Examining the neural basis of unitization: A review.

Associative memory refers to the ability to form and remember associations between individual pieces of information rather than memory for a single object or word. Encoding associations in memory tends to be a more difficult task than item (only) encoding, because associative memory requires encoding multiple items as well as the specific links amongst the items. Accordingly, researchers have worked to identify interventions and strategies to reduce the effort and neural resources required for successful associative memory processing. Unitization is one such strategy that has traditionally been defined as the process by which two or more discrete items are processed, or encoded, such that they are perceived as a single ensemble. The current review explores the neural research on unitization while considering the behavioral benefits that accompany the process.

Investigating the neural basis of schematic false memories by examining schematic and lure pattern similarity.

ABSTRACTSchemas allow us to make assumptions about the world based upon previous experiences and aid in memory organisation and retrieval. However, a reliance on schemas may also result in increased false memories to schematically related lures. Prior neuroimaging work has linked schematic processing in memory tasks to activity in prefrontal, visual, and temporal regions. Yet, it is unclear what type of processing in these regions underlies memory errors. The current study examined where schematic lures exhibit greater neural similarity to schematic targets, leading to this memory error, as compared to neural overlap with non-schematic lures, which, like schematic lures, are novel items at retrieval. Results showed that patterns of neural activity in ventromedial prefrontal cortex, medial frontal gyrus, middle temporal gyrus, hippocampus, and occipital cortices exhibited greater neural pattern similarity for schematic targets and schematic lures than between schematic lures and non-schematic lures. As such, results suggest that schematic membership, and not object history, may be more critical to the neural processes underlying memory retrieval in the context of a strong schema.

Does unitization really function like items? The role of interference on item and associative memory processes.

Associative memory declines as we age, while item memory remains relatively stable. Previous work has shown that, in both younger and older adults, while item recognition declines linearly across time and interference, associative recognition declines only with longer delays and more interference. Unitization is a memory process found to support associative memory by allowing pairs to presumably be processed like single items. Research has found that unitization can benefit memory in aging by boosting associative memory to be on par with that of younger adults. Yet it remains unclear exactly the mechanism responsible for this enhancement in memory. The current studies aimed to determine whether unitized pairs show similar memory to that of items or associations with increasing time and interference, and determine how physically similar unitized pairs must be to perform like items and examine the effect of age on unitization in a continuous recognition paradigm. The results show that while unitized pairs exhibit higher corrected recognition compared with associative pairs at all lags, unitized pairs are not remembered to the degree that items are. It is critical that unitization boosts accurate recognition of pairs in both age groups across all early and middle lags compared with associative pairs. The results suggest that unitization may promote a more efficient associative link than unrelated associations over increasing time and interference, but the benefit does not reach that of item memory. These results demonstrate that while unitization benefits corrected recognition with earlier interference, its effect may not hold with later interference.

The influence of item familiarization on neural discriminability during associative memory encoding and retrieval.

Associative memory requires one to encode and form memory representations not just for individual items, but for the association or link between those items. Past work has suggested that associative memory is facilitated when individual items are familiar rather than simultaneously learning the items and their associative link. The current study employed multivoxel pattern analyses (MVPA) to investigate whether item familiarization prior to associative encoding affects the distinctiveness of neural patterns, and whether that distinctiveness is also present during associative retrieval. Our results suggest that prior exposure to item stimuli impacts the representations of their shared association compared to stimuli that are novel at the time of associative encoding throughout most of the associative memory network. While this distinction was also present at retrieval, the overall extent of the difference was diminished. Overall the results suggest that stimulus familiarity influences the representation of associative pairings during memory encoding and retrieval, and the pair-specific representation is maintained across memory phases irrespective of this distinction.

Sensory Representations Supporting Memory Specificity: Age Effects on Behavioral and Neural Discriminability.

Older adults' difficulty in distinguishing between old and new information contributes to memory decline, which may occur because older adults are less likely than young adults to retrieve specific sensory details necessary to distinguish between similar items. In male and female human subjects, the present study measured the extent of age differences in the specificity of memory representations using a false memory paradigm in which studied items were linked to retrieval items at multiple levels of similarity. Older adults showed poorer behavioral discrimination than young adults, driven primarily by false recognition of lures that differed from targets only in perceptual details. Patterns of activation across several regions within ventral visual cortex could be used to distinguish between targets and lures when they differed in both perceptual details and a semantic label. However, of ventral visual regions, only signals in the midline occipital cortex could be used to distinguish targets from lures when they differed only in perceptual details. Although there was an overall age deficit for this neural discrimination in this region, the positive relationship between neural and behavioral discriminability did not differ across age groups. In contrast, age moderated the relationship between neural and behavioral discriminability in lateral occipital and fusiform cortices, suggesting that activation patterns within these regions represent different types of information in each age group. Therefore, the quality of perceptual signals is a key contributor to memory discrimination across age groups, with evidence that age differences in the nature of representations emerges outside early visual cortex.SIGNIFICANCE STATEMENT Age-related memory decline is due in part to older adults' difficulties in discriminating between old and new information. We tested whether this deficit arises from lack of specificity in the sensory representations underlying older adults' recognition judgments. Using pattern classification analyses in ventral visual cortices, we found that signals in a region early in the visual stream could distinguish between targets and lures at the highest level of similarity. The discriminability of targets and lures in this region was positively related to behavioral discriminability across age groups despite an overall age deficit in classification accuracy. Together, results showed that older adults' memory deficits are related to reduced discriminability of cognitive processes (old/new recognition) in portions of visual cortex.

Examining the Neural Basis of Congruent and Incongruent Configural Contexts during Associative Retrieval.

Disrupting the configural context, or relative organization and orientation of paired stimuli, between encoding and retrieval negatively impacts memory. Using univariate and multivariate fMRI analyses, we examined the effect of retaining and manipulating the configural context on neural mechanisms supporting associative retrieval. Behavioral results showed participants had significantly higher hit rates for recollecting pairs in a contextually congruent, versus incongruent, configuration. In addition, contextual congruency between memory phases was a critical determinant to characterizing both the magnitude and patterns of neural activation within visual and parietal cortices. Regions within visual cortices also exhibited higher correlations between patterns of activity at encoding and retrieval when configural context was congruent across memory phases than incongruent. Collectively, these findings shed light on how manipulating configural context between encoding and retrieval affects associative recognition, with changes in the configural context leading to reductions in information transfer and increases in task difficulty.

Memory for the usual: the influence of schemas on memory for non-schematic information in younger and older adults.

Schemas are abstract mental representations that influence perceptual and memory processes. Schemas can aide memory for information that is related or congruent with a given schema (i.e., schematic information), yet it is unclear how schemas affect memory for information that does not directly relate to the schema (i.e., non-schematic information). Using a novel scene paradigm, the current series of studies investigated how schemas affect memory for schematic and non-schematic information, as well as how directed encoding influences remembering of both types of information in younger and older adults. Results showed poorer accurate recognition of non-schematic information relative to schematic information, influenced largely by a bias in identifying non-schematic items as "new". While directed encoding was able to increase remembering of non-schematic information and decrease bias across both age groups, the present set of studies highlights the pervasive influence of a schema on memory for non-schematic information.

Repeated study of items with and without repeated context: aging effects on memory discriminability.

Presenting items multiple times during encoding is a common way to enhance recognition accuracy. Under such conditions, older adults often show an increase in false recognition that counteracts benefits of repeated study. Using a false-memory paradigm with related study items and related lures, we tested whether repetition within the same encoding task or repetition across two different encoding tasks would be more beneficial to older adults' memory discriminability. Results showed that, compared to items not repeated at study, items repeated in the same context and items repeated across different contexts showed improvements in memory discriminability in both young and older adults. This improvement was primarily reflected in improved recollection responses for both age groups across both repeat study conditions, as compared to no repetition. Importantly, the results demonstrated that repetition can be used to successfully mitigate age-related deficits by increasing memory discriminability and without incurring a cost of false recognition specific to any one age group.

Modulation of target recollection and recollection rejection networks due to retrieval facilitation and interference.

To better understand neural recollection processing, we induced interference in target recollection by presenting related lures before their respective targets and facilitated recollection rejection of lures by presenting targets before their related lures. Target recollection following interference recruited visual and prefrontal cortices, showing that these regions support recollection when related information has disrupted target representations. Recollection rejection following target presentation recruited angular gyrus, indicating that this region supports recollection rejection when target representations are strong and highly accessible. Thus, recollection networks are sensitive to the accessibility of target representations that are affected by the presentation of related information during retrieval.

Elucidating the neural correlates of related false memories using a systematic measure of perceptual relatedness.

Previous memory research has exploited the perceptual similarities between lures and targets in order to evoke false memories. Nevertheless, while some studies have attempted to use lures that are objectively more similar than others, no study has systematically controlled for perceptual overlap between target and lure items and its role in accounting for false alarm rates or the neural processes underlying such perceptual false memories. The current study looked to fill this gap in the literature by using a face-morphing program to systematically control for the amount of perceptual overlap between lures and targets. Our results converge with previous studies in finding a pattern of differences between true and false memories. Most importantly, expanding upon this work, parametric analyses showed false memory activity increases with respect to the similarity between lures and targets within bilateral middle temporal gyri and right medial prefrontal cortex (mPFC). Moreover, this pattern of activation was unique to false memories and could not be accounted for by relatedness alone. Connectivity analyses further find that activity in the mPFC and left middle temporal gyrus co-vary, suggestive of gist-based monitoring within the context of false memories. Interestingly, neither the MTL nor the fusiform face area exhibited modulation as a function of target-lure relatedness. Overall, these results provide insight into the processes underlying false memories and further enhance our understanding of the role perceptual similarity plays in supporting false memories.

From hippocampus to whole-brain: The role of integrative processing in episodic memory retrieval.

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242-2259, 2017. © 2017 Wiley Periodicals, Inc.

Memory-guided force control in healthy younger and older adults.

Successful performance of a memory-guided motor task requires participants to store and then recall an accurate representation of the motor goal. Further, participants must monitor motor output to make adjustments in the absence of visual feedback. The goal of this study was to examine memory-guided grip force in healthy younger and older adults and compare it to performance on behavioral tasks of working memory. Previous work demonstrates that healthy adults decrease force output as a function of time when visual feedback is not available. We hypothesized that older adults would decrease force output at a faster rate than younger adults, due to age-related deficits in working memory. Two groups of participants, younger adults (YA: N = 32, mean age 21.5 years) and older adults (OA: N = 33, mean age 69.3 years), completed four 20-s trials of isometric force with their index finger and thumb, equal to 25% of their maximum voluntary contraction. In the full-vision condition, visual feedback was available for the duration of the trial. In the no vision condition, visual feedback was removed for the last 12 s of each trial. Participants were asked to maintain constant force output in the absence of visual feedback. Participants also completed tasks of word recall and recognition and visuospatial working memory. Counter to our predictions, when visual feedback was removed, younger adults decreased force at a faster rate compared to older adults and the rate of decay was not associated with behavioral performance on tests of working memory.

Exploring the influence of encoding format on subsequent memory.

Distinctive encoding is greatly influenced by gist-based processes and has been shown to suffer when highly similar items are presented in close succession. Thus, elucidating the mechanisms underlying how presentation format affects gist processing is essential in determining the factors that influence these encoding processes. The current study utilised multivariate partial least squares (PLS) analysis to identify encoding networks directly associated with retrieval performance in a blocked and intermixed presentation condition. Subsequent memory analysis for successfully encoded items indicated no significant differences between reaction time and retrieval performance and presentation format. Despite no significant behavioural differences, behaviour PLS revealed differences in brain-behaviour correlations and mean condition activity in brain regions associated with gist-based vs. distinctive encoding. Specifically, the intermixed format encouraged more distinctive encoding, showing increased activation of regions associated with strategy use and visual processing (e.g., frontal and visual cortices, respectively). Alternatively, the blocked format exhibited increased gist-based processes, accompanied by increased activity in the right inferior frontal gyrus. Together, results suggest that the sequence that information is presented during encoding affects the degree to which distinctive encoding is engaged. These findings extend our understanding of the Fuzzy Trace Theory and the role of presentation format on encoding processes.

The Neural Basis of Recollection Rejection: Increases in Hippocampal-Prefrontal Connectivity in the Absence of a Shared Recall-to-Reject and Target Recollection Network.

Recollection rejection or "recall-to-reject" is a mechanism that has been posited to help maintain accurate memory by preventing the occurrence of false memories. Recollection rejection occurs when the presentation of a new item during recognition triggers recall of an associated target, a mismatch in features between the new and old items is registered, and the lure is correctly rejected. Critically, this characterization of recollection rejection involves a recall signal that is conceptually similar to recollection as elicited by a target. However, previous neuroimaging studies have not evaluated the extent to which recollection rejection and target recollection rely on a common neural signal but have instead focused on recollection rejection as a postretrieval monitoring process. This study utilized a false memory paradigm in conjunction with an adapted remember-know-new response paradigm that separated "new" responses based on recollection rejection from those that were based on a lack of familiarity with the item. This procedure allowed for parallel recollection rejection and target recollection contrasts to be computed. Results revealed that, contrary to predictions from theoretical and behavioral literature, there was virtually no evidence of a common retrieval mechanism supporting recollection rejection and target recollection. Instead of the typical target recollection network, recollection rejection recruited a network of lateral prefrontal and bilateral parietal regions that is consistent with the retrieval monitoring network identified in previous neuroimaging studies of recollection rejection. However, a functional connectivity analysis revealed a component of the frontoparietal rejection network that showed increased coupling with the right hippocampus during recollection rejection responses. As such, we demonstrate a possible link between PFC monitoring network and basic retrieval mechanisms within the hippocampus that was not revealed with univariate analyses alone.

The effects of item familiarity on the neural correlates of successful associative memory encoding.

Associative memory is considered to be resource-demanding, requiring individuals to learn individual items and the specific relationships between those items. Previous research has shown that prior studying of items aids in associative memory for pairs composed of those same items, as compared to pairs of items that have not been prelearned (e.g., Kilb & Naveh-Benjamin, 2011). In the present study, we sought to elucidate the neural correlates mediating this memory facilitation. After being trained on individual items, participants were scanned while encoding item pairs composed of items from the pretrained phase (familiarized-item pairs) and pairs whose items had not been previously learned (unfamiliarized-item pairs). Consistent with previous findings, the overall subsequent recollection showed the engagement of bilateral parahippocampal gyrus (PHG) and hippocampus, when compared to subsequent forgetting. However, a direct comparison between familiarized- and unfamiliarized-item pairs showed that subsequently recollected familiarized-item pairs were associated with decreased activity across much of the encoding network, including bilateral PHG, hippocampus, prefrontal cortex, and regions associated with item-specific processing within occipital cortex. Increased activity for familiarized-item pairs was found in a more limited set of regions, including bilateral parietal cortex, which has been associated with the formation of novel associations. Additionally, activity in the right parietal cortex correlated with associative memory success in the familiarized condition. Taken together, these results suggest that prior exposure to items can reduce the demands incurred on neural processing throughout the associative encoding network and can enhance associative memory performance by focusing resources within regions supporting the formation of associative links.

The neural correlates of correctly rejecting lures during memory retrieval: the role of item relatedness.

Successful memory retrieval is predicated not only on recognizing old information, but also on correctly rejecting new information (lures) in order to avoid false memories. Correctly rejecting lures is more difficult when they are perceptually or semantically related to information presented at study as compared to when lures are distinct from previously studied information. This behavioral difference suggests that the cognitive and neural basis of correct rejections differs with respect to the relatedness between lures and studied items. The present study sought to identify neural activity that aids in suppressing false memories by examining the network of brain regions underlying correct rejection of related and unrelated lures. Results showed neural overlap in the right hippocampus and anterior parahippocampal gyrus associated with both related and unrelated correct rejections, indicating that some neural regions support correctly rejecting lures regardless of their semantic/perceptual characteristics. Direct comparisons between related and unrelated correct rejections showed that unrelated correct rejections were associated with greater activity in bilateral middle and inferior temporal cortices, regions that have been associated with categorical processing and semantic labels. Related correct rejections showed greater activation in visual and lateral prefrontal cortices, which have been associated with perceptual processing and retrieval monitoring. Thus, while related and unrelated correct rejections show some common neural correlates, related correct rejections are driven by greater perceptual processing whereas unrelated correct rejections show greater reliance on salient categorical cues to support quick and accurate memory decisions.

Neural Activity Associated with Visual Search for Line Drawings on AAC Displays: An Exploration of the Use of fMRI.

Visual aided augmentative and alternative communication (AAC) consists of books or technologies that contain visual symbols to supplement spoken language. A common observation concerning some forms of aided AAC is that message preparation can be frustratingly slow. We explored the uses of fMRI to examine the neural correlates of visual search for line drawings on AAC displays in 18 college students under two experimental conditions. Under one condition, the location of the icons remained stable and participants were able to learn the spatial layout of the display. Under the other condition, constant shuffling of the locations of the icons prevented participants from learning the layout, impeding rapid search. Brain activation was contrasted under these conditions. Rapid search in the stable display was associated with greater activation of cortical and subcortical regions associated with memory, motor learning, and dorsal visual pathways compared to the search in the unpredictable display. Rapid search for line drawings on stable AAC displays involves not just the conceptual knowledge of the symbol meaning but also the integration of motor, memory, and visual-spatial knowledge about the display layout. Further research must study individuals who use AAC, as well as the functional effect of interventions that promote knowledge about array layout.

Neural correlates underlying true and false associative memories.

Despite the fact that associative memory studies produce a large number of false memories, neuroimaging analyses utilizing this paradigm typically focus only on neural activity mediating successful retrieval. The current study sought to expand on this prior research by examining the neural basis of both true and false associative memories. Though associative false memories are substantially different than those found in semantic or perceptual false memory paradigms, results suggest that associative false memories are mediated by similar neural mechanisms. Specifically, we found increased frontal activity that likely represents enhanced monitoring and evaluation compared to that needed for true memories and correct rejections. Results also indicated that true, and not false associative memories, are mediated by neural activity in the MTL, specifically the hippocampus. Finally, while activity in early visual cortex distinguished true from false memories, a lack of neural differences between hits and correct rejections failed to support previous findings suggesting that activity in early visual cortex represents sensory reactivation of encoding-related processing.

Investigating the neural basis of schematic false memories by examining schematic and lure pattern similarity.

Schemas allow us to make assumptions about the world based upon previous experiences and aid in memory organization and retrieval. However, a reliance on schemas may also result in increased false memories to schematically related lures. Prior neuroimaging work has linked schematic processing in memory tasks to activity in prefrontal, visual, and temporal regions. Yet, it is unclear what type of processing in these regions underlies memory errors. The current study examined where schematic lures exhibit greater neural similarity to schematic targets, leading to this memory error, as compared to neural overlap with non-schematic lures, which, like schematic lures, are novel items at retrieval. Results showed that patterns of neural activity in ventromedial prefrontal cortex, medial frontal gyrus, middle temporal gyrus, hippocampus, and occipital cortices exhibited greater neural pattern similarity for schematic targets and schematic lures than between schematic lures and non-schematic lures. As such, results suggest that schematic membership, and not object history, may be more critical to the neural processes underlying memory retrieval in the context of a strong schema.

The neural correlates of cognitive control: successful remembering and intentional forgetting.

The ability to control how we process information by remembering that which is important and forgetting that which is irrelevant is essential to maintain accurate, up-to-date memories. As such, memory success is predicated on both successful intentional encoding and successful intentional forgetting. The current study used an item-method directed forgetting paradigm to elucidate the cognitive and neural processes that underlie both processes while also examining the relationship between them to understand how the two may work together. Results indicated that encoding-related processes in the left inferior PFC and medial-temporal lobe (MTL) contribute to subsequent memory success, whereas inhibitory processes in the right superior frontal gyrus and right inferior parietal lobe contribute to subsequent forgetting success. Furthermore, connectivity analyses found a negative correlation between activity in the right superior frontal cortex and activity in the left MTL during successful intentional forgetting but not during successful encoding, incidental forgetting, or incidental encoding. Results support the theory that intentional forgetting is mediated by inhibition-related activity in the right frontal cortex and the interaction of this activity with that of encoding-related activity in the MTL. Further support for this inhibitory-related account was found through a clear dissociation between intentional and incidental forgetting, such that intentional forgetting was associated with regions shown to support inhibition, whereas incidental forgetting was associated with regions supporting encoding.