Divided attention at retrieval does not influence neural correlates of recollection in young or older adults

Age-related decline in episodic memory has been partially attributed to older adults’ reduced domain general processing resources. In the present study, we examined the effects of divided attention (DA) - a manipulation assumed to further deplete the already limited processing resources of older adults - on the neural correlates of recollection in young and older adults. Participants underwent fMRI scanning while they performed an associative recognition test in single and dual (tone detection) task conditions. Recollection effects were operationalized as greater BOLD activity elicited by test pairs correctly endorsed as ‘intact’ than pairs correctly or incorrectly endorsed as ‘rearranged’. Detrimental effects of DA on associative recognition performance were identified in older but not young adults. The magnitudes of recollection effects did not differ between the single and dual (tone detection) tasks in either age group. Across the task conditions, age-invariant recollection effects were evident in most members of the core recollection network. However, while young adults demonstrated robust recollection effects in left angular gyrus, angular gyrus effects were undetectable in the older adults in either task condition. With the possible exception of this result, the findings suggest that DA did not influence processes supporting the retrieval and representation of associative information in either young or older adults, and converge with prior behavioral findings to suggest that episodic retrieval operations are little affected by DA

Recollection-Related Increases in Functional Connectivity Predict Individual Differences in Memory Accuracy

Recollection involves retrieving specific contextual details about a prior event. Functional neuroimaging studies have identified several brain regions that are consistently more active during successful versus failed recollection—the “core recollection network.” In the present study, we investigated whether these regions demonstrate recollection-related increases not only in activity but also in functional connectivity in healthy human adults. We used fMRI to compare time-series correlations during successful versus unsuccessful recollection in three separate experiments, each using a different operational definition of recollection. Across experiments, a broadly distributed set of regions consistently exhibited recollection-related increases in connectivity with different members of the core recollection network. Regions that demonstrated this effect included both recollection-sensitive regions and areas where activity did not vary as a function of recollection success. In addition, in all three experiments the magnitude of connectivity increases correlated across individuals with recollection accuracy in areas diffusely distributed throughout the brain. These findings suggest that enhanced functional interactions between distributed brain regions are a signature of successful recollection. In addition, these findings demonstrate that examining dynamic modulations in functional connectivity during episodic retrieval will likely provide valuable insight into neural mechanisms underlying individual differences in memory performance

Neural correlates of post-retrieval monitoring in older adults are preserved under divided attention, but are decoupled from memory performance

Post-retrieval monitoring is associated with engagement of anterior cingulate and dorsolateral prefrontal cortex. Recent fMRI studies reported age-invariant monitoring effects in these regions and an age-invariant correlation between these effects and memory performance. The present study examined monitoring effects during associative recognition (difference in activity elicited by ‘rearranged’ and ‘intact’ test pairs) under single and dual (tone detection) task conditions in young and older adults (Ns = 28 per group). It was predicted that, for the older adults only, dual tasking would attenuate memory performance and monitoring effects and weaken their correlation. Consistent with this prediction, in the older group imposition of the secondary task led to lower memory performance and elimination of the relationship between monitoring effects and performance. However, the size of the effects did not differ between single and dual task conditions. The findings suggest that the decline in older adults’ memory performance in the dual task condition resulted not from impaired monitoring, but from a different cause that also weakened the dependence of performance on monitoring

Specific and general relationships between cortical thickness and cognition in older adults: a longitudinal study

Prior studies suggest that relationships between regional cortical thickness and domain-specific cognitive performance can be mediated by the relationship between global cortical thickness and domain-general cognition. Whether such findings extend to longitudinal cognitive change remains unclear. Here, we examined the relationships in healthy older adults between cognitive performance, longitudinal cognitive change over three years, and cortical thickness at baseline of the left and right inferior frontal gyrus (IFG) and left and right hemispheres. Both right IFG and right hemisphere thickness predicted baseline general cognition and domain-specific cognitive performance. Right IFG thickness was also predictive of longitudinal memory change. However, right IFG thickness was uncorrelated with cognitive performance and memory change after controlling for the mean thickness of other ipsilateral cortical regions. Additionally, most identified associations between cortical thickness and specific cognitive domains were non-significant after controlling for the variance shared with other cognitive domains. Thus, relationships between right IFG thickness, cognitive performance and memory change appear to be largely accounted for by more generic relationships between cortical thickness and cognition

Influence of aging on the neural correlates of autobiographical, episodic, and semantic memory retrieval

We used fMRI to assess the neural correlates of autobiographical, semantic, and episodic memory retrieval in healthy young and older adults. Participants were tested with an eventrelated paradigm in which retrieval demand was the only factor varying between trials. A spatio-temporal partial least square analysis was conducted to identify the main patterns of activity characterizing the groups across conditions. We identified brain regions activated by all three memory conditions relative to a control condition. This pattern was expressed equally in both age groups and replicated previous findings obtained in a separate group of younger adults. We also identified regions whose activity differentiated among the different memory conditions. These patterns of differentiation were expressed less strongly in the older adults than in the young adults, a finding that was further confirmed by a barycentric discriminant analysis. This analysis showed an age-related dedifferentiation in autobiographical and episodic memory tasks but not in the semantic memory task or the control condition. These findings suggest that the activation of a common memory retrieval network is maintained with age, whereas the specific aspects of brain activity that differ with memory content are more vulnerable and less selectively engaged in older adults. Our results provide a potential neural mechanism for the well-known age differences in episodic/autobiographical memory, and preserved semantic memory, observed when older adults are compared with younger adults

Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults

Prior fMRI studies have reported relationships between memory-related activity in the hippocampus and in-scanner memory performance, but whether such activity is predictive of longitudinal memory change remains unclear. Here, we administered a neuropsychological test battery to a sample of cognitively healthy older adults on three occasions, the second and third sessions occurring one month and three years after the first session. Structural and functional MRI data were acquired between the first two sessions. The fMRI data were derived from an associative recognition procedure and allowed estimation of hippocampal effects associated with both successful associative encoding and successful associative recognition (recollection). Baseline memory performance and memory change were evaluated using memory component scores derived from a principal components analysis of the neuropsychological test scores. Across participants, right hippocampal encoding effects correlated significantly with baseline memory performance after controlling for chronological age. Additionally, both left and right hippocampal associative recognition effects correlated negatively with longitudinal memory decline after controlling for age, and the relationship with the left hippocampal effect remained after also controlling for left hippocampal volume. Thus, in cognitively healthy older adults, the magnitude of hippocampal recollection effects appears to be a robust predictor of future memory change

Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task

Introduction: The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers. Methods: In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non-e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay. Results: In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words. Conclusions: Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences

Dopamine and memory dedifferentiation in aging.

The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (1.25mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between aging, dopaminergic function and dedifferentiation in the hippocampus.This research was funded mainly by a Fellowship to AMM from Research into Ageing, UK, and by an RCUK Academic Fellowship at the University of Edinburgh. Some of the research was conducted by Hunar Abdulrahman as part of a dissertation for the MSc in Neurosciences at the University of Edinburgh. The research was also supported by a Human Brain Project grant from the National Institute of Mental Health and the National Institute of Biomedical Imaging & Bioengineering. PCF was supported by a Wellcome Trust Senior Fellowship in Clinical Science, and by the Bernard Wolfe Health Neuroscience Fund. ETB is a part-time (50%) employee and shareholder of GSK. AMM is a member of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative, Grant number G0700704/84698.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1016/j.neuroimage.2015.03.03

Advances in studying brain morphology: the benefits of open-access data

Until recently, neuroimaging data for a research study needed to be collected within one’s own lab. However, when studying inter-individual differences in brain structure, a large sample of participants is necessary. Given the financial costs involved in collecting neuroimaging data from hundreds or thousands of participants, large-scale studies of brain morphology could previously only be conducted by well-funded laboratories with access to MRI facilities and to large samples of participants. With the advent of broad open-access data-sharing initiatives, this has recently changed–here the primary goal of the study is to collect large datasets to be shared, rather than sharing of the data as an afterthought. This paradigm shift is evident as increase in the pace of discovery, leading to a rapid rate of advances in our characterization of brain structure. The utility of open-access brain morphology data is numerous, ranging from observing novel patterns of agerelated differences in subcortical structures to the development of more robust cortical parcellation atlases, with these advances being translatable to improved methods for characterizing clinical disorders (see Figure 1 for an illustration). Moreover, structural MRIs are generally more robust than functional MRIs, relative to potential artifacts and in being not task-dependent, resulting in large potential yields. While the benefits of open-access data have been discussed more broadly within the field of cognitive neuroscience elsewhere (Van Horn and Gazzaniga, 2013; Poldrack and Gorgolewski, 2014; Van Horn and Toga, 2014; Vogelstein et al., 2016; Voytek, 2016; Gilmore et al., 2017), as well as in other fields (Choudhury et al., 2014; Ascoli et al., 2017; Davies et al., 2017), this opinion paper is focused specifically on the implications of open data to brain morphology research

Effects of age on goal-dependent modulation of episodic memory retrieval

Retrieval gating refers to the ability to modulate the retrieval of features of a single memory episode according to behavioral goals. Recent findings demonstrate that younger adults engage retrieval gating by attenuating the representation of task-irrelevant features of an episode. Here, we examine whether retrieval gating varies with age. Younger and older adults incidentally encoded words superimposed over scenes or scrambled backgrounds that were displayed in one of three spatial locations. Participants subsequently underwent fMRI as they completed two memory tasks: the background task, which tested memory for the word's background, and the location task, testing memory for the word's location. Employing univariate and multivariate approaches, we demonstrated that younger, but not older adults, exhibited attenuated reinstatement of scene information when it was goal-irrelevant (during the location task). Additionally, in younger adults only, the strength of scene reinstatement in the parahippocampal place area during the background task was related to item and source memory performance. Together, these findings point to an age-related decline in the ability to engage retrieval gating