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

Word Familiarity Modulated the Effects of Category Familiarity on Memory Performance

Previous studies have shown that prior knowledge can have both enhancing and detrimental effects on memory for relevant information. Few studies have explored the boundary conditions under which prior knowledge facilitates or interferes with memory processes. In addition, to what extent the effects of prior knowledge change over time is unclear. In this study, we addressed this question by separating category familiarity (i.e., prior conceptual knowledge) and stimulus familiarity at different retention intervals. Participants were tested with a recognition task after they learned four types of words, that is., familiar words from familiar categories (FwordFcate) and unfamiliar categories (FwordUcate) as well as unfamiliar words from familiar (UwordFcate) and unfamiliar categories (UwordUcate). The results showed a significant interaction between category familiarity and word familiarity, that is, unfamiliar words, but not familiar words, from familiar categories were remembered better than those from unfamiliar categories. The enhancing effect of category familiarity depended on the recollection process and remained stable over time. This study suggested that stimulus familiarity modulates the effects of category familiarity on memory performance, and clarified the boundary conditions for the effects of prior knowledge

Effects of Unconscious Processing on Implicit Memory for Fearful Faces

Emotional stimuli can be processed even when participants perceive them without conscious awareness, but the extent to which unconsciously processed emotional stimuli influence implicit memory after short and long delays is not fully understood. We addressed this issue by measuring a subliminal affective priming effect in Experiment 1 and a long-term priming effect in Experiment 2. In Experiment 1, a flashed fearful or neutral face masked by a scrambled face was presented three times, then a target face (either fearful or neutral) was presented and participants were asked to make a fearful/neutral judgment. We found that, relative to a neutral prime face (neutral–fear face), a fearful prime face speeded up participants' reaction to a fearful target (fear–fear face), when they were not aware of the masked prime face. But this response pattern did not apply to the neutral target. In Experiment 2, participants were first presented with a masked faces six times during encoding. Three minutes later, they were asked to make a fearful/neutral judgment for the same face with congruent expression, the same face with incongruent expression or a new face. Participants showed a significant priming effect for the fearful faces but not for the neutral faces, regardless of their awareness of the masked faces during encoding. These results provided evidence that unconsciously processed stimuli could enhance emotional memory after both short and long delays. It indicates that emotion can enhance memory processing whether the stimuli are encoded consciously or unconsciously

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

Sustained activity within the default mode network during an implicit memory task

Recent neuroimaging studies have shown that several brain regions - namely, the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (vmPFC), and the bilateral angular gyrus - are more active during resting states than during cognitive tasks (i.e., default mode network). Although there is evidence showing that the default mode network is associated with unconscious state, it is unclear whether this network is associated with unconscious processing when normal human subjects perform tasks without awareness. We manipulated the level of conscious processing in normal subjects by asking them to perform an implicit and an explicit memory task, and analyzed signal changes in the default mode network for the stimuli versus baseline in both tasks. The functional magnetic resonance imaging (fMRI) analysis showed that the level of activation in regions within this network during the implicit task was not significantly different from that during the baseline, except in the left angular gyrus and the insula. There was strong deactivation for the explicit task when compared with the implicit task in the default mode regions, except in the left angular gyrus and the left middle temporal gyrus. These data suggest that the activity in the default network is sustained and less disrupted when an implicit memory task is performed, but is suspended when explicit retrieval is required. These results provide evidence that the default mode network is associated with unconscious processing when human subjects perform an implicit memory task. (c) 2009 Elsevier Srl. All rights reserved

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

From Tuberculosis Bedside to Bench: UBE2B Splicing as a Potential Biomarker and Its Regulatory Mechanism

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB

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