Marlieke T. R. van Kesteren

How schema and novelty augment memory formation

Information that is congruent with existing knowledge (a schema) is usually better remembered than less congruent information. Only recently, however, has the role of schemas in memory been studied from a systems neuroscience perspective. Moreover, incongruent (novel) information is also sometimes better remembered. Here, we review lesion and neuroimaging findings in animals and humans that relate to this apparent paradoxical relationship between schema and novelty. In addition, we sketch a framework relating key brain regions in medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) during encoding, consolidation and retrieval of information as a function of its congruency with existing information represented in neocortex. An important aspect of this framework is the efficiency of learning enabled by congruency-dependent MTL-mPFC interactions.

Stress-related noradrenergic activity prompts large-scale neural network reconfiguration

Acute stress leads to reorganization of large-scale neural network connectivity in the brain that is driven by noradrenaline. Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. β-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.

Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans

The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process. Thus, hippocampal-vmPFC crosstalk may support integration of new memories, particularly in the absence of a relevant prior schema. To address this issue, we used functional magnetic resonance imaging (fMRI) and prior schema manipulation to track hippocampal-vmPFC connectivity during encoding and postencoding rest. We manipulated prior schema knowledge by exposing 30 participants to the first part of a movie that was temporally scrambled for 15 participants. The next day, participants underwent fMRI while encoding the movies final 15 min in original order and, subsequently, while resting. Schema knowledge and item recognition performance show that prior schema was successfully and selectively manipulated. Intersubject synchronization (ISS) and interregional partial correlation analyses furthermore show that stronger prior schema was associated with more vmPFC ISS and less hippocampal-vmPFC interregional connectivity during encoding. Notably, this connectivity pattern persisted during postencoding rest. These findings suggest that additional crosstalk between hippocampus and vmPFC is required to compensate for difficulty integrating novel information during encoding and provide tentative support for the notion that functionally relevant hippocampal-neocortical crosstalk persists during off-line periods after learning.

Retrieval of Associative Information Congruent with Prior Knowledge Is Related to Increased Medial Prefrontal Activity and Connectivity

We remember information that is congruent instead of incongruent with prior knowledge better, but the underlying neural mechanisms related to this enhancement are still relatively unknown. Recently, this memory enhancement due to a prior schema has been suggested to be based on rapid neocortical assimilation of new information, related to optimized encoding and consolidation processes. The medial prefrontal cortex (mPFC) is thought to be important in mediating this process, but its role in retrieval of schema-consistent information is still unclear. In this study, we regarded multisensory congruency with prior knowledge as a schema and used this factor to probe retrieval of consolidated memories either consistent or inconsistent with prior knowledge. We conducted a visuotactile learning paradigm in which participants studied visual motifs randomly associated with word–fabric combinations that were either congruent or incongruent with common knowledge. The next day, participants were scanned using functional magnetic resonance imaging while their memory was tested. Congruent associations were remembered better than incongruent ones. This behavioral finding was parallelized by stronger retrieval-related activity in and connectivity between medial prefrontal and left somatosensory cortex. Moreover, we found a positive across-subject correlation between the connectivity enhancement and the behavioral congruency effect. These results show that successful retrieval of congruent compared to incongruent visuotactile associations is related to enhanced processing in an mPFC–somatosensory network, and support the hypothesis that new information that fits a preexisting schema is more rapidly assimilated in neocortical networks, a process that may be mediated, at least in part, by the mPFC.

Differential roles for medial prefrontal and medial temporal cortices in schema-dependent encoding: From congruent to incongruent

Information that is congruent with prior knowledge is generally remembered better than incongruent information. This effect of congruency on memory has been attributed to a facilitatory influence of activated schemas on memory encoding and consolidation processes, and hypothesised to reflect a shift between processing in medial temporal lobes (MTL) towards processing in medial prefrontal cortex (mPFC). To investigate this shift, we used functional magnetic resonance imaging (fMRI) to compare brain activity during paired-associate encoding across three levels of subjective congruency of the association with prior knowledge. Participants indicated how congruent they found an object-scene pair during scanning, and were tested on item and associative recognition memory for these associations one day later. Behaviourally, we found a monotonic increase in memory performance with increasing congruency for both item and associative memory. Moreover, as hypothesised, encoding-related activity in mPFC increased linearly with increasing congruency, whereas MTL showed the opposite pattern of increasing encoding-related activity with decreasing congruency. Additionally, mPFC showed increased functional connectivity with a region in the ventral visual stream, presumably related to the binding of visual representations. These results support predictions made by a recent neuroscientific framework concerning the effects of schema on memory. Specifically, our findings show that enhanced memory for more congruent information is mediated by the mPFC, which is hypothesised to guide integration of new information into a pre-existing schema represented in cortical areas, while memory for more incongruent information relies instead on automatic encoding of arbitrary associations by the MTL.

Building on prior knowledge: Schema-dependent encoding processes relate to academic performance

The acquisition and retention of conceptual knowledge is more effective in well-structured curricula that provide an optimal conceptual framework for learning new material. However, the neural mechanisms by which preexisting conceptual schemas facilitate learning are not yet well understood despite their fundamental importance. A preexisting schema has been shown to enhance memory by influencing the balance between activity within the medial-temporal lobe and the medial pFC during mnemonic processes such as encoding, consolidation, and retrieval. Specifically, correctly encoding and retrieving information that is related to preexisting schemas appears rather related to medial prefrontal processing, whereas information unrelated or inconsistent with preexisting schemas rather relates to enhanced medial temporal processing and enhanced interaction between these structures. To further investigate interactions between these regions during conceptual encoding in a real-world university setting, we probed human brain activity and connectivity using fMRI during educationally relevant conceptual encoding carefully embedded within two course programs. Early second-year undergraduate biology and education students were scanned while encoding new facts that were either related or unrelated to the preexisting conceptual knowledge they had acquired during their first year of study. Subsequently, they were tested on their knowledge of these facts 24 hr later. Memory scores were better for course-related information, and this enhancement was associated with larger medial-prefrontal, but smaller medial-temporal subsequent memory effects. These activity differences went along with decreased functional interactions between these regions. Furthermore, schema-related medial-prefrontal subsequent memory effects measured during this experiment were found to be predictive of second-year course performance. These results, obtained in a real-world university setting, reveal brain mechanisms underlying acquisition of new knowledge that can be integrated into preexisting conceptual schemas and may indicate how relevant this process is for study success.

How to achieve synergy between medical education and cognitive neuroscience? An exercise on prior knowledge in understanding.

A major challenge in contemporary research is how to connect medical education and cognitive neuroscience and achieve synergy between these domains. Based on this starting point we discuss how this may result in a common language about learning, more educationally focused scientific inquiry, and multidisciplinary research projects. As the topic of prior knowledge in understanding plays a strategic role in both medical education and cognitive neuroscience it is used as a central element in our discussion. A critical condition for the acquisition of new knowledge is the existence of prior knowledge, which can be built in a mental model or schema. Formation of schemas is a central event in student-centered active learning, by which mental models are constructed and reconstructed. These theoretical considerations from cognitive psychology foster scientific discussions that may lead to salient issues and questions for research with cognitive neuroscience. Cognitive neuroscience attempts to understand how knowledge, insight and experience are established in the brain and to clarify their neural correlates. Recently, evidence has been obtained that new information processed by the hippocampus can be consolidated into a stable, neocortical network more rapidly if this new information fits readily into a schema. Opportunities for medical education and medical education research can be created in a fruitful dialogue within an educational multidisciplinary platform. In this synergetic setting many questions can be raised by educational scholars interested in evidence-based education that may be highly relevant for integrative research and the further development of medical education.

Consolidation differentially modulates schema effects on memory for items and associations

Newly learned information that is congruent with a preexisting schema is often better remembered than information that is incongruent. This schema effect on memory has previously been associated to more efficient encoding and consolidation mechanisms. However, this effect is not always consistently supported in the literature, with differential schema effects reported for different types of memory, different retrieval cues, and the possibility of time-dependent effects related to consolidation processes. To examine these effects more directly, we tested participants on two different types of memory (item recognition and associative memory) for newly encoded visuo-tactile associations at different study-test intervals, thus probing memory retrieval accuracy for schema-congruent and schema-incongruent items and associations at different time points (t = 0, t = 20, and t = 48 hours) after encoding. Results show that the schema effect on visual item recognition only arises after consolidation, while the schema effect on associative memory is already apparent immediately after encoding, persisting, but getting smaller over time. These findings give further insight into different factors influencing the schema effect on memory, and can inform future schema experiments by illustrating the value of considering effects of memory type and consolidation on schema-modulated retrieval.

Interactions between Memory and New Learning: Insights from fMRI Multivoxel Pattern Analysis.

Declarative memory—long-term memory for events and facts—is a key form of cognition that depends on distributed neural coding. Given the rich, multifaceted nature of life events, their neural representations (episodic memory “engrams”) typically incorporate a broad set of cortical and subcortical regions whose coding properties underlie event features (Paller and Wagner, 2002; Rugg et al., 2002; Tulving, 2002; Schacter et al., 2007). With continued experience, representations of individual events may form a foundation for more generalized semantic knowledge about the world (van Kesteren et al., 2012). A fundamental theoretical question is how existing memories interact with encoding of new experiences to enable formation of integrated knowledge structures. The distributed nature of memory content in the brain, both locally (i.e., across neurons within a region) and across relevant cortical and subcortical regions, creates challenges for measurement of mnemonic content across various stages of memory encoding and retrieval. By combining non-invasive imaging techniques (e.g., functional magnetic resonance imaging–fMRI) with multivariate pattern-analyses (MVPA), such representational content can be decoded from distributed patterns of brain activity (Polyn et al., 2005; Norman et al., 2006; Rissman and Wagner, 2012). Moreover, quantitative measures of mnemonic representations can be related to behavioral performance measures, thus informing mechanistic models of memory. At a macroscopic level, mnemonic representations of events are distributed across perceptual, motor, affective, and associative brain regions (Tulving and Markowitsch, 1997). Episodic memory retrieval entails the reinstatement or reconstruction of information encoded in memory (for reviews see Danker and Anderson, 2010; Ben-Yakov et al., 2015). MVPA provides a means of measuring distributed neural representations, and quantifying reinstatement processes (Norman et al., 2006; Rissman and Wagner, 2012). Importantly, a myriad of externally and internally generated retrieval cues can drive reinstatement of existing memory traces during encoding of related information. Such reinstatement may support the formation of more generalized knowledge through integration of new with old memories (Shohamy and Wagner, 2008; Preston and Eichenbaum, 2013). As such, elements of new memories that overlap with prior experiences can trigger reinstatement and integration processes allowing for extension and strengthening of existing associative knowledge structures, or “schemas” (Tse et al., 2007; van Kesteren et al., 2012). The medial temporal lobe (MTL)—with the hippocampus at its core—is the most prominently studied region in memory research (Burgess et al., 2002; Squire et al., 2004; Eichenbaum et al., 2007). The hippocampus serves as an integrative hub for the binding of disparate neocortical representations of event features into unified memories (Eichenbaum et al., 2004; Andersen, 2007). Through creating flexibly addressable memory traces that link to the driving cortical representations of event content, the hippocampus can support subsequent reactivation of a remembered events feature representations in the neocortex during retrieval. MVPA techniques can index expressions of distributed memory representations and processes in MTL as they unfold, as well as probe reinstatement and integration processes in content-selective cortical regions (Polyn et al., 2005; Johnson et al., 2009; Staresina et al., 2012; Gordon et al., 2014; Sigman et al., 2014). Beyond the MTL, other cortical areas have been posited to contribute to across-event integration. In particular, the integration of associated memories is thought to also depend on computations within the medial prefrontal cortex (mPFC), a prefrontal region intimately connected with the hippocampus and suggested to be involved in the building of knowledge structures (van Kesteren et al., 2012; Preston and Eichenbaum, 2013). Recent evidence from direct neuronal recordings in non-human models of memory has linked hippocampus and mPFC population coding to the expression of schema knowledge (McKenzie and Eichenbaum, 2011; McKenzie et al., 2014; Richards et al., 2014). In humans, MVPA provides a powerful means to assess how mPFC and the hippocampus underlie integration of newly learned experiences with existing memories, and critically, to link this integration process with cortical reinstatement (Dudai and Eisenberg, 2004; Kuhl et al., 2010; Nadel et al., 2012). Here we review how MVPA, applied to fMRI-data, is leveraged to address fundamental questions about reinstatement and subsequent integration of memory representations in the human brain. We discuss a framework in which reinstatement of prior knowledge during new learning can facilitate formation of integrated knowledge across experiences, highlight evidence for potentially disruptive effects of such processes on other expressions of memory (e.g., memory for episodic details), and suggest future research directions.

Autobiographical Memory Transformation across Consolidation

One of the greatest mysteries of the brain is how it can recall particular events vividly, sometimes after many decades, whereas the bulk of day-to-day experiences are forgotten. This question has sparked a vigorous search for the memory engram, i.e., the mnemonic representations in the brain.