The Contributions of Eye Gaze Fixations and Target-Lure Similarity to Behavioral and fMRI Indices of Pattern Separation and Pattern Completion

Pattern separation and pattern completion are generally studied in humans using mnemonic discrimination tasks such as the Mnemonic Similarity Task (MST) where participants identify similar lures and repeated items from a series of images. Failures to correctly discriminate lures are thought to reflect a failure of pattern separation and a propensity toward pattern completion. Recent research has challenged this perspective, suggesting that poor encoding rather than pattern completion accounts for the occurrence of false alarm responses to similar lures. In two experiments, participants completed a continuous recognition task version of the MST while eye movement (Experiment 1 and 2) and fMRI data (Experiment 2) were collected. While we replicated the result that fixation counts at study predicted accuracy on lure trials, we found that target-lure similarity was a much stronger predictor of accuracy on lure trials across both experiments. Lastly, we found that fMRI activation changes in the hippocampus were significantly correlated with the number of fixations at study for correct but not incorrect mnemonic discrimination judgments when controlling for target-lure similarity. Our findings indicate that while eye movements during encoding predict subsequent hippocampal activation changes, mnemonic discrimination performance is better described by pattern separation and pattern completion processes that are influenced by target-lure similarity than simply poor encoding.

Unfamiliar Contexts Compared to Familiar Contexts Impair Learning in Humans

Context plays a key role in learning and memory processes. Re-exposure to the context that information was learned in facilitates memory retrieval of this information. However, it is currently unclear whether context changes also influence the ability to learn new information, which the present work investigated in two experiments with healthy participants (n = 40 per experiment; 20 female). In experiment 1, participants learned a list of word-pairs (A-B) in the morning and a second non-overlapping list (C-D) in the evening, either in the same context or in a different context than the first list (between-subjects). We confirmed that new learning is enhanced if it takes place in the same context, putatively driven by context-dependent retrieval of meta-learning processes. In addition, new learning in the other context was significantly decreased compared to baseline. In experiment 2, participants were exposed to both contexts in the morning, but only learned word-pairs in one of them. Familiarity with the other context abolished differences between the same and other context group. These data point to the novelty of the context interfering with new learning rather than the familiarity of the context enhancing it. Importantly, the reduction of new learning in the other context in the first experiment, where the context was unfamiliar in both learning sessions, suggests mechanisms beyond attention processes that are bound by the novelty of the other context. Rather, the old context impairs the processing of the new context, possibly by biasing pattern completion and pattern separation trade-offs within the hippocampus.

Neural dynamics of retrieval suppression in abolishing item-specific cortical pattern of unwanted emotional memories

When reminded of an unpleasant experience, people often try to exclude the unwanted memory from awareness in an effort to forget it, a process known as retrieval suppression. Yet, how fast can individual memories be targeted and controlled, and the neural dynamics in modulating cortical traces of individual memories, remain elusive. Here, using multivariate decoding analyses on time-domain and time-frequency-domain EEGs, we found that retrieval suppression of aversive memories was distinct from retrieval and passive viewing, when given a reminder. Specifically, early elevation of mid-frontal theta power during the first 500 ms distinguished retrieval suppression from passive viewing, suggesting that suppression recruited early active control processes. On an item-level, we could discern activities relating to individual memories during active retrieval-initially, based on perceptual responses to reminders (0-500 ms) and later, via the reinstatement and maintenance of the target aversive scenes (500-3000 ms). Critically, suppressing retrieval significantly weakened (during 420-600 ms) and eventually abolished these item-specific cortical patterns till cue disappeared (1200-3000 ms), suggesting the successful exclusion of the unwelcome memory from awareness. Suppression of item-specific cortical patterns bore behavioral consequences in predicting subsequent episodic forgetting. These findings provide unique insight into the neural dynamics underlying the control of unwelcome memories: upon perceiving an unwelcome reminder, people rapidly deploy inhibitory control to truncate retrieval within 500 ms, which likely terminate the reminder-to-memory conversion at around 500 ms that would ordinarily arise through hippocampal pattern completion. We concluded that both rapid and sustained control are critical in abolishing cortical patterns of individual memories, limiting unwelcome awareness, and precipitating later forgetting.

Proximal CA3 is the primary locus of age-related pattern separation deficits in rats

Age-related deficits in pattern separation have been postulated to bias the output of hippocampal memory processing toward pattern completion, which can cause deficits in accurate memory retrieval. While the CA3 region of the hippocampus is often conceptualized as a homogeneous network involved in pattern completion, growing evidence demonstrates a functional gradient in CA3 along the transverse axis, with proximal CA3 supporting pattern separation and distal CA3 supporting pattern completion. We examined the neural representations along the CA3 transverse axis in young (Y), aged memory-unimpaired (AU), and aged memory-impaired (AI) rats when different changes were made to the environment. When the environmental similarity was high (e.g., altered cues or altered environment shapes in the same room), Y and AU rats showed more orthogonalized representations in proximal CA3 than in distal CA3, consistent with prior studies showing a functional dissociation along the transverse axis of CA3. In contrast, AI rats showed less orthogonalization in proximal CA3 than Y and AU rats but showed more normal (i.e., generalized) representations in distal CA3, with little evidence of a functional gradient. When the environmental similarity was low (e.g., recordings were done in different rooms), representations in proximal and distal CA3 remapped in all rats, showing that AI rats are able to dissociate representations when inputs show greater dissimilarity. These results provide evidence that the aged-related bias towards pattern completion is due to the loss in AI rats of the normal transition from pattern separation to pattern completion along the CA3 transverse axis and, furthermore, that proximal CA3 is the primary locus of this age-related dysfunction in neural coding.

Negative Overgeneralization is Associated with Anxiety and Mechanisms of Pattern Completion in Peripubertal Youth

This study examines neural mechanisms of negative overgeneralization, the increased likelihood of generalizing negative information, in peri-puberty. Theories suggest that weak pattern separation (overlapping representations are made distinct, indexed by DG/CA3 hippocampal subfield activation) underlies negative overgeneralization. We alternatively propose that neuro-maturational changes that favor pattern completion (cues reinstate stored representations, indexed by CA1 activation) are modulated by circuitry involved in emotional responding (amygdala, medial prefrontal cortices [mPFC]) to drive negative overgeneralization. Youth (N=34, 9-14 years) recruited from community and clinic settings participated in an emotional mnemonic similarity task while undergoing MRI. At Study, participants indicated the valence of images; at Test, participants made recognition memory judgments. Critical lure stimuli, that were similar to images at Study, were presented at Test, and errors (“false alarms”) to negative relative to neutral stimuli reflected negative overgeneralization. Negative overgeneralization was related to greater and more similar patterns of activation in CA1 and both dorsal and ventral mPFC for negative relative to neutral stimuli. At Study, amygdala exhibited greater functional coupling with CA1 and dorsal mPFC during negative items that were later generalized. Negative overgeneralization is rooted in amygdala and mPFC modulation at encoding and pattern completion at retrieval.

Compassion and skillful means: Cultural adaptation, psychological science, and creative responsiveness

In this article, we address two distinct, but interrelated aspects of “skillful means” that can inform compassion training: 1) the historical precedent and need for adapting meditation practices to meet new cultural contexts, and 2) the need to express compassion flexibly in ways that creatively meet the specific contexts and needs of particular persons and situations. We first discuss ways that the doctrine of skillful means was employed by Buddhists to rationalize the repeated adaptation of Buddhist teachings to meet the culturally situated mentalities and needs of diverse Asian peoples. Then, in continuity with that history of Buddhist adaptation, we explore how theories from modern psychological science, such as attachment theory, can be newly drawn upon to support adaptation of Buddhist compassion training for application in modern cultures. Finally, we draw on theories from cognitive science, namely situated conceptualization, that provide a tractable framework for understanding skillful compassion as embodied emptiness—involving the relaxation of pattern completion mechanisms, which helps open up greater discernment and presence to others, so that care and compassion can be more unrestricted, creative, and directly responsive to the person and situation at hand.