A neural mechanism of cognitive reserve: The case of bilingualism.

Cognitive Reserve (CR) refers to the preservation of cognitive function in the face of age- or disease-related neuroanatomical decline. While bilingualism has been shown to contribute to CR, the extent to which, and what particular aspect of, second language experience contributes to CR are debated, and the underlying neural mechanism(s) unknown. Intrinsic functional connectivity reflects experience-dependent neuroplasticity that occurs across timescales ranging from minutes to decades, and may be a neural mechanism underlying CR. To test this hypothesis, we used voxel-based morphometry and resting-state functional connectivity analyses of MRI data to compare structural and functional brain integrity between monolingual and bilingual older adults, matched on cognitive performance, and across levels of second language proficiency measured as a continuous variable. Bilingualism, and degree of second language proficiency specifically, were associated with lower gray matter integrity in a hub of the default mode network - a region that is particularly vulnerable to decline in aging and dementia - but preserved intrinsic functional network organization. Bilingualism moderated the association between neuroanatomical differences and cognitive decline, such that lower gray matter integrity was associated with lower executive function in monolinguals, but not bilinguals. Intrinsic functional network integrity predicted executive function when controlling for group differences in gray matter integrity and language status. Our findings confirm that lifelong bilingualism is a CR factor, as bilingual older adults performed just as well as their monolingual peers on tasks of executive function, despite showing signs of more advanced neuroanatomical aging, and that this is a consequence of preserved intrinsic functional network organization.

Gray Matter Volume as Evidence for Cognitive Reserve in Bilinguals With Mild Cognitive Impairment.

BACKGROUND: Compared with monolinguals, bilinguals have a later onset of mild cognitive impairment (MCI) and Alzheimer disease symptoms and greater neuropathology at similar cognitive and clinical levels. The present study follows a previous report showing the faster conversion from MCI to Alzheimer disease for bilingual patients than comparable monolinguals, as predicted by a cognitive reserve (CR). PURPOSE: Identify whether the increased CR found for bilinguals in the previous study was accompanied by greater gray matter (GM) atrophy than was present for the monolinguals. METHODS: A novel deep-learning technique based on convolutional neural networks was used to enhance clinical scans into 1 mm MPRAGEs and analyze the GM volume at the time of MCI diagnosis in the earlier study. PATIENTS: Twenty-four bilingual and 24 monolingual patients were diagnosed with MCI at a hospital memory clinic. RESULTS: Bilingual patients had more GM loss than monolingual patients in areas related to language processing, attention, decision-making, motor function, and episodic memory retrieval. Bilingualism and age were the strongest predictors of atrophy after other variables such as immigration and education were included in a multivariate model. DISCUSSION: CR from bilingualism is evident in the initial stages of neurodegeneration after MCI has been diagnosed.

The relation between brain signal complexity and task difficulty on an executive function task.

On a daily basis, we constantly deal with changing environmental cues and perceptual conflicts and as such, our brains must flexibly adapt to current demands in order to act appropriately. Brains become more efficient and are able to switch states more readily by increasing the complexity of their neural networks. However, it is unclear how brain signal complexity relates to behavior in young adults performing cognitively demanding executive function tasks. Here we used multiscale entropy analysis and multivariate statistics on EEG data while participants performed a bivalency effect task-switching paradigm to show that brain signal complexity in young adults increases as task demands increase, that increases in brain signal complexity are associated with both speed gains and losses depending on scalp location, and that more difficult tasks are associated with more circumscribed complexity across the scalp. Overall, these findings highlight a critical role for brain signal complexity in predicting behavior on an executive function task among young adults.

Effects of bilingualism on white matter integrity in older adults.

Bilingualism can delay the onset of dementia symptoms and has thus been characterized as a mechanism for cognitive or brain reserve, although the origin of this reserve is unknown. Studies with young adults generally show that bilingualism is associated with a strengthening of white matter, but there is conflicting evidence for how bilingualism affects white matter in older age. Given that bilingualism has been shown to help stave off the symptoms of dementia by up to four years, it is crucial that we clarify the mechanism underlying this reserve. The current study uses diffusion tensor imaging (DTI) to compare monolinguals and bilinguals while carefully controlling for potential confounds (e.g., I.Q., MMSE, and demographic variables). We show that group differences in Fractional Anisotropy (FA) and Radial Diffusivity (RD) arise from multivariable interactions not adequately controlled for by sequential bivariate testing. After matching and statistically controlling for confounds, bilinguals still had greater axial diffusivity (AD) in the left superior longitudinal fasciculus than monolingual peers, supporting a neural reserve account for healthy older bilinguals.

Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans.

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.

Do young adults show conceptual knowledge of previous distractors?

Using implicit tests, older adults have been found to retain conceptual knowledge of previously seen task-irrelevant information. While younger adults typically do not show the same effect, evidence from one study [Gopie, N., Craik, F. I. M., & Hasher, L. (2011). A double dissociation of implicit and explicit memory in younger and older adults. Psychological Science, 22, 634-640. doi: 10.1177/0956797611403321 ] suggests otherwise. In that study, young adults showed greater explicit than implicit memory for previous distractors on a word fragment completion task. This was interpreted as evidence for maintaining access to previous conceptual knowledge of the distractors. Here, we report two failures to replicate that original finding, followed by a third study designed to test directly whether young adults use conceptual-level information that was previously irrelevant. Our findings agree with others that young adults show weak to no evidence of conceptual knowledge of previously irrelevant information.

The language and social background questionnaire: Assessing degree of bilingualism in a diverse population.

Research examining the cognitive consequences of bilingualism has expanded rapidly in recent years and has revealed effects on aspects of cognition across the lifespan. However, these effects are difficult to find in studies investigating young adults. One problem is that there is no standard definition of bilingualism or means of evaluating degree of bilingualism in individual participants, making it difficult to directly compare the results of different studies. Here, we describe an instrument developed to assess degree of bilingualism for young adults who live in diverse communities in which English is the official language. We demonstrate the reliability and validity of the instrument in analyses based on 408 participants. The relevant factors for describing degree of bilingualism are: (1) the extent of non-English language proficiency and use at home, and (2) non-English language use socially. We then use the bilingualism scores obtained from the instrument to demonstrate their association with: (1) performance on executive function tasks, and (2) previous classifications of participants into categories of monolinguals and bilinguals.

Task-linked Diurnal Brain Network Reorganization in Older Adults: A Graph Theoretical Approach.

Testing older adults in the morning generally improves behavioral performance relative to afternoon testing. Morning testing is also associated with brain activity similar to that of young adults. Here, we used graph theory to explore how time of day (TOD) affects the organization of brain networks in older adults across rest and task states. We used nodes from the automated anatomical labeling atlas to construct participant-specific correlation matrices of fMRI data obtained during 1-back tasks with interference and rest. We computed pairwise group differences for key graph metrics, including small-worldness and modularity. We found that older adults tested in the morning and young adults did not differ on any graph metric. Both of these groups differed from older adults tested in the afternoon during the tasks-but not rest. Specifically, the latter group had lower modularity and small-worldness (indices of more efficient network organization). Across all groups, higher modularity and small-worldness strongly correlated with reduced distractibility on an implicit priming task. Increasingly, TOD is seen as important for interpreting and reproducing neuroimaging results. Our study emphasizes how TOD affects brain network organization and executive control in older adults.

Bilinguals have more complex EEG brain signals in occipital regions than monolinguals.

Brain signal complexity increases with development and is associated with better cognitive outcomes in older age. Research has also shown that bilinguals are able to stave off cognitive decline for longer periods of time than monolinguals, but no studies to date have examined whether bilinguals have more complex brain signals than monolinguals. Here we explored the hypothesis that bilingualism leads to greater brain signal complexity by examining multiscale entropy (MSE) in monolingual and bilingual young adults while EEG was recorded during a task-switching paradigm. Results revealed that bilinguals had greater brain signal complexity than monolinguals in occipital regions. Furthermore, bilinguals performed better with increasing occipital brain signal complexity, whereas monolinguals relied on coupling with frontal regions to demonstrate gains in performance. These findings are discussed in terms of how a lifetime of experience with a second language leads to more automatic and efficient processing of stimuli and how these adaptations could contribute to the prevention of cognitive decline in older age.

Neuropsychological Assessments of Cognitive Aging in Monolingual and Bilingual Older Adults.

Standardized neuropsychological tests are routinely used as diagnostic criteria in aging populations and are an important piece of evidence for the identification of clinical pathology and neurodegenerative conditions such as Alzheimer's disease. Tests include such measures as the Mini Mental Status Exam, Delis-Kaplan Executive Function System, Montreal Cognitive Assessment, and others. These tests cover a range of functions including working memory, verbal fluency, prospective memory, and task switching. Interpretation of test results is based on comparison of the participant's score to standard scores that have been normed on a population database. However, a growing body of research has shown that the skills underlying these tests may be significantly different in monolingual and bilingual older adults, especially for those experiencing cognitive impairment, yet the standardized test scores do not account for such differences. Therefore, results of neuropsychological tests may be different for bilingual populations than for monolinguals, and those differences may be misinterpreted. The issue is important because the consequences of these interpretative errors may be over- or under- diagnosis of cognitive impairment. The present study examined the neuropsychological test scores of monolingual and bilingual older adults who were experiencing healthy aging or cognitive impairment to establish patterns in these scores that can more accurately guide the interpretation for bilingual older adults by considering group differences in the underlying abilities.

Age differences in the neural correlates of distraction regulation: A network interaction approach.

Older adults show decrements in the ability to ignore or suppress distraction relative to younger adults. However, age differences in the neural correlates of distraction control and the role of large-scale network interaction in regulating distractors are scarcely examined. In the current study, we investigated age differences in how the anticorrelation between an externally oriented dorsal attention network (DAN) and an internally focused default mode network (DMN) is related to inhibiting distractors presented during a 1-back working memory task. For both young and older adults, the extent of DAN-DMN anticorrelation predicted reduced distractibility. Activation in a common set of frontal and insular control regions during the task was, however, associated with opposite patterns of network interaction and distractibility in the age groups. For older adults, recruitment of these regions was associated with greater DAN-DMN anticorrelation and less distractibility (better performance). For younger adults, it was associated with decreased DAN-DMN anticorrelation and more distractibility (worse performance). Our findings demonstrate the age-dependent relationship between DAN-DMN interaction patterns and engagement of control regions during an externally oriented distraction control task. This suggests that engagement of those regions may play a compensatory role for older adults but may be indicative of less efficient neural control mechanisms in younger adults.

Age-related deficits in inhibition in figure-ground assignment.

We assessed age differences in the ability to resolve competition for figural status in stationary displays using small, enclosed, symmetrical silhouettes that participants classified as depicting "novel" or "familiar" shapes. The silhouettes were biased such that the inside was perceived as the shaped figure, and the outside was perceived as a shapeless ground. The critical manipulation was whether a portion of a meaningful object was suggested on the outside of the border of some of the novel silhouettes but not others (M+Ground and M-Ground novel silhouettes, respectively). This manipulation was intended to induce greater inhibitory competition for figural status from the groundside in M+Ground silhouettes than M-Ground silhouettes. In previous studies, young adults classified M+Ground silhouettes as "novel" faster than M-Ground silhouettes (Trujillo, Allen, Schnyer, & Peterson, 2010), suggesting that young adults may recruit more inhibition to resolve figure-ground when there is more competition. We replicated this effect with young adults in the present study, but older adults showed the opposite pattern and were less accurate in classifying M+Ground than M-Ground silhouettes. These results extend the evidence for inhibitory deficits in older adults to figure assignment in stationary displays. The (M+Ground - M-Ground) RT differences were evident in observers' longest responses, consistent with the hypothesis that inhibitory deficits are evident when the need for inhibition is substantial.

Sexual orientation and cognition in aging populations: Results from the Canadian Longitudinal Study on Aging.

The current study utilized the Canadian Longitudinal Study on Aging (CLSA) data to investigate the relationship between sexual orientation and cognitive health of the aging population. Cognitive flexibility and verbal fluency were examined as outcome variables in the study. A total of 45,993 respondents were included in the analyses. Each model had social support or social participation as a mediator. A series of mediation analysis, stratified by gender, revealed that aging gay men performed better in cognitive tasks related to cognitive flexibility when compared to their heterosexual counterparts. The results also indicated that social support is a protective factor for cognitive health in aging lesbian women. This study provides an opportunity to consider how clinical and social services can strategize to build inclusive environments for the aging sexual minority population.

Examining the consistency in bilingualism and white matter research: A meta-analysis.

This study aimed to systematically investigate the relationship between bilingualism, age, L2 onset age of acquisition (AoA), and white matter integrity (operationalized as fractional anisotropy, FA), addressing inconsistencies in the literature. We conducted a meta-analysis of 23 studies and used meta-regression models to assess the influence of age and L2AoA on effect sizes in studies comparing monolinguals and bilinguals. Even though the overall between-group effect size across the whole brain was unreliable, bilingualism was associated with increased white matter integrity in specific tracts and in groups with a limited range of age and L2AoA. Age had a small, negative effect on white matter integrity, with differences between monolinguals and bilinguals more pronounced in younger adults, consistent with a view of an initial increase in white matter integrity, followed by remodeling for efficiency over time. In contrast, later L2AoA was associated with greater white matter integrity in bilinguals than monolinguals, again consistent with the remodeling for efficiency model. Our findings highlight the importance of considering age and L2AoA when examining the neural basis of bilingualism on white matter in the brain and how bilingualism contributes to structural changes that stave off cognitive decline in older age.

Age-Related Alterations in Gray Matter Microstructure in Older People With Remitted Major Depression at Risk for Dementia.

Background: Major depressive disorder (MDD) in late life is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease. However, studies of gray matter changes have produced varied estimates of which structures are implicated in MDD and dementia. Changes in gray matter volume and cortical thickness are macrostructural measures for the microstructural processes of free water accumulation and dendritic spine loss. Methods: We conducted multishell diffusion imaging to assess gray matter microstructure in 244 older adults with remitted MDD (n = 44), MCI (n = 115), remitted MDD+MCI (n = 61), or without psychiatric disorders or cognitive impairment (healthy control participants; n = 24). We estimated measures related to neurite density, orientation dispersion, and free water (isotropic volume fraction) using a biophysically plausible model (neurite orientation dispersion and density imaging). Results: Results showed that increasing age was correlated with an increase in isotropic volume fraction and a decrease in orientation dispersion index, which is consistent with neuropathology dendritic loss. In addition, this relationship between age and increased isotropic volume fraction was more disrupted in the MCI group than in the remitted MDD or healthy control groups. However, the association between age and orientation dispersion index was similar for all 3 groups. Conclusions: The findings suggest that the neurite orientation dispersion and density imaging measures could be used to identify biological risk factors for Alzheimer's disease, signifying both conventional neurodegeneration observed with MCI and dendritic loss seen in MDD.

From Lung to Brain: Respiration Modulates Neural and Mental Activity.

Respiration protocols have been developed to manipulate mental states, including their use for therapeutic purposes. In this systematic review, we discuss evidence that respiration may play a fundamental role in coordinating neural activity, behavior, and emotion. The main findings are: (1) respiration affects the neural activity of a wide variety of regions in the brain; (2) respiration modulates different frequency ranges in the brain's dynamics; (3) different respiration protocols (spontaneous, hyperventilation, slow or resonance respiration) yield different neural and mental effects; and (4) the effects of respiration on the brain are related to concurrent modulation of biochemical (oxygen delivery, pH) and physiological (cerebral blood flow, heart rate variability) variables. We conclude that respiration may be an integral rhythm of the brain's neural activity. This provides an intimate connection of respiration with neuro-mental features like emotion. A respiratory-neuro-mental connection holds the promise for a brain-based therapeutic usage of respiration in mental disorders.

OViTAD: Optimized Vision Transformer to Predict Various Stages of Alzheimer's Disease Using Resting-State fMRI and Structural MRI Data.

Advances in applied machine learning techniques for neuroimaging have encouraged scientists to implement models to diagnose brain disorders such as Alzheimer's disease at early stages. Predicting the exact stage of Alzheimer's disease is challenging; however, complex deep learning techniques can precisely manage this. While successful, these complex architectures are difficult to interrogate and computationally expensive. Therefore, using novel, simpler architectures with more efficient pattern extraction capabilities, such as transformers, is of interest to neuroscientists. This study introduced an optimized vision transformer architecture to predict the group membership by separating healthy adults, mild cognitive impairment, and Alzheimer's brains within the same age group (>75 years) using resting-state functional (rs-fMRI) and structural magnetic resonance imaging (sMRI) data aggressively preprocessed by our pipeline. Our optimized architecture, known as OViTAD is currently the sole vision transformer-based end-to-end pipeline and outperformed the existing transformer models and most state-of-the-art solutions. Our model achieved F1-scores of 97%±0.0 and 99.55%±0.39 from the testing sets for the rs-fMRI and sMRI modalities in the triple-class prediction experiments. Furthermore, our model reached these performances using 30% fewer parameters than a vanilla transformer. Furthermore, the model was robust and repeatable, producing similar estimates across three runs with random data splits (we reported the averaged evaluation metrics). Finally, to challenge the model, we observed how it handled increasing noise levels by inserting varying numbers of healthy brains into the two dementia groups. Our findings suggest that optimized vision transformers are a promising and exciting new approach for neuroimaging applications, especially for Alzheimer's disease prediction.

Impact of Neighborhood Deprivation on Aging Sexual Minority People's Depression: Results from the CANUE and CLSA data.

As the aging population grows across the world, exploring the impact of social environment on minority populations' aging and well-being would be an essential step towards building an inclusive society. Using the Canadian Longitudinal Study on Aging (CLSA) and Canadian Urban Environmental Health Research Consortium (CANUE) data, the study investigated the relationship between deprivation and depression level in aging sexual minority people to examine how neighborhood level social and material deprivation influence mental health. 48,792 survey respondents were included in our analyses and the average age was 62.9. The study had 47,792 heterosexual, 760 gay/lesbian, and 240 bisexual individuals (23,977 men and 24,815 women). Regression analyses were conducted while controlling for age in each model. Results revealed that neighborhood material deprivation has a significant impact on mental health outcomes of aging lesbian women and bisexual men. The study provides an opportunity for intervention considerations for materially deprived neighborhoods to serve the aging sexual minority people residing in such areas.

A multivariate analysis of age-related differences in default mode and task-positive networks across multiple cognitive domains.

We explored the effects of aging on 2 large-scale brain networks, the default mode network (DMN) and the task-positive network (TPN). During functional magnetic resonance imaging scanning, young and older participants carried out 4 visual tasks: detection, perceptual matching, attentional cueing, and working memory. Accuracy of performance was roughly matched at 80% across tasks and groups. Modulations of activity across conditions were assessed, as well as functional connectivity of both networks. Younger adults showed a broader engagement of the DMN and older adults a more extensive engagement of the TPN. Functional connectivity in the DMN was reduced in older adults, whereas the main pattern of TPN connectivity was equivalent in the 2 groups. Age-specific connectivity also was seen in TPN regions. Increased activity in TPN areas predicted worse accuracy on the tasks, but greater expression of a connectivity pattern associated with a right dorsolateral prefrontal TPN region, seen only in older adults, predicted better performance. These results provide further evidence for age-related differences in the DMN and new evidence of age differences in the TPN. Increased use of the TPN may reflect greater demand on cognitive control processes in older individuals that may be partially offset by alterations in prefrontal functional connectivity.