Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

Locus coeruleus integrity is related to an exploitation-based decision-making bias in older adulthood.

Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus integrity. Critically, we demonstrate that an exploitation bias in older adulthood, assessed with a foraging task, is sensitive and specific to lower locus coeruleus integrity. Because the locus coeruleus is uniquely vulnerable to Alzheimer's disease pathology, our findings suggest that aging, and a presymptomatic trajectory of Alzheimer's related decline, may fundamentally alter decision-making abilities in later life.

Neurobehavioral Mechanisms Influencing the Association Between Generativity, the Desire to Promote Well-Being of Younger Generations, and Purpose in Life in Older Adults at Risk for Alzheimer's Disease.

OBJECTIVES: Generativity, the desire and action to improve the well-being of younger generations, is associated with purpose in life among older adults. However, the neurobehavioral factors supporting the relationship between generativity and purpose in life remain unknown. This study aims to identify the functional neuroanatomy of generativity and mechanisms linking generativity with purpose in life in at-risk older adults. METHODS: Fifty-eight older adults (mean age = 70.8, SD = 5.03, 45 females) with a family history of Alzheimer's disease (AD) were recruited from the PREVENT-AD cohort. Participants underwent brain imaging and completed questionnaires assessing generativity, social support, and purpose in life. Mediation models examined whether social support mediated the association between generativity and purpose in life. Seed-to-voxel analyses investigated the association between generativity and resting-state functional connectivity (rsFC) to the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS), and whether this rsFC moderated the relationship between generativity and purpose in life. RESULTS: Affectionate social support mediated the association between generative desire and purpose in life. Generative desire was associated with rsFC between VS and precuneus, and, vmPFC and right dorsolateral prefrontal cortex (rdlPFC). The vmPFC-rdlPFC rsFC moderated the association between generative desire and purpose in life. DISCUSSION: These findings provide insight into how the brain supports complex social behavior and, separately, purpose in life in at-risk aging. Affectionate social support may be a putative target process to enhance purpose in life in older adults. This knowledge contributes to future developments of personalized interventions that promote healthy aging.

Iron Deposition and Distribution Across the Hippocampus Is Associated with Pattern Separation and Pattern Completion in Older Adults at Risk for Alzheimer's Disease.

Elevated iron deposition in the brain has been observed in older adult humans and persons with Alzheimer's disease (AD), and has been associated with lower cognitive performance. We investigated the impact of iron deposition, and its topographical distribution across hippocampal subfields and segments (anterior, posterior) measured along its longitudinal axis, on episodic memory in a sample of cognitively unimpaired older adults at elevated familial risk for AD (N = 172, 120 females, 52 males; mean age = 68.8 ± 5.4 years). MRI-based quantitative susceptibility maps were acquired to derive estimates of hippocampal iron deposition. The Mnemonic Similarity Task was used to measure pattern separation and pattern completion, two hippocampally mediated episodic memory processes. Greater hippocampal iron load was associated with lower pattern separation and higher pattern completion scores, both indicators of poorer episodic memory. Examination of iron levels within hippocampal subfields across its long axis revealed topographic specificity. Among the subfields and segments investigated here, iron deposition in the posterior hippocampal CA1 was the most robustly and negatively associated with the fidelity memory representations. This association remained after controlling for hippocampal volume and was observed in the context of normal performance on standard neuropsychological memory measures. These findings reveal that the impact of iron load on episodic memory performance is not uniform across the hippocampus. Both iron deposition levels as well as its spatial distribution, must be taken into account when examining the relationship between hippocampal iron and episodic memory in older adults at elevated risk for AD.

The biological role of local and global fMRI BOLD signal variability in human brain organization.

Variability drives the organization and behavior of complex systems, including the human brain. Understanding the variability of brain signals is thus necessary to broaden our window into brain function and behavior. Few empirical investigations of macroscale brain signal variability have yet been undertaken, given the difficulty in separating biological sources of variance from artefactual noise. Here, we characterize the temporal variability of the most predominant macroscale brain signal, the fMRI BOLD signal, and systematically investigate its statistical, topographical and neurobiological properties. We contrast fMRI acquisition protocols, and integrate across histology, microstructure, transcriptomics, neurotransmitter receptor and metabolic data, fMRI static connectivity, and empirical and simulated magnetoencephalography data. We show that BOLD signal variability represents a spatially heterogeneous, central property of multi-scale multi-modal brain organization, distinct from noise. Our work establishes the biological relevance of BOLD signal variability and provides a lens on brain stochasticity across spatial and temporal scales.

Relation of resting brain signal variability to cognitive and socioemotional measures in an adult lifespan sample.

Temporal variability of the fMRI-derived blood-oxygen-level-dependent (BOLD) signal during cognitive tasks shows important associations with individual differences in age and performance. Less is known about relations between spontaneous BOLD variability measured at rest and relatively stable cognitive measures, such as IQ or socioemotional function. Here, we examined associations among resting BOLD variability, cognitive/socioemotional scores from the NIH Toolbox and optimal time of day for alertness (chronotype) in a sample of 157 adults from 20 to 86 years of age. To investigate individual differences in these associations independently of age, we regressed age out from both behavioral and BOLD variability scores. We hypothesized that greater BOLD variability would be related to higher fluid cognition scores, more positive scores on socioemotional scales and a morningness chronotype. Consistent with this idea, we found positive correlations between resting BOLD variability, positive socioemotional scores (e.g. self-efficacy) and morning chronotype, as well as negative correlations between variability and negative emotional scores (e.g. loneliness). Unexpectedly, we found negative correlations between BOLD variability and fluid cognition. These results suggest that greater resting brain signal variability facilitates optimal socioemotional function and characterizes those with morning-type circadian rhythms, but individuals with greater fluid cognition may be more likely to show less temporal variability in spontaneous measures of BOLD activity.

The influence of generativity on purpose in life is mediated by social support and moderated by prefrontal functional connectivity in at-risk older adults.

Objectives: Generativity, the desire and action to improve the well-being of younger generations, is positively associated with purpose in life among older adults. However, the neural basis of generativity and the neurobehavioral factors supporting the relationship between generativity and purpose in life remain unknown. This study aims to identify the functional neuroanatomy of generativity and mechanisms linking generativity with purpose in life in at-risk older adults. Methods: Fifty-eight cognitively healthy older adults (mean age = 70.78, 45 females) with a family history of Alzheimer's disease were recruited from the PREVENT-AD aging cohort. Participants underwent brain imaging and completed questionnaires assessing generativity, social support, and purpose in life. Mediation models examined whether social support mediated the association between generativity and purpose in life. Seed-to-voxel analyses investigated the association between resting-state functional connectivity (rsFC) to the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS) and whether this rsFC moderated the relationship between generativity and purpose in life. Results: Affectionate social support mediated the association between generative desire and purpose in life. Generative desire was associated with rsFC between VS and precuneus and vmPFC and right dorsolateral prefrontal cortex (rdlPFC). The vmPFC-rdlPFC connectivity moderated the association between generative desire and purpose in life. Discussion: These findings provide insight into how the brain supports social behavior and, separately, purpose in life in at-risk aging. Affectionate social support may be a putative target process to enhance purpose and life in older adults. This knowledge contributes to future developments of personalized interventions that promote healthy aging.

Reduced modulation of BOLD variability as a function of cognitive load in healthy aging.

BOLD variability, which measures moment-to-moment fluctuations in brain signal, is sensitive to age differences in cognitive performance. However, the effect of aging on BOLD variability in the context of different cognitive demands is still unclear. The current study examined how aging affects brain variability across cognitive loads and the contribution of BOLD variability to working memory abilities. Participants (N = 149, ages 20‒86) completed an fMRI n-back paradigm with 3 loads and 10-minute resting state scan. We found that BOLD variability was greater during rest compared to task and decreased even further as n-back load increased. Older age was associated with smaller load-related modulations of BOLD variability in default mode and fronto-parietal control networks. Increased variability in default mode, fronto-parietal control, and limbic regions and decreased variability in sensori-motor regions during the n-back task was associated with better working memory performance, regardless of age. Our findings suggest that working memory reductions in older ages are related to failure of core cognitive control and default mode regions to modulate dynamic range of activity in the face of increased demands.

Age differences in the functional architecture of the human brain.

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience-dependent changes, or both, is uncertain. We employed a multimethod strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n = 181) and older (n = 120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multiscale, multimethod approaches to characterize the architecture of functional brain aging.

White matter lesion load is associated with lower within- and greater between- network connectivity across older age.

White matter hyperintensities (WMH) are among the most prominent structural changes observed in older adulthood. These changes coincide with functional changes to the intrinsic network organization of the aging brain. Yet little is known about how WMH are associated with changes to the whole-brain functional connectome in normal aging. We used a lesion prediction algorithm to quantify WMH as well as resting-state multiecho functional magnetic resonance imaging to characterize resting-state functional connectivity in a cross-sectional sample of healthy older adults (N = 105, 60-83 years of age). In a multivariate analysis, we found that higher lesion load was associated with a global pattern of network dedifferentiation, marked by lower within- and greater between- network connectivity. Network specific changes included greater visual network integration and greater posterior-anterior connectivity. The relationship between WMH and resting-state functional connectivity was negatively associated with fluid IQ as well as Blood Oxygen Level Dependent signal dimensionality. Reduced functional network segregation is a widely observed pattern of age-related change. Our findings show that these functional changes are associated with the accumulation of WMH in older adulthood.

Dataset of functional connectivity during cognitive control for an adult lifespan sample.

We provide functional connectivity matrices generated during functional magnetic resonance imaging (fMRI) during different tasks of cognitive control in healthy aging adults. These data can be used to replicate the primary results from the related manuscript: Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan (Rieck et al., 2021). One-hundred-forty-four participants (ages 20-86) were scanned on a Siemens 3T MRI scanner while they were completing tasks to measure functional activity during inhibition, initiation, shifting, and working memory. Estimates of functional connectivity (quantified with timeseries correlations) between different brain regions were computed using three different brain atlases: Schaefer 100 parcel 17 network atlas (Schaefer et al., 2018; Yeo et al., 2011), Power 229 node 10 network atlas (Power et al., 2011), and Schaefer 200 parcel 17 network atlas (Schaefer et al., 2018; Yeo et al., 2011). The resulting functional connectivity correlation matrices are provided as text files with this article. Cov-STATIS (Abdi et al., 2012; a multi-table multivariate statistical technique; https://github.com/HerveAbdi/DistatisR) was used to examine similarity between functional connectivity during the different domains of cognitive control. The effect of aging on these functional connectivity patterns was also examined by computing measures of "task differentiation" and "network segregation." This dataset also provides supplemental analyses from the related manuscript (Rieck et al., 2021) to replicate the primary age findings with additional brain atlases. Cognitive neuroscience researchers can benefit from these data by further investigating the age effects on functional connectivity during tasks of cognitive control, in addition to examining the impact of different brain atlases on functional connectivity estimates. These data can also be used for the development of other multi-table and network-based statistical methods in functional neuroimaging.

Centering inclusivity in the design of online conferences-An OHBM-Open Science perspective.

As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.

Contributions of Brain Function and Structure to Three Different Domains of Cognitive Control in Normal Aging.

Cognitive control involves the flexible allocation of mental resources during goal-directed behavior and comprises three correlated but distinct domains-inhibition, shifting, and working memory. The work of Don Stuss and others has demonstrated that frontal and parietal cortices are crucial to cognitive control, particularly in normal aging, which is characterized by reduced control mechanisms. However, the structure-function relationships specific to each domain and subsequent impact on performance are not well understood. In the current study, we examined both age and individual differences in functional activity associated with core domains of cognitive control in relation to fronto-parietal structure and task performance. Participants (n = 140, aged 20-86 years) completed three fMRI tasks: go/no-go (inhibition), task switching (shifting), and n-back (working memory), in addition to structural and diffusion imaging. All three tasks engaged a common set of fronto-parietal regions; however, the contributions of age, brain structure, and task performance to functional activity were unique to each domain. Aging was associated with differences in functional activity for all tasks, largely in regions outside common fronto-parietal control regions. Shifting and inhibition showed greater contributions of structure to overall decreases in brain activity, suggesting that more intact fronto-parietal structure may serve as a scaffold for efficient functional response. Working memory showed no contribution of structure to functional activity but had strong effects of age and task performance. Together, these results provide a comprehensive and novel examination of the joint contributions of aging, performance, and brain structure to functional activity across multiple domains of cognitive control.

Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan.

Healthy aging is accompanied by reduced cognitive control and widespread alterations in the underlying brain networks; but the extent to which large-scale functional networks in older age show reduced specificity across different domains of cognitive control is unclear. Here we use cov-STATIS (a multi-table multivariate technique) to examine similarity of functional connectivity during different domains of cognitive control-inhibition, initiation, shifting, and working memory-across the adult lifespan. We report two major findings: (1) Functional connectivity patterns during initiation, inhibition, and shifting were more similar in older ages, particularly for control and default networks, a pattern consistent with dedifferentiation of the neural correlates associated with cognitive control; and (2) Networks exhibited age-related reconfiguration such that frontal, default, and dorsal attention networks were more integrated whereas sub-networks of somato-motor system were more segregated in older age. Together these findings offer new evidence for dedifferentiation and reconfiguration of functional connectivity underlying different aspects of cognitive control in normal aging.

Inter-regional BOLD signal variability is an organizational feature of functional brain networks.

Neuronal variability patterns promote the formation and organization of neural circuits. Macroscale similarities in regional variability patterns may therefore be linked to the strength and topography of inter-regional functional connections. To assess this relationship, we used multi-echo resting-state fMRI and investigated macroscale connectivity-variability associations in 154 adult humans (86 women; mean age = 22yrs). We computed inter-regional measures of moment-to-moment BOLD signal variability and related them to inter-regional functional connectivity. Region pairs that showed stronger functional connectivity also showed similar BOLD signal variability patterns, independent of inter-regional distance and structural similarity. Connectivity-variability associations were predominant within all networks and followed a hierarchical spatial organization that separated sensory, motor and attention systems from limbic, default and frontoparietal control association networks. Results were replicated in a second held-out fMRI run. These findings suggest that macroscale BOLD signal variability is an organizational feature of large-scale functional networks, and shared inter-regional BOLD signal variability may underlie macroscale brain network dynamics.

Development of a Small Thermoelectric Generators Prototype for Energy Harvesting from Low Temperature Waste Heat at Industrial Plant.

A 39-W thermoelectric generator prototype has been realized and then installed in industrial plant for on-line trials. The prototype was developed as an energy harvesting demonstrator using low temperature cooling water waste heat as energy source. The objective of the research program is to measure the actual performances of this kind of device working with industrial water below 90 °C, as hot source, and fresh water at a temperature of about 15 °C, as cold sink. The article shows the first results of the research program. It was verified, under the tested operative conditions, that the produced electric power exceeds the energy required to pump the water from the hot source and cold sink to the thermoelectric generator unit if they are located at a distance not exceeding 50 m and the electric energy conversion efficiency is 0.33%. It was calculated that increasing the distance of the hot source and cold sink to the thermoelectric generator unit to 100 m the produced electric energy equals the energy required for water pumping, while reducing the distance of the hot source and cold sink to zero meters the developed unit produces an electric energy conversion efficiency of 0.61%.

Adsorption Device Based on a Langatate Crystal Microbalance for High Temperature High Pressure Gas Adsorption in Zeolite H-ZSM-5.

We present a high-temperature and high-pressure gas adsorption measurement device based on a high-frequency oscillating microbalance (5 MHz langatate crystal microbalance, LCM) and its use for gas adsorption measurements in zeolite H-ZSM-5. Prior to the adsorption measurements, zeolite H-ZSM-5 crystals were synthesized on the gold electrode in the center of the LCM, without covering the connection points of the gold electrodes to the oscillator, by the steam-assisted crystallization (SAC) method, so that the zeolite crystals remain attached to the oscillating microbalance while keeping good electroconductivity of the LCM during the adsorption measurements. Compared to a conventional quartz crystal microbalance (QCM) which is limited to temperatures below 80 °C, the LCM can realize the adsorption measurements in principle at temperatures as high as 200-300 °C (i.e., at or close to the reaction temperature of the target application of one-stage DME synthesis from the synthesis gas), owing to the absence of crystalline-phase transitions up to its melting point (1,470 °C). The system was applied to investigate the adsorption of CO2, H2O, methanol and dimethyl ether (DME), each in the gas phase, on zeolite H-ZSM-5 in the temperature and pressure range of 50-150 °C and 0-18 bar, respectively. The results showed that the adsorption isotherms of these gases in H-ZSM-5 can be well fitted by Langmuir-type adsorption isotherms. Furthermore, the determined adsorption parameters, i.e., adsorption capacities, adsorption enthalpies, and adsorption entropies, compare well to literature data. In this work, the results for CO2 are shown as an example.