Resting-state functional connectivity of ventral parietal regions associated with attention reorienting and episodic recollection.

In functional neuroimaging studies, ventral parietal cortex (VPC) is recruited by very different cognitive tasks. Explaining the contributions of VPC to these tasks has become a topic of intense study and lively debate. Perception studies frequently find VPC activations during tasks involving attention-reorienting, and memory studies frequently find them during tasks involving episodic recollection. According to the Attention to Memory (AtoM) model, both phenomena can be explained by the same VPC function: bottom-up attention. Yet, a recent functional MRI (fMRI) meta-analysis suggested that attention-reorienting activations are more frequent in anterior VPC, whereas recollection activations are more frequent in posterior VPC. Also, there is evidence that anterior and posterior VPC regions have different functional connectivity patterns. To investigate these issues, we conducted a resting-state functional connectivity analysis using as seeds the center-of-mass of attention-reorienting and recollection activations in the meta-analysis, which were located in the supramarginal gyrus (SMG, around the temporo-parietal junction-TPJ) and in the angular gyrus (AG), respectively. The SMG seed showed stronger connectivity with ventrolateral prefrontal cortex (VLPFC) and occipito-temporal cortex, whereas the AG seed showed stronger connectivity with the hippocampus and default network regions. To investigate whether these connectivity differences were graded or sharp, VLPFC and hippocampal connectivity was measured in VPC regions traversing through the SMG and AG seeds. The results showed a graded pattern: VLPFC connectivity gradually decreases from SMG to AG, whereas hippocampal connectivity gradually increases from SMG to AG. Importantly, both gradients showed an abrupt break when extended beyond VPC borders. This finding suggests that functional differences between SMG and AG are more subtle than previously thought. These connectivity differences can be explained by differences in the input and output to anterior and posterior VPC regions, without the need of postulating markedly different functions. These results are as consistent with integrative accounts of VPC function, such as the AtoM model, as they are with models that ascribe completely different functions to VPC regions.

Explaining the encoding/retrieval flip: memory-related deactivations and activations in the posteromedial cortex.

The posteromedial cortex (PMC) is strongly linked to episodic memory and age-related memory deficits. The PMC shows deactivations during a variety of demanding cognitive tasks as compared to passive baseline conditions and has been associated with the default-mode of the brain. Interestingly, the PMC exhibits opposite levels of functional MRI activity during encoding (learning) and retrieval (remembering), a pattern dubbed the encoding/retrieval flip (E/R-flip). Yet, the exact role of the PMC in memory function has remained unclear. This review discusses the possible neurofunctional and clinical significance of the E/R-flip pattern. Regarding neurofunctional relevance, we will review four hypotheses on PMC function: (1) the internal orienting account, (2) the self-referential processing account, (3) the reallocation account, and (4) the bottom-up attention account. None of these accounts seem to provide a complete explanation for the E/R-flip pattern in PMC. Regarding clinical relevance, we review work on aging and Alzheimer's disease, indicating that amyloid deposits within PMC, years before clinical memory deficits become apparent. High amyloid burden within PMC is associated with detrimental influences on memory encoding, in particular, the attenuation of beneficial PMC deactivations. Finally, we discuss functional subdivisions within PMC that help to provide a more precise picture of the variety of signals observed within PMC. Collective data from anatomical, task-related fMRI and resting-state studies all indicate that the PMC is composed of three main regions, the precuneus, retrosplenial, and posterior cingulate cortex, each with a distinct function. We will conclude with a summary of the findings and provide directions for future research.

Experience-dependent alterations in conscious resting state activity following perceptuomotor learning.

In monkeys and rats, neural activity patterns during learning are reactivated during subsequent periods of rest or sleep. According to the reactivation-consolidation account, this process underlies the consolidation of memories. Brain imaging studies have extended these findings to humans during sleep, but not yet, during rest. Here, we show that learning-related reactivation also occurs in humans during rest. During functional MRI-scanning, participants trained on a perceptuomotor task flanked by rest periods. During training, we found robust activity in the superior parietal cortex. During post-training rest, this same area reactivated. We also found a link between parietal reactivation and learning. Activity in superior parietal cortex was associated with learning during training, and a control group that did not train on the perceptuomotor task did not show any difference between the pre- and post-training rest blocks in this region. These findings indicate that, during rest, reactivation also occurs in humans. This process may contribute to consolidation of perceptuomotor memories.

Dissociating the "retrieval success" regions of the brain: effects of retrieval delay.

There is abundant evidence that the hippocampal formation critically supports episodic memory retrieval, the remembering of episodes including contextual details. Yet, a group of other brain regions has also been consistently implicated in successful episodic retrieval. This retrieval success network (RSN) includes the posterior midline region, medial prefrontal cortex (mPFC), and posterior parietal cortex (PPC). Despite these consistent findings, the functional roles of the RSN regions remain poorly understood. Given that vivid remembering leads to high-confidence retrieval decisions, it is unclear whether activity in these regions reflects episodic long-term memory, or is merely associated with retrieval confidence. In order to distinguish between these alternatives, we manipulated study-test delays within the context of a continuous recognition task during fMRI-scanning. The design was based on previous evidence indicating that retrieval at short delays is easier leading to high-evidence mnemonic decisions, whereas retrieval at longer delays is more difficult but also more hippocampus-dependent. Confirming previous findings, we found that retrieval decisions at short delays were more accurate and faster, and that the hippocampus showed greater activity at longer delays. Within the other RSN regions, we found three distinct activation patterns as a function of delay. Similar to the hippocampus, the retrosplenial cortex showed increased activity as a function of retrieval delay. Dorsal PPC and the precuneus showed decreased activity. Finally, the posterior cingulate, medial PFC and ventral PPC showed a V-shaped pattern. These findings support the idea that dorsal PPC and the precuneus are involved in decision-related retrieval processes rather than successful remembering.

Triple dissociation in the medial temporal lobes: recollection, familiarity, and novelty.

Memory for past events may be based on retrieval accompanied by specific contextual details (recollection) or on the feeling that an item is old (familiarity) or new (novelty) in the absence of contextual details. There are indications that recollection, familiarity, and novelty involve different medial temporal lobe subregions, but available evidence is scarce and inconclusive. Using functional magnetic resonance imaging (MRI), we isolated retrieval-related activity associated with recollection, familiarity, and novelty by distinguishing between linear and nonlinear oldness functions derived from recognition confidence levels. Within the medial temporal lobes (MTLs), we found a triple dissociation among the posterior half of the hippocampus, which was associated with recollection, the posterior parahippocampal gyrus, which was associated with familiarity, and anterior half of the hippocampus and rhinal regions, which were associated with novelty. Furthermore, multiple regression analyses based on individual trial activity showed that all three memory signals, i.e., recollection, familiarity, and novelty, make significant and independent contributions to recognition memory performance. Finally, functional dissociations among recollection, familiarity, and novelty were also found in posterior midline, left parietal cortex, and prefrontal cortex regions. This is the first study to reveal a triple dissociation within the MTL associated with distinct retrieval processes. This finding has direct implications for current memory models.

When less means more: deactivations during encoding that predict subsequent memory.

In event-related functional MRI (fMRI) studies, greater activity for items that are subsequently remembered (R-items) than for items that are subsequently forgotten (F-items), or Dm effect (Difference in memory), has been attributed to successful encoding operations. In contrast, regions showing a reverse DM effect (revDM = F-items > R-items) have been linked to detrimental processes leading to forgetting. Yet, revDMs may reflect not only activations for F-items (aFs) but also deactivations for R-items (dRs), and the latter alternative is more likely to reflect beneficial rather than detrimental encoding processes. To investigate this issue, we used a paradigm that included a fixation baseline and could distinguish between the two types of revDMs (aF vs. dR). Participants were scanned while encoding semantic associations between words or perceptual associations between words and fonts, and their memory was measured with associative recognition tests. For both semantic and perceptual encoding, dR effects were found in dorsolateral prefrontal, temporoparietal, and posterior midline regions. In contrast with a prior study that attributed revDMs in these regions to detrimental processes, the present results suggest that these effects reflect beneficial processes, that is, the efficient reallocation of neurocognitive resources. At the same time, aF effects were found in other regions, such as the insula, and these are more consistent with an interpretation in terms of detrimental processes. Whereas most fMRI studies of encoding have focused on activation increases, the present study indicates that activation decreases are also critical for successful learning of new information.

Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects.

Lesion studies have shown convincingly that the medial temporal lobes (MTL) and frontal lobes are critical to episodic memory. Ageing generally has been found to have a generally negative effect on episodic memory performance, which might relate to neurofunctional changes in the frontal and medial temporal brain regions. In the present study, we used functional MRI (fMRI) to investigate separately the contributions of encoding and retrieval to the age-related decline in memory. To this end, we compared brain activity patterns obtained during incidental encoding (pleasant/unpleasant judgements about nouns) and subsequent retrieval (recognition) in three groups: a group of young subjects, a group of elderly subjects showing reduced memory performance (ELD-RED), and a group of elderly subjects who still performed in the normal range (ELD-NORM). This allowed us to differentiate between age-related changes in brain activity that affect memory function and those that do not have an apparent effect on memory function, because they are found in both elderly groups. Contrary to previous imaging studies on this topic, we used (self-paced) event-related fMRI to control for differences in performance level across groups by including correct responses only. Comparing the encoding of successfully remembered items with baseline (press left/press right), the young subjects showed a significant increase in brain activation in the left anterior MTL compared with the ELD-RED but not the ELD-NORM subjects. Comparing correctly rejected items (retrieval attempt) with baseline, the ELD-RED group showed much increased overall activity throughout the brain compared with the other groups. However, when correctly recognized items (retrieval attempt + success) were compared directly with correctly rejected items (retrieval attempt), these differences were greatly reduced, revealing common activity in the left parietal, retrosplenial and left anterior prefrontal regions. Therefore, we conclude that the reduced performance in the ELD-RED group is likely to be due to MTL dysfunction during encoding. The differences observed during retrieval attempts may reflect strategic differences. The lack of differences observed in relation to retrieval success suggests that ageing does not affect the processes that support the actual recovery of information.

Parahippocampal activation during successful recognition of words: a self-paced event-related fMRI study.

In this study, we investigated retrieval from verbal episodic memory using a self-paced event-related fMRI paradigm, similar to the designs typically used in behavioral studies of memory function. We tested the hypothesis that the medial temporal lobe (MTL) is involved in the actual recovery of verbal information (retrieval success) rather than in the attempt to retrieve information (retrieval attempt). To this end, we used a verbal recognition task, distinguishing correctly recognized words, correctly rejected words, and a low-level baseline condition. Directly contrasting correct recognition with correct rejection of words, we found activation in the left fusiform/parahippocampal gyrus, indicating that this region has a distinct role in the successful retrieval of verbal information. Furthermore, our results were in agreement with those of previous imaging studies that compared a fixed-paced verbal recognition task to a baseline condition, showing activation in bilateral inferior frontal cortex, left dorsolateral prefrontal cortex, left anterior insular cortex, and anterior cingulate. This demonstrates the applicability of a self-paced event-related design within imaging studies of memory function.