The effects of mnemonic variability and spacing on memory over multiple timescales.

The memory benefit that arises from distributing learning over time rather than in consecutive sessions is one of the most robust effects in cognitive psychology. While prior work has mainly focused on repeated exposures to the same information, in the real world, mnemonic content is dynamic, with some pieces of information staying stable while others vary. Thus, open questions remain about the efficacy of the spacing effect in the face of variability in the mnemonic content. Here, in two experiments, we investigated the contributions of mnemonic variability and the timescale of spacing intervals, ranging from seconds to days, to long-term memory. For item memory, both mnemonic variability and spacing intervals were beneficial for memory; however, mnemonic variability was greater at shorter spacing intervals. In contrast, for associative memory, repetition rather than mnemonic variability was beneficial for memory, and spacing benefits only emerged in the absence of mnemonic variability. These results highlight a critical role for mnemonic variability and the timescale of spacing intervals in the spacing effect, bringing this classic memory paradigm into more ecologically valid contexts.

Social feedback biases emerge during recall but not prediction and shift across the development of social anxiety.

Memory is a reconstructive process that can result in events being recalled as more positive or negative than they actually were. While positive recall biases may contribute to well-being, negative recall biases may promote internalizing symptoms, such as social anxiety. Adolescence is characterized by increased salience of peers and peak incidence of social anxiety. Symptoms often wax and wane before becoming more intractable during adulthood. Open questions remain regarding how and when biases for social feedback are expressed and how individual differences in biases may contribute to social anxiety across development. Two studies used a social feedback and cued response task to assess biases about being liked or disliked when retrieving memories vs. making predictions. Findings revealed a robust positivity bias about memories for social feedback, regardless of whether memories were true or false. Moreover, memory bias was associated with social anxiety in a developmentally sensitive way. Among adults (study 1), more severe symptoms of social anxiety were associated with a negativity bias. During the transition from adolescence to adulthood (study 2), age strengthened the positivity bias in those with less severe symptoms and strengthened the negativity bias in those with more severe symptoms. These patterns of bias were isolated to perceived memory retrieval and did not generalize to predictions about social feedback. These results provide initial support for a model by which schemas may infiltrate perceptions of memory for past, but not predictions of future, social events, shaping susceptibility for social anxiety, particularly during the transition into adulthood.

Motivation as a Lens for Understanding Information-seeking Behaviors.

Most prior research characterizes information-seeking behaviors as serving utilitarian purposes, such as whether the obtained information can help solve practical problems. However, information-seeking behaviors are sensitive to different contexts (i.e., threat vs. curiosity), despite having equivalent utility. Furthermore, these search behaviors can be modulated by individuals' life history and personality traits. Yet the emphasis on utilitarian utility has precluded the development of a unified model, which explains when and how individuals actively seek information. To account for this variability and flexibility, we propose a unified information-seeking framework that examines information-seeking through the lens of motivation. This unified model accounts for integration across individuals' internal goal states and the salient features of the environment to influence information-seeking behavior. We propose that information-seeking is determined by motivation for information, invigorated either by instrumental utility or hedonic utility, wherein one's personal or environmental context moderates this relationship. Furthermore, we speculate that the final common denominator in guiding information-seeking is the engagement of different neuromodulatory circuits centered on dopaminergic and noradrenergic tone. Our framework provides a unified framework for information-seeking behaviors and generates several testable predictions for future studies.

Representational Dissimilarity of Faces and Places during a Working Memory Task is Associated with Subsequent Recognition Memory during Development.

Nearly 50 years of research has focused on faces as a special visual category, especially during development. Yet it remains unclear how spatial patterns of neural similarity of faces and places relate to how information processing supports subsequent recognition of items from these categories. The current study uses representational similarity analysis and functional imaging data from 9- and 10-year-old youth during an emotional n-back task from the Adolescent Brain and Cognitive Development Study 3.0 data release to relate spatial patterns of neural similarity during working memory to subsequent out-of-scanner performance on a recognition memory task. Specifically, we examine how similarities in representations within face categories (neutral, happy, and fearful faces) and representations between visual categories (faces and places) relate to subsequent recognition memory of these visual categories. Although working memory performance was higher for faces than places, subsequent recognition memory was greater for places than faces. Representational similarity analysis revealed category-specific patterns in face-and place-sensitive brain regions (fusiform gyrus, parahippocampal gyrus) compared with a nonsensitive visual region (pericalcarine cortex). Similarity within face categories and dissimilarity between face and place categories in the parahippocampus was related to better recognition of places from the n-back task. Conversely, in the fusiform, similarity within face categories and their relative dissimilarity from places was associated with better recognition of new faces, but not old faces. These findings highlight how the representational distinctiveness of visual categories influence what information is subsequently prioritized in recognition memory during development.

In vivo structural connectivity of the reward system along the hippocampal long axis.

Recent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI (dMRI) and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N = 628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (ventral tegmental area) showed stronger connectivity with the anterior versus posterior hippocampus, the ventromedial prefrontal cortex showed stronger connectivity with the posterior hippocampus. The limbic (ventral) striatum demonstrated a more homogeneous connectivity profile along the hippocampal long axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Temporal memory for threatening events encoded in a haunted house.

Despite the salient experience of encoding threatening events, these memories are prone to distortions and often non-veridical from encoding to recall. Further, threat has been shown to preferentially disrupt the binding of event details and enhance goal-relevant information. While extensive work has characterised distinctive features of emotional memory, research has not fully explored the influence threat has on temporal memory, a process putatively supported by the binding of event details into a temporal context. Two primary competing hypotheses have been proposed; that threat can impair or enhance temporal memory. We analysed two datasets to assess temporal memory for an in-person haunted house experience. In study 1, we examined the temporal structure of memory by characterising memory contiguity in free recall as a function of individual levels of heart rate as a proxy of threat. In study 2, we replicated marginal findings of threat-related increases in memory contiguity found in study 1. We extended these findings by showing threat-related increases in recency discriminations, an explicit test of temporal memory. Together, these findings demonstrate that threat enhances temporal memory regarding free recall structure and during explicit memory judgments.

Midbrain-Hippocampus Structural Connectivity Selectively Predicts Motivated Memory Encoding.

Motivation is a powerful driver of learning and memory. Functional MRI studies show that interactions among the dopaminergic midbrain substantia nigra/ventral tegmental area (SN/VTA), hippocampus, and nucleus accumbens (NAc) are critical for motivated memory encoding. However, it is not known whether these effects are transient and purely functional, or whether individual differences in the structure of this circuit underlie motivated memory encoding. To quantify individual differences in structure, diffusion-weighted MRI and probabilistic tractography were used to quantify SN/VTA-striatum and SN/VTA-hippocampus pathways associated with motivated memory encoding in humans. Male and female participants completed a motivated source memory paradigm. During encoding, words were randomly assigned to one of three conditions, reward ($1.00), control ($0.00), or punishment (-$1.00). During retrieval, participants were asked to retrieve item and source information of the previously studied words and were rewarded or penalized according to their performance. Source memory for words assigned to both reward and punishment conditions was greater than those for control words, but there were no differences in item memory based on value. Anatomically, probabilistic tractography results revealed a heterogeneous, topological arrangement of the SN/VTA. Tract density measures of SN/VTA-hippocampus pathways were positively correlated with individual differences in reward-and-punishment-modulated memory performance, whereas density of SN/VTA-striatum pathways showed no association. This novel finding suggests that pathways emerging from the human SV/VTA are anatomically separable and functionally heterogeneous. Individual differences in structural connectivity of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.SIGNIFICANCE STATEMENT Functional MRI studies show that interactions among the SN/VTA, hippocampus, and NAc are critical for motivated memory encoding. This has led to competing theories that posit either SN/VTA-NAc reward prediction errors or SN/VTA-hippocampus signals underlie motivated memory encoding. Additionally, it is not known whether these effects are transient and purely functional or whether individual differences in the structure of these circuits underlie motivated memory encoding. Using diffusion-weighted MRI and probabilistic tractography, we show that tract density measures of SN/VTA-hippocampus pathways are positively correlated with motivated memory performance, whereas density of SN/VTA-striatum pathways show no association. This finding suggests that anatomic individual differences of the dopaminergic hippocampus-VTA loop are selectively associated with motivated memory encoding.

Awake Hippocampal-Cortical Co-reactivation Is Associated with Forgetting.

Systems consolidation theories posit that consolidation occurs primarily through a coordinated communication between hippocampus and neocortex [Moscovitch, M., & Gilboa, A. Systems consolidation, transformation and reorganization: Multiple trace theory, trace transformation theory and their competitors. PsyArXiv, 2021; Kumaran, D., Hassabis, D., & McClelland, J. L. What learning systems do intelligent agents need? Complementary learning systems theory updated. Trends in Cognitive Sciences, 20, 512-534, 2016; McClelland, J. L., & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419-457, 1995]. Recent sleep studies in rodents have shown that hippocampus and visual cortex replay the same information at temporal proximity ("co-replay"; Lansink, C. S., Goltstein, P. M., Lankelma, J. V., McNaughton, B. L., & Pennartz, C. M. A. Hippocampus leads ventral striatum in replay of place-reward information. PLoS Biology, 7, e1000173, 2009; Peyrache, A., Khamassi, M., Benchenane, K., Wiener, S. I., & Battaglia, F. P. Replay of rule-learning related neural patterns in the prefrontal cortex during sleep. Nature Neuroscience, 12, 919-926, 2009; Wierzynski, C. M., Lubenov, E. V., Gu, M., & Siapas, A. G. State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep. Neuron, 61, 587-596, 2009; Ji, D., & Wilson, M. A. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nature Neuroscience, 10, 100-107, 2007). We developed a novel repetition time (TR)-based co-reactivation analysis method to study hippocampal-cortical co-replays in humans using fMRI. Thirty-six young adults completed an image (face or scene) and location paired associate encoding task in the scanner, which were preceded and followed by resting state scans. We identified post-encoding rest TRs (± 1) that showed neural reactivation of each image-location trials in both hippocampus (HPC) and category-selective cortex (fusiform face area [FFA]). This allowed us to characterize temporally proximal coordinated reactivations ("co-reactivations") between HPC and FFA. Moreover, we found that increased HPC-FFA co-reactivations were associated with incorrectly recognized trials after a 1-week delay (p = .004). Finally, we found that these HPC-FFA co-reactivations were also associated with trials that were initially correctly recognized immediately after encoding but were later forgotten in 1-day (p = .043) and 1-week delay period (p = .031). We discuss these results from a trace transformation perspective [Sekeres, M. J., Winocur, G., & Moscovitch, M. The hippocampus and related neocortical structures in memory transformation. Neuroscience Letters, 680, 39-53, 2018; Winocur, G., & Moscovitch, M. Memory transformation and systems consolidation. Journal of the International Neuropsychological Society, 17, 766-780, 2011] and speculate that HPC-FFA co-reactivations may be integrating related events, at the expense of disrupting event-specific details, hence leading to forgetting.

Setting boundaries: Development of neural and behavioral event cognition in early childhood.

The ongoing stream of sensory experience is so complex and ever-changing that we tend to parse this experience at "event boundaries," which structures and strengthens memory. Memory processes undergo profound change across early childhood. Whether young children also divide their ongoing processing along event boundaries, and if those boundaries relate to memory, could provide important insight into the development of memory systems. In Study 1, 4-7-year-old children and adults segmented a cartoon, and we tested their memory. Children's event boundaries were more variable than adults' and differed in location and consistency of agreement. Older children's event segmentation was more adult-like than younger children's, and children who segmented events more like adults had better memory for those events. In Study 2, we asked whether these developmental differences in event segmentation had their roots in distinct neural representations. A separate group of 4-8-year-old children watched the same cartoon while undergoing an fMRI scan. In the right hippocampus, greater pattern dissimilarity across event boundaries compared to within events was evident for both child and adult behavioral boundaries, suggesting children and adults share similar event cognition. However, the boundaries identified by a data-driven Hidden Markov Model found that a different brain region-the left and right angular gyrus-aligned only with event boundaries defined by children. Overall, these data suggest that children's event cognition is reasonably well-developed by age 4 but continues to become more adult-like across early childhood. RESEARCH HIGHLIGHTS: Adults naturally break their experience into events, which structures and strengthens memory, but less is known about children's event perception and memory. Study 1 had adults and children segment and remember events from an animated show, and Study 2 compared those segmentations to other children's fMRI data. Children show better recognition and temporal order memory and more adult-like event segmentation with age, and children who segment more like adults have better memory. Children's and adults' behavioral boundaries mapped onto pattern similarity differences in hippocampus, and children's behavioral boundaries matched a data-driven model's boundaries in angular gyrus.

The interactive effect of external rewards and self-determined choice on memory.

Both external motivational incentives (e.g., monetary reward) and internal motivational incentives (e.g., self-determined choice) have been found to promote memory, but much less is known about how these two types of incentives interact with each other to affect memory. The current study (N = 108) examined how performance-dependent monetary rewards affected the role of self-determined choice in memory performance, also known as the choice effect. Using a modified and better controlled version of the choice paradigm and manipulating levels of reward, we demonstrated an interactive effect between monetary reward and self-determined choice on 1-day delayed memory performance. Specifically, the choice effect on memory decreased when we introduced the performance-dependent external rewards. These results are discussed in terms of understanding how external and internal motivators interact to impact learning and memory.

Decision uncertainty during hypothesis testing enhances memory accuracy for incidental information.

Humans actively seek information to reduce uncertainty, providing insight on how our decisions causally affect the world. While we know that episodic memories can help support future goal-oriented behaviors, little is known about how hypothesis testing during exploration influences episodic memory. To investigate this question, we designed a hypothesis testing paradigm, in which participants figured out rules to unlock treasure chests. Using this paradigm, we characterized how hypothesis testing during exploration influenced memory for the contents of the treasure chests. We found that there was an inverted U-shaped relationship between decision uncertainty and memory, such that memory was best when decision uncertainty was moderate. An exploratory analysis also showed that surprising outcomes lead to lower memory confidence independent of accuracy. These findings support a model in which moderate decision uncertainty during hypothesis testing enhances incidental information encoding.

Hippocampus Guides Adaptive Learning during Dynamic Social Interactions.

How do we evaluate whether someone will make a good friend or collaborative peer? A hallmark of human cognition is the ability to make adaptive decisions based on information garnered from limited prior experiences. Using an interactive social task measuring adaptive choice (deciding who to reengage or avoid) in male and female participants, we find the hippocampus supports value-based social choices following single-shot learning. These adaptive choices elicited a suppression signal in the hippocampus, revealing sensitivity for the subjective perception of a person and how well they treat you during choice. The extent to which the hippocampus was suppressed was associated with flexibly interacting with prior generous individuals and avoiding selfish individuals. Further, we found that hippocampal signals during decision-making were related to subsequent memory for a person and the offer they made before. Consistent with the hippocampus leveraging previously executed choices to solidify a reliable neural signature for future adaptive behavior, we also observed a later hippocampal enhancement. These findings highlight the hippocampus playing a multifaceted role in socially adaptive learning.SIGNIFICANCE STATEMENT Adaptively navigating social interactions requires an integration of prior experiences with information gleaned from the current environment. While most research has focused on striatal-based feedback learning, open questions remain regarding the role of hippocampal-based episodic memory systems. Here, we show that during social decisions based on prior experience, hippocampal suppression signals were sensitive to adaptive choice, while hippocampal enhancements was related to subsequent memory for the original social interaction. These findings highlight the hippocampus playing a multifaceted role in socially adaptive learning.

VTA and Anterior Hippocampus Target Dissociable Neocortical Networks for Post-Novelty Enhancements.

The detection of novelty indicates changes in the environment and the need to update existing representations. In response to novelty, interactions across the VTA-hippocampal circuit support experience-dependent plasticity in the hippocampus. While theories have broadly suggested plasticity-related changes are also instantiated in the cortex, research has also shown evidence for functional heterogeneity in cortical networks. It therefore remains unclear how the hippocampal-VTA circuit engages cortical networks, and whether novelty targets specific cortical regions or diffuse, large-scale cortical networks. To adjudicate the role of the VTA and hippocampus in cortical network plasticity, we used fMRI to compare resting-state functional coupling before and following exposure to novel scene images in human subjects of both sexes. Functional coupling between right anterior hippocampus and VTA was enhanced following novelty exposure. However, we also found evidence for a double dissociation, with anterior hippocampus and VTA showing distinct patterns of post-novelty functional coupling enhancements, targeting task-relevant regions versus large-scale networks, respectively. Further, significant correlations between these networks and the novelty-related plasticity in the anterior hippocampal-VTA functional network suggest that the central hippocampal-VTA network may facilitate the interactions with the cortex. These findings support an extended model of novelty-induced plasticity, in which novelty elicits plasticity-related changes in both local and global cortical networks.SIGNIFICANCE STATEMENT Novelty detection is critical for adaptive behavior, signaling the need to update existing representations. By engaging the bidirectional hippocampal-VTA circuit, novelty has been shown to induce plasticity-related changes in the hippocampus. However, it remains an open question how novelty targets such plasticity-related changes in cortical networks. We show that anterior hippocampus and VTA target cortical networks at different spatial scales, with respective enhancements in post-novelty functional coupling with a task-relevant cortical region and a large-scale memory network. The results presented here support an extended model of novelty-related plasticity, in which engaging the anterior hippocampal-VTA circuit through novelty exposure propagates cortical plasticity through hippocampal and VTA functional pathways at distinct scales, targeting specific or diffuse cortical networks.

Context-specific abnormalities of the central executive network in first-episode psychosis: relationship with cognition.

BACKGROUND: Cognitive impairments, which contribute to the profound functional deficits observed in psychotic disorders, have found to be associated with abnormalities in trial-level cognitive control. However, neural tasks operate within the context of sustained cognitive states, which can be assessed with 'background connectivity' following the removal of task effects. To date, little is known about the integrity of brain processes supporting the maintenance of a cognitive state in individuals with psychotic disorders. Thus, here we examine background connectivity during executive processing in a cohort of participants with first-episode psychosis (FEP). METHODS: The following fMRI study examined background connectivity of the dorsolateral prefrontal cortex (DLPFC), during working memory engagement in a group of 43 patients with FEP, relative to 35 healthy controls (HC). Findings were also examined in relation to measures of executive function. RESULTS: The FEP group relative to HC showed significantly lower background DLPFC connectivity with bilateral superior parietal lobule (SPL) and left inferior parietal lobule. Background connectivity between DLPFC and SPL was also positively associated with overall cognition across all subjects and in our FEP group. In comparison, resting-state frontoparietal connectivity did not differ between groups and was not significantly associated with overall cognition, suggesting that psychosis-related alterations in executive networks only emerged during states of goal-oriented behavior. CONCLUSIONS: These results provide novel evidence indicating while frontoparietal connectivity at rest appears intact in psychosis, when engaged during a cognitive state, it is impaired possibly undermining cognitive control capacities in FEP.

The effect of choice on intentional and incidental memory.

Recent studies have revealed that memory performance is better when participants have the opportunity to make a choice regarding the experimental task (choice condition) than when they do not have such a choice (fixed condition). These studies, however, used intentional memory tasks, leaving open the question whether the choice effect also applies to incidental memory. In the current study, we first repeated the choice effect on the 24-h delayed intentional memory performance (experiment 1). Next, using an incidental paradigm in which participants were asked to judge the category of the items instead of intentionally memorizing them, we observed the choice effect on judgment during encoding and memory performance in a 24-h delayed surprise test (experiment 2). Participants judged more accurately and quickly and had better recognition memory for items in the choice condition than for items in the fixed condition. These results are discussed in terms of the role of choice in both intentional and incidental memory.

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Emotional learning selectively and retroactively strengthens memories for related events.

Neurobiological models of long-term memory propose a mechanism by which initially weak memories are strengthened through subsequent activation that engages common neural pathways minutes to hours later. This synaptic tag-and-capture model has been hypothesized to explain how inconsequential information is selectively consolidated following salient experiences. Behavioural evidence for tag-and-capture is provided by rodent studies in which weak early memories are strengthened by future behavioural training. Whether a process of behavioural tagging occurs in humans to transform weak episodic memories into stable long-term memories is unknown. Here we show, in humans, that information is selectively consolidated if conceptually related information, putatively represented in a common neural substrate, is made salient through an emotional learning experience. Memory for neutral objects was selectively enhanced if other objects from the same category were paired with shock. Retroactive enhancements as a result of emotional learning were observed following a period of consolidation, but were not observed in an immediate memory test or for items strongly encoded before fear conditioning. These findings provide new evidence for a generalized retroactive memory enhancement, whereby inconsequential information can be retroactively credited as relevant, and therefore selectively remembered, if conceptually related information acquires salience in the future.

Development of Hippocampal-Prefrontal Cortex Interactions through Adolescence.

Significant improvements in cognitive control occur from childhood through adolescence, supported by the maturation of prefrontal systems. However, less is known about the neural basis of refinements in cognitive control proceeding from adolescence to adulthood. Accumulating evidence indicates that integration between hippocampus (HPC) and prefrontal cortex (PFC) supports flexible cognition and has a protracted neural maturation. Using a longitudinal design (487 scans), we characterized developmental changes from 8 to 32 years of age in HPC-PFC functional connectivity at rest and its associations with cognitive development. Results indicated significant increases in functional connectivity between HPC and ventromedial PFC (vmPFC), but not dorsolateral PFC. Importantly, HPC-vmPFC connectivity exclusively predicted performance on the Stockings of Cambridge task, which probes problem solving and future planning. These data provide evidence that maturation of high-level cognition into adulthood is supported by increased functional integration across the HPC and vmPFC through adolescence.

Amygdala and ventral tegmental area differentially interact with hippocampus and cortical medial temporal lobe during rest in humans.

Neuromodulatory regions that detect salience, such as amygdala and ventral tegmental area (VTA), have distinct effects on memory. Yet, questions remain about how these modulatory regions target subregions across the hippocampus and medial temporal lobe (MTL) cortex. Here, we sought to characterize how VTA and amygdala subregions (i.e., basolateral amygdala and central-medial amygdala) interact with hippocampus head, body, and tail, as well as cortical MTL areas of perirhinal cortex and parahippocampal cortex in a task-free state. To quantify these interactions, we used high-resolution resting state fMRI and characterized pair-wise, partial correlations across regions-of-interest. We found that basolateral amygdala showed greater functional coupling with hippocampus head, hippocampus tail, and perirhinal cortex when compared to either VTA or central-medial amygdala. Furthermore, the VTA showed greater functional coupling with hippocampus tail when compared to central-medial amygdala. There were no significant differences in functional coupling with hippocampus body and parahippocampal cortex. These results support a framework by which neuromodulatory regions do not indiscriminately influence all MTL subregions equally, but rather bias information processing to discrete MTL targets. These findings provide a more specified model of the intrinsic properties of systems underlying MTL neuromodulation. This emphasizes the need to consider heterogeneity both across and within neuromodulatory systems to better understand affective memory.