Understanding perirhinal contributions to perception and memory: Evidence through the lens of selective perirhinal damage.

Although a memory systems view of the medial temporal lobe (MTL) has been widely influential in understanding how memory processes are implemented, a large body of work across humans and animals has converged on the idea that the MTL can support various other decisions, beyond those involving memory. Specifically, recent work suggests that perception of and memory for visual representations may interact in order to support ongoing cognition. However, given considerations involving lesion profiles in neuropsychological investigations and the correlational nature of fMRI, the precise nature of representations supported by the MTL are not well understood in humans. In the present investigation, three patients with highly specific lesions to MTL were administered a task that taxed perceptual and mnemonic judgments with highly similar face stimuli. A striking double dissociation was observed such that I.R., a patient with a cyst localized to right posterior PRc, displayed a significant impairment in perceptual discriminations, whereas patient A.N., an individual with a lesion in right posterior parahippocampal cortex and the tail of the right hippocampus, and S.D., an individual with bilateral hippocampal damage, did not display impaired performance on the perceptual task. A.N. and S.D. did, however, show impairments in memory performance, whereas patient I.R. did not. These results causally implicate right PRc in successful perceptual oddity judgments, however they suggest that representations supported by PRc are not necessary for correct mnemonic judgments, even in situations of high featural overlap.

Dynamic integration of conceptual information during learning.

The development and application of concepts is a critical component of cognition. Although concepts can be formed on the basis of simple perceptual or semantic features, conceptual representations can also capitalize on similarities across feature relationships. By representing these types of higher-order relationships, concepts can simplify the learning problem and facilitate decisions. Despite this, little is known about the neural mechanisms that support the construction and deployment of these kinds of higher-order concepts during learning. To address this question, we combined a carefully designed associative learning task with computational model-based functional magnetic resonance imaging (fMRI). Participants were scanned as they learned and made decisions about sixteen pairs of cues and associated outcomes. Associations were structured such that individual cues shared feature relationships, operationalized as shared patterns of cue pair-outcome associations. In order to capture the large number of possible conceptual representational structures that participants might employ and to evaluate how conceptual representations are used during learning, we leveraged a well-specified Bayesian computational model of category learning [1]. Behavioral and model-based results revealed that participants who displayed a tendency to link experiences in memory benefitted from faster learning rates, suggesting that the use of the conceptual structure in the task facilitated decisions about cue pair-outcome associations. Model-based fMRI analyses revealed that trial-by-trial integration of cue information into higher-order conceptual representations was supported by an anterior temporal (AT) network of regions previously implicated in representing complex conjunctions of features and meaning-based information.

Differentiation of Human Medial Prefrontal Cortex Activity Underlies Long-Term Resistance to Forgetting in Memory.

It is well known that distributing study events over time leads to better memory over long time scales, compared with massing study events together. One explanation for such long-term resistance to forgetting is that distributed study leads to neural differentiation in memory, which supports retrieval of past experiences by disambiguating highly similar memory representations. Neuroanatomical models of episodic memory retrieval propose that the hippocampus and medial prefrontal cortex (MPFC) work together to enable retrieval of behaviorally appropriate memories. However, it is not known how representations in these regions jointly support resistance to forgetting long after initial learning. Using fMRI, we measured differentiation in retrieved memory representations following an extended delay in male and female human participants. After 1 week, word-object associations were better remembered if studied across 2 d (overnight), allowing associations to be learned in distinct temporal contexts, compared with learning within a single day (same day). MPFC retrieval patterns showed differentiation for overnight relative to same day memories, whereas hippocampal patterns reflected associative retrieval success. Overnight memory differentiation in MPFC was higher for associative than item memories and higher than differentiation assessed over a brain-wide set of retrieval-active voxels. The memory-related difference in MPFC pattern differentiation correlated with memory success for overnight learning and with hippocampal-MPFC functional connectivity. These results show that learning information across days leads to differentiated MPFC memory representations, reducing forgetting after 1 week, and suggest this arises from persistent interactions between MPFC and hippocampus.SIGNIFICANCE STATEMENT Neural activity in both the hippocampus and medial prefrontal cortex (MPFC) has been linked to memory-related representations, but prior work has not examined how these representations support episodic memory retrieval over extended time scales that are characteristic of everyday retrieval. We show that differentiation in MPFC activity 1 week after encoding is higher for retrieved information learned across 2 d compared with within a single day. In hippocampus, differentiation was greater for detailed memory retrieval but was not influenced by whether information had been learned over 1 or 2 d. Differentiation in MPFC predicted behavioral robustness to forgetting and was correlated with hippocampal-MPFC connectivity. The results suggest that context-based differentiation supports robust long-term memory via persistent MPFC-hippocampal interactions.

Brain activity related to working memory for temporal order and object information.

Maintaining items in an appropriate sequence is important for many daily activities; however, remarkably little is known about the neural basis of human temporal working memory. Prior work suggests that the prefrontal cortex (PFC) and medial temporal lobe (MTL), including the hippocampus, play a role in representing information about temporal order. The involvement of these areas in successful temporal working memory, however, is less clear. Additionally, it is unknown whether regions in the PFC and MTL support temporal working memory across different timescales, or at coarse or fine levels of temporal detail. To address these questions, participants were scanned while completing 3 working memory task conditions (Group, Position and Item) that were matched in terms of difficulty and the number of items to be actively maintained. Group and Position trials probed temporal working memory processes, requiring the maintenance of hierarchically organized coarse and fine temporal information, respectively. To isolate activation related to temporal working memory, Group and Position trials were contrasted against Item trials, which required detailed working memory maintenance of visual objects. Results revealed that working memory encoding and maintenance of temporal information relative to visual information was associated with increased activation in dorsolateral PFC (DLPFC), and perirhinal cortex (PRC). In contrast, maintenance of visual details relative to temporal information was characterized by greater activation of parahippocampal cortex (PHC), medial and anterior PFC, and retrosplenial cortex. In the hippocampus, a dissociation along the longitudinal axis was observed such that the anterior hippocampus was more active for working memory encoding and maintenance of visual detail information relative to temporal information, whereas the posterior hippocampus displayed the opposite effect. Posterior parietal cortex was the only region to show sensitivity to temporal working memory across timescales, and was particularly involved in the encoding and maintenance of fine temporal information relative to maintenance of temporal information at more coarse timescales. Collectively, these results highlight the involvement of PFC and MTL in temporal working memory processes, and suggest a dissociation in the type of working memory information represented along the longitudinal axis of the hippocampus.

Getting Over It: Long-Lasting Effects of Emotion Regulation on Amygdala Response.

Little is known about whether emotion regulation can have lasting effects on the ability of a stimulus to continue eliciting affective responses in the future. We addressed this issue in this study. Participants cognitively reappraised negative images once or four times, and then 1 week later, they passively viewed old and new images, so that we could identify lasting effects of prior reappraisal. As in prior work, active reappraisal increased prefrontal responses but decreased amygdala responses and self-reported emotion. At 1 week, amygdala responses remained attenuated for images that had been repeatedly reappraised compared with images that had been reappraised once, new control images, and control images that had been seen as many times as reappraised images but had never been reappraised. Prefrontal activation was not selectively elevated for repeatedly reappraised images and was not related to long-term attenuation of amygdala responses. These results suggest that reappraisal can exert long-lasting "dose-dependent" effects on amygdala response that may cause lasting changes in the neural representation of an unpleasant event's emotional value.

Significance of objects in the perirhinal cortex.

The perirhinal cortex is known to play a role in recognition memory and visual perception of objects. A recent single-unit recording study adds to our understanding of perirhinal cortex function, suggesting that it may also play a role in evaluating the significance of objects in a context-dependent manner.