PRKCA polymorphism changes the neural basis of episodic remembering in healthy individuals.
ABSTRACT: Everyday functioning relies on episodic memory, the conscious retrieval of past experiences, but this crucial cognitive ability declines severely with aging and disease. Vulnerability to memory decline varies across individuals however, producing differences in the time course and severity of memory problems that complicate attempts at diagnosis and treatment. Here we identify a key source of variability, by examining gene dependent changes in the neural basis of episodic remembering in healthy adults, targeting seven polymorphisms previously linked to memory. Scalp recorded Event-Related Potentials (ERPs) were measured while participants remembered words, using an item recognition task that requires discrimination between studied and unstudied stimuli. Significant differences were found as a consequence of a Single Nucleotide Polymorphism (SNP) in just one of the tested genes, PRKCA (rs8074995). Participants with the common G/G variant exhibited left parietal old/new effects, which are typically seen in word recognition studies, reflecting recollection-based remembering. During the same stage of memory retrieval participants carrying a rarer A variant exhibited an atypical pattern of brain activity, a topographically dissociable frontally-distributed old/new effect, even though behavioural performance did not differ between groups. Results replicated in a second independent sample of participants. These findings demonstrate that the PRKCA genotype is important in determining how episodic memories are retrieved, opening a new route towards understanding individual differences in memory.
Project description:Although autobiographical memory and episodic simulations recruit similar core brain regions, episodic simulations engage additional neural recruitment in the frontoparietal control network due to greater demands on constructive processes. However, previous functional neuroimaging studies showing differences in remembering and episodic simulation have focused on veridical retrieval of past experiences, and thus have not fully considered how retrieving the past in different ways from how it was originally experienced may also place similar demands on constructive processes. Here we examined how alternative versions of the past are constructed when adopting different egocentric perspectives during autobiographical memory retrieval compared to simulating hypothetical events from the personal past that could have occurred, or episodic counterfactual thinking. Participants were asked to generate titles for specific autobiographical memories from the last five years, and then, during functional magnetic resonance (fMRI) scanning, were asked to repeatedly retrieve autobiographical memories or imagine counterfactual events cued by the titles. We used an fMRI adaptation paradigm in order to isolate neural regions that were sensitive to adopting alternative egocentric perspectives and counterfactual simulations of the personal past. The fMRI results revealed that voxels within left posterior inferior parietal and ventrolateral frontal cortices were sensitive to novel visual perspectives and counterfactual simulations. Our findings suggest that the neural regions supporting remembering become more similar to those underlying episodic simulation when we adopt alternative egocentric perspectives of the veridical past.
Project description:Researchers and clinicians routinely rely on patients' retrospective emotional self-reports to guide diagnosis and treatment, despite evidence of impaired autobiographical memory and retrieval of emotional information in depression and anxiety. To clarify the nature and specificity of these impairments, we conducted two large online data collections (Study 1, N = 1,983; Study 2, N = 900) examining whether depression and/or anxiety symptoms would uniquely predict the use of self-reported episodic (i.e., remembering) and/or semantic (i.e., knowing) retrieval when rating one's positive and negative emotional experiences over different time frames. Participants were randomly assigned to one of six time frames (ranging from at this moment to last few years) and were asked to rate how intensely they felt each of four emotions, anxious, sad, calm, and happy, over that period. Following each rating, they were asked several follow-up prompts assessing their perceived reliance on episodic and/or semantic information to rate how they felt, using procedures adapted from the traditional "remember/know" paradigm (Tulving, 1985). Across both studies, depression and anxiety symptoms each uniquely predicted increased likelihood of remembering across emotion types, and decreased likelihood of knowing how one felt when rating positive emotion types. Implications for the theory and treatment of emotion-related memory disturbances in depression and anxiety, and for dual-process theories of memory retrieval more generally, are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Project description:Autobiographical remembering can depend on two forms of memory: episodic (event) memory and autobiographical semantic memory (remembering personally relevant semantic knowledge, independent of recalling a specific experience). There is debate about the degree to which the neural signals that support episodic recollection relate to or build upon autobiographical semantic remembering. Pooling data from two fMRI studies of memory for real-world personal events, we investigated whether medial temporal lobe (MTL) and parietal subregions contribute to autobiographical episodic and semantic remembering. During scanning, participants made memory judgments about photograph sequences depicting past events from their life or from others' lives, and indicated whether memory was based on episodic or semantic knowledge. Results revealed several distinct functional patterns: activity in most MTL subregions was selectively associated with autobiographical episodic memory; the hippocampal tail, superior parietal lobule, and intraparietal sulcus were similarly engaged when memory was based on retrieval of an autobiographical episode or autobiographical semantic knowledge; and angular gyrus demonstrated a graded pattern, with activity declining from autobiographical recollection to autobiographical semantic remembering to correct rejections of novel events. Collectively, our data offer insights into MTL and parietal cortex functional organization, and elucidate circuitry that supports different forms of real-world autobiographical memory.
Project description:Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.
Project description:Episodic memory refers to a complex and multifaceted process which enables the retrieval of richly detailed evocative memories from the past. In contrast, semantic memory is conceptualized as the retrieval of general conceptual knowledge divested of a specific spatiotemporal context. The neural substrates of the episodic and semantic memory systems have been dissociated in healthy individuals during functional imaging studies, and in clinical cohorts, leading to the prevailing view that episodic and semantic memory represent functionally distinct systems subtended by discrete neurobiological substrates. Importantly, however, converging evidence focusing on widespread neural networks now points to significant overlap between those regions essential for retrieval of autobiographical memories, episodic learning, and semantic processing. Here we review recent advances in episodic memory research focusing on neurodegenerative populations which has proved revelatory for our understanding of the complex interplay between episodic and semantic memory. Whereas episodic memory research has traditionally focused on retrieval of autobiographical events from the past, we also include evidence from the recent paradigm shift in which episodic memory is viewed as an adaptive and constructive process which facilitates the imagining of possible events in the future. We examine the available evidence which converges to highlight the pivotal role of semantic memory in providing schemas and meaning whether one is engaged in autobiographical retrieval for the past, or indeed, is endeavoring to construct a plausible scenario of an event in the future. It therefore seems plausible to contend that semantic processing may underlie most, if not all, forms of episodic memory, irrespective of temporal condition.
Project description:The medial temporal lobes, prefrontal cortex and parts of parietal cortex form the neural underpinnings of episodic memory, which includes remembering both where and when an event occurred. However, the manner in which these three regions interact during retrieval of spatial and temporal context remains untested. We employed simultaneous electrocorticographical recordings across multilobular regions in patients undergoing seizure monitoring while they retrieved spatial and temporal context associated with an episode, and we used phase synchronization as a measure of network connectivity. Successful memory retrieval was characterized by greater global connectivity compared with incorrect retrieval, with the medial temporal lobe acting as a hub for these interactions. Spatial versus temporal context retrieval resulted in prominent differences in both the spectral and temporal patterns of network interactions. These results emphasize dynamic network interactions as being central to episodic memory retrieval, providing insight into how multiple contexts underlying a single event can be recreated in the same network.
Project description:Population transmembrane currents and neuronal firing in different layers of the human entorhinal cortex (ER) were recorded during semantic and episodic memory processes using a linear array of 24 laminar microelectrodes. Both measures, as well as local broadband spectral power, increased during retrieval of newly-learned characteristics, especially in superficial layers. No differences were observed in the activity evoked by remembering people as compared to places. Semantic retrieval evoked similar activity. In contrast, intentional encoding of declarative memory evoked relatively little activity. A double-dissociation of these responses with simultaneously recorded lateral inferotemporal recordings suggests that entorhinal cortex may be specifically engaged during retrieval, across multiple memory types and materials.
Project description:Memories are of the past but for the future, enabling individuals to implement intended plans and actions at the appropriate time. Prospective memory is the specific ability to remember and execute an intended behavior at some designated point in the future. Although sleep is well-known to benefit the consolidation of memories for past events, its role for prospective memory is still not well understood. Here, we show that sleep as compared to wakefulness after prospective memory instruction enhanced the successful execution of prospective memories two days later. We further show that sleep benefited both components of prospective memory, i.e. to remember that something has to be done (prospective component) and to remember what has to be done (retrospective component). Finally, sleep enhanced prospective remembering particularly when attentional resources were reduced during task execution, suggesting that subjects after sleep were able to recruit additional spontaneous-associative retrieval processes to remember intentions successfully. Our findings indicate that sleep supports the maintenance of prospective memory over time by strengthening intentional memory representations, thus favoring the spontaneous retrieval of the intended action at the appropriate time.
Project description:The content of episodic memory consists of representations of unique past events. Episodic memories are grounded in a temporal framework (i.e., we remember when an event occurred). It has recently been argued that episodic-like memory in rats is qualitatively different from human episodic memory because, rather than remembering when an earlier past event occurred, rats used the cue of how long ago it occurred. We asked, therefore, whether rats remember the time of day at which they encountered a distinctive event, in addition to what occurred and where it happened. Rats were tested in the morning and afternoon, on separate days. A distinctive flavor (chocolate) was replenished at a daily-unique location at only one of these times. The interval between first and second daily opportunities to eat (study and test, respectively) was constant. Rats adjusted their revisits to the chocolate location at different times of day by using time of day rather than the cue of how long ago an event occurred. Two lines of evidence suggest that rats remembered the time at which the distinctive event occurred. First, under conditions in which the time of test (but not time of study) was novel, rats immediately transferred their knowledge of the chocolate contingency to the new test time. Second, under conditions in which predictions for study and test times were put in conflict, rats again used study time. Our results suggest that, at the time of memory assessment, rats remember when a recent episode occurred, similar to human episodic memory.