Early cortical microstructural changes in aging are linked to vulnerability to Alzheimer's disease pathology.

BACKGROUND: Early identification of Alzheimer's disease (AD) risk is critical for improving treatment success. Cortical thickness is a macrostructural measure used to assess AD neurodegeneration. However, cortical microstructural changes appear to precede macrostructural atrophy and may improve early risk identification. Currently, whether cortical microstructural changes in aging are linked to vulnerability to AD pathophysiology remains unclear in non-clinical populations, who are precisely the target for early risk identification. METHODS: In 194 adults, we calculated MRI-derived maps of changes in cortical mean diffusivity (microstructure) and cortical thickness (macrostructure) over 5-6 years (meanage: Time1=61.82; Time2=67.48). Episodic memory was assessed using three well-established tests. We obtained PET-derived maps of AD pathology deposition (beta-amyloid, tau) and neurotransmitter receptors (cholinergic, glutamatergic) implicated in AD pathophysiology. Spatial correlational analyses were used to compare pattern similarity among maps. RESULTS: Spatial patterns of cortical macrostructural changes resembled patterns of cortical organization sensitive to age-related processes (r=-0.31, p<0.05), whereas microstructural changes resembled the patterns of tau (r=0.39, p=0.015) deposition in AD. Individuals with patterns of microstructural changes that more closely resembled stereotypical tau deposition exhibited greater memory decline (ß=0.21, p=0.036). Microstructural changes and AD pathology deposition were enriched in areas with greater densities of cholinergic and glutamatergic receptors (ps<0.05). CONCLUSIONS: Patterns of cortical microstructural changes were more AD-like than patterns of macrostructural changes, which appeared to reflect more general aging processes. Microstructural changes may better inform early risk prediction efforts as a sensitive measure of vulnerability to pathological processes prior to overt atrophy and cognitive decline.

Health Neuroscience-How the Brain/Mind and Body Affect our Health Behavior and Outcomes.

This Opinion piece discusses several key research questions in health neuroscience, a new interdisciplinary field that investigates how the brain and body interact to affect our health behavior such as health mindsets, decision-making, actions, and health outcomes across the lifespan. To achieve physical, mental, and cognitive health, and promote health behavior change, we propose that the prevention and treatment of diseases should target the root causes-the dysfunction and imbalance of brain-body biomarkers, through evidence-based body-mind interventions such as mindfulness meditation and Tai Chi, rather than dealing with each symptom or disorder in isolation through various treatment approaches.

Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men.

BACKGROUND: Plasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations. METHODS: We examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61-73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter. RESULTS: After adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals. CONCLUSIONS: These results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

On the psychometric evaluation of cognitive control tasks: An Investigation with the Dual Mechanisms of Cognitive Control (DMCC) battery.

The domain of cognitive control has been a major focus of experimental, neuroscience, and individual differences research. Currently, however, no theory of cognitive control successfully unifies both experimental and individual differences findings. Some perspectives deny that there even exists a unified psychometric cognitive control construct to be measured at all. These shortcomings of the current literature may reflect the fact that current cognitive control paradigms are optimized for the detection of within-subject experimental effects rather than individual differences. In the current study, we examine the psychometric properties of the Dual Mechanisms of Cognitive Control (DMCC) task battery, which was designed in accordance with a theoretical framework that postulates common sources of within-subject and individual differences variation. We evaluated both internal consistency and test-retest reliability, and for the latter, utilized both classical test theory measures (i.e., split-half methods, intraclass correlation) and newer hierarchical Bayesian estimation of generative models. Although traditional psychometric measures suggested poor reliability, the hierarchical Bayesian models indicated a different pattern, with good to excellent test-retest reliability in almost all tasks and conditions examined. Moreover, within-task, between-condition correlations were generally increased when using the Bayesian model-derived estimates, and these higher correlations appeared to be directly linked to the higher reliability of the measures. In contrast, between-task correlations remained low regardless of theoretical manipulations or estimation approach. Together, these findings highlight the advantages of Bayesian estimation methods, while also pointing to the important role of reliability in the search for a unified theory of cognitive control.

Childhood Disadvantage Moderates Late Midlife Default Mode Network Cortical Microstructure and Visual Memory Association.

BACKGROUND: Childhood disadvantage is a prominent risk factor for cognitive and brain aging. Childhood disadvantage is associated with poorer episodic memory in late midlife and functional and structural brain abnormalities in the default mode network (DMN). Although age-related changes in DMN are associated with episodic memory declines in older adults, it remains unclear if childhood disadvantage has an enduring impact on this later-life brain-cognition relationship earlier in the aging process. Here, within the DMN, we examined whether its cortical microstructural integrity-an early marker of structural vulnerability that increases the risk for future cognitive decline and neurodegeneration-is associated with episodic memory in adults at ages 56-66, and whether childhood disadvantage moderates this association. METHODS: Cortical mean diffusivity (MD) obtained from diffusion magnetic resonance imaging was used to measure microstructural integrity in 350 community-dwelling men. We examined both visual and verbal episodic memory in relation to DMN MD and divided participants into disadvantaged and nondisadvantaged groups based on parental education and occupation. RESULTS: Higher DMN MD was associated with poorer visual memory but not verbal memory (ß = -0.11, p = .040 vs ß = -0.04, p = .535). This association was moderated by childhood disadvantage and was significant only in the disadvantaged group (ß = -0.26, p = .002 vs ß = -0.00, p = .957). CONCLUSIONS: Lower DMN cortical microstructural integrity may reflect visual memory vulnerability in cognitively normal adults earlier in the aging process. Individuals who experienced childhood disadvantage manifested greater vulnerability to cortical microstructure-related visual memory dysfunction than their nondisadvantaged counterparts who exhibited resilience in the face of low cortical microstructural integrity.

The Dual Mechanisms of Cognitive Control (DMCC) project: Validation of an online behavioural task battery.

Cognitive control serves a crucial role in human higher mental functions. The Dual Mechanisms of Control theoretical framework provides a unifying account that decomposes cognitive control into two qualitatively distinct mechanisms-proactive control and reactive control. Here, we describe the Dual Mechanisms of Cognitive Control (DMCC) task battery, which was developed to probe cognitive control modes in a theoretically targeted manner, along with detailed descriptions of the experimental manipulations used to encourage shifts to proactive or reactive mode in each of four prototypical domains of cognition: selective attention, context processing, multitasking, and working memory. We present results from this task battery, conducted from a large (N > 100), online sample that rigorously evaluates the group effects of these manipulations in primary indices of proactive and reactive control, establishing the validity of the battery in providing dissociable yet convergent measures of the two cognitive control modes. The DMCC battery may be a useful tool for the research community to examine cognitive control in a theoretically targeted manner across different individuals and groups.

Longitudinal association of executive function and structural network controllability in the aging brain.

Executive function encompasses effortful cognitive processes that are particularly susceptible to aging. Functional brain networks supporting executive function-such as the frontoparietal control network and the multiple demand system-have been extensively investigated. However, it remains unclear how structural networks facilitate and constrain the dynamics of functional networks to contribute to aging-related executive function declines. We examined whether changes in structural network modal controllability-a network's ability to facilitate effortful brain state transitions that support cognitive functions-are associated with changes in executive function cross-sectionally and longitudinally. Diffusion-weighted imaging and neuropsychological testing were conducted at two time points (Time 1: ages 56 to 66, N = 172; Time 2: ages 61 to 70, N = 267) in community-dwelling men from the Vietnam Era Twin Study of Aging. An executive function factor score was computed from six neuropsychological tasks. Structural networks constructed from white matter connectivity were used to estimate modal controllability in control network and multiple demand system. We showed that higher modal controllability in control network and multiple demand system was associated with better executive function at Time 2, after controlling for age, young adult general cognitive ability, and physical health status. Moreover, changes in executive function over a period of 5 to 6 years (Time 1-Time 2, N = 105) were associated with changes in modal controllability of the multiple demand system and weakly in the control network over the same time period. These findings suggest that changes in the ability of structural brain networks in facilitating effortful brain state transitions may be a key neural mechanism underlying aging-related executive function declines and cognitive aging.

Association of neurofilament light chain with renal function: mechanisms and clinical implications.

BACKGROUND: Blood-based neurofilament light chain (NfL) is a promising biomarker of neurodegeneration across multiple neurodegenerative diseases. However, blood-based NfL is highly associated with renal function in older adults, which leads to the concern that blood-based NfL levels may be influenced by renal function, rather than neurodegeneration alone. Despite growing interest in using blood-based NfL as a biomarker of neurodegeneration in research and clinical practices, whether renal function should always be accounted for in these settings remains unclear. Moreover, the mechanisms underlying this association between blood-based measures of NfL and renal function remain elusive. In this study, we first evaluated the effect of renal function on the associations of plasma NfL with other measures of neurodegeneration. We then examined the extent of genetic and environmental contributions to the association between plasma NfL and renal function. METHODS: In a sample of 393 adults (mean age=75.22 years, range=54-90), we examined the associations of plasma NfL with cerebrospinal fluid (CSF) NfL and brain volumetric measures before and after adjusting for levels of serum creatinine (an index of renal function). In an independent sample of 969 men (mean age=67.57 years, range=61-73) that include monozygotic and dizygotic twin pairs, we replicated the same analyses and leveraged biometrical twin modeling to examine the genetic and environmental influences on the plasma NfL and creatinine association. RESULTS: Plasma NfL's associations with cerebrospinal fluid NfL and brain volumetric measures did not meaningfully change after adjusting for creatinine levels. Both plasma NfL and creatinine were significantly heritable (h2=0.54 and 0.60, respectively). Their phenotypic correlation (r=0.38) was moderately explained by shared genetic influences (genetic correlation=0.46) and unique environmental influences (unique environmental correlation=0.27). CONCLUSIONS: Adjusting for renal function is unnecessary when assessing associations between plasma NfL and other measures of neurodegeneration but is necessary if plasma NfL is compared to a cutoff for classifying neurodegeneration-positive versus neurodegeneration-negative individuals. Blood-based measures of NfL and renal function are heritable and share common genetic influences.

Effortless training of attention and self-control: mechanisms and applications.

For the past 50 years, cognitive scientists have assumed that training attention and self-control must be effortful. However, growing evidence suggests promising effects of effortless training approaches such as nature exposure, flow experience, and effortless practice on attention and self-control. This opinion article focuses on effortless training of attention and self-control. We begin by introducing our definitions of effortful and effortless training and reviewing the growing literature on these two different forms of training. We then discuss the similarities and differences in their respective behavioral outcomes and neural correlates. Finally, we propose a putative neural mechanism of effortless training. We conclude by highlighting promising directions for research, development, and application of effortless training.

Efficiency moderates the relationship between sleep-onset insomnia and resting-state electroencephalogram microstate.

BACKGROUND: Overactivation of the salience network (SN) causes hyperarousal in insomnia patients and is associated with sleep-onset insomnia (SOI). Resting-state microstate 3 (RS-MS3) duration is closely related to SN overactivation. However, whether RS-MS3 duration is a biomarker for SOI has not yet been reported in the literature. In addition, SN activity is also associated with efficiency. However, it is not clear whether there are individual differences in the neural mechanisms of SOI in different efficiency groups. METHODS: Considering that RS-MS3 duration characterizes the stability and persistent activation of the SN in the resting state, the current study investigated the link between SOI measured by sleep latency of Pittsburg Sleep Quality Index (PSQI), efficiency measured by Kirton Adaption-Innovation Inventory (KAI), and RS-MS3 in a Chinese healthy (subclinical) student population, using electroencephalography (EEG) microstate analysis. RESULTS: We found that RS-MS3 duration was positively correlated with sleep latency and efficiency. The interaction between sleep latency and efficiency was significant. Simple slope analysis showed that high sleep latency was positively correlated with longer RS-MS3 duration in participants with higher efficiency scores. This correlation did not exist in participants with low efficiency scores. CONCLUSIONS: RS-MS3 duration may serve as a biomarker for SOI. There is heterogeneity in the relationship between SOI and RS-MS3 duration between individuals with high and low efficiency.

The Dual Mechanisms of Cognitive Control dataset, a theoretically-guided within-subject task fMRI battery.

Cognitive control is a critical higher mental function, which is subject to considerable individual variation, and is impaired in a range of mental health disorders. We describe here the initial release of Dual Mechanisms of Cognitive Control (DMCC) project data, the DMCC55B dataset, with 55 healthy unrelated young adult participants. Each participant performed four well-established cognitive control tasks (AX-CPT, Cued Task-Switching, Sternberg Working Memory, and Stroop) while undergoing functional MRI scanning. The dataset includes a range of state and trait self-report questionnaires, as well as behavioural tasks assessing individual differences in cognitive ability. The DMCC project is on-going and features additional components (e.g., related participants, manipulations of cognitive control mode, resting state fMRI, longitudinal testing) that will be publicly released following study completion. This DMCC55B subset is released early with the aim of encouraging wider use and greater benefit to the scientific community. The DMCC55B dataset is suitable for benchmarking and methods exploration, as well as analyses of task performance and individual differences.

Investigating mindfulness influences on cognitive function: On the promise and potential of converging research strategies.

Research investigating the effects and underlying mechanisms of mindfulness on cognitive functioning has accelerated exponentially over the past two decades. Despite the rapid growth of the literature and its influential role in garnering public interest in mindfulness, inconsistent methods in defining and measuring mindfulness have yielded variable findings, which contribute to the overall dearth of clear generalizable conclusions. The focus of this article is to address the lack of cohesion in the collective methodologies used in this domain by providing a new perspective grounded in classic cognitive and experimental psychology principles. We leverage the concept of converging operations to demonstrate how seemingly disparate research strategies can be integrated towards a more unified and systematic approach. An organizing taxonomic framework is described to provide useful structure in how mindfulness can be operationalized, measured, and investigated. We illustrate the rationale and core organizing principles of the framework through a selective review of studies on mindfulness and cognitive control. We then demonstrate the utility of the approach by showing how it can be applied to synthesize extant methodologies and guide the development of future research. Specific suggestions and examples pertaining to experimental design and statistical analysis are provided.

A College First-Year Mindfulness Seminar to Enhance Psychological Well-Being and Cognitive Function.

Mindfulness training (MT) has shown promise in improving psychological health among college students, yet has rarely been evaluated as an addition to the college academic curriculum. Here, we demonstrate the feasibility and effectiveness of a first-year MT seminar offered to residential students at a selective private university, evaluating its impact on psychological and cognitive functioning, in relationship to a comparable positive psychology seminar. The results suggest the potential for first-year programs that promote student well-being.

The Dual Mechanisms of Cognitive Control Project.

We describe an ambitious ongoing study that has been strongly influenced and inspired by Don Stuss's career-long efforts to identify key cognitive processes that characterize executive control, investigate potential unifying dimensions that define prefrontal function, and carefully attend to individual differences. The Dual Mechanisms of Cognitive Control project tests a theoretical framework positing two key control dimensions: proactive and reactive. The framework's central tenets are that proactive and reactive control modes reflect domain-general dimensions of individual variation, with distinctive neural signatures, involving the lateral pFC as a central node within associated brain networks (e.g., fronto-parietal, cingulo-opercular). In the Dual Mechanisms of Cognitive Control project, each participant is scanned while performing theoretically targeted variants of multiple well-established cognitive control tasks (Stroop, cued task-switching, AX-CPT, Sternberg working memory) in three separate imaging sessions, that each encourages utilization of different control modes plus also completes an extensive out-of-scanner individual differences battery. Additional key features of the project include a high spatio-temporal resolution (multiband) acquisition protocol and a sample that includes a substantial subset of monozygotic twin pairs and participants recruited from the Human Connectome Project. Although data collection is still continuing (target n = 200), we provide an overview of the study design and protocol, along with initial results (n = 80) revealing evidence of a domain-general neural signature of cognitive control and its modulation under reactive conditions. Aligned with Don Stuss's legacy of scientific community building, a partial data set has been publicly released, with the full data set released at project completion, so it can serve as a valuable resource.

Frontoparietal pattern similarity analyses of cognitive control in monozygotic twins.

The ability to flexibly adapt thoughts and actions in a goal-directed manner appears to rely on cognitive control mechanisms that are strongly impacted by individual differences. A powerful research strategy for investigating the nature of individual variation is to study monozygotic (identical) twins. Evidence of twin effects have been observed in prior behavioral and neuroimaging studies, yet within the domain of cognitive control, it remains to be demonstrated that the neural underpinnings of such effects are specific and reliable. Here, we utilize a multi-task, within-subjects event-related neuroimaging design with functional magnetic resonance imaging to investigate twin effects through multivariate pattern similarity analyses. We focus on fronto-parietal brain regions exhibiting consistently increased activation associated with cognitive control demands across four task domains: selective attention, context processing, multi-tasking, and working memory. Healthy young adult monozygotic twin pairs exhibited increased similarity of within- and cross-task activation patterns in these fronto-parietal regions, relative to unrelated pairs. Twin activation pattern similarity effects were clearest under high control demands, were not present in a set of task-unrelated parcels or due to anatomic similarity, and were primarily observed during the within-trial timepoints in which the control demands peaked. Together, these results indicate that twin similarity in the neural representation of cognitive control may be domain-general but also functionally and temporally specific in relation to the level of control demand. The findings suggest a genetic and/or environmental basis for individual variation in cognitive control function, and highlight the potential of twin-based neuroimaging designs for exploring heritability questions within this domain.

Brief Mindfulness Meditation Induces Gray Matter Changes in a Brain Hub.

Previous studies suggest that the practice of long-term (months to years) mindfulness meditation induces structural plasticity in gray matter. However, it remains unknown whether short-term (<30 days) mindfulness meditation in novices could induce similar structural changes. Our previous randomized controlled trials (RCTs) identified white matter changes surrounding the anterior cingulate cortex (ACC) and the posterior cingulate cortex (PCC) within 2 to 4 weeks, following 5-10 h of mindfulness training. Furthermore, these changes were correlated with emotional states in healthy adults. The PCC is a key hub in the functional anatomy implicated in meditation and other perspectival processes. In this longitudinal study using a randomized design, we therefore examined the effect of a 10 h of mindfulness training, the Integrative Body-Mind Training (IBMT) on gray matter volume of the PCC compared to an active control-relaxation training (RT). We found that brief IBMT increased ventral PCC volume and that baseline temperamental trait-an index of individual differences was associated with a reduction in training-induced gray matter increases. Our findings indicate that brief mindfulness meditation induces gray matter plasticity, suggesting that structural changes in ventral PCC-a key hub associated with self-awareness, emotion, cognition, and aging-may have important implications for protecting against mood-related disorders and aging-related cognitive declines.

Relationship Between Trait Mindfulness and Sleep Quality in College Students: A Conditional Process Model.

Sleep quality can affect the physical and mental health, as well as the personal development of college students. Mindfulness practices are known to ameliorate sleep disorder and improve sleep quality. Trait mindfulness, an innate capacity often enhanced by mindfulness training, has been shown to relate to better sleep quality and different aspects of psychological well-being. However, how individual difference factors such as trait mindfulness relate to sleep quality remains largely unclear, which limits the optimization and further application of mindfulness-based intervention schemes targeting the improvement of sleep quality. In this study, we aimed to investigate how negative emotions and neuroticism may influence the relationship between trait mindfulness and sleep quality. A conditional process model was built to examine these relationships in 1,423 Chinese young adults. Specifically, the conditional process model was constructed with trait mindfulness as the independent variable, sleep quality as the dependent variable, negative emotions as the mediating variable, and neuroticism as the moderating variable. Our results showed that negative emotions mediated the link between mindfulness and sleep quality and that neuroticism had a moderating effect on the relationship between mindfulness and sleep quality. Together, these findings suggested a potential mechanism of how trait mindfulness influences sleep quality, provided a therapeutic target for which mindfulness-based interventions may act upon to improve sleep quality, and offered a basis for prediction of different intervention effects among individuals.

Predicting Individual Preferences in Mindfulness Techniques Using Personality Traits.

The growing popularity of mindfulness-based interventions (MBIs) has prompted exciting scientific research investigating their beneficial effects on well-being and health. Most mindfulness programs are provided as multi-faceted packages encompassing a set of different mindfulness techniques, each with distinct focus and mechanisms. However, this approach overlooks potential individual differences, which may arise in response to practicing various mindfulness techniques. The present study investigated preferences for four prototypical mindfulness techniques [focused attention (FA), open monitoring (OM), loving-kindness (LK), and body scan (BS)] and identified factors that may contribute to individual differences in these preferences. Participants without prior mindfulness experiences were exposed to each technique through audio-guided instructions and were asked to rank their preferences at the end of all practices. Results indicated that preferences for loving-kindness were predicted by empathy, and that females tended to prefer loving-kindness more than males. Conversely, preferences for open monitoring were predicted by nonreactivity and nonjudgment of present moment experiences. Additionally, higher state mindfulness was detected for individuals' preferred technique relative to other alternatives. These findings suggest that individuals tend to prefer techniques compatible with their personalities, as the predictor variables encompass trait capacities specifically relevant to practicing these techniques. Together, our results suggest the possibility that assessing individual difference and then tailoring MBIs to individual needs could be a useful way to improve intervention effectiveness and subsequent outcomes.

Towards an Individual Differences Perspective in Mindfulness Training Research: Theoretical and Empirical Considerations.

A growing body of research indicates that mindfulness training can have beneficial effects on critical aspects of psychological well-being, cognitive function, and brain health. Although these benefits have been generalized to the population level, individual variability in observed effects of mindfulness training has not been systematically investigated. Research on other similar forms of psychological intervention demonstrates that individual differences are prominent in terms of intervention responsiveness and outcomes. Furthermore, individual characteristics such as personality traits have been shown to play a crucial role in influencing the effects of intervention. In light of these lines of evidence, we review representative work on individual differences in mindfulness training and advocate for an individual difference perspective in mindfulness training research. We discuss relevant empirical evidence of individual differences potentially influencing behavioral outcomes of mindfulness training, focusing on both cognitive function and psychological well-being. Finally, theoretical considerations and potentially fruitful research strategies and directions for studying individual differences in mindfulness training are discussed, including those involving cognitive neuroscience methods.