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Large-scale brain networks undergo functional reorganization over the course of the lifespan, with concurrent implications for cognition. Characterizing network connectivity during a task may provide complementary insight into cognitive development and aging, to that provided by resting-state. We assessed network background connectivity, which refers to connectivity that remains after task effects have been regressed out, during a visual memory-encoding task in a lifespan sample. More specifically we assessed the within- and between-network background connectivity of the default mode, salience, and frontoparietal networks. Within-network background connectivity of salience and frontoparietal networks differed between age groups, with late-life adults showing lower connectivity. We did not find an effect of age group in default mode network background connectivity, contrary to previous findings using resting-state. However, default mode between-network background connectivity with salience and frontoparietal networks was greater in mid-life and late-life adults than in younger age groups. Overall, our findings in a lifespan sample are in line with previous observations of age-related network de-differentiation. However, the lack of age effect in default mode network background connectivity suggests that background connectivity indeed represents a complementary measure to resting-state connectivity, providing a differential glance of network connectivity during a particular state., Competing Interests: Declarations of interest None., (Copyright © 2022 Japan Neuroscience Society and Elsevier B.V. All rights reserved.)

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults., Competing Interests: Conflict of interest Nothing to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition., Objective: We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance., Methods: 112 older adults (70.7±7.3 years, range 54.6-89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models., Results: Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition., Conclusions: Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Over the past several years, there has been a surge in blood biomarker studies examining the value of plasma or serum neurofilament light (NfL) as a biomarker of neurodegeneration for Alzheimer's disease. However, there have been limited efforts to combine existing findings to assess the utility of blood NfL as a biomarker of neurodegeneration for Alzheimer's disease. In addition, we still need better insight into the specific aspects of neurodegeneration that are reflected by the elevated plasma or serum concentration of NfL. In this review, we survey the literature on the cross-sectional and longitudinal relationships between blood-based NfL levels and other, neuroimaging-based, indices of neurodegeneration in individuals on the Alzheimer's continuum. Then, based on the biomarker classification established by the FDA-NIH Biomarker Working group, we determine the utility of blood-based NfL as a marker for monitoring the disease status (i.e. monitoring biomarker) and predicting the severity of neurodegeneration in older adults with and without cognitive decline (i.e. a prognostic or a risk/susceptibility biomarker). The current findings suggest that blood NfL exhibits great promise as a monitoring biomarker because an increased NfL level in plasma or serum appears to reflect the current severity of atrophy, hypometabolism and the decline of white matter integrity, particularly in the brain regions typically affected by Alzheimer's disease. Longitudinal evidence indicates that blood NfL can be useful not only as a prognostic biomarker for predicting the progression of neurodegeneration in patients with Alzheimer's disease but also as a susceptibility/risk biomarker predicting the likelihood of abnormal alterations in brain structure and function in cognitively unimpaired individuals with a higher risk of developing Alzheimer's disease (e.g. those with a higher amyloid-β). There are still limitations to current research, as discussed in this review. Nevertheless, the extant literature strongly suggests that blood NfL can serve as a valuable prognostic and susceptibility biomarker for Alzheimer's disease-related neurodegeneration in clinical settings, as well as in research settings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Progress in scientific disciplines is accompanied by standardization of terminology. Network neuroscience, at the level of macroscale organization of the brain, is beginning to confront the challenges associated with developing a taxonomy of its fundamental explanatory constructs. The Workgroup for HArmonized Taxonomy of NETworks (WHATNET) was formed in 2020 as an Organization for Human Brain Mapping (OHBM)-endorsed best practices committee to provide recommendations on points of consensus, identify open questions, and highlight areas of ongoing debate in the service of moving the field toward standardized reporting of network neuroscience results. The committee conducted a survey to catalog current practices in large-scale brain network nomenclature. A few well-known network names (e.g., default mode network) dominated responses to the survey, and a number of illuminating points of disagreement emerged. We summarize survey results and provide initial considerations and recommendations from the workgroup. This perspective piece includes a selective review of challenges to this enterprise, including (1) network scale, resolution, and hierarchies; (2) interindividual variability of networks; (3) dynamics and nonstationarity of networks; (4) consideration of network affiliations of subcortical structures; and (5) consideration of multimodal information. We close with minimal reporting guidelines for the cognitive and network neuroscience communities to adopt., (© 2023 Massachusetts Institute of Technology.)

As the global population ages, the prevalence of cognitive decline and dementia is expected to rise, creating a significant health and economic burden. The purpose of this trial is to rigorously test, for the first time, the efficacy of yoga training as a physical activity intervention to mitigate age-related cognitive decline and impairment. We are conducting a 6-month randomized controlled trial (RCT) of exercise among 168 middle aged and older adults to compare the efficacy of yoga vs. aerobic exercise on cognitive function, brain structure and function, cardiorespiratory fitness, and circulating inflammatory and molecular markers. Using a single-blind, three arm RCT, 168 older adults ages 55-79 will be assigned to either: a Hatha yoga group, an aerobic exercise group or a stretching-toning active control group. Participants will engage in hour long group exercise 3x/week for 6-months. A comprehensive neurocognitive test battery, brain imaging, cardiovascular fitness test, and a blood draw will take place at baseline; end of the 6-month intervention, and at 12-month follow-up. Our primary outcomes of interest are brain regions, such as hippocampal volume and prefrontal cortex, and cognitive functions, such as episodic memory, working memory and executive functions, that are typically affected by aging and Alzheimer's disease. Not only will this RCT test whether yoga is a means to mitigate age-related cognitive decline, but it may also offer an alternative to aerobic exercise, which could be particularly appealing to older adults with compromised physical functioning. ClinicalTrials.gov Identifier: NCT04323163., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Depression amongst adolescents is a prevalent disorder consisting of heterogeneous emotional and functional symptoms-often involving impairments in social domains such as empathy. Cognitive and affective components of empathy as well as their associated neural networks (default mode network for cognitive empathy and salience network for affective empathy) are affected by depression. Depression commonly onsets during adolescence, a critical period for brain development underlying empathy. However, the available research in this area conceptualizes depression as a homogenous construct, and thereby miss to represent the full spectrum of symptoms. The present study aims to extend previous literature by testing whether cognitive and affective empathy indirectly account for associations between brain network connectivity and heterogeneous depression symptoms in adolescents. Heterogeneous functional and emotional symptoms of depression were measured using the child depression inventory. Our results indicate that cognitive empathy mediates the association between default mode network functional connectivity and emotional symptoms of depression. More specifically, that adolescents with a stronger positive association between the default mode network and cognitive empathy show lower emotional depression symptoms. This finding highlights the importance of cognitive empathy in the relationship between brain function and depression symptoms, which may be an important consideration for existing models of depression in adolescents., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cognitive complaints of attention/concentration problems are highly frequent in older adults with subjective cognitive decline (SCD). Functional connectivity in the cingulo-opercular network (CON-FC) supports cognitive control, tonic alertness, and visual processing speed. Thus, those complaints in SCD may reflect a decrease in CON-FC. Frontal white-matter tracts such as the forceps minor exhibit age- and SCD-related alterations and, therefore, might influence the CON-FC decrease in SCD. Here, we aimed to determine whether SCD predicts an impairment in CON-FC and whether neurite density in the forceps minor modulates that effect. To do so, we integrated cross-sectional and longitudinal analyses of multimodal data in a latent growth curve modeling approach. Sixty-nine healthy older adults (13 males; 68.33 ± 7.95 years old) underwent resting-state functional and diffusion-weighted magnetic resonance imaging, and the degree of SCD was assessed at baseline with the memory functioning questionnaire (greater score indicating more SCD). Forty-nine of the participants were further enrolled in two follow-ups, each about 18 months apart. Baseline SCD did not predict CON-FC after three years or its rate of change (p-values > 0.092). Notably, however, the forceps minor neurite density did modulate the relation between SCD and CON-FC (intercept; b = 0.21, 95% confidence interval, CI, [0.03, 0.39], p = 0.021), so that SCD predicted a greater CON-FC decrease in older adults with relatively lower neurite density in the forceps minor. The neurite density of the forceps minor, in turn, negatively correlated with age. These results suggest that CON-FC alterations in SCD are dependent upon the forceps minor neurite density. Accordingly, these results imply modifiable age-related factors that could help delay or mitigate both age and SCD-related effects on brain connectivity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Previous literature has focused on predicting a diagnostic label from structural brain imaging. Since subtle changes in the brain precede a cognitive decline in healthy and pathological aging, our study predicts future decline as a continuous trajectory instead. Here, we tested whether baseline multimodal neuroimaging data improve the prediction of future cognitive decline in healthy and pathological aging. Nonbrain data (demographics, clinical, and neuropsychological scores), structural MRI, and functional connectivity data from OASIS-3 (N = 662; age = 46-96 years) were entered into cross-validated multitarget random forest models to predict future cognitive decline (measured by CDR and MMSE), on average 5.8 years into the future. The analysis was preregistered, and all analysis code is publicly available. Combining non-brain with structural data improved the continuous prediction of future cognitive decline (best test-set performance: R2 = 0.42). Cognitive performance, daily functioning, and subcortical volume drove the performance of our model. Including functional connectivity did not improve predictive accuracy. In the future, the prognosis of age-related cognitive decline may enable earlier and more effective individualized cognitive, pharmacological, and behavioral interventions., Competing Interests: Disclosure statement The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Prenatal nutrition may significantly impact brain aging. Results from the Dutch Famine Birth Cohort indicated that prenatal undernutrition is negatively associated with cognition, brain volumes, perfusion and structural brain aging in late life, predominantly in men. This study investigates the association between prenatal undernutrition and late-life functional brain network connectivity. In an exploratory resting-state functional magnetic resonance imaging study of 112 participants from the Dutch Famine Birth Cohort, we investigated whether the within- and between-network functional connectivity of the default mode network, salience network and central executive network differ at age 68 in men (N = 49) and women (N = 63) either exposed or unexposed to undernutrition in early gestation. Additionally, we explored sex-specific effects. Compared to unexposed participants, exposed participants revealed multiple clusters of different functional connectivity within and between the three networks studied. Sex-specific analyses suggested a pattern of network desegregation fitting with brain aging in men and a more diffuse pattern of group differences in women. This study demonstrates that associations between prenatal undernutrition and brain network functional connectivity extend late into life., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Scenes with more perceptual detail can help detect subtle memory deficits more than scenes with less detail. Here, we investigated whether older adults with subjective cognitive decline (SCD) show less brain activation and more memory deficits to scenes with more (vs. scenes with less) perceptual detail compared to controls (CON)., Method: In 37 healthy older adults (SCD: 16), we measured blood oxygenation level-dependent-functional magnetic resonance imaging during encoding and behavioral performance during retrieval., Results: During encoding, higher activation to scenes with more (vs. less) perceptual detail in the parahippocampal place area predicted better memory performance in SCD and CON. During retrieval, superior performance for new scenes with more (vs. less) perceptual detail was significantly more pronounced in CON than inSCD., Conclusions: Together, these results suggest a present, but attenuated benefit from perceptual detail for memory retrieval in SCD. Memory complaints in SCD might, thus, refer to a decreased availability of perceptual detail of previously encoded stimuli., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Functional MRI (fMRI) is a key tool for investigating neural underpinnings of cognitive development. Yet, in recent years, the reliability of fMRI effects has come into question and with it, the feasibility of using task-based fMRI to identify developmental changes related to cognition. Here, we investigated the reliability of task-based fMRI activations with a widely used subsequent memory paradigm using two developmental samples: a cross-sectional sample (n = 85, age 8-25 years) and a test-retest sample (n = 24, one-month follow up, age 8-20 years). In the large cross-sectional sample, we found good to excellent group-level reliability when assessing activation patterns related to the encoding task and subsequent memory effects. In the test-retest sample, while group-level reliability was excellent, the consistency of activation patterns within individuals was low, particularly for subsequent memory effects. We observed consistent activation patterns in frontal, parietal, and occipital cortices, but comparatively lower test-retest reliability in subcortical regions and the hippocampus. Together, these findings highlight the limitations of interpreting task-based fMRI effects and the importance of incorporating reliability analyses in developmental studies. Leveraging larger and densely collected longitudinal data may help contribute to increased reproducibility and the accumulation of knowledge in developmental sciences., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Functional connectivity (FC), or the statistical interdependence of blood-oxygen dependent level (BOLD) signals between brain regions using fMRI, has emerged as a widely used tool for probing functional abnormalities in clinical populations due to the promise of the approach across conceptual, technical, and practical levels. With an already vast and steadily accumulating neuroimaging literature on neurodevelopmental, psychiatric, and neurological diseases and disorders in which FC is a primary measure, we aim here to provide a high-level synthesis of major concepts that have arisen from FC findings in a manner that cuts across different clinical conditions and sheds light on overarching principles. We highlight that FC has allowed us to discover the ubiquity of intrinsic functional networks across virtually all brains and clarify typical patterns of neurodevelopment over the lifespan. This understanding of typical FC maturation with age has provided important benchmarks against which to evaluate divergent maturation in early life and degeneration in late life. This in turn has led to the important insight that many clinical conditions are associated with complex, distributed, network-level changes in the brain, as opposed to solely focal abnormalities. We further emphasize the important role that FC studies have played in supporting a dimensional approach to studying transdiagnostic clinical symptoms and in enhancing the multimodal characterization and prediction of the trajectory of symptom progression across conditions. We highlight the unprecedented opportunity offered by FC to probe functional abnormalities in clinical conditions where brain function could not be easily studied otherwise, such as in disorders of consciousness. Lastly, we suggest high priority areas for future research and acknowledge critical barriers associated with the use of FC methods, particularly those related to artifact removal, data denoising and feasibility in clinical contexts., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Negative subsequent memory effects in functional MRI studies of memory formation have been linked to individual differences in memory performance, yet the effect of age on this association is currently unclear. To provide insight into the brain systems related to memory across the lifespan, we examined functional neuroimaging data acquired during episodic memory formation and behavioral performance from a memory recognition task in a sample of 109 participants, including three developmental age groups (8-12, 13-17, 18-25 year-olds) and one additional group of older adults (55-85 year-olds). Young adults showed the highest memory performance and strongest negative subsequent memory effects, while older adults showed reduced negative subsequent memory effects relative to young adults. Across the sample, negative subsequent memory effects were associated with better memory performance, and there was a significant interaction between negative subsequent memory effects and memory performance by age group. Posthoc analyses revealed that this moderation effect was driven by a stronger association between negative subsequent memory effects and memory performance in young adults than children, and that neither children nor older adults showed a significant association. These findings suggest that negative subsequent memory effects may differentially support memory performance across a lifespan trajectory characterized by developmental maturation and support further investigation of this effect in aging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Empathy, the capacity to understand and share others' emotions, can occur through cognitive and affective components. These components are different conceptually, behaviorally, and in the brain. Neuroimaging task-based research in adolescents and adults document that cognitive empathy associates with the default mode and frontoparietal networks, whereas regions of the salience network underlie affective empathy. However, cognitive empathy is slower to mature than affective empathy and the extant literature reveals considerable developmental differences between adolescent and adult brains within and between these three networks. We extend previous work by examining empathy's association with functional connectivity within and between these networks in adolescents. Participants (n = 84, aged 13-17; 46.4% female) underwent resting state fMRI and completed self-report measures (Interpersonal Reactivity Index) for empathy as part of a larger Nathan-Kline Institute study. Regression analyses revealed adolescents reporting higher cognitive empathy had higher within DMN connectivity. Post hoc analysis revealed cognitive empathy's association within DMN connectivity is independent of affective empathy or empathy in general; and this association is driven by positive pairwise connections between the bilateral angular gyri and medial prefrontal cortex. These results suggest introspective cognitive processes related to the DMN are specifically important for cognitive empathy in adolescence., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Subjective cognitive decline, perceived worsening of cognitive ability without apparent performance issues on clinical assessment, may be an important precursor to dementia. While previous cross-sectional research has demonstrated aberrant brain functional connectivity in subjective cognitive decline, longitudinal evaluation remains limited., Methods: Here, we examined trajectories of functional connectivity over three measurement occasions ~18 months apart, using voxelwise latent growth models in cognitively unimpaired older adults with varying self-report of subjective cognitive decline (N = 69)., Results: We found that individuals who reported a greater degree of subjective cognitive decline showed a larger subsequent decrease in connectivity between components of the default mode network and increase in connectivity between salience and default mode network components. The change in functional connectivity was observed in the absence of change in cognitive performance., Conclusion: The results indicate that functional brain changes may underly the experience of cognitive decline before deterioration reaches a level detected by formal cognitive assessment.

Background: White matter hyperintensities (WMH) show a robust relationship with arterial pressure as well as objective and subjective cognitive functioning. In addition, APOE ɛ4 carriership may influence how arterial pressure affects cognitive functioning., Objective: To determine the role of region-specific WMH burden and APOE ɛ4 carriership on the relationship between mean arterial pressure (MAP) and cognitive function as well as subjective cognitive decline (SCD)., Methods: The sample consisted of 87 cognitively unimpaired middle-aged to older adults aged 50-85. We measured WMH volume for the whole brain, anterior thalamic radiation (ATR), forceps minor, and superior longitudinal fasciculus (SLF). We examined whether WMH burden mediated the relationship between MAP and cognition (i.e., TMT-A score for processing speed; Stroop performance for executive function) as well as SCD (i.e., Frequency of Forgetting (FoF)), and whether APOE ɛ4 carriership moderated that mediation., Results: WMH burden within SLF mediated the effect of MAP on Stroop performance. Both whole brain and ATR WMH burden mediated the effect of MAP on FoF score. In the MAP-WMH-Stroop relationship, the mediation effect of SLF WMH and the effect of MAP on SLF WMH were significant only in APOE ɛ4 carriers. In the MAP-WMH-FoF relationship, the effect of MAP on whole brain WMH burden was significant only in ɛ4 carriers., Conclusion: WMH burden and APOE genotype explain the link between blood pressure and cognitive function and may enable a more accurate assessment of the effect of high blood pressure on cognitive decline and risk for dementia.

Neuroimaging evidence suggests that the development of the hippocampus, a brain structure critical for memory function, contributes to the improvements of episodic memory between middle childhood to adulthood. However, investigations on age differences in hippocampal activation and functional connectivity and their contributions to the development of memory have yielded mixed results. Given the known structural and functional heterogeneity along the long axis of the hippocampus, we investigated age differences in the activation and functional connectivity in hippocampal subregions with a cross-sectional sample of 96 participants ages 8-25 years. We found that anterior and posterior hippocampus supported memory formation, and there was overall stability in memory-related hippocampal activation with age. Without taking account of memory outcome, direct contrast between subregions showed higher functional connectivity of anterior, compared to the posterior hippocampus, with regions in the inferior frontal and lateral temporal lobes, and higher functional connectivity of posterior, compared to the anterior hippocampus, with regions in the medial and superior frontal, inferior parietal, and occipital lobes. A direct contrast between the memory-related connectivity patterns of anterior and posterior hippocampus identified a region in the medial frontal cortex, with which anterior and posterior hippocampus was differentially functionally connected. Finally, we identified age differences in memory-related differential hippocampal functional connectivity with several frontal and visual/sensory cortices, underscoring the importance of examining age differences in the patterns of hippocampal connectivity. Moreover, the specific patterns of differential anterior and posterior functional connectivity indicate an increase in the functional specialization along the long axis of the hippocampus and a dynamic shift in hippocampal connectivity patterns that supports memory development., (Copyright © 2020 Tang, Pruitt, Yu, Homayouni, Daugherty, Damoiseaux and Ofen.)

The personality traits of neuroticism, openness, and conscientiousness are relevant factors for cognitive aging outcomes. The present study examined how these traits were associated with cognitive abilities and corresponding resting-state functional connectivity (RSFC) of the default mode network (DMN) in an older and predominantly minority sample. A sample of 58 cognitively unimpaired, largely African-American, older adults ( M age = 68.28 ± 8.33) completed a standard RSFC magnetic resonance imaging sequence, a Big Five measure of personality, and delayed memory, Stroop, and verbal fluency tasks. Personality trait associations of within-network connectivity of the posterior cingulate cortex (PCC), a hub of the DMN, were examined using a seed-based approach. Trait scores were regressed on cognitive performance (delayed memory for neuroticism, Stroop for conscientiousness, and verbal fluency for openness). Greater openness predicted greater verbal fluency and greater RSFC between the PCC and eight clusters, including the medial prefrontal cortex, left middle frontal gyrus, and precuneus. Greater PCC-precuneus connectivity predicted greater verbal fluency. Neuroticism and conscientiousness did not significantly predict either cognitive performance or RSFC. Although requiring replication and elaboration, the results implicate openness as a contributing factor to cognitive aging via concomitant cognitive performance and connectivity within cortical hubs of the DMN and add to the sparse literature on these variables in a diverse group of older adults., (© The Author(s) 2020.)

Subjective cognitive decline is a putative precursor to dementia marked by perceived worsening of cognitive function without overt performance issues on neuropsychological assessment. Although healthy older adults with subjective cognitive decline may function normally, perceived worsening may indicate incipient dementia and predict future deterioration. Therefore, the experience of decline represents a possible entry point for clinical intervention. However, intervention requires a physical manifestation of neuroabnormality to both corroborate incipient dementia and to target clinically. While some individuals with subjective cognitive decline may harbor pathophysiology for specific neurodegenerative disorders, many do not display clear indicators. Thus, disorder-agnostic brain measures could be useful to track the trajectory of decline, and functional neuroimaging in particular may be sensitive to detect incipient dementia and have the ability to track disease-related change when the underlying disease etiology remains unclear. Therefore, in this review, we discuss functional neuroimaging studies of subjective cognitive decline and possible reconciliations to inconsistent findings. We conclude by proposing a functional model where noisy signal propagation and inefficient signal processing across whole-brain networks may lead to the subjective experience of decline and discuss future research directions guided by this model.

Yoga is the most popular complementary health approach practiced by adults in the United States. It is an ancient mind and body practice with origins in Indian philosophy. Yoga combines physical postures, rhythmic breathing and meditative exercise to offer the practitioners a unique holistic mind-body experience. While the health benefits of physical exercise are well established, in recent years, the active attentional component of breathing and meditation practice has garnered interest among exercise neuroscientists. As the scientific evidence for the physical and mental health benefits of yoga continues to grow, this article aims to summarize the current knowledge of yoga practice and its documented positive effects for brain structure and function, as assessed with MRI, fMRI, and SPECT. We reviewed 11 studies examining the effects of yoga practice on the brain structures, function and cerebral blood flow. Collectively, the studies demonstrate a positive effect of yoga practice on the structure and/or function of the hippocampus, amygdala, prefrontal cortex, cingulate cortex and brain networks including the default mode network (DMN). The studies offer promising early evidence that behavioral interventions like yoga may hold promise to mitigate age-related and neurodegenerative declines as many of the regions identified are known to demonstrate significant age-related atrophy., Competing Interests: The authors have no conflict of interest to report., (© 2019 – IOS Press and the authors. All rights reserved.)

Subjective cognitive decline, a perceived worsening of cognitive functioning without objective deficit on assessment, could indicate incipient dementia. However, the neural correlates of subjective cognitive decline as assessed by magnetic resonance imaging remain somewhat unclear. Here, we evaluated differences in functional connectivity across memory regions, and cognitive performance, between healthy older adults aged 50 to 85 with (n = 35, Age = 68.5 ± 7.7, 22 female), and without (n = 48, Age = 67.0 ± 8.8, 29 female) subjective cognitive decline. We also evaluated neurite density, fractional anisotropy, and mean diffusivity of the parahippocampal cingulum, cingulate gyrus cingulum, and uncinate fiber bundles in a subsample of participants (n = 37). Participants with subjective cognitive decline displayed lower average functional connectivity across regions of a putative posterior memory system, and lower retrosplenial-precuneus functional connectivity specifically, than those without memory complaints. Furthermore, participants with subjective cognitive decline performed poorer than controls on visual working memory. However, groups did not differ in cingulum or uncinate diffusion measures. Our results show differences in functional connectivity and visual working memory in participants with subjective cognitive decline that could indicate potential incipient dementia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigated the flexible modulation of undirected functional connectivity (uFC) of brain pathways during simple uni-manual responding. Two questions were central to our interests: (1) does response hand (dominant vs. non-dominant) differentially modulate connectivity and (2) are these effects related to responding under varying motor sets. fMRI data were acquired in twenty right-handed volunteers who responded with their right (dominant) or left (non-dominant) hand (blocked across acquisitions). Within acquisitions, the task oscillated between periodic responses (promoting the emergence of motor sets) or randomly induced responses (disrupting the emergence of motor sets). Conjunction analyses revealed eight shared nodes across response hand and condition, time series from which were analyzed. For right hand responses connectivity of the M1 ←→ Thalamus and SMA ←→ Parietal pathways was more significantly modulated during periodic responding. By comparison, for left hand responses, connectivity between five network pairs (including M1 and SMA, insula, basal ganglia, premotor cortex, parietal cortex, thalamus) was more significantly modulated during random responding. uFC analyses were complemented by directed FC based on multivariate autoregressive models of times series from the nodes. These results were complementary and highlighted significant modulation of dFC for SMA → Thalamus, SMA → M1, basal ganglia → Insula and basal ganglia → Thalamus. The results demonstrate complex effects of motor organization and task demand and response hand on different connectivity classes of fMRI data. The brain's sub-networks are flexibly modulated by factors related to motor organization and/or task demand, and our results have implications for assessment of medical conditions associated with motor dysfunction.

Background: Yoga is a mind-body based physical activity that has demonstrated a variety of physiological, psychological and cognitive health benefits. Although yoga practice has shown to improve cognitive performance, few studies have examined the underlying neurological correlates. Objective: The current study aimed to determine the differences in gray matter volume of the hippocampus, thalamus and caudate nucleus and brain activation during the Sternberg working memory task. Method: Participants were 13 experienced yoga practitioners (mean age = 35.8), defined as having more than 3 years of regular yoga practice, and 13 age- and sex-matched controls (mean age = 35.7). All participants completed a 6-min walk test to assess fitness, psychosocial and demographic questionnaires; and underwent magnetic resonance imaging to assess gray matter volume and brain activation. Results: There were no group differences on demographic measures of income, education and on estimated VO2max or physical activity levels. Gray matter volume differences were observed in the left hippocampus, showing greater volume in experienced yoga practitioners compared to controls ( p = 0.017). The functional MRI results revealed less activation in the dorsolateral prefrontal cortex in yoga practitioners compared to controls during the encoding phase of the Sternberg task ( p < 0.05). Reaction time and accuracy on the task did not differ between the groups. Conclusions: Our results suggest an association between regular long-term yoga practice and differential structure and function of specific brain regions involved in executive function, specifically working memory, which has previously shown to improve with yoga practice. Future studies need to examine intervention effects of yoga and explore its potential to maintain and improve cognitive health across the lifespan through longitudinal and intervention studies.

Background: Research in older adults with subjective cognitive decline (SCD) has mainly focused on Alzheimer's disease (AD)-related MRI markers, such as hippocampal volume. However, small vessel disease (SVD) is currently established as serious comorbidity in dementia and its preliminary stages. It is therefore important to examine SVD markers in addition to AD markers in older adults presenting with SCD., Objective: The aim of our study was to elucidate the role of SVD markers in late middle-aged to older adults with and without SCD in addition to the commonly found role of AD markers (hippocampal volume)., Methods: 67 healthy late middle-aged to older adults participated in this study (mean age 68 years); 25 participants with SCD and 42 participants without SCD. We evaluated quantitative as well as qualitative AD markers (i.e., hippocampal volume and medial temporal lobe atrophy (MTA) scale) and SVD markers (i.e., white matter hyperintensities (WMH) volume, Fazekas scale, microbleeds, and lacunar infarcts), and neuropsychological function and amount of memory complaints., Results: We found a significant effect of SCD on hippocampal atrophy, as assessed using the MTA scale, but not on hippocampal volume. In addition, we found a significant effect of SCD, and amount of memory complaints, on WMH volume and Fazekas score, suggesting larger WMH volumes in participants with SCD., Conclusion: SVD MRI markers are related to amount of memory complaints, in addition to the commonly observed AD MRI markers, as demonstrated by the greater WMHs in healthy late middle-aged to older adults with SCD.

Subjective memory complaints, the perceived decline in cognitive abilities in the absence of clinical deficits, may precede Alzheimer's disease. Individuals with subjective memory complaints show differential brain activation during memory encoding; however, whether such differences contribute to successful memory formation remains unclear. Here, we investigated how subsequent memory effects, activation which is greater for hits than misses during an encoding task, differed between healthy older adults aged 50 to 85 years with (n = 23) and without (n = 41) memory complaints. Older adults with memory complaints, compared to those without, showed lower subsequent memory effects in the occipital lobe, superior parietal lobe, and posterior cingulate cortex. In addition, older adults with more memory complaints showed a more negative subsequent memory effects in areas of the default mode network, including the posterior cingulate cortex, precuneus, and ventromedial prefrontal cortex. Our findings suggest that for successful memory formation, older adults with subjective memory complaints rely on distinct neural mechanisms which may reflect an overall decreased task-directed attention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Advanced age is associated with reduced within-network functional connectivity, particularly within the default mode network. Most studies to date have examined age differences in functional connectivity via static indices that are computed over the entire blood-oxygen-level dependent time series. Little is known about the effects of age on short-term temporal dynamics of functional connectivity. Here, we examined age differences in dynamic connectivity as well as associations between connectivity, metabolic risk, and cognitive performance in healthy adults (N = 168; age, 18-83 years). A sliding-window k-means clustering approach was used to assess dynamic connectivity from resting-state functional magnetic resonance imaging data. Three out of 8 dynamic connectivity profiles were associated with age. Furthermore, metabolic risk was associated with the relative amount of time allocated to 2 of these profiles. Finally, the relative amount of time allocated to a dynamic connectivity profile marked by heightened connectivity between default mode and medial temporal regions was positively associated with executive functions. Thus, dynamic connectivity analyses can enrich understanding of age-related differences beyond what is revealed by static analyses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Over the past decade there has been an enormous rise in the application of functional and structural connectivity approaches to explore the brain's intrinsic organization in healthy and clinical populations. The notion underlying the application of these approaches to study aging is that subtle age-related disruption of the brain's regional integrity and information flow across the brain, are expressed by age-related differences in functional and structural connectivity. In this review I will discus recent advances in our understanding of how age affects our brain's intrinsic organization, and I will share my perspective on potential challenges and future directions of the field., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aging is associated with declines in cognitive performance and multiple changes in the brain, including reduced default mode functional connectivity (FC). However, conflicting results have been reported regarding age differences in FC between hippocampal and default mode regions. This discrepancy may stem from the variation in selection of hippocampal regions. We therefore examined the effect of age on resting state FC of anterior and posterior hippocampal regions in an adult life-span sample. Advanced age was associated with lower FC between the posterior hippocampus and three regions: the posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortex. In addition, age-related reductions of FC between the left and right posterior hippocampus, and bilaterally along the posterior to anterior hippocampal axis were noted. Age differences in medial prefrontal and inter-hemispheric FC significantly differed between anterior and posterior hippocampus. Older age was associated with lower performance in all cognitive domains, but we observed no associations between FC and cognitive performance after controlling for age. We observed a significant effect of gender and a linear effect of COMT val158met polymorphism on hippocampal FC. Females showed higher FC of anterior and posterior hippocampus and medial prefrontal cortex than males, and the dose of val allele was associated with lower posterior hippocampus - posterior cingulate FC, independent of age. Vascular and metabolic factors showed no significant effects on FC. These results suggest differential age-related reduction in the posterior hippocampal FC compared to the anterior hippocampus, and an age-independent effect of gender and COMT on hippocampal FC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The neurobiology of Trichotillomania is poorly understood, although there is increasing evidence to suggest that TTM may involve alterations of reward processing. The current study represents the first exploration of reward processing in TTM and the first resting state fMRI study in TTM. We incorporate both event-related fMRI using a monetary incentive delay (MID) task, and resting state fMRI, using two complementary resting state analysis methodologies (functional connectivity to the nucleus accumbens and dual regression within a reward network) in a pilot study to investigate differences in reward processing between TTM and healthy controls (HC)., Methods: 21 unmedicated subjects with TTM and 14 HC subjects underwent resting state fMRI scans. A subset (13 TTM and 12 HC) also performed the MID task., Results: For the MID task, TTM subjects showed relatively decreased nucleus accumbens (NAcc) activation to reward anticipation, but relative over-activity of the NAcc to both gain and loss outcomes. Resting state functional connectivity analysis showed decreased connectivity of the dorsal anterior cingulate (dACC) to the NAcc in TTM. Dual regression analysis of a reward network identified through independent component analysis (ICA) also showed decreased dACC connectivity and more prominently decreased basolateral amygdala connectivity within the reward network in TTM., Conclusions: Disordered reward processing at the level of NAcc, also involving decreased modulatory input from the dACC and the basolateral amygdala may play a role in the pathophysiology of TTM., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Regional functional connectivity (FC) of 39 patients with Alzheimer's disease (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly controls was studied using resting-state functional magnetic resonance imaging (rs-fMRI). After a mean follow-up of 2.8 ± 1.9 years, 7 MCI patients converted to AD, while 14 patients remained cognitively stable. Resting-state functional magnetic resonance imaging scans were analyzed using independent component analysis (ICA), followed by a "dual-regression" technique to create and compare subject-specific maps of each independent spatiotemporal component, correcting for age, sex, and gray matter atrophy. AD patients displayed lower FC within the default-mode network (DMN) in the precuneus and posterior cingulate cortex compared with controls, independent of cortical atrophy. Regional FC values of MCI patients were numerically in between AD patients and controls, but only the difference between AD and stable MCI patients was statistically significant. Correlation with cognitive dysfunction demonstrated the clinical relevance of FC changes within the DMN. In conclusion, clinically relevant decreased FC within the DMN was observed in AD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We examined whether the effect of the apolipoprotein E (APOE) genotype on functional brain connectivity is modulated by gender in healthy older human adults. Our results confirm significantly decreased connectivity in the default mode network in healthy older APOE ε4 carriers compared with ε3 homozygotes. More important, further testing revealed a significant interaction between APOE genotype and gender in the precuneus, a major default mode hub. Female ε4 carriers showed significantly reduced default mode connectivity compared with either female ε3 homozygotes or male ε4 carriers, whereas male ε4 carriers differed minimally from male ε3 homozygotes. An additional analysis in an independent sample of healthy elderly using an independent marker of Alzheimer's disease, i.e., spinal fluid levels of tau, provided corresponding evidence for this gender-by-APOE interaction. Together, these results converge with previous work showing a higher prevalence of the ε4 allele among women with Alzheimer's disease and, critically, demonstrate that this interaction between APOE genotype and gender is detectable in the preclinical period.

While resting state functional connectivity has been shown to decrease in patients with mild and/or moderate Alzheimer's disease, it is not yet known how functional connectivity changes in patients as the disease progresses. Furthermore, it has been noted that the default mode network is not as homogenous as previously assumed and several fractionations of the network have been proposed. Here, we separately investigated the modulation of 3 default mode subnetworks, as identified with group independent component analysis, by comparing Alzheimer's disease patients to healthy controls and by assessing connectivity changes over time. Our results showed decreased connectivity at baseline in patients versus controls in the posterior default mode network, and increased connectivity in the anterior and ventral default mode networks. At follow-up, functional connectivity decreased across all default mode systems in patients. Our results suggest that earlier in the disease, regions of the posterior default mode network start to disengage whereas regions within the anterior and ventral networks enhance their connectivity. However, as the disease progresses, connectivity within all systems eventually deteriorates., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous. The current study shows more conclusive data on connectivity changes in early AD using graph analysis on resting-state condition fMRI data., Methodology/principal Findings: 18 mild AD patients and 21 healthy age-matched control subjects without memory complaints were investigated in resting-state condition with MRI at 1.5 Tesla. Functional coupling between brain regions was calculated on the basis of pair-wise synchronizations between regional time-series. Local (cluster coefficient) and global (path length) network measures were quantitatively defined. Compared to controls, the characteristic path length of AD functional networks is closer to the theoretical values of random networks, while no significant differences were found in cluster coefficient. The whole-brain average synchronization does not differ between Alzheimer and healthy control groups. Post-hoc analysis of the regional synchronization reveals increased AD synchronization involving the frontal cortices and generalized decreases located at the parietal and occipital regions. This effectively translates in a global reduction of functional long-distance links between frontal and caudal brain regions., Conclusions/significance: We present evidence of AD-induced changes in global brain functional connectivity specifically affecting long-distance connectivity. This finding is highly relevant for it supports the anterior-posterior disconnection theory and its role in AD. Our results can be interpreted as reflecting the randomization of the brain functional networks in AD, further suggesting a loss of global information integration in disease.

It is commonly assumed that functional brain connectivity reflects structural brain connectivity. The exact relationship between structure and function, however, might not be straightforward. In this review we aim to examine how our understanding of the relationship between structure and function in the 'resting' brain has advanced over the last several years. We discuss eight articles that directly compare resting-state functional connectivity with structural connectivity and three clinical case studies of patients with limited white matter connections between the cerebral hemispheres. All studies examined show largely convergent results: the strength of resting-state functional connectivity is positively correlated with structural connectivity strength. However, functional connectivity is also observed between regions where there is little or no structural connectivity, which most likely indicates functional correlations mediated by indirect structural connections (i.e. via a third region). As the methodologies for measuring structural and functional connectivity continue to improve and their complementary strengths are applied in parallel, we can expect important advances in our diagnostic and prognostic capacities in diseases like Alzheimer's, multiple sclerosis, and stroke.

The pattern of degenerative changes in the brain white matter (WM) in aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) has been under debate. Methods of image analysis are an important factor affecting the outcomes of various studies. Here we used diffusion tensor imaging (DTI) to obtain fractional anisotropy (FA) measures of the WM in healthy young (n = 8), healthy elderly (n = 22), MCI (n = 8), and AD patients (n = 16). We then applied "tract-based spatial statistics" (TBSS) to study the effects of aging, MCI, and AD on WM integrity. Our results show that changes in WM integrity (that is, decreases in FA) are different between healthy aging and AD: in healthy older subjects compared with healthy young subjects decreased FA was primarily observed in frontal, parietal, and subcortical areas whereas in AD, compared with healthy older subjects, decreased FA was only observed in the left anterior temporal lobe. This different pattern of decreased anatomical connectivity in normal aging and AD suggests that AD is not merely accelerated aging., (2008 Wiley-Liss, Inc.)

FMRI research in Alzheimer's disease (AD) and mild cognitive impairment (MCI) typically is aimed at determining regional changes in brain function, most commonly by creating a model of the expected BOLD-response and estimating its magnitude using a general linear model (GLM) analysis. This crucially depends on the suitability of the temporal assumptions of the model and on assumptions about normality of group distributions. Exploratory data analysis techniques such as independent component analysis (ICA) do not depend on these assumptions and are able to detect unknown, yet structured spatiotemporal processes in neuroimaging data. Tensorial probabilistic ICA (T-PICA) is a model free technique that can be used for analyzing multiple subjects and groups, extracting signals of interest (components) in the spatial, temporal, and also subject domain of FMRI data. We applied T-PICA and model-based GLM to study FMRI signal during face encoding in 18 AD, 28 MCI patients, and 41 healthy elderly controls. T-PICA showed activation in regions associated with motor, visual, and cognitive processing, and deactivation in the default mode network. Six networks showed a significantly decreased response in patients. For two networks the T-PICA technique was significantly more sensitive to detect group differences than the standard model-based technique. We conclude that T-PICA is a promising tool to identify and detect differences in (de)activated brain networks in elderly controls and dementia patients. The technique is more sensitive than the commonly applied model-based method. Consistent with other research, we show that networks of activation and deactivation show decreased reactivity in dementia., ((c) 2007 Wiley-Liss, Inc.)

Normal aging is associated with cognitive decline. Functions such as attention, information processing, and working memory are compromised. It has been hypothesized that not only regional changes, but also alterations in the integration of regional brain activity (functional brain connectivity) underlie the observed age-related deficits. Here, we examined the functional properties of brain networks based on spontaneous fluctuations within brain systems using functional magnetic resonance imaging. We hypothesized that functional connectivity of intrinsic brain activity in the "default-mode" network (DMN) is affected by normal aging and that this relates to cognitive function. Ten younger and 22 older subjects were scanned at "rest," that is, lying awake with eyes closed. Our results show decreased activity in older versus younger subjects in 2 resting-state networks (RSNs) resembling the previously described DMN, containing the superior and middle frontal gyrus, posterior cingulate, middle temporal gyrus, and the superior parietal region. These results remain significant after correction for RSN-specific gray matter volume. The relevance of these findings is illustrated by the correlation between reduced activity of one of these RSNs and less effective executive functioning/processing speed in the older group.

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11682-007-9003-2) contains supplementary material, which is available to authorized users.

Functional MRI (fMRI) can be applied to study the functional connectivity of the human brain. It has been suggested that fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain, representing the state of the human brain in the absence of goal-directed neuronal action and external input, and that these slow fluctuations correspond to functionally relevant resting-state networks. Several studies on resting fMRI have been conducted, reporting an apparent similarity between the identified patterns. The spatial consistency of these resting patterns, however, has not yet been evaluated and quantified. In this study, we apply a data analysis approach called tensor probabilistic independent component analysis to resting-state fMRI data to find coherencies that are consistent across subjects and sessions. We characterize and quantify the consistency of these effects by using a bootstrapping approach, and we estimate the BOLD amplitude modulation as well as the voxel-wise cross-subject variation. The analysis found 10 patterns with potential functional relevance, consisting of regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the so-called default-mode network, each with BOLD signal changes up to 3%. In general, areas with a high mean percentage BOLD signal are consistent and show the least variation around the mean. These findings show that the baseline activity of the brain is consistent across subjects exhibiting significant temporal dynamics, with percentage BOLD signal change comparable with the signal changes found in task-related experiments.