Relationship of prefrontal brain lateralization to optimal cognitive function differs with age.

There is considerable debate about whether additional fMRI-measured activity in the right prefrontal cortex readily observed in older adults represents compensatory activation that enhances cognition or whether maintenance of youthful brain activity best supports cognitive function in late adulthood. To investigate this issue, we tested a large lifespan sample of 461 adults (aged 20-89) and treated degree of left-lateralization in ventrolateral and dorsolateral prefrontal cortex during a semantic judgment fMRI task as an individual differences variable to predict cognition. We found that younger adults were highly left-lateralized, but lateralization did not predict better cognition, whereas higher left-lateralization of prefrontal cortex predicted better cognitive performance in middle-aged adults, providing evidence that left-lateralized, youth-like patterns are optimal in middle age. This relationship was reversed in older adults, with lower laterality scores associated with better cognition. The findings suggest that bilaterality in older adults facilitates cognition, but early manifestation of this pattern during middle age is characteristic of low performers. Implications of these findings for current theories of neurocognitive aging are discussed.

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.

Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important "signal" rather than measurement-related "noise." Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20-94 years; n = 171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0-2-3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0-2-3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.

Beta-amyloid burden predicts poorer mnemonic discrimination in cognitively normal older adults.

One of the earliest indicators of Alzheimer's disease pathology is the presence of beta-amyloid (Αß) protein deposition. Significant amyloid deposition is evident even in older adults who exhibit little or no overt cognitive or memory impairment. Hippocampal-based processes that help distinguish between highly similar memory representations may be the most susceptible to early disease pathology. Amyloid associations with memory have been difficult to establish, possibly because typical memory assessments do not tax hippocampal operations sufficiently. Thus, the present study utilized a spatial mnemonic discrimination task designed to tax hippocampal pattern separation/completion processes in a sample of cognitively normal middle-aged and older adults (53-98 years old) who underwent PET 18F-Florbetapir Αß scanning. The degree of interference between studied and new information varied, allowing for an examination of mnemonic discrimination as a function of mnemonic similarity. Results indicated that greater beta-amyloid burden was associated with poorer discrimination across decreasing levels of interference, suggesting that even subtle elevation of beta-amyloid in cognitively normal adults is associated with impoverished performance on a hippocampally demanding memory task. The present study demonstrates that degree of amyloid burden negatively impacts the ability of aging adults to accurately distinguish old from increasingly distinct new information, providing novel insight into the cognitive expression of beta-amyloid neuropathology.

Frontostriatal white matter connectivity: age differences and associations with cognition and BOLD modulation.

Despite the importance of cortico-striatal circuits to cognition, investigation of age effects on the structural circuitry connecting these regions is limited. The current study examined age effects on frontostriatal white matter connectivity, and identified associations with both executive function performance and dynamic modulation of blood-oxygen-level-dependent (BOLD) activation to task difficulty in a lifespan sample of 169 healthy humans aged 20-94 years. Greater frontostriatal diffusivity was associated with poorer executive function and this negative association strengthened with increasing age. Whole-brain functional magnetic resonance imaging (fMRI) analyses additionally indicated an association between frontostriatal mean diffusivity and BOLD modulation to difficulty selectively in the striatum across 2 independent fMRI tasks. This association was moderated by age, such that younger- and middle-aged individuals showed reduced dynamic range of difficulty modulation as a function of increasing frontostriatal diffusivity. Together these results demonstrate the importance of age-related degradation of frontostriatal circuitry on executive functioning across the lifespan, and highlight the need to capture brain changes occurring in early-to middle-adulthood.

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.

Contributions of White Matter Connectivity and BOLD Modulation to Cognitive Aging: A Lifespan Structure-Function Association Study.

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent magnetic resonance imaging (MRI) scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered blood-oxygen-level-dependent (BOLD) modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty-related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.

The impact of behavioral interventions on cognitive function in healthy older adults: A systematic review.

Behavioral interventions to improve cognitive function in older adults are widespread and can vary from theater classes to cognitive training programs. However, the effectiveness in maintaining different cognitive domains varies greatly both across and within intervention types. To date, no systematic reviews have synthesized findings across more than a few types of interventions (e.g., cognitive vs. exercise). This systematic review examined 11 types of behavioral interventions and the respective transfer to 19 cognitive domains, as well as transfer to everyday function. Study inclusion criteria were: peer-reviewed articles in English, samples of healthy adults aged 65 and older, and randomized controlled trials of behavioral interventions with reported cognitive outcomes. The 2017 search yielded 75 eligible articles comprising cognitive training, exercise training, combination interventions, cognitively-stimulating activities, and action video games. In general, process- (n = 26) and strategy-based (n = 16) cognitive training improved the trained domains but had weak transfer to non-trained domains. Aerobic training (n = 13) most consistently improved executive function, and strength/resistance (n = 8) and aerobic/resistance combination training (n = 6) most consistently improved cognitive inhibition and visual working memory. Combination interventions (n = 15 nonfactorial, n = 3 factorial) showed promise in improving verbal delayed recall and executive function. Few studies examined cognitively-stimulating activities or action video games, leaving inconclusive results about their effect on cognitive function. Few studies examined everyday function (n = 9), however, process- and strategy-based training demonstrated notable long-term transfer. Recommendations for future research and practice are highlighted.

The Effects of Useful Field of View Training on Brain Activity and Connectivity.

OBJECTIVES: Useful Field of View training (UFOVt) is an adaptive computerized cognitive intervention that improves visual attention and transfers to maintained health and everyday functioning in older adults. Although its efficacy is well established, the neural mechanisms underlying this intervention are unknown. This pilot study used functional MRI (fMRI) to explore neural changes following UFOVt. METHOD: Task-driven and resting-state fMRI were used to examine changes in brain activity and connectivity in healthy older adults randomized to 10 hr of UFOVt (n = 13), 10 hr of cognitively stimulating activities (CSA; n = 11), or a no-contact control (NC; n = 10). RESULTS: UFOVt resulted in reduced task-driven activity in the majority of regions of interest (ROIs) associated with task performance, CSA resulted in reduced activity in one ROI, and there were no changes within the NC group. Relative to NC, UFOVt reduced activity in ROIs involved in effortful information processing. There were no other significant between-group task-based differences. Resting-state functional connectivity between ROIs involved in executive function and visual attention was strengthened following UFOVt compared with CSA and NC. DISCUSSION: UFOVt enhances connections needed for visual attention. Together with prior work, this study provides evidence that improvement of the brain's visual attention efficiency is one mechanism underlying UFOVt.

Differentiating True and False Schematic Memories in Older Adults.

OBJECTIVE: While schemas aid memory for schematically related information, the gist induced by the schema can also lead to high rates of false memories, especially in older adults. The neural mechanisms that support and differentiate true and false memories in aging are not well understood. The current study sought to clarify this, using a novel scene paradigm to investigate the role of schemas on true and false memories in older adults. METHODS: Healthy older adults encoded schematic scenes (e.g., bathroom). At retrieval, participants were tested on their memory for both schematic and nonschematic targets and lures while functional magnetic resonance imaging data was collected. RESULTS: Results indicate that true memories were supported by the typical retrieval network, and activity in this network was greater for true than false memories. Schema specific retrieval was supported by medial prefrontal cortex, extending this common finding to aging. While no region differentiated false memories compared to correct rejections, results showed that individual differences in false memory rates were associated with variability in neural activity. DISCUSSION: The findings underscore the importance of elucidating the neural basis of cognition within older adults, as well as the specific contribution of individual differences to the neural basis of memory errors in aging.

What's the gist? The influence of schemas on the neural correlates underlying true and false memories.

The current study used a novel scene paradigm to investigate the role of encoding schemas on memory. Specifically, the study examined the influence of a strong encoding schema on retrieval of both schematic and non-schematic information, as well as false memories for information associated with the schema. Additionally, the separate roles of recollection and familiarity in both veridical and false memory retrieval were examined. The study identified several novel results. First, while many common neural regions mediated both schematic and non-schematic retrieval success, schematic recollection exhibited greater activation in visual cortex and hippocampus, regions commonly shown to mediate detailed retrieval. More effortful cognitive control regions in the prefrontal and parietal cortices, on the other hand, supported non-schematic recollection, while lateral temporal cortices supported familiarity-based retrieval of non-schematic items. Second, both true and false recollection, as well as familiarity, were mediated by activity in left middle temporal gyrus, a region associated with semantic processing and retrieval of schematic gist. Moreover, activity in this region was greater for both false recollection and false familiarity, suggesting a greater reliance on lateral temporal cortices for retrieval of illusory memories, irrespective of memory strength. Consistent with previous false memory studies, visual cortex showed increased activity for true compared to false recollection, suggesting that visual cortices are critical for distinguishing between previously viewed targets and related lures at retrieval. Additionally, the absence of common visual activity between true and false retrieval suggests that, unlike previous studies utilizing visual stimuli, when false memories are predicated on schematic gist and not perceptual overlap, there is little reliance on visual processes during false memory retrieval. Finally, the medial temporal lobe exhibited an interesting dissociation, showing greater activity for true compared to false recollection, as well as for false compared to true familiarity. These results provided an indication as to how different types of items are retrieved when studied within a highly schematic context. Results both replicate and extend previous true and false memory findings, supporting the Fuzzy Trace Theory.

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.

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.