Atsuko Takashima

Shift from Hippocampal to Neocortical Centered Retrieval Network with Consolidation

The standard model of system-level consolidation posits that the hippocampus is part of a retrieval network for recent memories. According to this theory, the memories are gradually transferred to neocortical circuits with consolidation, where the connections within this circuit grow stronger and reorganized so that redundant and/or contextual details may be lost. Thus, remote memories are based on neocortical networks and can be retrieved independently of the hippocampus. To test this model, we measured regional brain activity and connectivity during retrieval with functional magnetic resonance imaging. Subjects were trained on two sets of face-location association and were tested with two different delays, 15 min and 24 h including a whole night of sleep. We hypothesized that memory traces of the locations associated with specific faces will be linked through the hippocampus for the retrieval of recently learned association, but with consolidation, the activity and the functional connectivity between the neocortical areas will increase. We show that posterior hippocampal activity related to high-confidence retrieval decreased and neocortical activity increased with consolidation. Moreover, the connectivity between the hippocampus and the neocortical regions decreased and in turn, cortico-cortical connectivity between the representational areas increased. The results provide mechanistic support for a two-level process of the declarative memory system, involving initial representation of new associations in a network including the hippocampus and subsequent consolidation into a predominantly neocortical network.

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.

Memory stabilization with targeted reactivation during human slow-wave sleep

It is believed that neural representations of recent experiences become reactivated during sleep, and that this process serves to stabilize associated memories in long-term memory. Here, we initiated this reactivation process for specific memories during slow-wave sleep. Participants studied 50 object-location associations with object-related sounds presented concurrently. For half of the associations, the related sounds were re-presented during subsequent slow-wave sleep while participants underwent functional MRI. Compared with control sounds, related sounds were associated with increased activation of right parahippocampal cortex. Postsleep memory accuracy was positively correlated with sound-related activation during sleep in various brain regions, including the thalamus, bilateral medial temporal lobe, and cerebellum. In addition, postsleep memory accuracy was also positively correlated with pre- to postsleep changes in parahippocampal–medial prefrontal connectivity during retrieval of reactivated associations. Our results suggest that the brain is differentially activated by studied and unstudied sounds during deep sleep and that the thalamus and medial temporal lobe are involved in establishing the mnemonic consequences of externally triggered reactivation of associative memories.

Sleep supports selective retention of associative memories based on relevance for future utilization.

An outstanding question is whether memory consolidation occurs passively or involves active processes that selectively stabilize memories based on future utility. Here, we differentially modulated the expected future relevance of two sets of picture-location associations after learning. Participants first studied two sets of picture-location associations. After a baseline memory test, they were instructed that only one set of associations would be retested after a 14-hour delay. For half of the participants, this test-retest delay contained a night of sleep; for the other half the delay included a normal working day. At retest, participants were re-instructed and against their expectations tested on both sets of associations. Our results show that post-learning instruction about subsequent relevance selectively improves memory retention for specific associative memories. This effect was sleep-dependent; it was present only in the group of subjects for which the test-retest delay contained sleep. Moreover, time spent asleep for participants in this sleep group correlated with retention of relevant but not irrelevant associations; participants who slept longer forgot fewer associations from the relevant category. In contrast, participants that did not sleep forgot more relevant than irrelevant associations across the test-retest delay. In summary, our results indicate that it is possible to modulate the retention of selected memories after learning with simple verbal instructions on their future relevance. The finding that this effect depends on sleep demonstrates this state’s active role in memory consolidation and may have utility for educational settings.

Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences

It is becoming increasingly clear that demanding cognitive tasks rely on an extended network engaging task‐relevant areas and, importantly, disengaging task‐irrelevant areas. Given that alpha activity (8–12 Hz) has been shown to reflect the disengagement of task‐irrelevant regions in attention and working memory tasks, we here ask if alpha activity plays a related role for long‐term memory formation. Subjects were instructed to encode and maintain the order of word sequences while the ongoing brain activity was recorded using magnetoencephalography (MEG). In each trial, three words were presented followed by a 3.4 s rehearsal interval. Considering the good temporal resolution of MEG this allowed us to investigate the word presentation and rehearsal interval separately. The sequences were grouped in trials where word order either could be tested immediately (working memory trials; WM) or later (LTM trials) according to instructions. Subjects were tested on their ability to retrieve the order of the three words. The data revealed that alpha power in parieto‐occipital regions was lower during word presentation compared to rehearsal. Our key finding was that parieto‐occipital alpha power during the rehearsal period was markedly stronger for successfully than unsuccessfully encoded LTM sequences. This subsequent memory effect demonstrates that high posterior alpha activity creates an optimal brain state for successful LTM formation possibly by actively reducing parieto‐occipital activity that might interfere with sequence encoding. Hum Brain Mapp, 2011.

Neural correlates of testing effects in vocabulary learning

Tests that require memory retrieval strongly improve long-term retention in comparison to continued studying. For example, once learners know the translation of a word, restudy practice, during which they see the word and its translation again, is less effective than testing practice, during which they see only the word and retrieve the translation from memory. In the present functional magnetic resonance imaging (fMRI) study, we investigated the neuro-cognitive mechanisms underlying this striking testing effect. Twenty-six young adults without prior knowledge of Swahili learned the translation of 100 Swahili words and then further practiced the words in an fMRI scanner by restudying or by testing. Recall of the translations on a final memory test after one week was significantly better and faster for tested words than for restudied words. Brain regions that were more active during testing than during restudying included the left inferior frontal gyrus, ventral striatum, and midbrain areas. Increased activity in the left inferior parietal and left middle temporal areas during testing but not during restudying predicted better recall on the final memory test. Together, results suggest that testing may be more beneficial than restudying due to processes related to targeted semantic elaboration and selective strengthening of associations between retrieval cues and relevant responses, and may involve increased effortful cognitive control and modulations of memory through striatal motivation and reward circuits.

Attention for speaking: domain-general control from the anterior cingulate cortex in spoken word production

Accumulating evidence suggests that some degree of attentional control is required to regulate and monitor processes underlying speaking. Although progress has been made in delineating the neural substrates of the core language processes involved in speaking, substrates associated with regulatory and monitoring processes have remained relatively underspecified. We report the results of an fMRI study examining the neural substrates related to performance in three attention-demanding tasks varying in the amount of linguistic processing: vocal picture naming while ignoring distractors (picture-word interference, PWI); vocal color naming while ignoring distractors (Stroop); and manual object discrimination while ignoring spatial position (Simon task). All three tasks had congruent and incongruent stimuli, while PWI and Stroop also had neutral stimuli. Analyses focusing on common activation across tasks identified a portion of the dorsal anterior cingulate cortex (ACC) that was active in incongruent trials for all three tasks, suggesting that this region subserves a domain-general attentional control function. In the language tasks, this area showed increased activity for incongruent relative to congruent stimuli, consistent with the involvement of domain-general mechanisms of attentional control in word production. The two language tasks also showed activity in anterior-superior temporal gyrus (STG). Activity increased for neutral PWI stimuli (picture and word did not share the same semantic category) relative to incongruent (categorically related) and congruent stimuli. This finding is consistent with the involvement of language-specific areas in word production, possibly related to retrieval of lexical-semantic information from memory. The current results thus suggest that in addition to engaging language-specific areas for core linguistic processes, speaking also engages the ACC, a region that is likely implementing domain-general attentional control.

Functional connectivity during light sleep is correlated with memory performance for face–location associations

The consolidation of declarative memories benefits from sleep. The neural mechanisms involved in sleep-dependent consolidation, however, are largely unknown. Here, we used a combination of functional magnetic resonance imaging, polysomnography and a face-location associative memory task to target neural connectivity of a face sensitive area during an afternoon nap. Fusiform connectivity was substantially greater during sleep stage 1 than in wake in a network extending from early visual areas bilaterally to the fusiform gyrus, ventrally and into the posterior parietal cortices, dorsally. In sleep stage 2, fusiform connectivity was found to be larger in the precuneus, bilateral middle temporal gyrus and medial prefrontal cortex. Specific functional connectivity increases observed during light sleep were positively correlated with memory performance for face-location associations. A distinction could be made between fusiform-medial prefrontal connectivity during sleep stage 1 and 2 that was positively correlated with retention of associations learned prior to sleep and fusiform-hippocampal connectivity during sleep stage 1 that was correlated with better acquisition of new associations learned after sleep. Our results suggest that fusiform-medial prefrontal connectivity during sleep has a stabilizing effect on recently learned associative memories, possibly due to the existence of a task-related schema that allows rapid consolidation of related information. Our data further indicate that sleep-dependent connectivity between the fusiform gyrus and hippocampus correlated with new learning after sleep. Thus, our study provides correlational evidence for the behavioral relevance of specific medial prefrontal and hippocampal interactions with the fusiform gyrus during light sleep.

Evidence for Human Fronto-Central Gamma Activity during Long-Term Memory Encoding of Word Sequences

Although human gamma activity (30–80 Hz) associated with visual processing is often reported, it is not clear to what extend gamma activity can be reliably detected non-invasively from frontal areas during complex cognitive tasks such as long term memory (LTM) formation. We conducted a memory experiment composed of 35 blocks each having three parts: LTM encoding, working memory (WM) maintenance and LTM retrieval. In the LTM encoding and WM maintenance parts, participants had to respectively encode or maintain the order of three sequentially presented words. During LTM retrieval subjects had to reproduce these sequences. Using magnetoencephalography (MEG) we identified significant differences in the gamma and beta activity. Robust gamma activity (55–65 Hz) in left BA6 (supplementary motor area (SMA)/pre-SMA) was stronger during LTM rehearsal than during WM maintenance. The gamma activity was sustained throughout the 3.4 s rehearsal period during which a fixation cross was presented. Importantly, the difference in gamma band activity correlated with memory performance over subjects. Further we observed a weak gamma power difference in left BA6 during the first half of the LTM rehearsal interval larger for successfully than unsuccessfully reproduced word triplets. In the beta band, we found a power decrease in left anterior regions during LTM rehearsal compared to WM maintenance. Also this suppression of beta power correlated with memory performance over subjects. Our findings show that an extended network of brain areas, characterized by oscillatory activity in different frequency bands, supports the encoding of word sequences in LTM. Gamma band activity in BA6 possibly reflects memory processes associated with language and timing, and suppression of beta activity at left frontal sensors is likely to reflect the release of inhibition directly associated with the engagement of language functions.

Changes in theta and beta oscillations as signatures of novel word consolidation

The complementary learning systems account of word learning states that novel words, like other types of memories, undergo an offline consolidation process during which they are gradually integrated into the neocortical memory network. A fundamental change in the neural representation of a novel word should therefore occur in the hours after learning. The present EEG study tested this hypothesis by investigating whether novel words learned before a 24-hr consolidation period elicited more word-like oscillatory responses than novel words learned immediately before testing. In line with previous studies indicating that theta synchronization reflects lexical access, unfamiliar novel words elicited lower power in the theta band (4–8 Hz) than existing words. Recently learned words still showed a marginally lower theta increase than existing words, but theta responses to novel words that had been acquired 24 hr earlier were indistinguishable from responses to existing words. Consistent with evidence that beta desynchronization (16–21 Hz) is related to lexical-semantic processing, we found that both unfamiliar and recently learned novel words elicited less beta desynchronization than existing words. In contrast, no difference was found between novel words learned 24 hr earlier and existing words. These data therefore suggest that an offline consolidation period enables novel words to acquire lexically integrated, word-like neural representations.