Age Prediction Using Resting-State Functional MRI.

The increasing lifespan and large individual differences in cognitive capability highlight the importance of comprehending the aging process of the brain. Contrary to visible signs of bodily ageing, like greying of hair and loss of muscle mass, the internal changes that occur within our brains remain less apparent until they impair function. Brain age, distinct from chronological age, reflects our brain's health status and may deviate from our actual chronological age. Notably, brain age has been associated with mortality and depression. The brain is plastic and can compensate even for severe structural damage by rewiring. Functional characterization offers insights that structural cannot provide. Contrary to the multitude of studies relying on structural magnetic resonance imaging (MRI), we utilize resting-state functional MRI (rsfMRI). We also address the issue of inclusion of subjects with abnormal brain ageing through outlier removal. In this study, we employ the Least Absolute Shrinkage and Selection Operator (LASSO) to identify the 39 most predictive correlations derived from the rsfMRI data. The data is from a cohort of 176 healthy right-handed volunteers, aged 18-78 years (95/81 male/female, mean age 48, SD 17) collected at the Mind Research Imaging Center at the National Cheng Kung University. We establish a normal reference model by excluding 68 outliers, which achieves a leave-one-out mean absolute error of 2.48 years. By asking which additional features that are needed to predict the chronological age of the outliers with a smaller error, we identify correlations predictive of abnormal aging. These are associated with the Default Mode Network (DMN). Our normal reference model has the lowest prediction error among published models evaluated on adult subjects of almost all ages and is thus a candidate for screening for abnormal brain aging that has not yet manifested in cognitive decline. This study advances our ability to predict brain aging and provides insights into potential biomarkers for assessing brain age, suggesting that the role of DMN in brain aging should be studied further.

The effect of age and resilience on the dose-response function between the number of adversity factors and subjective well-being.

Background: Encountering challenges and stress heightens the vulnerability to mental disorders and diminishes well-being. This study explores the impact of psychological resilience in the context of adverse events, considering age-related variations in its influence on well-being. Methods: A total of 442 participants (male vs. female =48% vs. 52%) with a mean age of 41.79 ± 16.99 years were collected and completed the following questionnaires Brief Betrayal Trauma Survey (BBTS), Brief Resilience Scale (BRS), Peace of Mind (PoM), The World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Social Support Questionnaire (SSQ). They all underwent structural and resting-state functional magnetic resonance imaging (MRI) scans. Results: Participants were categorized based on adversity levels: 34.39% faced one, 26.24% none, and 19.91, 9.50, and 8.14% encountered two, three, and four adversities, respectively. This categorization helps assess the impact on participants' experiences. As adversity factors increased, PoM decreased. Controlling for age improved PoM model fit (ΔR2 = 0.123, p < 0.001). Adversity factors and age explained 14.6% of PoM variance (df = 2, F = 37.638, p < 0.001). PoM decreased with more adversity and increased with higher age. Conclusion: The study found most participants faced at least one adversity. Adversity negatively affected PoM scores, while resilience acted as a protective factor. Resilience plays a crucial role in buffering the impact of adversities on well-being. Among those with high adversity, higher resilience correlated with stronger DMN-right frontal pole connectivity. Brain volume showed no significant differences, but the quality of life and social support varied between subgroups, with no differences in personal demographic and biophysical features.

The role of attitudes towards contradiction in psychological resilience: the cortical mechanism of conflicting resolution networks.

Managing contradictions and building resilience help us overcome life's challenges. Here, we explored the link between attitudes towards contradictions and psychological resilience, examining the role of cortical conflict resolution networks. We enlisted 173 healthy young adults and used questionnaires to evaluate their cognitive thinking styles and resilience. They underwent structural and functional magnetic resonance imaging scans. Our results revealed that contrasting attitudes toward contradictions, formal logic, and naïve dialecticism thinking styles corresponded with varying degrees of resilience. We noted structural and functional differences in brain networks related to conflict resolution, including the inferior frontal and parietal cortices. The volumetric variations within cortical networks indicated right-hemispheric lateralization in different thinking styles. These findings highlight the potential links between conflict resolution and resilience in the frontoparietal network. We underscore the importance of frontoparietal brain networks for executive control in resolving conflicting information and regulating the impact of contradictions on psychological resilience.

Mediating role of resilience in the relationships of physical activity and mindful self-awareness with peace of mind among college students.

Peace of mind (PoM) is an index of mental health in Asian culture and emphasizes low arousal, happiness, harmony, and an internal state of peacefulness. While previous studies have found that mindful self-awareness can contribute to PoM, regular physical activity (PA) is also an important factor contributing to one's PoM due to its function in promoting one's resilience. The study aims to investigate a hypothetical model that assumes PA is associated with resilience while controlling for mindful self-awareness, contributing to PoM. The PoM scale, Connor-Davidson Resilience Scale, Chinese translation of Mindful Attention Awareness Scale, and PA self-report questionnaire were used. A path analysis was applied to test the association between these variables and the mediating role of resilience. A total of 436 students from a university in Taiwan were recruited; the mean age was 20.87, with 46.3% female and 73.6% engaging in over 150 min/week of moderate PA. Gender and age negatively correlated with PA. After controlling for age and gender, there was no direct effect of physical activity on PoM; both mindful self-awareness and PA predict resilience, which in turn predicts PoM, suggesting that both cognitive (i.e., mindful self-awareness) and PA are important to cultivate resilience and thus PoM.

Specific but not general declines in attention and executive function with aging: Converging cross-sectional and longitudinal evidence across the adult lifespan.

Objective: Attention and executive function (EF) are vulnerable to aging. However, whether all these functions generally decline with aging is not known. Furthermore, most evidence is based on cross-sectional data and fewer follow-up data are available in the literature. Longitudinal follow-up studies are necessary to characterize individualized and precise changes in cognitive function. Additionally, relatively few aging studies have included middle-aged adults to examine age-related differences in attention and EF. Therefore, this study aims to examine whether general or specific attention and EF decline with aging from adulthood to old age by combining cross-sectional and longitudinal follow-up approaches. Methods: This study recruited 253 participants aged 20 to 78 years. passing a prescreening procedure (see main text for detail) for the baseline session, and 123 of them were invited to return 1 ~ 2 years after their first visit to participate in the follow-up session. The participants completed a series of attention and EF tasks at both the baseline and follow-up sessions, which measured alerting, orienting, conflict control, stopping, memory updating, and switching abilities. We applied linear and nonlinear regression models to evaluate the cross-sectional age effect on attention and EF and employed a modified Brinley plot to inspect follow-up performance against baseline in attention and EF. Results: The results of cross-sectional data showed that older adults exhibited decreased efficiency in alerting, stopping, and memory updating but paradoxically increased efficiency in conflict control and switching abilities and no changes in orienting efficiency with age. However, the results of longitudinal data showed that only alerting and memory updating continued to show decreased efficiency. Furthermore, conflict control and switching showed increased efficiency with aging, whereas the orienting network, and stopping no longer showed decreased efficiency. Conclusion: Thus, converging the cross-sectional and longitudinal data showed that the alerting and memory updating function exhibited the most robust deficit with age (cross-sectional) and aging (longitudinal). Alerting and memory updating abilities are crucial survival skills for human beings. Therefore, developing methods to prevent and improve an individual's alertness and working memory ability is an important practical issue in aging research.

Social support enhances the mediating effect of psychological resilience on the relationship between life satisfaction and depressive symptom severity.

Psychosocial factors, including life satisfaction, resilience, and social support, have been proposed to influence depressive symptom severity in adults because the age of onset of depressive disorders, i.e. adolescence to early adulthood, is associated with various impairments in psychosocial functioning. In this study, a psychosocial model was constructed to verify these relationships to prevent depression. For this study, 370 participants were recruited from the community via poster or online advertisements. They completed several questionnaires to assess depressive symptom severity: the Connor-Davidson Resilience Scale (CD-RISC), Satisfaction with Life Scale (SwLS), Peace of Mind (PoM) scale, Social Support Questionnaire (SSQ), and Beck Depression Inventory (BDI-II). A negative association was found between depressive symptom severity and all other variables, including PoM and CD-RISC scores, life satisfaction, and social support. Such factors can be considered protective against increased depressive symptom severity. In addition, indirect effects of PoM and resilience on the negative association between SwLS scores and depressive symptom severity were observed. Moreover, social support was found to mediate the correlation between PoM and resilience, implying that social support mediates the relationship between state of mind and resilience. The psychosocial model suggested that depressive symptom severity is influenced by internal factors (an individual's state of mind, subjective view of events and their life) and external factors (including social support).

The Mediating Role of Brain Structural Imaging Markers in Connecting Adverse Childhood Experiences and Psychological Resilience.

The impact of adverse childhood experiences (ACEs) on brain structure has been noticed. Resilience has been considered a protective characteristic from being mentally ill; however, the link between ACEs, psychological resilience, and brain imaging remains untested. A total of 108 participants (mean age 22.92 ± 2.43 years) completed the ACEs questionnaire and the Resilience Scale for Adults (RSA), with five subscales: personal strength (RSA_ps), family cohesion (RSA_fc), social resources (RSA_sr), social competence (RSA_sc), and future structured style (RSA_fss), and Magnetic Resonance Imaging (MRI) to acquire imaging data, and the fusion-independent component analysis was employed to determine multimodal imaging components. The results showed a significantly negative association between ACE subscales and RSA_total score (ps < 0.05). The parallel mediation model showed significant indirect mediation of mean gray matter volumes in the regions of the middle frontal gyrus, superior frontal gyrus, posterior cingulate, superior temporal gyrus, middle temporal gyrus, postcentral gyrus, middle temporal gyrus, and precuneus between childhood maltreatment and RSA_sr and RSA_sc. (ps < 0.05). This study highlighted the ACEs effect on gray matter volumes in the regions of the middle frontal gyrus, superior frontal gyrus, posterior cingulate, superior temporal gyrus, middle temporal gyrus, postcentral gyrus, middle temporal gyrus, and precuneus leading to decreased psychological resilience.

The effect of age on task switching: updated and extended meta-analyses.

Cognitive flexibility is one of the crucial abilities for human survival. As people get older, whether their flexibility ability will be affected is one of the core research topics in aging research. Researchers have developed a task-switch paradigm in laboratories to mimic daily-life shifting task-set scenarios. However, the empirical evidence is equivocal. Considering every single study may have a biased sample; therefore, we hoped to combine smaller studies, making them into one extensive investigation, which may help show an actual effect. In the current study, we used two meta-analysis techniques, the Brinley plot (along with the State-trace plot) and conventional meta-analysis, to re-evaluate whether healthy aging influences cognitive flexibility. The results of the Brinley plot analysis showed no evidence of switch-specific age-related impairment as indexed by the local switch cost. Yet, older adults performed more slowly than younger adults across task conditions. The conventional meta-analysis further showed that the currently available findings were heterogenous and exhibited publication bias. Therefore, this study suggests that researchers should interpret their results cautiously while using a task-switching paradigm to address older adults' shifting abilities. More parametric variables must be considered and developed in a task-switching paradigm to enhance its sensitivity and reveal older adults' actual shifting ability.

DNA methylation signature aberration as potential biomarkers in treatment-resistant schizophrenia: Constructing a methylation risk score using a machine learning method.

Treatment-resistant schizophrenia (TRS) is defined as a non-response to at least two trials of antipsychotic medication with an adequate dose and duration. We aimed to evaluate the discriminant abilities of DNA methylation probes and methylation risk score between treatment-resistant schizophrenia and non-treatment-resistant schizophrenia. This study recruited 96 schizophrenia patients (TRS and non-TRS) and 56 healthy controls (HC). Participants were divided into a discovery set and a validation set. In the discovery set, we conducted genome-wide methylation analysis (human MethylationEPIC 850K BeadChip) on the subject's blood DNA and discriminated significant methylation signatures, then verified these methylation signatures in the validation set. Based on genome-wide scans of TRS versus non-TRS, thirteen differentially methylated probes were identified at FDR <0.05 and >20% differences in DNA methylation ß-values. Next, we selected six probes within gene coding regions (LOC404266, LOXL2, CERK, CHMP7, and SLC17A9) to conduct verification in the validation set using quantitative methylation-specific PCR (qMSP). These six methylation probes showed satisfactory discrimination between TRS patients and non-TRS patients, with an AUC ranging from 0.83 to 0.92, accuracy ranging from 77.8% to 87.3%, sensitivity ranging from 80% to 90%, and specificity ranging from 65.6% to 85%. This methylation risk score model showed satisfactory discrimination between TRS patients and non-TRS patients, with an accuracy of 88.3%. These findings support that methylation signatures may be used as an indicator of TRS vulnerability and provide a model for the clinical use of methylation to identify TRS.

Age differences in the functional organization of the prefrontal cortex: analyses of competing hypotheses.

We employed a mixed design task for block and event-related functional magnetic resonance imaging with manipulations of levels of abstraction and duration in task-relevant cues and probes. Age-related differences between younger and older adults in task-related functional brain activity patterns of the prefrontal cortex (PFC) were reported. The results showed that (1) the low episodic condition evoked more activity in the more anterior PFC than the high episodic control condition for both age groups; (2) the low abstraction condition evoked more activity in the more anterior PFC than the high abstraction condition for both age groups; and (3) the signal change did not vary as a function of activity dynamics (transient and sustained responses) and maintenance duration (single-trial and multiple-trial). The findings showed that baseline conditions evoked more activity in the more anterior PFC for the older group than the younger group across most task contrasts and conditions, where these additional activities in the brain regions overlapped within the default mode network (DMN). We tentatively concluded that deficiency in the anterior DMN deactivation during externally driven tasks might be attributed to less efficiency in modulating local connectivity propagate to surrounding tissue, which may paradoxically increase brain activity.

Potential Diffusion Tensor Imaging Biomarkers for Elucidating Intra-Individual Age-Related Changes in Cognitive Control and Processing Speed.

Cognitive aging, especially cognitive control, and processing speed aging have been well-documented in the literature. Most of the evidence was reported based on cross-sectional data, in which inter-individual age effects were shown. However, there have been some studies pointing out the possibility of overlooking intra-individual changes in cognitive aging. To systematically examine whether age-related differences and age-related changes might yield distinctive patterns, this study directly compared cognitive control function and processing speed between different cohorts versus follow-up changes across the adult lifespan. Moreover, considering that cognitive aging has been attributed to brain disconnection in white matter (WM) integrity, this study focused on WM integrity via acquiring diffusion-weighted imaging data with an MRI instrument that are further fitted to a diffusion tensor model (i.e., DTI) to detect water diffusion directionality (i.e., fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity, AxD). Following data preprocessing, 114 participants remained for further analyses in which they completed the two follow-up sessions (with a range of 1-2 years) containing a series of neuropsychology instruments and computerized cognitive control tasks. The results show that many significant correlations between age and cognitive control functions originally shown on cross-sectional data no longer exist on the longitudinal data. The current longitudinal data show that MD, RD, and AxD (especially in the association fibers of anterior thalamic radiation) are more strongly correlated to follow-up aging processes, suggesting that axonal/myelin damage is a more robust phenomenon for observing intra-individual aging processes. Moreover, processing speed appears to be the most prominent cognitive function to reflect DTI-related age (cross-sectional) and aging (longitudinal) effects. Finally, converging the results from regression analyses and mediation models, MD, RD, and AxD appear to be the representative DTI measures to reveal age-related changes in processing speed. To conclude, the current results provide new insights to which indicator of WM integrity and which type of cognitive changes are most representative (i.e., potentially to be neuroimaging biomarkers) to reflect intra-individual cognitive aging processes.

Age-related post-error slowing and stimulus repetition effect in motor inhibition during a stop-signal task.

This study aims to investigate how older adults react to a failed-inhibition error while performing a stop-signal task. That is, whether elderly people would exhibit enlarged post-error slowing and whether such slowing revealed an adaptive process, maladaptive process, or a mixture of maladaptive followed by adaptive processes. This study also addresses if the post-error process might further interact with a stimulus repetition effect based on the memory retrieval explanation. A group of 34 younger adults (age range 20-30 years) and a group of 34 older adults (age range 60-80 years) were included for the analyses. The results of the current study supported a mixture model by showing that older adults exhibited a larger post-error slowing than younger adults, and their post-error slowing was initially accompanied by deceased accuracy that then increased on the subsequent trial. Furthermore, such post-error slowing on older adults only occurred in the trial condition where the stimulus was repeated from the previous trial suggesting a memory-based process (a form of negative priming) involved in post-error processes. The implication of the current finding is that older adults might maintain the ability to detect and monitor the response error, yet their post-error adjustment might require a much longer time to start functioning well after the initial detrimental orienting response to the error and the entire process was memory-based.

Age Differences of the Hierarchical Cognitive Control and the Frontal Rostro-Caudal Functional Brain Activation.

Age-related differences in the functional hierarchical organization of the frontal lobe remain unclear. We adopted task-related functional magnetic resonance imaging (fMRI) to investigate age differences in the functional hierarchical organization of the frontal lobe. Behavioral results report both reaction time and efficiency declined as the levels of abstraction increased in the selection of a set of stimulus-response mappings in older adults compared with young adults. fMRI findings suggest trends of the hierarchical organization along the rostro-caudal axis in both groups, and brain-behavior correlation further suggests neural dedifferentiation in older adults when performing at the highest level of control demands experiment. Behavioral performances and age difference overactivations at the highest level of control demands were both associated with working memory capacity, suggesting the working memory capacity is important for processing the highest task demands. Region-of-interest analysis revealed age differences in brain overactivation and common activation across experiments in the primary motor cortex, parietal lobule, and the fusiform gyrus may serve as shared mechanisms underlying tasks that are required for the selection of stimulus-response mapping sets. Overall, older adults reflect maladaptive overactivation in task-irrelevant regions that are detrimental to performance with the highest control demands.

DNA methylation signature of psychological resilience in young adults: Constructing a methylation risk score using a machine learning method.

Resilience is a process associated with the ability to recover from stress and adversity. We aimed to explore the resilience-associated DNA methylation signatures and evaluate the abilities of methylation risk scores to discriminate low resilience (LR) individuals. The study recruited 78 young adults and used Connor-Davidson Resilience Scale (CD-RISC) to divide them into low and high resilience groups. We randomly allocated all participants of two groups to the discovery and validation sets. We used the blood DNA of the subjects to conduct a genome-wide methylation scan and identify the significant methylation differences of CpG Sites in the discovery set. Moreover, the classification accuracy of the DNA methylation probes was confirmed in the validation set by real-time quantitative methylation-specific polymerase chain reaction. In the genome-wide methylation profiling between LR and HR individuals, seventeen significantly differentially methylated probes were detected. In the validation set, nine DNA methylation signatures within gene coding regions were selected for verification. Finally, three methylation probes [cg18565204 (AARS), cg17682313 (FBXW7), and cg07167608 (LINC01107)] were included in the final model of the methylation risk score for LR versus HR. These methylation risk score models of low resilience demonstrated satisfactory discrimination by logistic regression and support vector machine, with an AUC of 0.81 and 0.93, accuracy of 72.3% and 87.1%, sensitivity of 75%, and 87.5%, and specificity of 70% and 80%. Our findings suggest that methylation signatures can be utilized to identify individuals with LR and establish risk score models that may contribute to the field of psychology.

Two-Year Follow-Up Study of the Relationship Between Brain Structure and Cognitive Control Function Across the Adult Lifespan.

Age-related decline in cognitive control and general slowing are prominent phenomena in aging research. These declines in cognitive functions have been shown to also involve age-related decline in brain structure. However, most evidence in support of these associations is based on cross-sectional data. Therefore, the aim of this study is to contrast cross-sectional and longitudinal analyses to re-examine if the relationship between age-related brain structure and cognitive function are similar between the two approaches. One hundred and two participants completed two sessions with an average interval of 2 years. All participants were assessed by questionnaires, a series of cognitive tasks, and they all underwent neuroimaging acquisition. The main results of this study show that the majority of the conclusions regarding age effect in cognitive control function and processing speed in the literature can be replicated based on the cross-sectional data. Conversely, when we followed up individuals over an average interval of 2 years, then we found much fewer significant relationships between age-related change in gray matter structure of the cognitive control network and age-related change in cognitive control function. Furthermore, there was no "initial age" effect in the relationships between age-related changes in brain structure and cognitive function. This finding suggests that the "aging" relationship between brain structure and cognitive function over a short period of time are independent of "initial age" difference at time point 1. The result of this study warrants the importance of longitudinal research for aging studies to elucidate actual aging processes on cognitive control function.

Young Adults View Smartphone Tracking Technologies for COVID-19 as Acceptable: The Case of Taiwan.

Taiwan has been successful in controlling the spread of SARS-CoV-2 during the COVID-19 pandemic; however, without a vaccine the threat of a second outbreak remains. Young adults who show few to no symptoms when infected have been identified in many countries as driving the virus' spread through unidentifiable community transmission. Mobile tracking technologies register nearby contacts of a user and notifies them if one later tests positive to the virus, potentially solving this issue; however, the effectiveness of these technologies depends on their acceptance by the public. The current study assessed attitudes towards three tracking technologies (telecommunication network tracking, a government app, and Apple and Google's Bluetooth exposure notification system) among four samples of young Taiwanese adults (aged 25 years or younger). Using Bayesian methods, we find high acceptance for all three tracking technologies (>75%), with acceptance for each technology surpassing 90% if additional privacy measures were included. We consider the policy implications of these results for Taiwan and similar cultures.

Multimodal Imaging Analysis Reveals Frontal-Associated Networks in Relation to Individual Resilience Strength.

Psychological resilience is regarded as a critical protective factor for preventing the development of mental illness from experienced adverse events. Personal strength is one key element of resilience that reflects an individual's reactions to negative life events and is crucial for successful adaptation. Previous studies have linked unimodal imaging measures with resilience. However, applying multimodal imaging measures could provide comprehensive organization information at the system level to examine whether an individual's resilience strength is reflected in the brain's structural and functional network. In this study, MRI was used to acquire multimodal imaging properties and subscales of personal strength in terms of resilience from 109 participants (48 females and 61 males). We employed a method of fusion independent component analysis to link the association between multimodal imaging components and personal strength of psychological resilience. The results reveal that a fusion component involving multimodal frontal networks in connecting with the parietal, occipital, and temporal regions is associated with the resilience score for personal strength. A multiple regression model further explains the predictive role of frontal-associated regions that cover a visual-related network regulating cognition and emotion to discern the perceived adverse experience. Overall, this study suggests that frontal-associated regions are related to individual resilience strength.

Adverse Childhood Experiences Are Associated with Reduced Psychological Resilience in Youth: A Systematic Review and Meta-Analysis.

BACKGROUND: Adverse childhood experiences (ACEs) are presumed to influence internalizing and externalizing behaviors that can significantly debilitate long-term biopsychological development in individuals. Psychological resilience has been shown to effectively mediate the relationship between ACEs and negative health outcomes since individuals with low levels of resilience may have difficulty with bouncing back from toxic exposure to ACEs. Thus, the present systematic review and meta-analysis was aimed toward synthesizing current knowledge of the relationship between ACEs and psychological resilience in youths. METHODS: A combination of key words relevant to the present study was searched on the PubMed, EMBASE, Scopus, Cochrane, and Google Scholar databases. The results were restricted to English publications and human studies, with subjects ranging between the age of 0 to 35 years. Effect-size measures inclusive of pooled correlation coefficients for correlation analyses and pooled odds ratios for regression analyses, respectively, were calculated using random-effect models to determine the relationship between ACEs and psychological resilience. RESULTS: The searches identified 85 potentially relevant studies. Among them, 76 were excluded due to limited access, irrelevant data, and the fact that the variables of interest were not explicitly measured or disclosed, leaving a final total of nine studies considered valid for the meta-analysis. Findings from correlational meta-analysis (n = 6) revealed a significantly negative association between ACEs and resilience (ß = -0.120 [-0.196, -0.043]). The meta-analysis of the studies (n = 3) reporting dichotomous outcomes (ACE ≥ 1 vs. no ACE) indicated that subjects who experienced an ACE were 63% less likely to display high resilience, in comparison to subjects without such experiences. CONCLUSION: Our results support a negative association between ACEs and psychological resilience and highlight the multiple dimensions that constitute resilience in an ACE-exposure context. These findings may be particularly useful to policy makers and healthcare institutions in terms of helping them devise effective medical interventions and community outreach programs intended to develop resilience in youths, thus reducing health-risk behaviors and negative health outcomes.