Effects of extended practice and unitization on relational memory in older adults and neuropsychological lesion cases.

Unitization - the fusion of objects into a single unit through an action/consequence sequence - can mitigate relational memory impairments, but the circumstances under which unitization is effective are unclear. Using transverse patterning (TP), we compared unitization (and its component processes of fusion, motion, and action/consequence) with extended practice on relational learning and transfer in older adults and neuropsychological cases with lesions (to varying extents) in the medial prefrontal cortex (mPFC) or hippocampus/medial temporal lobe (HC/MTL). The latter included a person with bilateral HC lesions primarily within the dentate gyrus. For older adults, TP accuracy increased, and transfer benefits were observed, with extended practice and unitization. Broadly, the lesion cases did not benefit from either extended practice or unitization, suggesting the mPFC and dentate gyrus play important roles in relational memory and in unitization. The results suggest that personalized strategy interventions must align with the cognitive and neural profiles of the user.

Impaired perceptual discrimination of complex objects in older adults at risk for dementia.

Tau pathology accumulates in the perirhinal cortex (PRC) of the medial temporal lobe (MTL) during the earliest stages of the Alzheimer's disease (AD), appearing decades before clinical diagnosis. Here, we leveraged perceptual discrimination tasks that target PRC function to detect subtle cognitive impairment even in nominally healthy older adults. Older adults who did not have a clinical diagnosis or subjective memory complaints were categorized into "at-risk" (score <26; n = 15) and "healthy" (score ≥26; n = 23) groups based on their performance on the Montreal Cognitive Assessment. The task included two conditions known to recruit the PRC: faces and complex objects (greebles). A scene condition, known to recruit the hippocampus, and a size control condition that does not rely on the MTL were also included. Individuals in the at-risk group were less accurate than those in the healthy group for discriminating greebles. Performance on either the face or size control condition did not predict group status above and beyond that of the greeble condition. Visual discrimination tasks that are sensitive to PRC function may detect early cognitive decline associated with AD.

The impact of aging and repetition on eye movements and recognition memory.

The modulation of gaze fixations on neural activity in the hippocampus, a region critical for memory, has been shown to be weaker in older adults compared to younger adults. However, as such research has relied on indirect measures of memory, it remains unclear whether the relationship between visual exploration and direct measures of memory is similarly disrupted in aging. The current study tested older and younger adults on a face memory eye-tracking task previously used by our group that showed that recognition memory for faces presented across variable, but not fixed, viewpoints relies on a hippocampal-dependent binding function. Here, we examined how aging influences eye movement measures that reveal the amount (cumulative sampling) and extent (distribution of gaze fixations) of visual exploration. We also examined how aging influences direct (subsequent conscious recognition) and indirect (eye movement repetition effect) expressions of memory. No age differences were found in direct recognition regardless of facial viewpoint. However, the eye movement measures revealed key group differences. Compared to younger adults, older adults exhibited more cumulative sampling, a different distribution of fixations, and a larger repetition effect. Moreover, there was a positive relationship between cumulative sampling and direct recognition in younger adults, but not older adults. Neither age group showed a relationship between the repetition effect and direct recognition. Thus, despite similar direct recognition, age-related differences were observed in visual exploration and in an indirect eye-movement memory measure, suggesting that the two groups may acquire, retain, and use different facial information to guide recognition.

Exploring the sociodemographic, clinical and neuropsychological factors associated with relational memory in schizophrenia.

INTRODUCTION: The Transverse Patterning (TP) task has been used to measure episodic relational memory (RM) deficits in clinical populations. Individuals with schizophrenia often fail to learn TP with standard, and sometimes extensive training. Identifying the differences between TP learners and non-learners can improve our understanding of successful TP performance and its underlying mechanisms, which may help improve interventions aimed at ameliorating RM performance. We investigated sociodemographic, clinical and neuropsychological factors associated with TP performance in schizophrenia. METHODS: Sixty-six participants with schizophrenia completed a semantically rich and a relational-binding dependent version of the TP task and reported on their task awareness and strategy use. RESULTS: Twenty-six participants failed to learn the task rules after extensive training. Learners had superior verbal, visual and working memory, executive functions and overall cognitive functioning compared to non-learners. Learners also had superior awareness of task rules and pairs relationships and used elaborated cognitive strategies more often. CONCLUSIONS: Our results support previous findings that some individuals with schizophrenia show RM impairment even with extensive TP training. We shed light on neuropsychological and metacognitive factors associated with TP performance. This knowledge could enhance interventions targeted to improve relational memory in schizophrenia when extensive training fails.

Unrestricted eye movements strengthen effective connectivity from hippocampal to oculomotor regions during scene construction.

Scene construction is a key component of memory recall, navigation, and future imagining, and relies on the medial temporal lobes (MTL). A parallel body of work suggests that eye movements may enable the imagination and construction of scenes, even in the absence of external visual input. There are vast structural and functional connections between regions of the MTL and those of the oculomotor system. However, the directionality of connections between the MTL and oculomotor control regions, and how it relates to scene construction, has not been studied directly in human neuroimaging. In the current study, we used dynamic causal modeling (DCM) to interrogate effective connectivity between the MTL and oculomotor regions using a scene construction task in which participants' eye movements were either restricted (fixed-viewing) or unrestricted (free-viewing). By omitting external visual input, and by contrasting free- versus fixed- viewing, the directionality of neural connectivity during scene construction could be determined. As opposed to when eye movements were restricted, allowing free-viewing during construction of scenes strengthened top-down connections from the MTL to the frontal eye fields, and to lower-level cortical visual processing regions, suppressed bottom-up connections along the visual stream, and enhanced vividness of the constructed scenes. Taken together, these findings provide novel, non-invasive evidence for the underlying, directional, connectivity between the MTL memory system and oculomotor system associated with constructing vivid mental representations of scenes.

Transcranial Direct Current Stimulation Combined With Listening to Preferred Music Alters Cortical Speech Processing in Older Adults.

Emerging evidence suggests transcranial direct current stimulation (tDCS) can improve cognitive performance in older adults. Similarly, music listening may improve arousal and stimulate subsequent performance on memory-related tasks. We examined the synergistic effects of tDCS paired with music listening on auditory neurobehavioral measures to investigate causal evidence of short-term plasticity in speech processing among older adults. In a randomized sham-controlled crossover study, we measured how combined anodal tDCS over dorsolateral prefrontal cortex (DLPFC) paired with listening to autobiographically salient music alters neural speech processing in older adults compared to either music listening (sham stimulation) or tDCS alone. EEG assays included both frequency-following responses (FFRs) and auditory event-related potentials (ERPs) to trace neuromodulation-related changes at brainstem and cortical levels. Relative to music without tDCS (sham), we found tDCS alone (without music) modulates the early cortical neural encoding of speech in the time frame of ∼100-150 ms. Whereas tDCS by itself appeared to largely produce suppressive effects (i.e., reducing ERP amplitude), concurrent music with tDCS restored responses to those of the music+sham levels. However, the interpretation of this effect is somewhat ambiguous as this neural modulation could be attributable to a true effect of tDCS or presence/absence music. Still, the combined benefit of tDCS+music (above tDCS alone) was correlated with listeners' education level suggesting the benefit of neurostimulation paired with music might depend on listener demographics. tDCS changes in speech-FFRs were not observed with DLPFC stimulation. Improvements in working memory pre to post session were also associated with better speech-in-noise listening skills. Our findings provide new causal evidence that combined tDCS+music relative to tDCS-alone (i) modulates the early (100-150 ms) cortical encoding of speech and (ii) improves working memory, a cognitive skill which may indirectly bolster noise-degraded speech perception in older listeners.

The structure of prior knowledge enhances memory in experts by reducing interference.

The influence of prior knowledge on memory is ubiquitous, making the specific mechanisms of this relationship difficult to disentangle. Here, we show that expert knowledge produces a fundamental shift in the way that interitem similarity (i.e., the perceived resemblance between items in a set) biases episodic recognition. Within a group of expert birdwatchers and matched controls, we characterized the psychological similarity space for a set of well-known local species and a set of less familiar, nonlocal species. In experts, interitem similarity was influenced most strongly by taxonomic features, whereas in controls, similarity judgments reflected bird color. In controls, perceived episodic oldness during a recognition memory task increased along with measures of global similarity between items, consistent with classic models of episodic recognition. Surprisingly, for experts, high global similarity did not drive oldness signals. Instead, for local birds memory tracked the availability of species-level name knowledge, whereas for nonlocal birds, it was mediated by the organization of generalized conceptual space. These findings demonstrate that episodic memory in experts can benefit from detailed subcategory knowledge, or, lacking that, from the overall relational structure of concepts. Expertise reshapes psychological similarity space, helping to resolve mnemonic separation challenges arising from high interitem overlap. Thus, even in the absence of knowledge about item-specific details or labels, the presence of generalized knowledge appears to support episodic recognition in domains of expertise by altering the typical relationship between psychological similarity and memory.

Aging changes the interactions between the oculomotor and memory systems.

The use of multi-modal approaches, particularly in conjunction with multivariate analytic techniques, can enrich models of cognition, brain function, and how they change with age. Recently, multivariate approaches have been applied to the study of eye movements in a manner akin to that of neural activity (i.e., pattern similarity). Here, we review the literature regarding multi-modal and/or multivariate approaches, with specific reference to the use of eyetracking to characterize age-related changes in memory. By applying multi-modal and multivariate approaches to the study of aging, research has shown that aging is characterized by moment-to-moment alterations in the amount and pattern of visual exploration, and by extension, alterations in the activity and function of the hippocampus and broader medial temporal lobe (MTL). These methodological advances suggest that age-related declines in the integrity of the memory system has consequences for oculomotor behavior in the moment, in a reciprocal fashion. Age-related changes in hippocampal and MTL structure and function may lead to an increase in, and change in the patterns of, visual exploration in an effort to upregulate the encoding of information. However, such visual exploration patterns may be non-optimal and actually reduce the amount and/or type of incoming information that is bound into a lasting memory representation. This research indicates that age-related cognitive impairments are considerably broader in scope than previously realized.

Neural Correlates of Subsequent Memory-Related Gaze Reinstatement.

Mounting evidence linking gaze reinstatement-the recapitulation of encoding-related gaze patterns during retrieval-to behavioral measures of memory suggests that eye movements play an important role in mnemonic processing. Yet, the nature of the gaze scanpath, including its informational content and neural correlates, has remained in question. In this study, we examined eye movement and neural data from a recognition memory task to further elucidate the behavioral and neural bases of functional gaze reinstatement. Consistent with previous work, gaze reinstatement during retrieval of freely viewed scene images was greater than chance and predictive of recognition memory performance. Gaze reinstatement was also associated with viewing of informationally salient image regions at encoding, suggesting that scanpaths may encode and contain high-level scene content. At the brain level, gaze reinstatement was predicted by encoding-related activity in the occipital pole and BG, neural regions associated with visual processing and oculomotor control. Finally, cross-voxel brain pattern similarity analysis revealed overlapping subsequent memory and subsequent gaze reinstatement modulation effects in the parahippocampal place area and hippocampus, in addition to the occipital pole and BG. Together, these findings suggest that encoding-related activity in brain regions associated with scene processing, oculomotor control, and memory supports the formation, and subsequent recapitulation, of functional scanpaths. More broadly, these findings lend support to Scanpath Theory's assertion that eye movements both encode, and are themselves embedded in, mnemonic representations.

Flexible Use of Spatial Frames of Reference for Object-Location Memory in Older Adults.

In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to age-related breakdown. Yet, recent findings on the heterogeneity of cognitive function and spatial ability in healthy older adults suggest that aging may not uniformly impact the flexible use of spatial representations. These factors have yet to be explored in a precisely controlled task that explicitly manipulates spatial frames of reference across learning and retrieval. We used a lab-based virtual reality task to investigate the relationship between object-location memory across frames of reference, cognitive status, and self-reported spatial ability. Memory error was measured using Euclidean distance from studied object locations to participants' responses at testing. Older adults recalled object locations less accurately when they switched between frames of reference from learning to testing, compared with when they remained in the same frame of reference. They also showed an allocentric learning advantage, producing less error when switching from an allocentric to an egocentric frame of reference, compared with the reverse direction of switching. Higher MoCA scores and better self-assessed spatial ability predicted less memory error, especially when learning occurred egocentrically. We suggest that egocentric learning deficits are driven by difficulty in binding multiple viewpoints into a coherent representation. Finally, we highlight the heterogeneity of spatial memory performance in healthy older adults as a potential cognitive marker for neurodegeneration, beyond normal aging.

The Relational Trip Task, a novel ecological measure of relational memory: data from a schizophrenia sample.

INTRODUCTION: Relational memory (RM) is severely impaired in schizophrenia. Unitisation can circumvent RM impairments in clinical populations as measured by the transverse-patterning (TP) task, a well-established measure of RM capacity. We compared memory performance on a new ecological RM measure, the Relational Trip Task (RTT), to that of TP at baseline and examined the effects of a unitisation intervention in RTT performance. RTT involves learning relational information of real-life stimuli, such as the relationship between people and places or objects. METHODS: TP and RTT performances were examined in 45 individuals with schizophrenia. TP-impaired participants (n = 22) were randomised to either the intervention or an active control group. TP and RTT were administered again after unitisation training. Task validity and reliability were assessed. Intervention group's pre- and post-RTT accuracies were compared and contrasted to that in the control group. RESULTS: RTT and TP were moderately correlated. TP non-learners had inferior performance in RTT at baseline. Improvement in RTT performance after unitisation training was observed in the intervention group; no pre-post improvement was observed in the control group. CONCLUSION: RTT has an acceptable criterion validity and excellent alternate-form reliability. Unitisation seemed to be successfully generalized to support associations of real-life stimuli.

The Role of the Ventromedial Prefrontal Cortex and Basal Forebrain in Relational Memory and Inference.

The ventromedial prefrontal cortex (vmPFC) is involved in diverse cognitive operations, from inhibitory control to processing of semantic schemas. When accompanied by damage to the basal forebrain, vmPFC lesions can also impair relational memory, the ability to form and recall relations among items. Impairments in establishing direct relations among items (e.g., A is related to B, B is related to C) can also hinder the transitive processing of indirect relationships (e.g., inferring that A and C are related through direct relations that each contain B). Past work has found that transitive inference improves when the direct relations are organized within an existing knowledge structure, or schema. This type of semantic support is most effective for individuals whose relational memory deficits are mild (e.g., healthy age-related decline) rather than pronounced (e.g., hippocampal amnesia, amnestic mild cognitive impairment). Given that vmPFC damage can produce both relational memory and schema processing deficits, such damage may pose a particular challenge in establishing the type of relational structure required for transitive inference, even when supported by preexisting knowledge. To examine this idea, we tested individuals with lesions to the mPFC on multiple conditions that varied in pre-experimental semantic support and explored the extent to which they could identify both previously studied (direct) and novel transitive (indirect) relations. Most of the mPFC cases showed marked transitive inference deficits and even showed impaired knowledge of preexisting, direct, semantic relations, consistent with disruptions to schema-related processes. However, one case with more dorsal mPFC damage showed preserved ability to identify direct relations and make novel inferences, particularly when pre-experimental knowledge could be used to support performance. These results suggest that damage to the mPFC and basal forebrain can impede establishment of ad hoc relational schemas upon which transitive inference is based, but that appealing to prior knowledge may still be useful for those neurological cases that have some degree of preserved relational memory.

Effects of transcranial direct current stimulation combined with listening to preferred music on memory in older adults.

Listening to autobiographically-salient music (i.e., music evoking personal memories from the past), and transcranial direct current stimulation (tDCS) have each been suggested to temporarily improve older adults' subsequent performance on memory tasks. Limited research has investigated the effects of combining both tDCS and music listening together on cognition. The present study examined whether anodal tDCS stimulation over the left dorsolateral prefrontal cortex (2 mA, 20 min) with concurrent listening to autobiographically-salient music amplified subsequent changes in working memory and recognition memory in older adults than either tDCS or music listening alone. In a randomized sham-controlled crossover study, 14 healthy older adults (64-81 years) participated in three neurostimulation conditions: tDCS with music listening (tDCS + Music), tDCS in silence (tDCS-only), or sham-tDCS with music listening (Sham + Music), each separated by at least a week. Working memory was assessed pre- and post-stimulation using a digit span task, and recognition memory was assessed post-stimulation using an auditory word recognition task (WRT) during which electroencephalography (EEG) was recorded. Performance on the backwards digit span showed improvement in tDCS + Music, but not in tDCS-only or Sham + Music conditions. Although no differences in behavioural performance were observed in the auditory WRT, changes in neural correlates underlying recognition memory were observed following tDCS + Music compared to Sham + Music. Findings suggest listening to autobiographically-salient music may amplify the effects of tDCS for working memory, and highlight the potential utility of neurostimulation combined with personalized music to improve cognitive performance in the aging population.

Encoding and retrieval eye movements mediate age differences in pattern completion.

Older adults often mistake new information as 'old', yet the mechanisms underlying this response bias remain unclear. Typically, false alarms by older adults are thought to reflect pattern completion - the retrieval of a previously encoded stimulus in response to partial input. However, other work suggests that age-related retrieval errors can be accounted for by deficient encoding processes. In the present study, we used eye movement monitoring to quantify age-related changes in behavioral pattern completion as a function of eye movements during both encoding and partially cued retrieval. Consistent with an age-related encoding deficit, older adults executed more gaze fixations and more similar eye movements across repeated image presentations than younger adults, and such effects were predictive of subsequent recognition memory. Analysis of eye movements at retrieval further indicated that in response to partial lure cues, older adults reactivated the similar studied image, indexed by the similarity between encoding and retrieval gaze patterns, and did so more than younger adults. Critically, reactivation of encoded image content via eye movements was associated with lure false alarms in older adults, providing direct evidence for a pattern completion bias. Together, these findings suggest that age-related changes in both encoding and retrieval processes, indexed by eye movements, underlie older adults' increased vulnerability to memory errors.

Vividness of recollection is supported by eye movements in individuals with high, but not low trait autobiographical memory.

There are marked individual differences in the recollection of personal past events or autobiographical memory (AM). Theory concerning the relationship between mnemonic and visual systems suggests that eye movements promote retrieval of spatiotemporal details from memory, yet assessment of this prediction within naturalistic AM has been limited. We examined the relationship of eye movements to free recall of naturalistic AM and how this relationship is modulated by individual differences in AM capacity. Participants freely recalled past episodes while viewing a blank screen under free and fixed viewing conditions. Memory performance was quantified with the Autobiographical Interview, which separates internal (episodic) and external (non-episodic) details. In Study 1, as a proof of concept, fixation rate was predictive of the number of internal (but not external) details recalled across both free and fixed viewing. In Study 2, using an experimenter-controlled staged event (a museum-style tour) the effect of fixations on free recall of internal (but not external) details was again observed. In this second study, however, the fixation-recall relationship was modulated by individual differences in autobiographical memory, such that the coupling between fixations and internal details was greater for those endorsing higher than lower episodic AM. These results suggest that those with congenitally strong AM rely on the visual system to produce episodic details, whereas those with lower AM retrieve such details via other mechanisms.

Restricting Visual Exploration Directly Impedes Neural Activity, Functional Connectivity, and Memory.

We move our eyes to explore the visual world, extract information, and create memories. The number of gaze fixations-the stops that the eyes make-has been shown to correlate with activity in the hippocampus, a region critical for memory, and with later recognition memory. Here, we combined eyetracking with fMRI to provide direct evidence for the relationships between gaze fixations, neural activity, and memory during scene viewing. Compared to free viewing, fixating a single location reduced: 1) subsequent memory, 2) neural activity along the ventral visual stream into the hippocampus, 3) neural similarity between effects of subsequent memory and visual exploration, and 4) functional connectivity among the hippocampus, parahippocampal place area, and other cortical regions. Gaze fixations were uniquely related to hippocampal activity, even after controlling for neural effects due to subsequent memory. Therefore, this study provides key causal evidence supporting the notion that the oculomotor and memory systems are intrinsically related at both the behavioral and neural level. Individual gaze fixations may provide the basic unit of information on which memory binding processes operate.

Effect of age at time of injury on long-term changes in intrinsic functional connectivity in traumatic brain injury.

BACKGROUND: Alterations in resting-state functional connectivity (rsFC) occur in the acute and chronic phases following traumatic brain injury (TBI); however, few studies have assessed long-term (>1 year) changes in rsFC. METHODS: Resting-state functional magnetic resonance imaging (rsfMRI) scans were obtained from the Federal Interagency Traumatic Brain Injury Research Informatics Systems. Patients with primarily mild TBI (n = 39) completed rsfMRI scans at the sub-acute (~10 days) and long-term (~18 months) phases. We examined changes in voxel-based rsFC from anterior medial prefrontal cortex (aMPFC) and posterior cingulate cortex (PCC) seeds in the default mode network (DMN) between both phases. The effect of age at the time of injury on long-term rsFC was also examined. RESULTS: Increased rsFC from the aMPFC and the PCC to frontal and temporal regions was shown at ~18-months post-injury. Widespread increases in rsFC from the aMPFC and between the PCC and frontal regions were shown for younger patients at time of injury, but limited increases of rsFC were noted at ~18 months in older patients. CONCLUSION: Long-term increases in rsFC were found following TBI, but age at the time of injury was associated with distinct rsFC profiles suggesting that younger patients show greater increases in rsFC over time.

Resting State BOLD Variability of the Posterior Medial Temporal Lobe Correlates with Cognitive Performance in Older Adults with and without Risk for Cognitive Decline.

Local brain signal variability [SD of the BOLD signal (SDBOLD]] correlates with age and cognitive performance, and recently differentiated Alzheimer's disease (AD) patients from healthy controls. However, it is unknown whether changes to SDBOLD precede diagnosis of AD or mild cognitive impairment. We compared ostensibly healthy older adult humans who scored below the recommended threshold on the Montreal cognitive assessment (MoCA) and who showed reduced medial temporal lobe (MTL) volume in a previous study ("at-risk" group, n = 20), with healthy older adults who scored within the normal range on the MoCA ("control" group, n = 20). Using multivariate partial least-squares analysis we assessed the correlations between SDBOLD and age, MoCA score, global fractional anisotropy, global mean diffusivity, and four cognitive factors. Greater SDBOLD in the MTL and occipital cortex positively correlated with performance on cognitive control/speed tasks but negatively correlated with memory scores in the control group. These relations were weaker in the at-risk group. A post hoc analysis assessed associations between MTL volumes and SDBOLD in both groups. This revealed a negative correlation, most robust in the at-risk group, between MTL SDBOLD and MTL subregion volumetry, particularly the entorhinal and parahippocampal regions. Together, these results suggest that the association between SDBOLD and cognition differs between the at-risk and control groups, which may be because of lower MTL volumes in the at-risk group. Our data indicate relations between MTL SDBOLD and cognition may be helpful in understanding brain differences in individuals who may be at risk for further cognitive decline.

Eye movements support behavioral pattern completion.

The ability to recall a detailed event from a simple reminder is supported by pattern completion, a cognitive operation performed by the hippocampus wherein existing mnemonic representations are retrieved from incomplete input. In behavioral studies, pattern completion is often inferred through the false endorsement of lure (i.e., similar) items as old. However, evidence that such a response is due to the specific retrieval of a similar, previously encoded item is severely lacking. We used eye movement (EM) monitoring during a partial-cue recognition memory task to index reinstatement of lure images behaviorally via the recapitulation of encoding-related EMs or gaze reinstatement. Participants reinstated encoding-related EMs following degraded retrieval cues and this reinstatement was negatively correlated with accuracy for lure images, suggesting that retrieval of existing representations (i.e., pattern completion) underlies lure false alarms. Our findings provide evidence linking gaze reinstatement and pattern completion and advance a functional role for EMs in memory retrieval.