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.

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.

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.

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.

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.

Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe.

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity--or the number of items in a set--which is thought to rely on an "approximate number sense" (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.

Commonalities for numerical and continuous quantity skills at temporo-parietal junction.

How do our abilities to process number and other continuous quantities such as time and space relate to each other? Recent evidence suggests that these abilities share common magnitude processing and neural resources, although other findings also highlight the role of dimension-specific processes. To further characterize the relation between number, time, and space, we first examined them in a population with a developmental numerical dysfunction (developmental dyscalculia) and then assessed the extent to which these abilities correlated both behaviorally and anatomically in numerically normal participants. We found that (1) participants with dyscalculia showed preserved continuous quantity processing and (2) in numerically normal adults, numerical and continuous quantity abilities were at least partially dissociated both behaviorally and anatomically. Specifically, gray matter volume correlated with both measures of numerical and continuous quantity processing in the right TPJ; in contrast, individual differences in number proficiency were associated with gray matter volume in number-specific cortical regions in the right parietal lobe. Together, our new converging evidence of selective numerical impairment and of number-specific brain areas at least partially distinct from common magnitude areas suggests that the human brain is equipped with different ways of quantifying the outside world.

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.

Number skills are maintained in healthy ageing.

Numerical skills have been extensively studied in terms of their development and pathological decline, but whether they change in healthy ageing is not well known. Longer exposure to numbers and quantity-related problems may progressively refine numerical skills, similar to what happens to other cognitive abilities like verbal memory. Alternatively, number skills may be sensitive to ageing, reflecting either a decline of number processing itself or of more auxiliary cognitive abilities that are involved in number tasks. To distinguish between these possibilities we tested 30 older and 30 younger participants on an established numerosity discrimination task requiring to judge which of two sets of items is more numerous, and on arithmetical tasks. Older participants were remarkably accurate in performing arithmetical tasks although their numerosity discrimination (also known as 'number acuity') was impaired. Further analyses indicate that this impairment was limited to numerosity trials requiring inhibiting information incongruent to numerosity (e.g., fewer but larger items), and that this also correlated with poor inhibitory processes measured by standard tests. Therefore, rather than a numerical impairment, poor numerosity discrimination is likely to reflect elderly's impoverished inhibitory processes. This conclusion is supported by simulations with a recent neuro-computational model of numerosity perception, where only the specific degradation of inhibitory processes produced a pattern that closely resembled older participants' performance. Numeracy seems therefore resilient to ageing but it is influenced by the decline of inhibitory processes supporting number performance, consistent with the 'Inhibitory Deficit' Theory.

Time counts: bidirectional interaction between time and numbers in human adults.

Number is known for influencing time processing, but to what extent time influences number in human adults is unclear. We investigated possible bidirectional interactions (number on time and time on number) using a novel Stroop-like task; participants compared numbers or temporal durations in congruent (larger number presented for longer duration) or incongruent conditions (smaller number presented for longer duration). Time and number tasks were presented in different blocks (Experiment 1) or within the same block of trials with task instructions provided at the offset of the stimuli (Experiment 2). Analyses of response times (RTs) and their distribution revealed that number affected time from early RTs, and time affected number at late RTs - an asymmetry observed only when time and number tasks were presented in separate blocks. Thus, carefully chosen tasks and appropriate data analysis can reveal bidirectionality between time and number, consistent with shared magnitude or decision mechanisms.

The role of right and left parietal lobes in the conceptual processing of numbers.

Neuropsychological and functional imaging studies have associated the conceptual processing of numbers with bilateral parietal regions (including intraparietal sulcus). However, the processes driving these effects remain unclear because both left and right posterior parietal regions are activated by many other conceptual, perceptual, attention, and response-selection processes. To dissociate parietal activation that is number-selective from parietal activation related to other stimulus or response-selection processes, we used fMRI to compare numbers and object names during exactly the same conceptual and perceptual tasks while factoring out activations correlating with response times. We found that right parietal activation was higher for conceptual decisions on numbers relative to the same tasks on object names, even when response time effects were fully factored out. In contrast, left parietal activation for numbers was equally involved in conceptual processing of object names. We suggest that left parietal activation for numbers reflects a range of processes, including the retrieval of learnt facts that are also involved in conceptual decisions on object names. In contrast, number selectivity in right parietal cortex reflects processes that are more involved in conceptual decisions on numbers than object names. Our results generate a new set of hypotheses that have implications for the design of future behavioral and functional imaging studies of patients with left and right parietal damage.

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.

Quantity without numbers and numbers without quantity in the parietal cortex.

A dominant view in numerical cognition is that processing the quantity indicated by numbers (e.g. deciding the larger between two numbers such as '12.07' or '15.02') relies on the intraparietal regions (IPS) of the cerebral cortex. However, it remains unclear whether the IPS could play a more general role in numerical cognition, for example in (1) quantity processing even with non-numerical stimuli (e.g. choosing the larger of 'bikini' and 'coat'); and/or (2) conceptual tasks involving numbers beyond those requiring quantity processing (e.g. attributing a summer date to either '12.07' or '15.02'). In this study we applied fMRI-guided TMS to the left and right IPS, while independently manipulating stimulus and task. Our results showed that IPS involvement in numerical cognition is neither stimulus-specific nor specific for conceptual tasks. Thus, quantity judgments with numerical and non-numerical stimuli were equally affected by IPS-TMS, as well as a number conceptual task not requiring quantity comparisons. However, IPS-TMS showed no impairment for perceptual decisions on numbers without any conceptual processing (i.e. colour judgment), nor for conceptual decisions that did not involve quantity or number stimuli (e.g. summer object: 'bikini' or 'coat'?). These results are consistent with proposals that the parietal areas are engaged in the conceptual representation of numbers but they challenge the most common view that number processing is so automatic that the simple presentation of numbers activates the IPS and a sense of magnitude. Rather, our results show that the IPS is only necessary when conceptual operations need to be explicitly oriented to numerical concepts.

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.