Reactivation of schema representation in lateral occipital cortex supports successful memory encoding.

Schemas provide a scaffold onto which we can integrate new memories. Previous research has investigated the brain activity and connectivity underlying schema-related memory formation. However, how schemas are represented and reactivated in the brain, in order to enhance memory, remains unclear. To address this issue, we used an object-location spatial schema that was learned over multiple sessions, combined with similarity analyses of neural representations, to investigate the reactivation of schema representations of object-location memories when a new object-scene association is learned. In addition, we investigated how this reactivation affects subsequent memory performance under different strengths of schemas. We found that reactivation of a schema representation in the lateral occipital cortex (LOC) during object-scene encoding affected subsequent associative memory performance only in the schema-consistent condition and increased the functional connectivity between the LOC and the parahippocampal place area. Taken together, our findings provide new insight into how schema acts as a scaffold to support the integration of novel information into existing cortical networks and suggest a neural basis for schema-induced rapid cortical learning.

Interplay of the long axis of the hippocampus and ventromedial prefrontal cortex in schema-related memory retrieval.

When new information is relevant to prior knowledge or schema, it can be learned and remembered better. Rodent studies have suggested that the hippocampus and ventromedial prefrontal cortex (vmPFC) are important for processing schema-related information. However, there are inconsistent findings from human studies on the involvement of the hippocampus and its interaction with the vmPFC in schema-related memory retrieval. To address these issues, we used a human analog of the rodent spatial schema task to compare brain activity during immediate retrieval of paired associations (PAs) in schema-consistent and schema-inconsistent conditions. The results showed that the anterior hippocampus was more involved in retrieving PAs in the schema-consistent condition than in the schema-inconsistent condition. Connectivity analyses showed that the anterior hippocampus had stronger coupling with the vmPFC when the participants retrieved newly learned PAs successfully in the schema-consistent (vs. schema-inconsistent) condition, whereas the coupling of the posterior hippocampus with the vmPFC showed the opposite. Taken together, the results shed light on how the long axis of the hippocampus and vmPFC interact to serve memory retrieval via different networks that differ by schema condition.

Effects of schema on the relationship between post-encoding brain connectivity and subsequent durable memory.

Schemas can facilitate memory consolidation. Studies have suggested that interactions between the hippocampus and the ventromedial prefrontal cortex (vmPFC) are important for schema-related memory consolidation. However, in humans, how schema accelerates the consolidation of new information and relates to durable memory remains unclear. To address these knowledge gaps, we used a human analogue of the rodent spatial schema task and resting-state fMRI to investigate how post-encoding brain networks can predict long-term memory performance in different schema conditions. After participants were trained to obtain schema-consistent or schema-inconsistent object-location associations, they learned new object-location associations. The new associations were tested after the post-encoding rest in the scanner and 24 h later outside the scanner. The Bayesian multilevel modelling was applied to analyse the post-encoding brain networks. The results showed that during the post-encoding, stronger vmPFC- anterior hippocampal connectivity was associated with durable memory in the schema-consistent condition, whereas stronger object-selective lateral occipital cortex (LOC)-ventromedial prefrontal connectivity and weaker connectivity inside the default mode network were associated with durable memory in the schema inconsistent condition. In addition, stronger LOC-anterior hippocampal connectivity was associated with memory in both schema conditions. These results shed light on how schemas reconfigure early brain networks, especially the prefrontal-hippocampal and stimuli-relevant cortical networks and influence long-term memory performance.

Effects of prior knowledge on brain activation and functional connectivity during memory retrieval.

Previous studies have shown that the ventral medial prefrontal cortex (vmPFC) plays an important role in schema-related memory. However, there is an intensive debate to what extent the activation of subregions of the hippocampus is involved in retrieving schema-related memory. In addition, it is unclear how the functional connectivity (FC) between the vmPFC and the hippocampus, as well as the connectivity of the vmPFC with other regions, are modulated by prior knowledge (PK) during memory retrieval over time. To address these issues, participants learned paragraphs that described features of each unfamiliar word from familiar and unfamiliar categories (i.e., high and low PK conditions) 20 min, 1 day, and 1 week before the test. They then performed a recognition task to judge whether the sentences were old in the scanner. The results showed that the activation of the anterior-medial hippocampus (amHPC) cluster was stronger when the old sentences with high (vs. low) PK were correctly retrieved. The activation of the posterior hippocampus (pHPC) cluster, as well as the vmPFC, was stronger when the new sentences with high (vs. low) PK were correctly rejected (i.e., CR trials), whereas the cluster of anterior-lateral hippocampus (alHPC) showed the opposite. The FC of the vmPFC with the amHPC and perirhinal cortex/inferior temporal gyrus was stronger in the high (vs. low) PK condition, whereas the FC of the vmPFC with the alHPC, thalamus and frontal regions showed the opposite for the CR trials. This study highlighted that different brain networks, which were associated with the vmPFC, subregions of the hippocampus and cognitive control regions, were responsible for retrieving the information with high and low PK.

Differential activation of the medial temporal lobe during item and associative memory across time.

Studies have shown that the hippocampus plays a crucial role in associative memory. One central issue is whether the involvement of the hippocampus in associative memory remains stable or declines with the passage of time. In the majority of studies, memory performance declines with delay, confounding attempts at interpreting differences in hippocampal activation over time. To address this issue, we tried to equate behavioral performance as much as possible across time for memory of items and associations separately. After encoding words and word pairs, participants were tested for item and associative memories at four time intervals: 20-min, 1-day, 1-week, and 1-month. The results revealed that MTL activation differed over time for associative and item memories. For associative memory, the activation of the anterior hippocampus decreased from 20-min to 1-day then remained stable, whereas in the posterior hippocampus, the activation was comparable for different time intervals when old pairs were correctly retrieved. The hippocampal activation also remained stable when recombined pairs were correctly rejected. As this condition controls for familiarity of the individual items, correct performance depends only on associative memory. For item memory, hippocampal activation declined progressively from 20-min to 1-week and remained stable afterwards. By contrast, the activation in the perirhinal/entorhinal cortex increased over time irrespective of item and associative memories. Drawing on Tulving's distinction between recollection and familiarity, we interpret this pattern of results in accordance with Trace Transformation Theory, which states that as memories are transformed with time and experience, the neural structures mediating item and associative memories will vary according to the underlying representations to which the memories have been transformed.

Effects of Repetition Learning on Associative Recognition Over Time: Role of the Hippocampus and Prefrontal Cortex.

When stimuli are learned by repetition, they are remembered better and retained for a longer time. However, current findings are lacking as to whether the medial temporal lobe (MTL) and cortical regions are involved in the learning effect when subjects retrieve associative memory, and whether their activations differentially change over time due to learning experience. To address these issues, we designed an fMRI experiment in which face-scene pairs were learned once (L1) or six times (L6). Subjects learned the pairs at four retention intervals, 30-min, 1-day, 1-week and 1-month, after which they finished an associative recognition task in the scanner. The results showed that compared to learning once, learning six times led to stronger activation in the hippocampus, but weaker activation in the perirhinal cortex (PRC) as well as anterior ventrolateral prefrontal cortex (vLPFC). In addition, the hippocampal activation was positively correlated with that of the parahippocampal place area (PPA) and negatively correlated with that of the vLPFC when the L6 group was compared to the L1 group. The hippocampal activation decreased over time after L1 but remained stable after L6. These results clarified how the hippocampus and cortical regions interacted to support associative memory after different learning experiences.