The multisensory attentional consequences of tool use : a functional magnetic resonance imaging study

Background: Tool use in humans requires that multisensory information is integrated across different locations, from objects seen to be distant from the hand, but felt indirectly at the hand via the tool. We tested the hypothesis that using a simple tool to perceive vibrotactile stimuli results in the enhanced processing of visual stimuli presented at the distal, functional part of the tool. Such a finding would be consistent with a shift of spatial attention to the location where the tool is used. Methodology/Principal Findings: We tested this hypothesis by scanning healthy human participants’ brains using functional magnetic resonance imaging, while they used a simple tool to discriminate between target vibrations, accompanied by congruent or incongruent visual distractors, on the same or opposite side to the tool. The attentional hypothesis was supported: BOLD response in occipital cortex, particularly in the right hemisphere lingual gyrus, varied significantly as a function of tool position, increasing contralaterally, and decreasing ipsilaterally to the tool. Furthermore, these modulations occurred despite the fact that participants were repeatedly instructed to ignore the visual stimuli, to respond only to the vibrotactile stimuli, and to maintain visual fixation centrally. In addition, the magnitude of multisensory (visual-vibrotactile) interactions in participants’ behavioural responses significantly predicted the BOLD response in occipital cortical areas that were also modulated as a function of both visual stimulus position and tool position. Conclusions/Significance: These results show that using a simple tool to locate and to perceive vibrotactile stimuli is accompanied by a shift of spatial attention to the location where the functional part of the tool is used, resulting in enhanced processing of visual stimuli at that location, and decreased processing at other locations. This was most clearly observed in the right hemisphere lingual gyrus. Such modulations of visual processing may reflect the functional importance of visuospatial information during human tool use

Allostatic load as a predictor of grey matter volume and white matter integrity in old age: The Whitehall II MRI study.

The allostatic load index quantifies the cumulative multisystem physiological response to chronic everyday stress, and includes cardiovascular, metabolic and inflammatory measures. Despite its central role in the stress response, research of the effect of allostatic load on the ageing brain has been limited. We investigated the relation of mid-life allostatic load index and multifactorial predictors of stroke (Framingham stroke risk) and diabetes (metabolic syndrome) with voxelwise structural grey and white matter brain integrity measures in the ageing Whitehall II cohort (N = 349, mean age = 69.6 (SD 5.2) years, N (male) = 281 (80.5%), mean follow-up before scan = 21.4 (SD 0.82) years). Higher levels of all three markers were significantly associated with lower grey matter density. Only higher Framingham stroke risk was significantly associated with lower white matter integrity (low fractional anisotropy and high mean diffusivity). Our findings provide some empirical support for the concept of allostatic load, linking the effect of everyday stress on the body with features of the ageing human brain

Inter- and intra-individual variation in brain structural-cognition relationships in aging

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure

Distinct resting-state functional connections associated with episodic and visuospatial memory in older adults.

Episodic and spatial memory are commonly impaired in ageing and Alzheimer's disease. Volumetric and task-based functional magnetic resonance imaging (fMRI) studies suggest a preferential involvement of the medial temporal lobe (MTL), particularly the hippocampus, in episodic and spatial memory processing. The present study examined how these two memory types were related in terms of their associated resting-state functional architecture. 3T multiband resting state fMRI scans from 497 participants (60-82 years old) of the cross-sectional Whitehall II Imaging sub-study were analysed using an unbiased, data-driven network-modelling technique (FSLNets). Factor analysis was performed on the cognitive battery; the Hopkins Verbal Learning test and Rey-Osterreith Complex Figure test factors were used to assess verbal and visuospatial memory respectively. We present a map of the macroscopic functional connectome for the Whitehall II Imaging sub-study, comprising 58 functionally distinct nodes clustered into five major resting-state networks. Within this map we identified distinct functional connections associated with verbal and visuospatial memory. Functional anticorrelation between the hippocampal formation and the frontal pole was significantly associated with better verbal memory in an age-dependent manner. In contrast, hippocampus-motor and parietal-motor functional connections were associated with visuospatial memory independently of age. These relationships were not driven by grey matter volume and were unique to the respective memory domain. Our findings provide new insights into current models of brain-behaviour interactions, and suggest that while both episodic and visuospatial memory engage MTL nodes of the default mode network, the two memory domains differ in terms of the associated functional connections between the MTL and other resting-state brain networks

Resilience and MRI correlates of cognitive impairment in community-dwelling elders.

BACKGROUND: The contribution of education and intelligence to resilience against age-related cognitive decline is not clear, particularly in the presence of 'normal for age' minor brain abnormalities. METHOD: Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes. RESULTS: Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) <26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy. CONCLUSIONS: Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment

Associations between Mobility, Cognition, and Brain Structure in Healthy Older Adults.

Mobility limitations lead to a cascade of adverse events in old age, yet the neural and cognitive correlates of mobility performance in older adults remain poorly understood. In a sample of 387 adults (mean age 69.0 ± 5.1 years), we tested the relationship between mobility measures, cognitive assessments, and MRI markers of brain structure. Mobility was assessed in 2007-2009, using gait, balance and chair-stands tests. In 2012-2015, cognitive testing assessed executive function, memory and processing-speed; gray matter volumes (GMV) were examined using voxel-based morphometry, and white matter microstructure was assessed using tract-based spatial statistics of fractional anisotropy, axial diffusivity (AD), and radial diffusivity (RD). All mobility measures were positively associated with processing-speed. Faster walking speed was also correlated with higher executive function, while memory was not associated with any mobility measure. Increased GMV within the cerebellum, basal ganglia, post-central gyrus, and superior parietal lobe was associated with better mobility. In addition, better performance on the chair-stands test was correlated with decreased RD and AD. Overall, our results indicate that, even in non-clinical populations, mobility measures can be sensitive to sub-clinical variance in cognition and brain structures

Sub-threshold depressive symptoms and brain structure: A magnetic resonance imaging study within the Whitehall II cohort.

BACKGROUND: Late-life sub-threshold depressive symptoms (i.e. depressive symptoms that do not meet the criteria for a diagnosis of major depressive disorder) are associated with impaired physical health and function, and increased risk of major depressive disorder. Magnetic resonance imaging (MRI) studies examining late-life major depressive disorder find structural brain changes in grey and white matter. However, the extent to which late-life sub-threshold depression is associated with similar hallmarks is not well established. METHODS: Participants with no history of major depressive disorder were selected from the Whitehall Imaging Sub-Study (n=358, mean age 69±5 years, 17% female). Depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale (CES-D) at three previous Whitehall II Study phases (2003-04, 2007-09 and 2012-13) and at the time of the MRI scan (2012-14). The relationships between current and cumulative depressive symptoms and MRI brain measures were explored using Voxel-Based Morphometry (VBM) for grey matter and Tract Based Spatial Statistics (TBSS) for white matter. RESULTS: Current sub-threshold depressive symptoms were associated with significant reductions in fractional anisotropy and increases in axial and radial diffusivity. There were no significant relationships between current depressive symptoms and grey matter measures, or cumulative depressive symptoms and MRI measures. LIMITATIONS: The prevalence (10%) of sub-threshold depressive symptoms means that analyses may be underpowered to detect subtle differences in brain structure. CONCLUSIONS: Current sub-threshold depressive symptoms are associated with changes in white matter microstructure, indicating that even mild depressive symptoms are associated with similar MRI hallmarks to those in major depressive disorder

A criteria-driven approach to the CO2 storage site selection of East Mey for the acorn project in the North Sea

Carbon Capture and Storage (CCS) is an essential tool in the fight against climate change. Any prospective storage site must meet various criteria that ensure the effectiveness, safety and economic viability of the storage operations. Finding the most suitable site for the storage of the captured CO2 is an essential part of the CCS chain of activity. This work addresses the site selection of a second site for the Acorn CCS project, a project designed to develop a scalable, full-chain CCS project in the North Sea (offshore northeast Scotland). This secondary site has been designed to serve as a backup and upscaling option for the Acorn Site, and has to satisfy pivotal project requirements such as low cost and high storage potential. The methodology followed included the filtering of 113 input sites from the UK CO2Stored database, according to general and project-specific criteria in a multi-staged approach. This criteria-driven workflow allowed for an early filtering out of the less suitable sites, followed by a more comprehensive comparison and ranking of the 15 most suitable sites. A due diligence assessment was conducted of the top six shortlisted sites to produce detailed assessment of their storage properties and suitability, including new geological interpretation and capacity calculations for each site. With the new knowledge generated during this process, a critical comparison of the sites led to selection of East Mey as the most suitable site, due to its outstanding storage characteristics and long-lasting hydrocarbon-production history, that ensure excellent data availability to risk-assess storage structures. A workshop session was held to present methods and results to independent stakeholders; feedback informed the final selection criteria. This paper provides an example of a criteria-driven approach to site selection that can be applied elsewhere.Project ACT-Acorn is gratefully thanked for funding this study. ACT Acorn, project 271500, received funding from BEIS (UK), RCN (Norway) and RVO (Netherland), and was co-funded by the European Commission under the ERA-Net instrument of the Horizon 2020 programme. ACT Grant number 691712. J. Alcalde is funded by MICINN (Juan de la Cierva fellowship - IJC2018-036074-I). S. Ghanbari is currently supported by the Energi Simulation. Energi Simulation is also thanked for funding the chair in reactive transport simulation held by E. Mackay.Peer reviewe

Classification and characterization of periventricular and deep white matter hyperintensities on MRI: A study in older adults.

White matter hyperintensities (WMH) are frequently divided into periventricular (PWMH) and deep (DWMH), and the two classes have been associated with different cognitive, microstructural, and clinical correlates. However, although this distinction is widely used in visual ratings scales, how to best anatomically define the two classes is still disputed. In fact, the methods used to define PWMH and DWMH vary significantly between studies, making results difficult to compare. The purpose of this study was twofold: first, to compare four current criteria used to define PWMH and DWMH in a cohort of healthy older adults (mean age: 69.58 ± 5.33 years) by quantifying possible differences in terms of estimated volumes; second, to explore associations between the two WMH sub-classes with cognition, tissue microstructure and cardiovascular risk factors, analysing the impact of different criteria on the specific associations. Our results suggest that the classification criterion used for the definition of PWMH and DWMH should not be considered a major obstacle for the comparison of different studies. We observed that higher PWMH load is associated with reduced cognitive function, higher mean arterial pressure and age. Higher DWMH load is associated with higher body mass index. PWMH have lower fractional anisotropy than DWMH, which also have more heterogeneous microstructure. These findings support the hypothesis that PWMH and DWMH are different entities and that their distinction can provide useful information about healthy and pathological aging processes

Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study.

Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were "alcohol dependent" according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US