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Decline in fluid abilities in normal aging is associated with increased white matter lesions, measured on T1-weighted images as white matter signal abnormalities (WMSAs). WMSAs are particularly evident in hypertensive older adults, suggesting vascular involvement. However, because hypertension is assessed systemically, the specific role of cerebral arterial stiffening in WMSAs has yet to be demonstrated. In 93 cognitively normal adults (aged 18-87 years), we used a novel method to measure cerebral arterial elasticity (pulse relaxation function [PReFx]) with diffuse optical tomography (pulse-DOT) and investigated its association with WMSAs, age, and cognition. PReFx was associated with WMSAs, with older adults with low PReFx showing the greatest WMSA burden. PReFx in brain regions perfused by the middle cerebral artery showed the largest associations with WMSAs and partially mediated the relationship between age and WMSAs. Finally, WMSAs partially mediated the relationship between PReFx and fluid but not crystallized abilities scores. Taken together, these findings suggest that loss of cerebral arterial elasticity is associated with cerebral white matter lesions and age-related cognitive decline. Accepted version

Skin-interfaced medical devices are critically important for diagnosing disease, monitoring physiological health and establishing control interfaces with prosthetics, computer systems and wearable robotic devices. Skin-like epidermal electronic technologies can support these use cases in soft and ultrathin materials that conformally interface with the skin in a manner that is mechanically and thermally imperceptible. Nevertheless, schemes so far have limited the overall sizes of these devices to less than a few square centimetres. Here, we present materials, device structures, handling and mounting methods, and manufacturing approaches that enable epidermal electronic interfaces that are orders of magnitude larger than previously realized. As a proof-of-concept, we demonstrate devices for electrophysiological recordings that enable coverage of the full scalp and the full circumference of the forearm. Filamentary conductive architectures in open-network designs minimize radio frequency-induced eddy currents, forming the basis for structural and functional compatibility with magnetic resonance imaging. We demonstrate the use of the large-area interfaces for the multifunctional control of a transhumeral prosthesis by patients who have undergone targeted muscle-reinnervation surgery, in long-term electroencephalography, and in simultaneous electroencephalography and structural and functional magnetic resonance imaging.

In both humans and animal models, consumption of a high-saturated-fat diet has been linked to vascular dysfunction and cognitive impairments. Laboratory animals provide excellent models for more invasive high-fat-diet-related research. However, the physiological differences between humans and common animal models in terms of how they react metabolically to high-fat diets need to be considered. Here, we review the factors that may affect the translatability of mechanistic research in animal models, paying special attention to the effects of a high-fat diet on vascular outcomes. We draw attention to the dissociation between metabolic syndrome and dyslipidemia in rodents, unlike the state in humans, where the two commonly occur. We also discuss the differential vulnerability between species to the metabolic and vascular effects of macronutrients in the diet. Findings from animal studies are better interpreted as modeling specific aspects of dysfunction. We conclude that the differences between species provide an opportunity to explore why some species are protected from the detrimental aspects of high-fat-diet-induced dysfunction, and to translate these findings into benefits for human health.

The process of aging includes changes in cellular biology that affect local interactions between cells and their environments and eventually propagate to systemic levels. In the brain, where neurons critically depend on an efficient and dynamic supply of oxygen and glucose, age‐related changes in the complex interaction between the brain parenchyma and the cerebrovasculature have effects on health and functioning that negatively impact cognition and play a role in pathology. Thus, cerebrovascular health is considered one of the main mechanisms by which a healthy lifestyle, such as habitual cardiorespiratory exercise and a healthful diet, could lead to improved cognitive outcomes with aging. This review aims at detailing how the physiology of the cerebral vascular system changes with age and how these changes lead to differential trajectories of cognitive maintenance or decline. This provides a framework for generating specific mechanistic hypotheses about the efficacy of proposed interventions and lifestyle covariates that contribute to enhanced cognitive well‐being. Finally, we discuss the methodological implications of age‐related changes in the cerebral vasculature for human cognitive neuroscience research and propose directions for future experiments aimed at investigating age‐related changes in the relationship between physiology and cognitive mechanisms., Impact Statement In this comprehensive review, we discuss, in detail, the physiology of how the cerebrovasculature can change with age and how these changes lead to differences in cognitive outcomes. The review provides a framework for generating mechanistic hypotheses about the efficacy of proposed interventions and lifestyle covariates that contribute to enhanced cognitive well‐being in aging and discusses methodological issues in human cognitive aging research related to cerebrovascular physiology.

Background Neurodevelopmental studies utilize the pig as a translational animal model due to anatomical and morphological similarities between the pig and human brain. However, neuroimaging resources are not as well developed for the pig as they are for humans and other animal models. We established a magnetic resonance imaging-based brain atlas at two different ages for biomedical studies utilizing the pig as a preclinical model. New Method Twenty artificially-reared domesticated male pigs (Sus scrofa) and thirteen sow-reared adolescent domesticated male pigs (Sus scrofa) underwent a series of scans measuring brain macrostructure, microstructure, and arterial cerebral blood volume. Results An atlas for the 4-week-old and 12-week-old pig were created along with twenty-six regions of interest. Normative data for brain measures were obtained and detailed descriptions of the data processing pipelines were provided. Comparison with Existing Method Atlases at the two different ages were created for the pig utilizing newer imaging technology and software. This facilitates the performance of longitudinal studies and enables more precise volume measurements in pigs of various ages by appropriately representing the neuroanatomical features of younger and older pigs and accommodating the proportion differences of the brain over time. Conclusion Two high-resolution MRI brain atlases specific to the domesticated young and adolescent pig were created using defined image acquisition and data processing methods to facilitate the generation of high-quality normative data for neurodevelopmental research.

The consumption of a diet high in fat and refined sugars has several health risks, including the development of cognitive decline and neurodegeneration. For women, menopause carries additional health risks that may interact with a high-fat diet in negative ways. Some symptoms of menopause, including cognitive impairments, can be modulated by hormone replacement therapy (HRT), but the hormonal formulation and the timing of the treatment relative to the onset of menopause are critical factors determining its efficacy. Little is known about how obesogenic, high-fat, high-sugar diets interact with HRT in menopause to affect cognition and neurodegeneration. Given the high prevalence of the consumption of an obesogenic Western-style diet, understanding how the effects of HRT are modulated by an obesogenic diet is critical for developing optimized therapeutic strategies for peri- and post-menopausal women. In this study, we investigated by magnetic resonance imaging (MRI) the effects of either immediate or delayed estradiol hormone therapy on cognition and neuroanatomy following ovo-hysterectomy (OvH) of aged, female rhesus macaques on an obesogenic diet. The macaques were followed for 2.5 years after ovo-hysterectomy, with four time points at which anatomical MRIs were acquired. Analysis of hippocampal volumes revealed an interaction between time point and treatment; hippocampal volumes in the delayed estrogen group, but not the immediate estrogen group, increased over time compared to those in untreated controls. Performance on a hippocampal-dependent spatial maze task showed improved performance in estrogen treated animals compared to OvH macaques given placebo. These results indicate that HRT may contribute to beneficial cognitive outcomes after menopause under an obesogenic diet.

In this study, we investigated gray and white matter changes in subgroups within the larger tinnitus population related to differences in severity or duration of tinnitus symptoms. Tinnitus is the illusory perception of sound in the absence of an external source, most often experienced as a chronic condition. The psychological reaction to the sound constitutes the severity, or degree of discomfort experienced, and the duration refers to the time since onset of chronic tinnitus. We used voxel- and surface-based morphometry to investigate gray matter changes and diffusion tensor imaging (using fractional anisotropy, or FA, metrics) to assess changes in orientation of white matter tracts, using both whole brain and region of interest analyses. Whole brain analyses revealed decreased cortical thickness in the left parahippocampal gyrus in those with more severe tinnitus compared to a group with a milder reaction, and reduced gray matter volume in left anterior cingulate in those with mild tinnitus compared to a normal hearing control group without tinnitus. In the analysis based on FA, no significant differences were revealed between the subgroups or with respect to control groups in either whole brain or region of interest analyses. Our results suggest that these subgroups within the tinnitus population likely exhibit different anatomical alterations related to the disorder, which may explain the variable findings in the literature, particularly in terms of gray matter.

Aging is often accompanied by changes in brain anatomy and cerebrovascular health. However, the specific relationship between declines in regional cortical volumes and loss of cerebral arterial elasticity is less clear, as only global or very localized estimates of cerebrovascular health have been available. Here we employed a novel tomographic optical method (pulse-DOT) to derive local estimates of cerebral arterial elasticity and compared regional volumetric estimates (obtained with FreeSurfer) with optical arterial elasticity estimates from the same regions in 47 healthy adults (aged 18–75). Between-subject analyses revealed a global correlation between cortical volume and cortical arterial elasticity, which was a significant mediator of the association between age and cortical volume. Crucially, a novel within-subject analysis highlighted the spatial association between regional variability in cortical volumes and arterial elasticity in the same regions. This association strengthened with age. Gains in the predictability of cortical volumes from arterial elasticity data were obtained by sharpening the resolution up to individual cortical regions. These results indicate that some of the variance of sub-clinical age-related brain atrophy is associated with differences in the status of cerebral arteries, and can help to explain the unique patterns of brain atrophy found within each individual.

Mindfulness-based therapies have been introduced as a treatment option to reduce the psychological severity of tinnitus, a currently incurable chronic condition. This pilot study of twelve subjects with chronic tinnitus investigates the relationship between measures of both task-based and resting state functional magnetic resonance imaging (fMRI) and measures of tinnitus severity, assessed with the Tinnitus Functional Index (TFI). MRI was measured at three time points: before, after, and at follow-up of an 8-week long mindfulness-based cognitive therapy intervention. During the task-based fMRI with affective sounds, no significant changes were observed between sessions, nor was the activation to emotionally salient compared to neutral stimuli significantly predictive of TFI. Significant results were found using resting state fMRI. There were significant decreases in functional connectivity among the default mode network, cingulo-opercular network, and amygdala across the intervention, but no differences were seen in connectivity with seeds in the dorsal attention network (DAN) or fronto-parietal network and the rest of the brain. Further, only resting state connectivity between the brain and the amygdala, DAN, and fronto-parietal network significantly predicted TFI. These results point to a mostly differentiated landscape of functional brain measures related to tinnitus severity on one hand and mindfulness-based therapy on the other. However, overlapping results of decreased amygdala connectivity with parietal areas and the negative correlation between amygdala-parietal connectivity and TFI is suggestive of a brain imaging marker of successful treatment.

Objective: We used a minimally-modified version of Mindfulness-Based Cognitive Therapy (MBCT) to treat symptoms of distress associated with tinnitus.Design: Audiological screening (establishing a baseline) was conducted prior to treatment and at three time-points: pre-intervention, post-intervention and follow-up, 8 weeks after completion of training. MRI tests were also conducted at these three time-points.Study sample: Twenty-one participants were enrolled in the study, of whom 15 completed training and audiological testing and eight completed the MRI portion of the study.Results: Scores on tinnitus-related questionnaires showed a significant decline either from pre- to post-intervention or from pre-intervention to follow-up, despite no significant change during baseline. Voxel-based morphometric analysis of the structural MRI scans revealed clusters in bilateral superior frontal gyrus that exhibited significant increases in grey matter volume over the period of intervention and follow-up. Further, grey matter changes in occipital and cingulate regions correlated with declines in tinnitus handicap.Conclusions: This pilot study supports MBCT as an adequate approach for treating distressing tinnitus and suggests that neuroanatomical changes may reflect reductions in tinnitus-related severity. Although our small sample size precludes drawing strong conclusions, there is potential for assessing neuroanatomical changes due to mindfulness-based interventions in tinnitus.

Aging is accompanied by widespread changes in brain tissue. Here, we hypothesized that head tissue opacity to near-infrared light provides information about the health status of the brain&rsquo, s cortical mantle. In diffusive media such as the head, opacity is quantified through the Effective Attenuation Coefficient (EAC), which is proportional to the geometric mean of the absorption and reduced scattering coefficients. EAC is estimated by the slope of the relationship between source&ndash, detector distance and the logarithm of the amount of light reaching the detector (optical density). We obtained EAC maps across the head in 47 adults (age range 18&ndash, 75 years), using a high-density dual-wavelength optical system. We correlated regional and global EAC measures with demographic, neuropsychological, structural and functional brain data. Results indicated that EAC values averaged across wavelengths were strongly associated with age-related changes in cortical thickness, as well as functional and neuropsychological measures. This is likely because the EAC largely depends on the thickness of the sub-arachnoid cerebrospinal fluid layer, which increases with cortical atrophy. In addition, differences in EAC values between wavelengths were correlated with tissue oxygenation and cardiorespiratory fitness, indicating that information about cortical health can be derived non-invasively by quantifying the EAC.

Cerebrovascular health is important for maintaining a high level of cognitive performance, not only in old age, but also throughout the lifespan. Recently, it was first demonstrated that diffuse optical imaging measures of pulse amplitude and arterial compliance can provide estimates of cerebral arterial health throughout the cortex, and were associated with age, estimated cardiorespiratory fitness (eCRF), neuroanatomy and cognitive function in older adults (aged 55-87). The current study replicates and extends the original findings using a broader age range (a new adult sample aged 18-75), longer recording periods (360 s), and a more extensive optical montage (1536 channels). These methodological improvements represent a 5-fold increase in recording time and a 4-fold increase in coverage compared to the initial study. Results show that reliability for both pulse amplitude and compliance measures across recording blocks was very high (r(45) = .99 and .75, respectively). Pulse amplitude and pulse pressure were shown to correlate with age across the broader age range. We also found correlations between arterial health and both cortical and subcortical gray matter volumes. Additionally, we replicated the correlations between arterial compliance and age, eCRF, global brain atrophy, and cognitive flexibility. New regional analyses revealed that higher performance on the operation span (OSPAN) working memory task was associated with greater localized arterial compliance in frontoparietal cortex, but not with global arterial compliance. Further, greater arterial compliance in frontoparietal regions was associated with younger age and higher eCRF. These associations were not present in the visual cortex. The current study not only replicates the initial one in a sample including a much wider age range, but also provides new evidence showing that frontoparietal regions may be especially vulnerable to vascular degeneration during brain aging, with potential functional consequences in cognition.

In Fig. 4c of this Article, the scale bar units were incorrectly stated as ‘μV’; the correct units are ‘mV’. The figure has now been amended accordingly.

Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors.

The human cerebral vasculature responds to changes in blood pressure and demands for oxygenation via cerebral autoregulation. Changes in cerebrovascular tone (vasoconstriction and vasodilation) also mediate the changes in blood flow measured by the BOLD fMRI signal. This cerebrovascular reactivity is known to vary with age. In two experiments, we demonstrate that cerebral pulse parameters measured using optical imaging can quantify changes in cerebral vascular tone, both globally and locally. In experiment 1, 51 older adults (age range = 55–87) performed a voluntary breath-holding task while cerebral pulse amplitude measures were taken. We found significant pulse amplitude variations across breath-holding periods, indicating vasodilation during, and vasoconstriction after breath holding. The breath-holding index (BHI), a measure of cerebrovascular reactivity (CVR) was derived and found to correlate with age. BHI was also correlated with performance in the Modified Mini-Mental Status Examination, even after controlling for age and education. In experiment 2, the same participants performed a Sternberg task, and changes in regional pulse amplitude between high (set-size 6) and low (set-size 2) task loads were compared. Only task-related areas in the fronto-parietal network (FPN) showed significant reduction in pulse amplitude, indicating vasodilation. Non-task-related areas such as the somatosensory and auditory cortices did not show such reductions. Taken together, these experiments suggest that optical pulse parameters can index changes in brain vascular tone both globally and locally, using both physiological and cognitive load manipulations.

The brain’s vasculature is likely to be subjected to the same age-related physiological and anatomical changes affecting the rest of the cardiovascular system. Since aerobic fitness is known to alleviate both cognitive and volumetric losses in the brain, it is important to investigate some of the possible mechanisms underlying these beneficial changes. Here we investigated the role that estimated cardiorespiratory fitness (eCRF) plays in determining the relationship between aging and cerebral blood flow (CBF) in a group of older adults (ages 55-85). Using arterial spin labeling to quantify CBF, we found that blood flow in the gray matter was positively correlated with eCRF and negatively correlated with age. Subsequent analyses revealed that eCRF fully mediated the effects of age on CBF in the gray matter, but not in the white matter. Additionally, regional measures of CBF were related to regional measures of brain volume. These findings provide evidence that age-related effects on cerebrovascular health and perfusion in older adults are largely influenced by their eCRF levels.