Functional modular architecture underlying attentional control in aging.

Previous research suggests that age-related differences in attention reflect the interaction of top-down and bottom-up processes, but the cognitive and neural mechanisms underlying this interaction remain an active area of research. Here, within a sample of community-dwelling adults 19-78 years of age, we used diffusion reaction time (RT) modeling and multivariate functional connectivity to investigate the behavioral components and whole-brain functional networks, respectively, underlying bottom-up and top-down attentional processes during conjunction visual search. During functional MRI scanning, participants completed a conjunction visual search task in which each display contained one item that was larger than the other items (i.e., a size singleton) but was not informative regarding target identity. This design allowed us to examine in the RT components and functional network measures the influence of (a) additional bottom-up guidance when the target served as the size singleton, relative to when the distractor served as the size singleton (i.e., size singleton effect) and (b) top-down processes during target detection (i.e., target detection effect; target present vs. absent trials). We found that the size singleton effect (i.e., increased bottom-up guidance) was associated with RT components related to decision and nondecision processes, but these effects did not vary with age. Also, a modularity analysis revealed that frontoparietal module connectivity was important for both the size singleton and target detection effects, but this module became central to the networks through different mechanisms for each effect. Lastly, participants 42 years of age and older, in service of the target detection effect, relied more on between-frontoparietal module connections. Our results further elucidate mechanisms through which frontoparietal regions support attentional control and how these mechanisms vary in relation to adult age.

Frontoparietal activation during visual conjunction search: Effects of bottom-up guidance and adult age.

We conducted functional magnetic resonance imaging (fMRI) with a visual search paradigm to test the hypothesis that aging is associated with increased frontoparietal involvement in both target detection and bottom-up attentional guidance (featural salience). Participants were 68 healthy adults, distributed continuously across 19 to 78 years of age. Frontoparietal regions of interest (ROIs) were defined from resting-state scans obtained prior to task-related fMRI. The search target was defined by a conjunction of color and orientation. Each display contained one item that was larger than the others (i.e., a size singleton) but was not informative regarding target identity. Analyses of search reaction time (RT) indicated that bottom-up attentional guidance from the size singleton (when coincident with the target) was relatively constant as a function of age. Frontoparietal fMRI activation related to target detection was constant as a function of age, as was the reduction in activation associated with salient targets. However, for individuals 35 years of age and older, engagement of the left frontal eye field (FEF) in bottom-up guidance was more prominent than for younger individuals. Further, the age-related differences in left FEF activation were a consequence of decreasing resting-state functional connectivity in visual sensory regions. These findings indicate that age-related compensatory effects may be expressed in the relation between activation and behavior, rather than in the magnitude of activation, and that relevant changes in the activation-RT relation may begin at a relatively early point in adulthood. Hum Brain Mapp 38:2128-2149, 2017. © 2017 Wiley Periodicals, Inc.

Human brain activity and functional connectivity associated with verbal long-term memory consolidation across 1 month.

Introduction: Declarative memories are initially dependent on the hippocampus and become stabilized through the neural reorganization of connections between the medial temporal lobe and neocortex. The exact time-course of these neural changes is not well established, although time-dependent changes in retrieval-related brain function can be detected across relatively short time periods in humans (e.g., hours to months). Methods: In a study involving older adults with normal cognition (N = 24), we investigated changes in brain activity and functional connectivity associated with the long-term memory consolidation of verbal material over one month. Participants studied fact-like, three-word sentences at 1-month, 1-week, 1-day, and 1-hour intervals before a recognition memory test inside an MRI scanner. Old/new recognition with confidence ratings and response times were recorded. We examined whole-brain changes in retrieval-related brain activity, as well as functional connectivity of the hippocampus and ventromedial prefrontal cortex (vmPFC), as memories aged from 1 hour to 1 month. Secondary analyses minimized the effect of confounding factors affected by memory age (i.e., changes in confidence and response time or re-encoding of targets). Results: Memory accuracy, confidence ratings, and response times changed with memory age. A memory age network was identified where retrieval-related brain activity in cortical regions increased or decreased as a function of memory age. Hippocampal brain activity in an anatomical region of interest decreased with memory age. Importantly, these changes in retrieval-related activity were not confounded with changes in activity related to concomitant changes in behavior or encoding. Exploratory analyses of vmPFC functional connectivity as a function of memory age revealed increased connectivity with the posterior parietal cortex, as well as with the vmPFC itself. In contrast, hippocampal functional connectivity with the vmPFC and orbitofrontal cortex decreased with memory age. Discussion: The observed changes in retrieval-related brain activity and functional connectivity align with the predictions of standard systems consolidation theory. These results suggest that processes consistent with long-term memory consolidation can be identified over short time periods using fMRI, particularly for verbal material.

A way forward for design and analysis of neuroimaging studies of memory consolidation.

Several novel ideas and suggestions were made in response to our discussion paper (Tallman et al., this issue). Careful consideration of the content and context of memory while accounting for the neuroanatomy and functional specialization of the hippocampus may reveal more consistent patterns in fMRI studies of memory consolidation. Below we address these ideas as well as issues that arise when interpreting the fMRI signal in memory consolidation studies. In addition, we describe new analyses suggested by the commentators that clarify our findings with respect to current theories.

Human brain activity and functional connectivity as memories age from one hour to one month.

Theories of memory consolidation suggest the role of brain regions and connectivity between brain regions change as memories age. Human lesion studies indicate memories become hippocampus-independent over years, whereas animal studies suggest this process occurs across relatively short intervals, from days to weeks. Human neuroimaging studies suggest that changes in hippocampal and cortical activity and connectivity can be detected over these short intervals, but many of these studies examined only two time periods. We examined memory and fMRI activity for photos of indoor and outdoor scenes across four time periods to examine these neural changes more carefully. Participants (N = 21) studied scenes 1 hour, 1 day, 1 week, or 1 month before scanning. During scanning, participants viewed scenes, made old/new recognition memory judgments, and gave confidence ratings. Memory accuracy, confidence ratings, and response times changed with memory age. Brain activity in a widespread cortical network either increased or decreased with memory age, whereas hippocampal activity was not related to memory age. These findings were almost identical when effects of behavioral changes across time periods were minimized. Functional connectivity of the ventromedial prefrontal cortex with the posterior parietal cortex increased with memory age. By contrast, functional connectivity of the hippocampus with the parahippocampal cortex and fusiform gyrus decreased with memory age. In sum, we detected changes in cortical activity and changes in hippocampal and cortical connectivity with memory age across short intervals. These findings provide support for the predictions of systems consolidation and suggest that these changes begin soon after memories are formed.

Response-level processing during visual feature search: Effects of frontoparietal activation and adult age.

Previous research suggests that feature search performance is relatively resistant to age-related decline. However, little is known regarding the neural mechanisms underlying the age-related constancy of feature search. In this experiment, we used a diffusion decision model of reaction time (RT), and event-related functional magnetic resonance imaging (fMRI) to investigate age-related differences in response-level processing during visual feature search. Participants were 80 healthy, right-handed, community-dwelling individuals, 19-79 years of age. Analyses of search performance indicated that targets accompanied by response-incompatible distractors were associated with a significant increase in the nondecision-time (t0) model parameter, possibly reflecting the additional time required for response execution. Nondecision time increased significantly with increasing age, but no age-related effects were evident in drift rate, cautiousness (boundary separation, a), or in the specific effects of response compatibility. Nondecision time was also associated with a pattern of activation and deactivation in frontoparietal regions. The relation of age to nondecision time was indirect, mediated by this pattern of frontoparietal activation and deactivation. Response-compatible and -incompatible trials were associated with specific patterns of activation in the medial and superior parietal cortex, and frontal eye field, but these activation effects did not mediate the relation between age and search performance. These findings suggest that, in the context of a highly efficient feature search task, the age-related influence of frontoparietal activation is operative at a relatively general level, which is common to the task conditions, rather than at the response level specifically.

Task difficulty modulates brain activation in the emotional oddball task.

Previous functional magnetic resonance imaging (fMRI) studies have reported that task-irrelevant, emotionally salient events can disrupt target discrimination, particularly when attentional demands are low, while others demonstrate alterations in the distracting effects of emotion in behavior and neural activation in the context of attention-demanding tasks. We used fMRI, in conjunction with an emotional oddball task, at different levels of target discrimination difficulty, to investigate the effects of emotional distractors on the detection of subsequent targets. In addition, we distinguished different behavioral components of target detection representing decisional, nondecisional, and response criterion processes. Results indicated that increasing target discrimination difficulty led to increased time required for both the decisional and nondecisional components of the detection response, as well as to increased target-related neural activation in frontoparietal regions. The emotional distractors were associated with activation in ventral occipital and frontal regions and dorsal frontal regions, but this activation was attenuated with increased difficulty. Emotional distraction did not alter the behavioral measures of target detection, but did lead to increased target-related frontoparietal activation for targets following emotional images as compared to those following neutral images. This latter effect varied with target discrimination difficulty, with an increased influence of the emotional distractors on subsequent target-related frontoparietal activation in the more difficult discrimination condition. This influence of emotional distraction was in addition associated specifically with the decisional component of target detection. These findings indicate that emotion-cognition interactions, in the emotional oddball task, vary depending on the difficulty of the target discrimination and the associated limitations on processing resources.

Sources of disconnection in neurocognitive aging: cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume.

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19-79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the 3 imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function.