mesenchymal transition and migration of human lung cancer A549 cells through Smad2/3 and p38 MAPK activation

Background: The endoplasmic reticulum (ER) is a cellular membrane-bound organelle whereby proteins are synthesized, folded and glycosylated. Due to intrinsic (e.g., genetic) and extrinsic (e.g., environmental stressors) perturbations, ER proteostasis can be deregulated within cells which triggers unfolded protein response (UPR) as an adaptive stress response that may impact the migration and invasion properties of cancer cells. However, the mechanisms underlying the nickel compounds on lung cancer cell migration and invasion remain uncertain. Objective: We aimed to study whether Nickel chloride (NiCl2) induces ER stress in lung cancer cells, and whether ER stress is involved in modulating epithelial-mesenchymal transition (EMT) and migration by Smads and MAPKs pathways activation following NiCl2 treatment. Methods: A549 cells were treated with NiCl2 to determine the cell viability using MTT assay. The wound healing assay was used to evaluate cell migration ability. ER ultrastructure was observed by transmission electron microscopy. Western blotting assay was performed to evaluate the protein levels of BIP, PERK, IRE-1α, XBP-1 s, and ATF6 for ER stress and UPR, E-cadherin and Vimentin for EMT, p-Smad2/3, p-ERK, p-JNK, and p-P38 for activation of Smads and MAPKs signaling pathways. Results: The expression levels of BIP, PERK, IRE-1α, XBP-1 s, and ATF6 were significantly increased following treatment with NiCl2 in time- and dose-effect relationship. The ER stress inhibitor 4-PBA downregulated the expression levels of the above five proteins, and reversed the decrease in E-cadherin protein level and the increase in vimentin protein expression and cell migration abilities caused by NiCl2. Furthermore, 4-PBA significantly reduced nickel chloride-induced Smad2/3 and p38 MAPK pathway activation, while not affected ERK and JNK MAPK pathways. Conclusion: NiCl2 triggers ER stress and UPR in A549 cells. Moreover, 4-PBA alleviates NiCl2-induced EMT and migration ability of A549 cells possibly through the Smad2/3 and p38 MAPK pathways activation, rather than ERK and JNK MAPK pathways