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Age-related changes in neural circuits, neural networks, and their plasticity are central to our understanding of age changes in cognition and brain structure and function. This paper summarizes selected findings on these topics presented at the Cognitive Aging Summit II. Specific areas discussed were synaptic vulnerability and plasticity, including the role of different types of synaptic spines, and hormonal effects in the dorsolateral prefrontal cortex of nonhuman primates, the impact of both compensatory processes and dedifferentiation on demand-dependent differences in prefrontal activation in relation to age and performance, the role of vascular disease, indexed by white matter signal abnormalities, on prefrontal activation during a functional magnetic resonance imaging-based cognitive control paradigm, and the influence of amyloid-β neuropathology on memory performance in older adults and the networks of brain activity underlying variability in performance. A greater understanding of age-related changes in brain plasticity and neural networks in healthy aging and in the presence of underlying vascular disease or amyloid pathology will be essential to identify new targets for intervention. Moreover, this understanding will assist in promoting the utilization of existing interventions, such as lifestyle and therapeutic modifiers of vascular disease. [ABSTRACT FROM AUTHOR]

In this article, marking the 65th anniversary of the Journal of Gerontology, we offer a broad-brush overview of the new synthesis between neuroscientific and psychological approaches to cognitive aging. We provide a selective review of brain imaging studies and their relevance to mechanisms of cognitive aging first identified primarily from behavioral measurements. We also examine some new key discoveries, including evidence favoring plasticity and compensation that have emerged specifically from using cognitive neuroscience methods to study healthy aging. We then summarize several recent neurocognitive theories of aging, including our own model-the Scaffolding Theory of Aging and Cognition. We close by discussing some newly emerging trends and future research trajectories for investigating the aging mind and brain. [ABSTRACT FROM AUTHOR]

The microgravity environment results in transient changes in sensorimotor behavior upon astronauts' return to Earth; the effects on behavior inflight are less understood. We examined whether adaptation to sensory conflict is disrupted in microgravity, suggesting competition for adaptive resources. We evaluated sensorimotor adaptation pre-, in-, and post-flight, as well as functional brain changes at pre- and post-flight, in astronauts participating in International Space Station missions. Astronauts (n = 13) performed this task pre- and four times post-flight within an MRI scanner and performed the task three times in microgravity during a 6-mo mission. We collected behavioral data from Earth-bound controls (n = 13) along the same timeline. Astronauts displayed no change in adaptation from pre- to inflight or following their return to Earth. They showed greater aftereffects of adaptation inflight; controls did not. Astronauts also displayed increased brain activity from pre- to post-flight. These increases did not return to baseline levels until 90 d post-flight. This pattern of brain activity may reflect compensation, allowing astronauts to maintain pre-flight performance levels. These findings indicate that microgravity does not alter short-term visuomotor adaptation; however, it does affect de-adaptation, and post-flight sensorimotor neural activation can take up to 90 d to return to pre-flight levels., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The long-term fate of to-be-remembered information depends in part on the conditions of initial learning, including mental operations engaged via working memory. However, the mechanistic role of working memory (WM) processes in subsequent episodic memory (EM) remains unclear. Does re-exposure to word-pairs during WM recognition testing improve EM for those associations? Are benefits from WM re-exposure greater after an opportunity for retrieval practice compared to mere re-exposure to the memoranda? These questions are addressed in three experiments (N = 460) designed to assess whether WM-based recognition testing benefits long-term associative memory relative to WM-based restudying. Our results show null or negative benefits of WM recognition testing minutes later when initial WM accuracy was not considered. An EM benefit of WM recognition testing only emerges when the analyses are limited to pairs responded to correctly during WM. However, even when compared with accurate WM recognition, restudying can lead to similar associative EM benefits in specific experimental conditions. Taken together, the present results suggest that while WM re-exposure to studied pairs is beneficial to long-term associative memory, successful retrieval on initial tests may be a necessary but insufficient condition for the emergence of a "WM-based testing effect." We consider these results in relation to several hypotheses proposed to explain the testing effect in long-term memory (LTM). In view of empirical parallels with the LTM testing effect, we propose that similar processes influence the benefits of practice tests administered within the canonical boundaries of WM, suggesting continuities in memory over the short and long term., (© 2024. The Psychonomic Society, Inc.)

Our understanding of human neurocognitive aging, its developmental roots, and life course influences has been transformed by brain imaging technologies, increasing availability of longitudinal data sets, and analytic advances. The Scaffolding Theory of Aging and Cognition is a life course model, proposed originally in 2009, featuring adaptivity and compensatory potential as lifelong mechanisms for meeting neurocognitive challenges posed by the environment and by developing or declining brain circuitry. Here, we review the scaffolding theory in relation to new evidence addressing when during the life course potentially enriching and depleting factors exert their effects on brain health and scaffolding, and we consider the implications for separable, and potentially reciprocal, influences on the level of cognitive function and the rate of decline in later life., Competing Interests: Declaration of competing interest The author declares no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Affective forecasting-the ability to predict how different outcomes will make us feel-is a crucial aspect of making optimal decisions. Recent laboratory evidence suggests that working memory for emotion is a basic psychological mechanism underlying forecasting ability: Individual differences in affective working memory predict how accurately people can forecast their future feelings whereas measures of "cognitive" working memory do not. Here, we demonstrate that this selective relationship between affective forecasting and affective working memory generalizes to forecasted feelings about a major real-world event. We report results from a preregistered (online) study ( N = 76) demonstrating that affective working memory performance predicted how accurately people anticipate their feelings about the outcome of the 2020 U.S. presidential election. This relationship was specific to affective working memory and was also demonstrated in a description-based forecasting measure with emotionally evocative photographs, replicating previous results. However, neither affective nor cognitive working memory was related to a novel event-based forecasting questionnaire, adapted to compare predicted and experienced feelings to everyday events. Together, these findings advance a mechanistic understanding of affective forecasting and underscore the potential importance of affective working memory in some forms of higher order emotional thought. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Spaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission duration or spaceflight experience history (i.e., novice or experienced, number of prior missions, time between missions). Here we addressed this issue by quantifying regional voxelwise changes in brain gray matter volume, white matter microstructure, extracellular free water (FW) distribution, and ventricular volume from pre- to post-flight in a sample of 30 astronauts. We found that longer missions were associated with greater expansion of the right lateral and third ventricles, with the majority of expansion occurring during the first 6 months in space then appearing to taper off for longer missions. Longer inter-mission intervals were associated with greater expansion of the ventricles following flight; crew with less than 3 years of time to recover between successive flights showed little to no enlargement of the lateral and third ventricles. These findings demonstrate that ventricle expansion continues with spaceflight with increasing mission duration, and inter-mission intervals less than 3 years may not allow sufficient time for the ventricles to fully recover their compensatory capacity. These findings illustrate some potential plateaus in and boundaries of human brain changes with spaceflight., (© 2023. The Author(s).)

The Value Learning Task (VLT; e.g., Raymond & O'Brien, 2009) is widely used to investigate how acquired value impacts how we perceive and process stimuli. The task consists of a series of trials in which participants attempt to maximize accumulated winnings as they make choices from a pair of presented images associated with probabilistic win, loss, or no-change outcomes. The probabilities and outcomes are initially unknown to the participant and thus the task involves decision making and learning under uncertainty. Despite the symmetric outcome structure for win and loss pairs, people learn win associations better than loss associations (Lin, Cabrera-Haro, & Reuter-Lorenz, 2020). This learning asymmetry could lead to differences when the stimuli are probed in subsequent tasks, compromising inferences about how acquired value affects downstream processing. We investigate the nature of the asymmetry using a standard error-driven reinforcement learning model with a softmax choice rule. Despite having no special role for valence, the model yields the learning asymmetry observed in human behavior, whether the model parameters are set to maximize empirical fit, or task payoff. The asymmetry arises from an interaction between a neutral initial value estimate and a choice policy that exploits while exploring, leading to more poorly discriminated value estimates for loss stimuli. We also show how differences in estimated individual learning rates help to explain individual differences in the observed win-loss asymmetries, and how the final value estimates produced by the model provide a simple account of a post-learning explicit value categorization task., (© 2022. The Author(s).)

Aging is associated with declines in walking function. To understand these mobility declines, many studies have obtained measurements while participants walk on flat surfaces in laboratory settings during concurrent cognitive task performance (dual-tasking). This may not adequately capture the real-world challenges of walking at home and around the community. Here, we hypothesized that uneven terrains in the walking path impose differential changes to walking speed compared to dual-task walking. We also hypothesized that changes in walking speed resulting from uneven terrains will be better predicted by sensorimotor function than cognitive function. Sixty-three community-dwelling older adults (65-93 yrs old) performed overground walking under varying walking conditions. Older adults were classified into two mobility function groups based on scores of the Short Physical Performance Battery. They performed uneven terrain walking across four surface conditions (Flat, Low, Medium, and High unevenness) and performed single and verbal dual-task walking on flat ground. Participants also underwent a battery of cognitive (cognitive flexibility, working memory, inhibition) and sensorimotor testing (grip strength, 2-pt discrimination, pressure pain threshold). Our results showed that walking speed decreased during both dual-task walking and across uneven terrain walking conditions compared to walking on flat terrain. Participants with lower mobility function had even greater decreases in uneven terrain walking speeds. The change in uneven terrain speed was associated with attention and inhibitory function. Changes in both dual-task and uneven terrain walking speeds were associated with 2-point tactile discrimination. This study further documents associations between mobility, executive functions, and somatosensation, highlights the differential costs to walking imposed by uneven terrains, and identifies that older adults with lower mobility function are more likely to experience these changes to walking function., Competing Interests: STATEMENTS AND DECLARATIONS On behalf of all authors, the corresponding author states that there are no conflicts of interest.

We studied the longitudinal effects of approximately 6 months of spaceflight on brain activity and task-based connectivity during a spatial working memory (SWM) task. We further investigated whether any brain changes correlated with changes in SWM performance from pre- to post-flight. Brain activity was measured using functional magnetic resonance imaging while astronauts (n = 15) performed a SWM task. Data were collected twice pre-flight and 4 times post-flight. No significant effects on SWM performance or brain activity were found due to spaceflight; however, significant pre- to post-flight changes in brain connectivity were evident. Superior occipital gyrus showed pre- to post-flight reductions in task-based connectivity with the rest of the brain. There was also decreased connectivity between the left middle occipital gyrus and the left parahippocampal gyrus, left cerebellum, and left lateral occipital cortex during SWM performance. These results may reflect increased visual network modularity with spaceflight. Further, increased visual and visuomotor connectivity were correlated with improved SWM performance from pre- to post-flight, while decreased visual and visual-frontal cortical connectivity were associated with poorer performance post-flight. These results suggest that while SWM performance remains consistent from pre- to post-flight, underlying changes in connectivity among supporting networks suggest both disruptive and compensatory alterations due to spaceflight., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Voluntary forgetting is accomplished via top-down control over memory contents. Age-related declines in cognitive control may compromise voluntary forgetting. Using a working-memory variant of a directed forgetting task, we examined age differences in forgetting efficacy by analyzing direct measures of memory accuracy and two indirect measures of retention: proactive interference and semantic distortions. The directed forgetting effect in long-term memory was virtually absent in older adults. Further, compared to young adults, older adults recognized fewer to-be-remembered and more to-be-forgotten items in working memory. However, indirect measures of forgetting efficacy suggest some spared ability to control working memory contents in older adults: Both young and older adult participants exhibited reduced proactive interference for to-be-forgotten words (Experiment 1) and reduced semantic errors to to-be-forgotten list associates (Experiment 2) in working memory. Indirect memory measures of forgetting efficacy can provide a fuller understanding of spared and impaired control processes in older adults.

Astronauts returning from spaceflight typically show transient declines in mobility and balance. Other sensorimotor behaviors and cognitive function have not been investigated as much. Here, we tested whether spaceflight affects performance on various sensorimotor and cognitive tasks during and after missions to the International Space Station (ISS). We obtained mobility (Functional Mobility Test), balance (Sensory Organization Test-5), bimanual coordination (bimanual Purdue Pegboard), cognitive-motor dual-tasking and various other cognitive measures (Digit Symbol Substitution Test, Cube Rotation, Card Rotation, Rod and Frame Test) before, during and after 15 astronauts completed 6 month missions aboard the ISS. We used linear mixed effect models to analyze performance changes due to entering the microgravity environment, behavioral adaptations aboard the ISS and subsequent recovery from microgravity. We observed declines in mobility and balance from pre- to post-flight, suggesting disruption and/or down weighting of vestibular inputs; these behaviors recovered to baseline levels within 30 days post-flight. We also identified bimanual coordination declines from pre- to post-flight and recovery to baseline levels within 30 days post-flight. There were no changes in dual-task performance during or following spaceflight. Cube rotation response time significantly improved from pre- to post-flight, suggestive of practice effects. There was also a trend for better in-flight cube rotation performance on the ISS when crewmembers had their feet in foot loops on the "floor" throughout the task. This suggests that tactile inputs to the foot sole aided orientation. Overall, these results suggest that sensory reweighting due to the microgravity environment of spaceflight affected sensorimotor performance, while cognitive performance was maintained. A shift from exocentric (gravity) spatial references on Earth toward an egocentric spatial reference may also occur aboard the ISS. Upon return to Earth, microgravity adaptions become maladaptive for certain postural tasks, resulting in transient sensorimotor performance declines that recover within 30 days., Competing Interests: YD, NB, IK, and AM were employed by the company KBR, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tays, Hupfeld, McGregor, Salazar, De Dios, Beltran, Reuter-Lorenz, Kofman, Wood, Bloomberg, Mulavara and Seidler.)

A prominent trend in the functional brain imaging literature is that older adults exhibit increased brain activity compared to young adults to perform a given task. This phenomenon has been extensively studied for cognitive tasks, with the field converging on interpretations described in two alternative accounts. One account interprets over-activation in older adults as reflecting neural dysfunction (increased brain activity - indicates poorer performance), whereas another interprets it as neural compensation (increased brain activity - supports better performance). Here we review studies that have recorded brain activity and walking measurements in older adults, and we categorize their findings as reflecting either neural dysfunction or neural compensation. Based on this synthesis, we recommend including multiple task difficulty levels in future work to help differentiate if and when compensation fails as the locomotion task becomes more difficult. Using multiple task difficulty levels with neuroimaging will lead to a more advanced understanding of how age-related changes in locomotor brain activity fit with existing accounts of brain aging and support the development of targeted neural rehabilitation techniques., (Copyright © 2021. Published by Elsevier Inc.)

Demanding cognitive functions like working memory (WM) depend on functional brain networks being able to communicate efficiently while also maintaining some degree of modularity. Evidence suggests that aging can disrupt this balance between integration and modularity. In this study, we examined how cognitive training affects the integration and modularity of functional networks in older and younger adults. Twenty three younger and 23 older adults participated in 10 days of verbal WM training, leading to performance gains in both age groups. Older adults exhibited lower modularity overall and a greater decrement when switching from rest to task, compared to younger adults. Interestingly, younger but not older adults showed increased task-related modularity with training. Furthermore, whereas training increased efficiency within, and decreased participation of, the default-mode network for younger adults, it enhanced efficiency within a task-specific salience/sensorimotor network for older adults. Finally, training increased segregation of the default-mode from frontoparietal/salience and visual networks in younger adults, while it diffusely increased between-network connectivity in older adults. Thus, while younger adults increase network segregation with training, suggesting more automated processing, older adults persist in, and potentially amplify, a more integrated and costly global workspace, suggesting different age-related trajectories in functional network reorganization with WM training., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Emerging plans for travel to Mars and other deep space destinations make it critical for us to understand how spaceflight affects the human brain and behavior. Research over the past decade has demonstrated two co-occurring patterns of spaceflight effects on the brain and behavior: dysfunction and adaptive plasticity. Evidence indicates the spaceflight environment induces adverse effects on the brain, including intracranial fluid shifts, gray matter changes, and white matter declines. Past work also suggests that the spaceflight environment induces adaptive neural effects such as sensory reweighting and neural compensation. Here, we introduce a new conceptual framework to synthesize spaceflight effects on the brain, Spaceflight Perturbation Adaptation Coupled with Dysfunction (SPACeD). We review the literature implicating neurobehavioral dysfunction and adaptation in response to spaceflight and microgravity analogues, and we consider pre-, during-, and post-flight factors that may interact with these processes. We draw several instructive parallels with the aging literature which also suggests co-occurring neurobehavioral dysfunction and adaptive processes. We close with recommendations for future spaceflight research, including: 1) increased efforts to distinguish between dysfunctional versus adaptive effects by testing brain-behavioral correlations, and 2) greater focus on tracking recovery time courses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Affective forecasting (AF), the ability to predict one's future feelings, is important for decision making. We posit that AF entails the ability to maintain and evaluate an emotional feeling state, and thus requires affective working memory (AWM; Mikels & Reuter-Lorenz, 2019). To test this hypothesis, a series of studies investigated whether individual differences in AWM are related to AF ability. In the first study, we document that measures of AWM and AF are positively related, whereas an analogous measure of visual working memory is unrelated to AF in separate groups of participants. Two further within-group studies (1 preregistered) demonstrate that maintenance of affective information predicts AF performance, whereas maintenance of brightness information does not. Further, 2 additional measures of visual working memory (Corsi block-tapping and change detection) did not independently predict AF ability. Taken together the results demonstrate a reliable and selective relationship between AWM and AF, suggesting that AWM is a separable working memory subsystem and an elemental capacity that contributes to the type of higher-order emotional processes involved in AF. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neutral stimuli can acquire value when people learn to associate them with positive or negative outcomes (i.e., gain versus loss associations). Acquired value has been shown to affect how gain and loss associated stimuli are attended, remembered, and acted upon. Here we investigate a potential and previously unreported learning asymmetry in the acquisition of gain and loss associations that may have consequences for subsequent cognitive processing. In our first study, we provide meta-analytic evidence that in probabilistic learning tasks that pair neutral stimuli with intermixed win, loss, and no-change outcomes, people learn win-associations better than loss-associations despite the symmetrical task structure and symmetrical outcome probabilities. Then in two empirical studies, we demonstrate that this learning asymmetry is evident when acquiring gain versus loss associations to gray-scale landscape images whether participants earn points or money (Study 2), and whether or not they receive explicit instructions about the outcome contingencies (Study 3). Furthermore, performance on a post-learning source recognition task was also asymmetrical: explicit knowledge of associated outcomes was superior for optimal gain than optimal loss scenes. These findings indicate the acquisition of gain and loss associations need not be equivalent, despite symmetrical outcome probabilities, equivalent numbers of learning trials, and a constant learning criterion. Consequently, learning asymmetries could contribute to valence and optimality differences in subsequent cognitive processing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level., Competing Interests: Declaration of competing interest M.B. is employed at the MIND Research Institute, whose interest is related to this work. S.M.J. has an indirect financial interest in the MIND Research Institute. None of the other authors declare any competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The majority of the population will experience some cognitive decline with age. Therefore, the development of effective interventions to mitigate age-related decline is critical for older adults' cognitive functioning and their quality of life., Methods: In our randomized controlled multisite trial, we target participants' working memory (WM) skills, and in addition, we focus on the intervention's optimal scheduling in order to test whether and how the distribution of training sessions might affect task learning, and ultimately, transfer. Healthy older adults completed an intervention targeting either WM or general knowledge twice per day, once per day, or once every-other-day. Before and after the intervention and 3 months after training completion, participants were tested in a variety of cognitive domains, including those representing functioning in everyday life., Results: In contrast to our hypotheses, spacing seems to affect learning only minimally. We did observe some transfer effects, especially within the targeted cognitive domain (WM and inhibition/interference), which remained stable at the 3-month follow-up., Discussion: Our findings have practical implications by showing that the variation in training schedule, at least within the range used here, does not seem to be a crucial element for training benefits., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses 1 . The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset 2-5 . Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

Age-related declines in sensorimotor performance have been linked to dedifferentiation of neural representations (i.e., more widespread activity during task performance in older versus younger adults). However, it remains unclear whether changes in neural representations across the adult lifespan are related between the motor and somatosensory systems, and whether alterations in these representations are associated with age declines in motor and somatosensory performance. To investigate these issues, we collected functional magnetic resonance imaging and behavioral data while participants aged 19-76 years performed a visuomotor tapping task or received vibrotactile stimulation. Despite one finding indicative of compensatory mechanisms with older age, we generally observed that 1) older age was associated with greater activity and stronger positive connectivity within sensorimotor and LOC regions during both visuomotor and vibrotactile tasks; 2) increased activation and stronger positive connectivity were associated with worse performance; and 3) age differences in connectivity in the motor system correlated with those in the somatosensory system. Notwithstanding the difficulty of disentangling the relationships between age, brain, and behavioral measures, these results provide novel evidence for neural dedifferentiation across the adult lifespan in both motor and somatosensory systems and suggest that dedifferentiation in these two systems is related., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

[This corrects the article on p. 358 in vol. 11, PMID: 31969814.]., (Copyright © 2020 Clark, Manini, Ferris, Hass, Brumback, Cruz-Almeida, Pahor, Reuter-Lorenz and Seidler.)

Age-related brain changes likely contribute to mobility impairments, but the specific mechanisms are poorly understood. Current brain measurement approaches (e.g., functional magnetic resonance imaging (fMRI), functional near infrared spectroscopy (fNIRS), PET) are limited by inability to measure activity from the whole brain during walking. The Mind in Motion Study will use cutting edge, mobile, high-density electroencephalography (EEG). This approach relies upon innovative hardware and software to deliver three-dimensional localization of active cortical and subcortical regions with good spatial and temporal resolution during walking. Our overarching objective is to determine age-related changes in the central neural control of walking and correlate these findings with a comprehensive set of mobility outcomes (clinic-based, complex walking, and community mobility measures). Our hypothesis is that age-related walking deficits are explained in part by the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH). CRUNCH is a well-supported model that describes the over-recruitment of brain regions exhibited by older adults in comparison to young adults, even at low levels of task complexity. CRUNCH also describes the limited brain reserve resources available with aging. These factors cause older adults to quickly reach a ceiling in brain resources when performing tasks of increasing complexity, leading to poor performance. Two hundred older adults and twenty young adults will undergo extensive baseline neuroimaging and walking assessments. Older adults will subsequently be followed for up to 3 years. Aim 1 will evaluate whether brain activity during actual walking explains mobility decline. Cross sectional and longitudinal designs will be used to study whether poorer walking performance and steeper trajectories of decline are associated with CRUNCH indices. Aim 2 is to harmonize high-density EEG during walking with fNIRS (during actual and imagined walking) and fMRI (during imagined walking). This will allow integration of CRUNCH-related hallmarks of brain activity across neuroimaging modalities, which is expected to lead to more widespread application of study findings. Aim 3 will study central and peripheral mechanisms (e.g., cerebral blood flow, brain regional volumes, and connectivity, sensory function) to explain differences in CRUNCH indices during walking. Research performed in the Mind in Motion Study will comprehensively characterize the aging brain during walking for developing new intervention targets., (Copyright © 2020 Clark, Manini, Ferris, Hass, Brumback, Cruz-Almeida, Pahor, Reuter-Lorenz and Seidler.)

As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month ( n  = 2 astronauts) versus 6-month ( n  = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with long-duration spaceflight and demonstrate the need for closer study of fluid shifts., (© The Author(s) 2020. Published by Oxford University Press.)

Aging is associated with declines in motor and somatosensory function. Some of these motor declines have been linked to age-related reductions in inhibitory function. Here we examined whether tactile surround inhibition also changes with age and whether these changes are associated with those in the motor domain. We tested a group of 56 participants spanning a wide age range (18-76 years old), allowing us to examine when age differences emerge across the lifespan. Participants performed tactile and motor tasks that have previously been linked to inter- and intra-hemispheric inhibition in the somatosensory and motor systems. The results showed that aging is associated with reductions in inhibitory function in both the tactile and motor systems starting around 40 years of age; however, age effects in the two systems were not correlated. The independent effects of age on tactile and motor inhibitory function suggest that distinct mechanisms may underlie age-related reductions in inhibition in the somatosensory and motor systems.

When people ruminate about an unfortunate encounter with a loved one, savor a long-sought accomplishment, or hold in mind feelings from a marvelous or regretfully tragic moment, what mental processes orchestrate these psychological phenomena? Such experiences typify how affect interacts with working memory, which we posit can occur in three primary ways: emotional experiences can modulate working memory, working memory can modulate emotional experiences, and feelings can be the mental representations maintained by working memory. We propose that this last mode constitutes distinct neuropsychological processes that support the integration of particular cognitive and affective processes: affective working memory . Accumulating behavioral and neural evidence suggests that affective working memory processes maintain feelings and are partially separable from their cognitive working memory counterparts. Affective working memory may be important for elucidating the contribution of affect to decision making, preserved emotional processes in later life, and mechanisms of psychological dysfunction in clinical disorders. We review basic behavioral, neuroscience, and clinical research that provides evidence for affective working memory; consider its theoretical implications; and evaluate its functional role within the psychological architecture. In sum, the perspective we advocate is that affective working memory is a fundamental mechanism of mind.

Evidence for false recognition within seconds of encoding suggests that semantic-associative influences are not restricted to long-term memory, consistent with unitary memory accounts but contrary to dual store models. The present study sought further relevant evidence using a modified free recall converging associates task where participants studied 12-item lists composed of 3 semantically distinct quartets (sublists) related to a separate, non-presented theme word (i.e., words 1-4/theme1, 5-8/theme2, and 9-12/theme3). This list construction permits assessment of false recall errors from each sublist, and, particularly, the primacy and recency sublists that have been linked to long- and short-term memory stores. Experiment 1 tested immediate free recall for items. Associative false memories were evident from all sublists, however, significantly less so from the recent sublist, which also showed the highest levels of veridical memory. By inserting a brief (3 s) distractor prior to recall, Experiment 2 selectively reduced veridical memory and increased false memory for the recent sublist while leaving the primacy sublist unaffected. These recall results converge with prior evidence indicating the immediacy of false recognition, and can be understood within a unitary framework where the differential availability of verbatim features and gist-based cues affect memory for primacy and recency sublists.

Several studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as "chemobrain", is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remain poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. Mediation analysis showed that the functional connectivity alteration pattern is a separable treatment symptom from the decreased cognitive health. Current study indicates that more targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In Figure 3b of the originally published article, the colours of the bars were incorrectly reversed. The bars shown in green should have been shown in blue to represent the findings from older adults, whereas the bars shown in blue should have been shown in green to represent the findings from young adults. This has been corrected in the HTML and PDF versions of the article. Images of the original figure are shown in the correction notice.

Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed 'optimally ageing'. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular - compensation, maintenance and reserve - have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.

Purpose: Spaceflight negatively affects sensorimotor behavior; exercise mitigates some of these effects. Head down tilt bed rest (HDBR) induces body unloading and fluid shifts, and is often used to investigate spaceflight effects. Here, we examined whether exercise mitigates effects of 70 days HDBR on the brain and if fitness and brain changes with HDBR are related., Methods: HDBR subjects were randomized to no-exercise (n = 5) or traditional aerobic and resistance exercise (n = 5). Additionally, a flywheel exercise group was included (n = 8). Exercise protocols for exercise groups were similar in intensity, therefore these groups were pooled in statistical analyses. Pre and post-HDBR MRI (structure and structural/functional connectivity) and physical fitness measures (lower body strength, muscle cross sectional area, VO2 max, body composition) were collected. Voxel-wise permutation analyses were used to test group differences in brain changes, and their associations with fitness changes., Results: Comparisons of exercisers to controls revealed that exercise led to smaller fitness deterioration with HDBR but did not affect brain volume or connectivity. Group comparisons showed that exercise modulated post-HDBR recovery of brain connectivity in somatosensory regions. Posthoc analysis showed that this was related to functional connectivity decrease with HDBR in non-exercisers but not in exercisers. Correlational analyses between fitness and brain changes showed that fitness decreases were associated with functional connectivity and volumetric increases (all r >.74), potentially reflecting compensation. Modest brain changes or even decreases in connectivity and volume were observed in subjects who maintained or showed small fitness gains. These results did not survive Bonferroni correction, but can be considered meaningful because of the large effect sizes., Conclusion: Exercise performed during HDBR mitigates declines in fitness and strength. Associations between fitness and brain connectivity and volume changes, although unadjusted for multiple comparisons in this small sample, suggest that supine exercise reduces compensatory HDBR-induced brain changes., Competing Interests: Support from KBRwyle in the form of salaries (MED, YED, NEG, IK, and APM) did not alter our adherence to PLOS ONE policies on sharing data and materials.

In the present study we evaluated changes in neural activation that occur over the time course of multiple days of sensorimotor adaptation, and identified individual neural predictors of adaptation and savings magnitude. We collected functional MRI data while participants performed a manual adaptation task during four separate test sessions over a three-month period. This allowed us to examine changes in activation and associations with adaptation and savings at subsequent sessions. Participants exhibited reliable savings of adaptation across the four sessions. Brain activity associated with early adaptation increased across the sessions in a variety of frontal, parietal, cingulate, and temporal cortical areas, as well as various subcortical areas. We found that savings was positively associated with activation in several striatal, parietal, and cingulate cortical areas including the putamen, precuneus, angular gyrus, dorsal anterior cingulate cortex (dACC), and cingulate motor area. These findings suggest that participants may learn how to better engage cognitive processes across days, potentially reflecting improvements in action selection. We propose that such improvements may rely on action-value assignments, which previously have been linked to the dACC and striatum. As correct movements are assigned a higher value than incorrect movements, the former are more likely to be performed again.

Using an individual differences approach, we evaluated whether manual and locomotor adaptation are associated in terms of adaptation and savings across days, and whether they rely on shared underlying mechanisms involving visuospatial working memory or visual field dependence. Participants performed a manual and a locomotor adaptation task during 4 separate test sessions over a 3-month period. Reliable adaptation and savings were observed for both tasks. It was further found that higher visuospatial working memory performance and lower visual field dependence scores were associated with faster learning in the manual and locomotor tasks, respectively. Moreover, adaptation rates were correlated between the 2 tasks in the final test session, suggesting that people may gradually be learning something generalizable about the adaptation process.

Growing evidence suggests that healthy aging affects the configuration of large-scale functional brain networks. This includes reducing network modularity and local efficiency. However, the stability of these effects over time and their potential role in learning remain poorly understood. The goal of the present study was to further clarify previously reported age effects on "resting-state" networks, to test their reliability over time, and to assess their relation to subsequent learning during training. Resting-state fMRI data from 23 young (YA) and 20 older adults (OA) were acquired in 2 sessions 2 weeks apart. Graph-theoretic analyses identified both consistencies in network structure and differences in module composition between YA and OA, suggesting topological changes and less stability of functional network configuration with aging. Brain-wide, OA showed lower modularity and local efficiency compared to YA, consistent with the idea of age-related functional dedifferentiation, and these effects were replicable over time. At the level of individual networks, OA consistently showed greater participation and lower local efficiency and within-network connectivity in the cingulo-opercular network, as well as lower intra-network connectivity in the default-mode network and greater participation of the somato-sensorimotor network, suggesting age-related differential effects at the level of specialized brain modules. Finally, brain-wide network properties showed associations, albeit limited, with learning rates, as assessed with 10 days of computerized working memory training administered after the resting-state sessions, suggesting that baseline network configuration may influence subsequent learning outcomes. Identification of neural mechanisms associated with learning-induced plasticity is important for further clarifying whether and how such changes predict the magnitude and maintenance of training gains, as well as the extent and limits of cognitive transfer in both younger and older adults.

Background: Adverse effects of spaceflight on sensorimotor function have been linked to altered somatosensory and vestibular inputs in the microgravity environment. Whether these spaceflight sequelae have a central nervous system component is unknown. However, experimental studies have shown spaceflight-induced brain structural changes in rodents' sensorimotor brain regions. Understanding the neural correlates of spaceflight-related motor performance changes is important to ultimately develop tailored countermeasures that ensure mission success and astronauts' health., Method: Head down-tilt bed rest (HDBR) can serve as a microgravity analog because it mimics body unloading and headward fluid shifts of microgravity. We conducted a 70-day 6° HDBR study with 18 right-handed males to investigate how microgravity affects focal gray matter (GM) brain volume. MRI data were collected at 7 time points before, during and post-HDBR. Standing balance and functional mobility were measured pre and post-HDBR. The same metrics were obtained at 4 time points over ~90 days from 12 control subjects, serving as reference data., Results: HDBR resulted in widespread increases GM in posterior parietal regions and decreases in frontal areas; recovery was not yet complete by 12 days post-HDBR. Additionally, HDBR led to balance and locomotor performance declines. Increases in a cluster comprising the precuneus, precentral and postcentral gyrus GM correlated with less deterioration or even improvement in standing balance. This association did not survive Bonferroni correction and should therefore be interpreted with caution. No brain or behavior changes were observed in control subjects., Conclusions: Our results parallel the sensorimotor deficits that astronauts experience post-flight. The widespread GM changes could reflect fluid redistribution. Additionally, the association between focal GM increase and balance changes suggests that HDBR also may result in neuroplastic adaptation. Future studies are warranted to determine causality and underlying mechanisms.

The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Neural dysfunction and cognitive complaints are associated with chemotherapy for breast cancer although trajectory and contributory factors remain unclear. We prospectively examined neurocognition using fMRI and self-reported cognitive, physical and psychological symptoms in women treated with adjuvant chemotherapy over one year. Patients treated with (n = 28) or without (n = 34) chemotherapy for localized breast cancer and healthy controls (n = 30) performed a Verbal Working Memory Task (VWMT) during fMRI and provided self-reports at baseline (pre-adjuvant treatment), five- (M5) and 12-months (M12). Repeated measures ANOVA and multivariable regression determined change over time and possible predictors (e.g., hemoglobin, physical symptoms, worry) of VWMT performance, fMRI activity in the frontoparietal executive network, and cognitive complaints at M12. Trajectories of change in VWMT performance for chemotherapy and healthy control groups differed significantly with the chemotherapy group performing worse at M12. Chemotherapy patients had persistently higher spatial variance (neural inefficiency) in executive network fMRI-activation than both other groups from baseline to M12. Cognitive complaints were similar among groups over time. At M12, VWMT performance and executive network spatial variance were each independently predicted by chemotherapy treatment and their respective baseline values, while cognitive complaints were predicted by baseline level, physical symptoms and worry. Executive network inefficiency and neurocognitive performance deficits pre-adjuvant treatment predict cognitive dysfunction one-year post-baseline, particularly in chemotherapy-treated patients. Persistent cognitive complaints are linked with physical symptom severity and worry regardless of treatment. Pre-chemotherapy interventions should target both neurocognitive deficits and symptom burden to improve cognitive outcomes for breast cancer survivors.

This is a commentary on Campbell and Schacter (2016), 'Aging and the Resting State: Is Cognition Obsolete?'

Directed forgetting tasks instruct people to forget targeted memoranda. In the context of working memory, people attempt to forget representations that are currently held in mind. Here, we evaluated candidate mechanisms of directed forgetting within working memory, by (a) testing the influence of articulatory suppression, a rehearsal-reducing and attention-demanding secondary task, on directed forgetting efficacy, and by (b) assessing the ability of people to perform forgetting in the absence of to-be-remembered competitors to rehearse. In Experiment 1, articulatory suppression interfered with directed forgetting, increasing the proportion of false alarms to to-be-forgotten probes in the working memory phase and decreasing the magnitude of the directed forgetting effect as assessed by an incidental long-term memory recognition test. Experiment 2 replicated the effects of articulatory suppression and tested whether the simultaneous requirement to retain, and presumably rehearse, to-be-remembered items was necessary for successful forgetting. The long-term directed forgetting effect was equivalent whether or not participants had to-be-remembered items to rehearse during the working memory phase. Experiment 3 included an additional comparison condition and confirmed that articulatory suppression interfered with directed forgetting and that participants were as efficient at directed forgetting with and without competitors to remember. In combination, these experiments suggest that directed forgetting in working memory requires an active control process that is limited by articulatory suppression, and that the demand to remember a concurrent memory set is unnecessary for this control process to operate. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

In this review we provide a broad overview of major trends in the cognitive neuroscience of aging and illustrate their roots in the pioneering ideas and discoveries of Morris Moscovitch and his close collaborators, especially Gordon Winocur. These trends include an on-going focus on the specific and dissociable contributions of medial temporal and frontal lobe processes to cognitive aging, especially in the memory domain, the role of individual variability stemming from different patterns of underlying neural decline, the possibility of compensatory neural and cognitive influences that alter the expression of neurobiological aging, and the investigation of lifestyle and psychosocial factors that affect plasticity and may contribute to the rate and level of neurocognitive decline. These prescient ideas, evident in the early work of Moscovitch and Winocur, continue to drive on-going research efforts in the cognitive neuroscience of aging., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to simulate the effects of microgravity exposure on human physiology, sensorimotor function, and cognition on Earth. Previous studies have reported that concurrent performance of motor and cognitive tasks can be impaired during space missions. Understanding the consequences of HDBR for neural control of dual tasking may possibly provide insight into neural efficiency during spaceflight. In the current study, we evaluated how dual task performance and the underlying brain activation changed as a function of HDBR. Eighteen healthy men participated in this study. They remained continuously in the 6° head-down tilt position for 70 days. Functional MRI for bimanual finger tapping was acquired during both single task and dual task conditions, and repeated at 7 time points pre-, during- and post-HDBR. Another 12 healthy males participated as controls who did not undergo HDBR. A widely distributed network involving the frontal, parietal, cingulate, temporal, and occipital cortices exhibited increased activation for dual tasking and increased activation differences between dual and single task conditions during HDBR relative to pre- or post-HDBR. This HDBR-related brain activation increase for dual tasking implies that more neurocognitive control is needed for dual task execution during HDBR compared to pre- and post-HDBR. We observed a positive correlation between pre-to-post HDBR changes in dual-task cost of reaction time and pre-to-post HDBR change in dual-task cost of brain activation in several cerebral and cerebellar regions. These findings could be predictive of changes in dual task processing during spaceflight.

There is growing evidence that fluctuations in brain activity may exhibit scale-free ("fractal") dynamics. Scale-free signals follow a spectral-power curve of the form P(f ) ∝ f(-β), where spectral power decreases in a power-law fashion with increasing frequency. In this study, we demonstrated that fractal scaling of BOLD fMRI signal is consistently suppressed for different sources of cognitive effort. Decreases in the Hurst exponent (H), which quantifies scale-free signal, was related to three different sources of cognitive effort/task engagement: 1) task difficulty, 2) task novelty, and 3) aging effects. These results were consistently observed across multiple datasets and task paradigms. We also demonstrated that estimates of H are robust across a range of time-window sizes. H was also compared to alternative metrics of BOLD variability (SDBOLD) and global connectivity (Gconn), with effort-related decreases in H producing similar decreases in SDBOLD and Gconn. These results indicate a potential global brain phenomenon that unites research from different fields and indicates that fractal scaling may be a highly sensitive metric for indexing cognitive effort/task engagement.

Although emotion is known to reciprocally interact with cognitive and motor performance, contemporary theories of motor learning do not specifically consider how dynamic variations in a learner's affective state may influence motor performance during motor learning. Using a prism adaptation paradigm, we assessed emotion during motor learning on a trial-by-trial basis. We designed two dart-throwing experiments to dissociate motor performance and reward outcomes by giving participants maximum points for accurate throws and reduced points for throws that hit zones away from the target (i.e., "accidental points"). Experiment 1 dissociated motor performance from emotional responses and found that affective ratings tracked points earned more closely than error magnitude. Further, both reward and error uniquely contributed to motor learning, as indexed by the change in error from one trial to the next. Experiment 2 manipulated accidental point locations vertically, whereas prism displacement remained horizontal. Results demonstrated that reward could bias motor performance even when concurrent sensorimotor adaptation was taking place in a perpendicular direction. Thus, these experiments demonstrate that affective states were dissociable from error magnitude during motor learning and that affect more closely tracked points earned. Our findings further implicate reward as another factor, other than error, that contributes to motor learning, suggesting the importance of incorporating affective states into models of motor learning.