Sander M. Daselaar

Neural correlates of relational memory: successful encoding and retrieval of semantic and perceptual associations

Using event-related functional magnetic resonance imaging, we identified brain regions involved in successful relational memory (RM) during encoding and retrieval for semantic and perceptual associations or in general, independent of phase and content. Participants were scanned while encoding and later retrieving associations between pairs of words (semantic RM) or associations between words and fonts (perceptual RM). Encoding success activity (ESA) was identified by comparing study-phase activity for items subsequently remembered (hits) versus forgotten (misses) and retrieval success activity (RSA) by comparing test-phase activity for hits versus misses. The study yielded three main sets of findings. First, ESA-RSA differences were found within the medial temporal lobes (MTLs) and within the prefrontal cortex (PFC). Within the left MTL, ESA was greater in the anterior hippocampus, and RSA was greater in the posterior parahippocampal cortex/hippocampus. This finding is consistent with the notion of an encoding-retrieval gradient along the longitudinal MTL axis. Within the left PFC, ESA was greater in ventrolateral PFC, and RSA was greater in dorsolateral and anterior PFC. This is the first evidence of a dissociation in successful encoding and retrieval activity within left PFC. Second, consistent with the transfer-appropriate processing principle, some ESA regions were reactivated during RSA in a content-specific manner. For semantic RM, these regions included the left ventrolateral PFC, whereas for perceptual RM, they included occipitoparietal and right parahippocampal regions. Finally, only one region in the entire brain was associated with RM in general (i.e., for both semantic and perceptual ESA and RSA): the left hippocampus. This finding highlights the fundamental role of the hippocampus in RM.

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.

Brain Activity during Episodic Retrieval of Autobiographical and Laboratory Events: An fMRI Study using a Novel Photo Paradigm

Functional neuroimaging studies of episodic memory retrieval generally measure brain activity while participants remember items encountered in the laboratory (controlled laboratory condition) or events from their own life (open autobiographical condition). Differences in activation between these conditions may reflect differences in retrieval processes, memory remoteness, emotional content, retrieval success, self-referential processing, visual/spatial memory, and recollection. To clarify the nature of these differences, a functional MRI study was conducted using a novel photo paradigm, which allows greater control over the autobiographical condition, including a measure of retrieval accuracy. Undergraduate students took photos in specified campus locations (controlled autobiographical condition), viewed in the laboratory similar photos taken by other participants (controlled laboratory condition), and were then scanned while recognizing the two kinds of photos. Both conditions activated a common episodic memory network that included medial temporal and prefrontal regions. Compared with the controlled laboratory condition, the controlled autobiographical condition elicited greater activity in regions associated with self-referential processing (medial prefrontal cortex), visual/ spatial memory (visual and parahippocampal regions), and recollection (hippocampus). The photo paradigm provides a way of investigating the functional neuroanatomy of real-life episodic memory under rigorous experimental control.

Similar network activated by young and old adults during the acquisition of a motor sequence

In this functional MRI (fMRI) study, we investigated ageing effects on motor skill learning. We applied an adapted version of the serial reaction time (SRT) task to extensive groups of young (N=26) and elderly (N=40) subjects. Since indications have been provided for age-related shrinkage of brain regions assumed to be critical to motor skill learning, we tested the hypothesis that age effects on implicit sequence learning are larger on a neurofunctional level than on a behavioural level. The SRT task consisted of two identical scan sessions, in which subjects had to manually trail an asterisk appearing serially in one of four spatial positions by means of button-pressing. Reliable response time reductions were already found in the first session for both the young and the elderly groups, when comparing a fixed sequence condition to a random sequence, but the learning effect was greater for the young subjects. In the second session, though, both groups showed a similar degree of learning. This indicates that implicit sequence learning is still intact in elderly adults, but that the rate of learning is somewhat slower. Reliable learning-related changes in brain activity were also observed. A similar network of brain regions was recruited by both groups during the fixed compared to the random sequence, involving several regions that have been previously associated with implicit sequence learning, including bilateral parietal, and frontal regions, the supplementary motor area (SMA), cerebellum and the basal ganglia. The direct group comparison did not reveal any differences in brain activity. In addition, we did not observe any significant differences in activity when comparing the different sessions either, neither for the young nor for the elderly subjects. Hence, we did not find indications for an age-related functional reorganisation of neural networks involved in motor sequence learning. In view of earlier reports of pronounced ageing effects on the performance on declarative memory tasks, our finding of age-related sparing of processes that sustain motor skill learning, provides further support for the proposition of different memory systems relying on different brain substrates.

Posterior midline and ventral parietal activity is associated with retrieval success and encoding failure

The ventral part of lateral posterior parietal cortex (VPC) and the posterior midline region (PMR), including the posterior cingulate cortex and precuneus, tend to show deactivation during demanding cognitive tasks, and have been associated with the default mode of the brain. Interestingly, PMR and VPC activity has been associated with successful episodic retrieval but also with unsuccessful episodic encoding. However, the differential contributions of PMR and VPC to retrieval vs. encoding has never been demonstrated within-subjects and within the same experiment. Here, we directly tested the prediction that PMR and VPC activity should be associated with retrieval success but with encoding failure. Consistent with this prediction, we found across five different fMRI experiments that, during retrieval, activity in these regions is greater for hits than misses, whereas during encoding, it is greater for subsequent misses than hits. We also found that these regions overlap with the ones that show deactivations during conscious rest. Our findings further aid in clarifying the role of the default mode regions in learning and memory.

Overlapping brain activity between episodic memory encoding and retrieval: Roles of the task-positive and task-negative networks

The notion that the brain is organized into two complementary networks, one that is task-positive and supports externally-oriented processing, and the other that is task-negative and supports internally-oriented processing, has recently attracted increasing attention. The goal of the present study was to investigate involvement of the task-positive and task-negative networks in overlapping activity between episodic memory encoding and retrieval. To this end, we performed a functional MRI study that included both encoding and retrieval tasks. We hypothesized that during the study phase, encoding success activity (remembered > forgotten) involves mainly the task-positive network, whereas encoding failure activity (forgotten > remembered) involves mainly the task-negative network. We also hypothesized that during the test phase, retrieval success activity (old > new) involves mainly the task-negative network, whereas novelty detection activity (new > old) involves mainly the task-positive network. Based on these hypotheses, we made 3 predictions regarding study-test overlap. First, there would be relatively high level of overlap between encoding success and novelty detection activity involving the task-positive network. Second, there would be relatively high level of overlap between encoding failure and retrieval success activity involving the task-negative network. Third, there would be relatively low level of overlap between encoding success and retrieval success activity as well as between encoding failure and novelty detection activity. The results fully confirmed our 3 predictions. Taken together, the present findings clarify roles of the task-positive and task-negative networks in encoding and retrieval and the function of overlapping brain activity between encoding and retrieval.

Effects of aging on transient and sustained successful memory encoding activity.

Event-related fMRI studies have investigated age-related changes in encoding by identifying greater activity for items that are later remembered than for those that are forgotten (difference in memory, or Dm). The present study used hybrid blocked/event-related analyses to distinguish between transient Dm versus sustained Dm. Dm was identified as parametric increases in encoding activity as a function of a combined subsequent memory/confidence scale. Dm was measured in each trial (transient activity) and in blocks of eight trials (sustained activity). Transient Dm analyses showed age-related reductions in the left hippocampus but increases in left prefrontal cortex (PFC). Sustained Dm analyses showed age-related reductions in right PFC, but no region showing increased activity in older adults. These findings suggests that during semantic classification older adults show less spontaneous hippocampal-mediated encoding processes, but greater PFC-mediated semantic processes. Additionally, the decline in sustained Dm in PFC may involve age-related deficits in sustained attention that impact encoding processes. The results underscore the importance of investigating aging effects on both transient and sustained neural activity.

Deep processing activates the medial temporal lobe in young but not in old adults

Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that elderly adults are not able to perform certain cognitive operations under deep processing conditions. We further hypothesised that this inability does not involve regions commonly associated with lexical/semantic retrieval processes, but rather involves a dysfunction of the medial temporal lobe (MTL) memory system. To this end, we used functional MRI on rather extensive groups of young and elderly adults to compare brain activity patterns obtained during a deep (living/nonliving) and a shallow (uppercase/lowercase) classification task. Common activity in relation to semantic classification was observed in regions that have been previously related to semantic retrieval, including mainly left-lateralised activity in the inferior prefrontal, middle temporal, and middle frontal/anterior cingulate gyrus. Although the young adults showed more activity in some of these areas, the finding of mainly overlapping activation patterns during semantic classification supports the idea that lexical/semantic retrieval processes are still intact in elderly adults. This received further support by the finding that both groups showed similar behavioural performances as well on the deep and shallow classification tasks. Importantly, though, the young revealed significantly more activity than the elderly adults in the left anterior hippocampus during deep relative to shallow classification. This finding is in line with the idea that age-related impairments in episodic encoding are, at least partly, due to an under-recruitment of the medial temporal lobe memory system.

The Hippocampus Is Coupled with the Default Network during Memory Retrieval but Not during Memory Encoding

The brains default mode network (DMN) is activated during internally-oriented tasks and shows strong coherence in spontaneous rest activity. Despite a surge of recent interest, the functional role of the DMN remains poorly understood. Interestingly, the DMN activates during retrieval of past events but deactivates during encoding of novel events into memory. One hypothesis is that these opposing effects reflect a difference between attentional orienting towards internal events, such as retrieved memories, vs. external events, such as to-be-encoded stimuli. Another hypothesis is that hippocampal regions are coupled with the DMN during retrieval but decoupled from the DMN during encoding. The present fMRI study investigated these two hypotheses by combining a resting-state coherence analysis with a task that measured the encoding and retrieval of both internally-generated and externally-presented events. Results revealed that the main DMN regions were activated during retrieval but deactivated during encoding. Counter to the internal orienting hypothesis, this pattern was not modulated by whether memory events were internal or external. Consistent with the hippocampal coupling hypothesis, the hippocampus behaved like other DMN regions during retrieval but not during encoding. Taken together, our findings clarify the relationship between the DMN and the neural correlates of memory retrieval and encoding.

Imagery and retrieval of auditory and visual information: Neural correlates of successful and unsuccessful performance

Remembering past events - or episodic retrieval - consists of several components. There is evidence that mental imagery plays an important role in retrieval and that the brain regions supporting imagery overlap with those supporting retrieval. An open issue is to what extent these regions support successful vs. unsuccessful imagery and retrieval processes. Previous studies that examined regional overlap between imagery and retrieval used uncontrolled memory conditions, such as autobiographical memory tasks, that cannot distinguish between successful and unsuccessful retrieval. A second issue is that fMRI studies that compared imagery and retrieval have used modality-aspecific cues that are likely to activate auditory and visual processing regions simultaneously. Thus, it is not clear to what extent identified brain regions support modality-specific or modality-independent imagery and retrieval processes. In the current fMRI study, we addressed this issue by comparing imagery to retrieval under controlled memory conditions in both auditory and visual modalities. We also obtained subjective measures of imagery quality allowing us to dissociate regions contributing to successful vs. unsuccessful imagery. Results indicated that auditory and visual regions contribute both to imagery and retrieval in a modality-specific fashion. In addition, we identified four sets of brain regions with distinct patterns of activity that contributed to imagery and retrieval in a modality-independent fashion. The first set of regions, including hippocampus, posterior cingulate cortex, medial prefrontal cortex and angular gyrus, showed a pattern common to imagery/retrieval and consistent with successful performance regardless of task. The second set of regions, including dorsal precuneus, anterior cingulate and dorsolateral prefrontal cortex, also showed a pattern common to imagery and retrieval, but consistent with unsuccessful performance during both tasks. Third, left ventrolateral prefrontal cortex showed an interaction between task and performance and was associated with successful imagery but unsuccessful retrieval. Finally, the fourth set of regions, including ventral precuneus, midcingulate cortex and supramarginal gyrus, showed the opposite interaction, supporting unsuccessful imagery, but successful retrieval performance. Results are discussed in relation to reconstructive, attentional, semantic memory, and working memory processes. This is the first study to separate the neural correlates of successful and unsuccessful performance for both imagery and retrieval and for both auditory and visual modalities.