Cognitive reserve modulates mental health in adulthood.

Cognitive Reserve (CR) reflects acquired knowledge, skills, and abilities throughout life, and it is known for modulating cognitive efficiency in healthy and clinical populations. CR, which was initially proposed to explain individual differences in the clinical presentation of dementia, has subsequently been extended to healthy ageing, showing its role in cognitive efficiency also during middle age. Recently, CR has been linked to affective processes in psychiatric conditions such as schizophrenia, major depressive and anxiety symptoms, and psychological distress, suggesting its potential role in emotional expression and regulation. Whether the role of CR in mental health extends to non-pathological adults, and whether this is only relevant in older age is not yet clear. The aim of this work was therefore to explore the relationship between CR and mental health in healthy adults, with a focus on middle adulthood (40-60). In a sample of 96 participants, we found a positive association between CR and mental health outcomes, such that a higher cognitive reserve index corresponded to fewer mental health reported symptoms. Specifically, a higher CR reflecting professional activities was associated with lower stress levels, especially in middle agers. Taken together, these data therefore suggest that engaging occupations may help maintain a robust mental health, especially by reducing stress symptoms during middle age. These results broaden previous findings suggesting that CR relates to affective components of mental health in middle aged and older adults.

The Role of Beta Oscillations in Mental Time Travel.

The brain processes short-interval timing but also allows people to project themselves into the past and the future (i.e., mental time travel [MTT]). Beta oscillations index seconds-long-interval timing (i.e., higher beta power is associated with longer durations). Here, we used parietal transcranial alternating current stimulation (tACS) to investigate whether MTT is also supported by parietal beta oscillations and to test the link between MTT and short intervals. Thirty adults performed a novel MTT task while receiving beta and alpha tACS, in addition to no stimulation. Beta tACS corresponded to a temporal underestimation in past but not in future MTT. Furthermore, participants who overestimated seconds-long intervals also overestimated temporal distances in the past-projection MTT condition and showed a stronger effect of beta tACS. These data provide a unique window into temporal perception, showing how beta oscillations may be a common mechanism for short intervals and MTT.

Multivariate patterns and long-range temporal correlations of alpha oscillations are associated with flexible manipulation of visual working memory representations.

The ability to flexibly manipulate memory representations is embedded in visual working memory (VWM) and can be tested using paradigms with retrospective cues. Although valid retrospective cues often facilitate memory recall, invalid ones may or may not result in performance costs. We investigated individual differences in utilising retrospective cues and evaluated how these individual differences are associated with brain oscillatory activity at rest. At the behavioural level, we operationalised flexibility as the ability to make effective use of retrospective cues or disregard them if required. At the neural level, we tested whether individual differences in such flexibility were associated with properties of resting-state alpha oscillatory activity (8-12 Hz). To capture distinct aspects of these brain oscillations, we evaluated their power spectral density and temporal dynamics using long-range temporal correlations (LRTCs). In addition, we performed multivariate patterns analysis (MVPA) to classify individuals' level of behavioural flexibility based on these neural measures. We observed that alpha power alone (magnitude) at rest was not associated with flexibility. However, we found that the participants' ability to manipulate VWM representations was correlated with alpha LRTC and could be decoded using MVPA on patterns of alpha power. Our findings suggest that alpha LRTC and multivariate patterns of alpha power at rest may underlie some of the individual differences in using retrospective cues in working memory tasks.

Gamma oscillations modulate working memory recall precision.

Working memory (WM)-the ability to keep information in mind for short periods of time-is linked to attention and inhibitory abilities, i.e., the capacity to ignore task-irrelevant information. These abilities have been associated with brain oscillations, especially parietal gamma and alpha bands, but it is yet unknown whether these oscillations also modulate attention and inhibitory abilities. To test this, we compared parietal gamma-transcranial alternating current stimulation (tACS) to alpha-tACS and to a non-stimulation condition (Sham) in 51 young participants. Stimulation was coupled with a WM task probing memory-based attention and inhibitory abilities by means of probabilistic retrospective cues, including informative (valid), uninformative (invalid) and neutral. Our results show that relative to alpha and sham stimulation, parietal gamma-tACS significantly increased working memory recall precision. Additional post hoc analyses also revealed strong individual variability before and following stimulation; low-baseline performers showed no significant changes in performance following both gamma and alpha-tACS relative to sham. In contrast, in high-baseline performers gamma- (but not alpha) tACS selectively and significantly improved misbinding-feature errors as well as memory precision, particularly in uninformative (invalid) cues which rely more strongly on attentional abilities. We concluded that parietal gamma oscillations, therefore, modulate working memory recall processes, although baseline performance may further influence the effect of stimulation.

Parietal alpha-based inhibitory abilities are causally linked to numerosity discrimination.

Processing numerosities relies on the innate capacity to understand and manipulate the number of items in a set, and to additional abilities such as inhibitory skills -which are known to be linked to brain oscillations in the alpha range. Whether these inhibitory skills are causally linked to numerosity processing and critical for it is unclear. To address this question, we used alpha-based brain stimulation (transcranial alternate current stimulation, tACS) to target inhibitory abilities in the context of numerosity discrimination. Twenty-nine young adults received bilateral tACS to the parietal lobe, a brain region critical for numerical processes. tACS at target (alpha, 10 Hz), control oscillation frequencies (theta, 4 Hz; beta, 22 Hz; sham, no stimulation), and control areas (bilateral frontal regions) was paired to an established numerosity paradigm that allows distinguishing between congruent and incongruent numerosity trials, the latter requiring to inhibit task-irrelevant information. Performance significantly and specifically worsened in incongruent numerosity trials following bilateral parietal alpha-tACS relative to sham and to the other stimulations used, possibly due to the desynchronization of parietal neuronal oscillations in the alpha range. No significant changes in performance were observed in parietal beta and theta-tACS, relative to sham, nor in frontal alpha-tACS. Likewise, there were no changes in performing congruent numerosity trials. We therefore concluded that parietal alpha oscillations are causally linked to inhibitory abilities, and reinforced the view that these abilities are intrinsic to numerosity discrimination.

The influence of motor preparation on the processing of action-relevant visual features.

Action preparation can facilitate performance in tasks of visual perception, for instance by speeding up responses to action-relevant stimulus features. However, it is unknown whether this facilitation reflects an influence on early perceptual processing, or instead post-perceptual processes. In three experiments, a combination of psychophysics and electroencephalography was used to investigate whether visual features are influenced by action preparation at the perceptual level. Participants were cued to prepare oriented reach-to-grasp actions before discriminating target stimuli oriented in the same direction as the prepared grasping action (congruent) or not (incongruent). As expected, stimuli were discriminated faster if their orientation was congruent, compared to incongruent, with the prepared action. However, action-congruency had no influence on perceptual sensitivity, regardless of cue-target interval and discrimination difficulty. The reaction time effect was not accompanied by modulations of early visual-evoked potentials. Instead, beta-band (13-30 Hz) synchronization over sensorimotor brain regions was influenced by action preparation, indicative of improved response preparation. Together, the results suggest that action preparation may not modulate early visual processing of orientation, but likely influences higher order response or decision related processing. While early effects of action on spatial perception are well documented, separate mechanisms appear to govern non-spatial feature selection.

Spatial gradients of healthy aging: a study of myelin-sensitive maps.

Protracted development of a brain network may entail greater susceptibility to aging decline, supported by evidence of an earlier onset of age-related changes in late-maturing anterior areas, that is, an anterior-to-posterior gradient of brain aging. Here we analyzed the spatiotemporal features of age-related differences in myelin content across the human brain indexed by magnetization transfer (MT) concentration in a cross-sectional cohort of healthy adults. We described age-related spatial gradients in MT, which may reflect the reversal of patterns observed in development. We confirmed an anterior-to-posterior gradient of age-related MT decrease and also showed a lateral-to-ventral gradient inversely mirroring the sequence of connectivity development and myelination. MT concentration in the lateral white matter regions continued to increase up to the age of 45 years and decreased moderately following a peak. In contrast, ventral white matter regions reflected life-long stable MT concentration levels, followed by a rapid decrease at a later age. We discussed our findings in relation with existing theories of brain aging, including the lack of support for the proposal that areas which mature later decline at an accelerated rate.

Probing the architecture of visual number sense with parietal tRNS.

Theoretical accounts of the visual number sense (VNS), i.e., an ability to discriminate approximate numerosities, remain controversial. A proposal that the VNS represents a process of numerosity extraction, leading to an abstract number representation in the brain, has been challenged by the view that the VNS is non-numerical in its essence and amounts to a weighted integration of continuous magnitude features that typically change with numerosity. In the present study, using two-alternative forced-choice paradigm, we aimed to distinguish between these proposals by probing brain areas implicated in the VNS with transcranial random noise stimulation (tRNS). We generated predictions for the stimulation-related changes in behavioural performance which would be compatible with alternative mechanisms proposed for the VNS. First, we investigated whether the superior parietal (SP) area hosts a numerosity code or whether its function is to modulate weighting of continuous stimulus features. We predicted that stimulation may affect the VNS precision if the SP role is representational, and that it may affect decision threshold if its role is modulatory. Second, we investigated whether the intraparietal (IP) area hosts a numerosity code independently of codes for continuous stimulus features, or whether their representations overlap. If the numerosity code is independent, we predicted that IP stimulation may improve the VNS but not continuous magnitude judgements. Our results were consistent with the hypotheses of a modulatory role of the SP and of the independence of the numerosity code in the IP, whereby suggesting that VNS is an emergent abstract property based on continuous magnitude statistics.

Learning facts during aging: the benefits of curiosity.

Background/study context: Recent studies have shown that young adults better remember factual information they are curious about. It is not entirely clear, however, whether this effect is retained during aging. Here, the authors investigated curiosity-driven memory benefits in young and elderly individuals. METHODS: In two experiments, young (age range 18-26) and older (age range 65-89) adults read trivia questions and rated their curiosity to find out the answer. They also attended to task-irrelevant faces presented between the trivia question and the answer. The authors then administered a surprise memory test to assess recall accuracy for trivia answers and recognition memory performance for the incidentally learned faces. RESULTS: In both young and elderly adults, recall performance was higher for answers to questions that elicited high levels of curiosity. In Experiment 1, the authors also found that faces presented in temporal proximity to curiosity-eliciting trivia questions were better recognized, indicating that the beneficial effects of curiosity extended to the encoding of task-irrelevant material. CONCLUSIONS: These findings show that elderly individuals benefit from the memory-enhancing effects of curiosity. This may lead to the implementation of learning strategies that target and stimulate curiosity in aging.

Alpha Oscillations Are Causally Linked to Inhibitory Abilities in Ageing.

Aging adults typically show reduced ability to ignore task-irrelevant information, an essential skill for optimal performance in many cognitive operations, including those requiring working memory (WM) resources. In a first experiment, young and elderly human participants of both genders performed an established WM paradigm probing inhibitory abilities by means of valid, invalid, and neutral retro-cues. Elderly participants showed an overall cost, especially in performing invalid trials, whereas younger participants' general performance was comparatively higher, as expected.Inhibitory abilities have been linked to alpha brain oscillations but it is yet unknown whether in aging these oscillations (also typically impoverished) and inhibitory abilities are causally linked. To probe this possible causal link in aging, we compared in a second experiment parietal alpha-transcranial alternating current stimulation (tACS) with either no stimulation (Sham) or with two control stimulation frequencies (theta- and gamma-tACS) in the elderly group while performing the same WM paradigm. Alpha- (but not theta- or gamma-) tACS selectively and significantly improved performance (now comparable to younger adults' performance in the first experiment), particularly for invalid cues where initially elderly showed the highest costs. Alpha oscillations are therefore causally linked to inhibitory abilities and frequency-tuned alpha-tACS interventions can selectively change these abilities in the elderly.SIGNIFICANCE STATEMENT Ignoring task-irrelevant information, an ability associated to rhythmic brain activity in the alpha frequency band, is fundamental for optimal performance. Indeed, impoverished inhibitory abilities contribute to age-related decline in cognitive functions like working memory (WM), the capacity to briefly hold information in mind. Whether in aging adults alpha oscillations and inhibitory abilities are causally linked is yet unknown. We experimentally manipulated frequency-tuned brain activity using transcranial alternating current stimulation (tACS), combined with a retro-cue paradigm assessing WM and inhibition. We found that alpha-tACS induced a significant improvement in target responses and misbinding errors, two indexes of inhibition. We concluded that in aging alpha oscillations are causally linked to inhibitory abilities, and that despite being impoverished, these abilities are still malleable.

How serially organized working memory information interacts with timing.

The temporary storage of serial order information in working memory (WM) has been demonstrated to be crucial to higher order cognition. The previous studies have shown that the maintenance of serial order can be a consequence of the construction of position markers to which to-be-remembered information will be bound. However, the nature of these position markers remains unclear. In this study, we demonstrate the crucial involvement of time in the construction of these markers by establishing a bidirectional relationship. First, results of the first experiment show that the initial items in WM result in faster responding after shorter time presentations, while we observe the opposite for items stored further in WM. Second, in the next experiment, we observe an effect of temporal cueing on WM retrieval; longer time cues facilitate responding to later WM items compared with items stored at the beginning of WM. These findings are discussed in the context of position marker theories, reviewing the functional involvement of time in the construction of these markers and its association with space.

Cathodal transcranial direct current stimulation over posterior parietal cortex enhances distinct aspects of visual working memory.

In this study, we investigated the effects of tDCS over the posterior parietal cortex (PPC) during a visual working memory (WM) task, which probes different sources of response error underlying the precision of WM recall. In two separate experiments, we demonstrated that tDCS enhanced WM precision when applied bilaterally over the PPC, independent of electrode configuration. In a third experiment, we demonstrated with unilateral electrode configuration over the right PPC, that only cathodal tDCS enhanced WM precision and only when baseline performance was low. Looking at the effects on underlying sources of error, we found that cathodal stimulation enhanced the probability of correct target response across all participants by reducing feature-misbinding. Only for low-baseline performers, cathodal stimulation also reduced variability of recall. We conclude that cathodal- but not anodal tDCS can improve WM precision by preventing feature-misbinding and hereby enhancing attentional selection. For low-baseline performers, cathodal tDCS also protects the memory trace. Furthermore, stimulation over bilateral PPC is more potent than unilateral cathodal tDCS in enhancing general WM precision.

Enhancing duration processing with parietal brain stimulation.

Numerosity and duration are thought to share common magnitude-based mechanisms in brain regions including the right parietal and frontal cortices like the supplementary motor area, SMA. Numerosity and duration are, however, also different in several intrinsic features. For instance, in a quantification context, numerosity is known for being more automatically accessed than temporal events, and durations are by definition sequential whereas numerosity can be both sequential and simultaneous. Moreover, numerosity and duration processing diverge in terms of their neuronal correlates. Whether these observed neuronal specificities can be accounted for by differences in automaticity or presentation-mode is however not clear. To address this issue, we used brain stimulation (transcranial random noise stimulation, tRNS) to the right parietal cortex or the SMA combined with experimental stimuli differing in their level of automaticity (numerosity and duration) and presentation mode (sequential or simultaneous). Compared to a no stimulation group, performance changed in duration but not in numerosity categorisation following right parietal but not SMA stimulation. These results indicate that the right parietal cortex is critical for duration processing, and suggest that tRNS has a stronger effect on less automatic processes such as duration.

The Remapping of Time by Active Tool-Use.

Multiple, action-based space representations are each based on the extent to which action is possible toward a specific sector of space, such as near/reachable and far/unreachable. Studies on tool-use revealed how the boundaries between these representations are dynamic. Space is not only multidimensional and dynamic, but it is also known for interacting with other dimensions of magnitude, such as time. However, whether time operates on similar action-driven multiple representations and whether it can be modulated by tool-use is yet unknown. To address these issues, healthy participants performed a time bisection task in two spatial positions (near and far space) before and after an active tool-use training, which consisted of performing goal-directed actions holding a tool with their right hand (Experiment 1). Before training, perceived stimuli duration was influenced by their spatial position defined by action. Hence, a dissociation emerged between near/reachable and far/unreachable space. Strikingly, this dissociation disappeared after the active tool-use training since temporal stimuli were now perceived as nearer. The remapping was not found when a passive tool-training was executed (Experiment 2) or when the active tool-training was performed with participants' left hand (Experiment 3). Moreover, no time remapping was observed following an equivalent active hand-training but without a tool (Experiment 4). Taken together, our findings reveal that time processing is based on action-driven multiple representations. The dynamic nature of these representations is demonstrated by the remapping of time, which is action- and effector-dependent.

'How many' and 'how much' dissociate in the parietal lobe.

We investigated whether two features that are fundamental for quantity processing, namely numerosity and continuous quantity - or 'how many' versus 'how much' - may dissociate in the parietal lobe. Fourteen mathematically-normal participants performed a well-established numerosity discrimination task after receiving continuous theta burst transcranial magnetic stimulation (TBS) over the left or right intraparietal sulcus (IPS) or the Vertex. We performed a detailed analysis of accuracy (based on the Weber Fraction, wf), which distinguished between trials in which numerosity was anti-correlated or 'incongruent' to other continuous measures of quantity, and trials in which numerosity and other continuous features were 'congruent'. Congruent trials can be processed by integrating numerosity or continuous quantity features like cumulative area since they correlate. Instead incongruent trials can only be processed based on numerosity and requires inhibiting cumulative area or other continuous quantity features like dot size and would lead to incorrect judgment if these features are used as a proxy for numerosity. We found an increase of wf, i.e., weakened numerosity processing in incongruent but not congruent trials following left IPS-TBS, which suggests that numerosity processing was impaired while continuous quantity processing remained unchanged. Moreover, wf increased in congruent but not in incongruent trials following right IPS stimulation. We concluded that left and right parietal are respectively critical for numerosity discrimination, i.e., 'how many' or alternatively for response selection, and for integrating numerosity and continuous quantity features.

Learning to integrate versus inhibiting information is modulated by age.

Cognitive training aiming at improving learning is often successful, but what exactly underlies the observed improvements and how these differ across the age spectrum are currently unknown. Here we asked whether learning in young and older people may reflect enhanced ability to integrate information required to perform a cognitive task or whether it may instead reflect the ability to inhibit task-irrelevant information for successful task performance. We trained 30 young and 30 aging human participants on a numerosity discrimination task known to engage the parietal cortex and in which cue-integration and inhibitory abilities can be distinguished. We coupled training with parietal, motor, or sham transcranial random noise stimulation, known for modulating neural activity. Numerosity discrimination improved after training and was maintained long term, especially in the training + parietal stimulation group, regardless of age. Despite the quantitatively similar improvement in the two age groups, the content of learning differed remarkably: aging participants improved more in inhibitory abilities, whereas younger subjects improved in cue-integration abilities. Moreover, differences in the content of learning were reflected in different transfer effects to untrained but related abilities: in the younger group, improvements in cue integration paralleled improvements in continuous quantity (time and space), whereas in the elderly group, improvements in numerosity-based inhibitory abilities generalized to other measures of inhibition and corresponded to a decline in space discrimination, possibly because conflicting learning resources are used in numerosity and continuous quantity processing. These results indicate that training can enhance different, age-dependent cognitive processes and highlight the importance of identifying the exact processes underlying learning for effective training programs.

Better together? The cognitive advantages of synaesthesia for time, numbers, and space.

Synaesthesia for time, numbers, and space (TNS synaesthesia) is thought to have costs and benefits for recalling and manipulating time and number. There are two competing theories about how TNS synaesthesia affects cognition. The "magnitude" account predicts that TNS synaesthesia may affect cardinal magnitude judgements, whereas the "sequence" account suggests that it may affect ordinal sequence judgements and could rely on visuospatial working memory. We aimed to comprehensively assess the cognitive consequences of TNS synaesthesia and distinguish between these two accounts. TNS synaesthetes, grapheme-colour synaesthetes, and nonsynaesthetes completed a behavioural task battery. Three tasks involved cardinal and ordinal comparisons of temporal, numerical, and spatial stimuli; we also examined visuospatial working memory. TNS synaesthetes were significantly more accurate than nonsynaesthetes in making ordinal judgements about space. This difference was explained by significantly higher visuospatial working memory accuracy. Our findings demonstrate an advantage of TNS synaesthesia that is more in line with the sequence account.

Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging.

A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19-75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.