Assessment of the effects of aerobic fitness on cerebrovascular function in young adults using multiple inversion time arterial spin labeling MRI

This cross-sectional study investigated the effects of aerobic fitness on cerebrovascular function in the healthy brain. Gray matter cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were quantified in a sample of young adults within a normal fitness range. Based on existing Transcranial Doppler ultrasound and fMRI evidence, we predicted a positive relationship between fitness and resting gray matter CBF and CVR. Exploratory hypotheses that higher V.O2peak would be associated with higher GM volume and cognitive performance were also investigated. 20 adults underwent a V.O2peak test and a battery of cognitive tests. All subjects also underwent an MRI scan where multiple inversion time (MTI) pulsed arterial spin labeling (PASL) was used to quantify resting CBF and CVR to 5% CO2. Region of interest analysis showed a non-significant inverse correlation between whole-brain gray matter CBF and V.O2peak; r = −0.4, p = 0.08, corrected p (p′) = 0.16 and a significant positive correlation between V.O2peak and whole-brain averaged gray matter CVR; r = 0.62, p = 0.003, p′ = 0.006. Voxel-wise analysis revealed a significant inverse association between V.O2peak and resting CBF in the left and right thalamus, brainstem, right lateral occipital cortex, left intra-calcarine cortex and cerebellum. The results of this study suggest that aerobic fitness is associated with lower baseline CBF and greater CVR in young adults

Cerebral metabolic changes during visuomotor adaptation assessed using quantitative fMRI

The brain retains a lifelong ability to adapt through learning and in response to injury or disease-related damage, a process known as functional neuroplasticity. The neural energetics underlying functional brain plasticity have not been thoroughly investigated experimentally in the healthy human brain. A better understanding of the blood flow and metabolic changes that accompany motor skill acquisition, and which facilitate plasticity, is needed before subsequent translation to treatment interventions for recovery of function in disease. The aim of the current study was to characterize cerebral blood flow (CBF) and oxygen consumption (relative CMRO2) responses, using calibrated fMRI conducted in 20 healthy participants, during performance of a serial reaction time task which induces rapid motor adaptation. Regions of interest (ROIs) were defined from areas showing task-induced BOLD and CBF responses that decreased over time. BOLD, CBF and relative CMRO2 responses were calculated for each block of the task. Motor and somatosensory cortices and the cerebellum showed statistically significant positive responses to the task compared to baseline, but with decreasing amplitudes of BOLD, CBF, and CMRO2 response as the task progressed. In the cerebellum, there was a sustained positive BOLD response in the absence of a significant CMRO2 increase from baseline, for all but the first task blocks. This suggests that the brain may continue to elevate the supply energy even after CMRO2 has returned to near baseline levels. Relying on BOLD fMRI data alone in studies of plasticity may not reveal the nature of underlying metabolic responses and their changes over time. Calibrated fMRI approaches may offer a more complete picture of the energetic changes supporting plasticity and learning

Designing assisted living technologies 'in the wild' : preliminary experiences with cultural probe methodology

Background There is growing interest in assisted living technologies to support independence at home. Such technologies should ideally be designed ‘in the wild’ i.e. taking account of how real people live in real homes and communities. The ATHENE (Assistive Technologies for Healthy Living in Elders: Needs Assessment by Ethnography) project seeks to illuminate the living needs of older people and facilitate the co-production with older people of technologies and services. This paper describes the development of a cultural probe tool produced as part of the ATHENE project and how it was used to support home visit interviews with elders with a range of ethnic and social backgrounds, family circumstances, health conditions and assisted living needs. Method Thirty one people aged 60 to 98 were visited in their homes on three occasions. Following an initial interview, participants were given a set of cultural probe materials, including a digital camera and the ‘Home and Life Scrapbook’ to complete in their own time for one week. Activities within the Home and Life Scrapbook included maps (indicating their relationships to people, places and objects), lists (e.g. likes, dislikes, things they were concerned about, things they were comfortable with), wishes (things they wanted to change or improve), body outline (indicating symptoms or impairments), home plan (room layouts of their homes to indicate spaces and objects used) and a diary. After one week, the researcher and participant reviewed any digital photos taken and the content of the Home and Life Scrapbook as part of the home visit interview. Findings The cultural probe facilitated collection of visual, narrative and material data by older people, and appeared to generate high levels of engagement from some participants. However, others used the probe minimally or not at all for various reasons including limited literacy, physical problems (e.g. holding a pen), lack of time or energy, limited emotional or psychological resources, life events, and acute illness. Discussions between researchers and participants about the materials collected (and sometimes about what had prevented them completing the tasks) helped elicit further information relevant to assisted living technology design. The probe materials were particularly helpful when having conversations with non-English speaking participants through an interpreter. Conclusions Cultural probe methods can help build a rich picture of the lives and experiences of older people to facilitate the co-production of assisted living technologies. But their application may be constrained by the participant’s physical, mental and emotional capacity. They are most effective when used as a tool to facilitate communication and development of a deeper understanding of older people’s needs

Hippocampal blood flow is increased after 20 min of moderate-intensity exercise

Long-term exercise interventions have been shown to be a potent trigger for both neurogenesis and vascular plasticity. However, little is known about the underlying temporal dynamics and specifically when exercise-induced vascular adaptations first occur, which is vital for therapeutic applications. In this study, we investigated whether a single session of moderate-intensity exercise was sufficient to induce changes in the cerebral vasculature. We employed arterial spin labeling magnetic resonance imaging to measure global and regional cerebral blood flow (CBF) before and after 20 min of cycling. The blood vessels’ ability to dilate, measured by cerebrovascular reactivity (CVR) to CO2 inhalation, was measured at baseline and 25-min postexercise. Our data showed that CBF was selectively increased by 10–12% in the hippocampus 15, 40, and 60 min after exercise cessation, whereas CVR to CO2 was unchanged in all regions. The absence of a corresponding change in hippocampal CVR suggests that the immediate and transient hippocampal adaptations observed after exercise are not driven by a mechanical vascular change and more likely represents an adaptive metabolic change, providing a framework for exploring the therapeutic potential of exercise-induced plasticity (neural, vascular, or both) in clinical and aged populations

Diagenetic priming of submarine landslides in ooze-rich substrates

Oozes are the most widespread deep-sea sediment in the global ocean, but very little is known about how changes in their physical properties during burial impact slope stability and related geohazards. We used three-dimensional seismic reflection, geochemical, and petrophysical data acquired both within and adjacent to 13 large (in total ~6330 km2) submarine slides on the Exmouth Plateau, North West Shelf, Australia, to investigate how the pre-slide physical properties of oozes control slope failure and emplacement processes. Our integrated data set allows potential slide surfaces to be detected within ooze successions, a crucial advance for improved submarine geohazard assessment. Moreover, we demonstrate that the interplay of tectonics, ocean current activity, and silica diagenesis can prime multiple slides on very low-gradient slopes in tropical oceanic basins. Therefore, the diagenetic state of silica-rich sediments should be considered in future studies to improve slope stability assessments

Changes in white matter microstructure and MRI-derived cerebral blood flow after one-week of exercise training

Exercise is beneficial for brain health, inducing neuroplasticity and vascular plasticity in the hippocampus, which is possibly mediated by brain-derived neurotrophic factor (BDNF) levels. Here we investigated the short-term effects of exercise, to determine if a 1-week intervention is sufficient to induce brain changes. Fifteen healthy young males completed five supervised exercise training sessions over seven days. This was preceded and followed by a multi-modal magnetic resonance imaging (MRI) scan (diffusion-weighted MRI, perfusion-weighted MRI, dual-calibrated functional MRI) acquired 1 week apart, and blood sampling for BDNF. A diffusion tractography analysis showed, after exercise, a significant reduction relative to baseline in restricted fraction—an axon-specific metric—in the corpus callosum, uncinate fasciculus, and parahippocampal cingulum. A voxel-based approach found an increase in fractional anisotropy and reduction in radial diffusivity symmetrically, in voxels predominantly localised in the corpus callosum. A selective increase in hippocampal blood flow was found following exercise, with no change in vascular reactivity. BDNF levels were not altered. Thus, we demonstrate that 1 week of exercise is sufficient to induce microstructural and vascular brain changes on a group level, independent of BDNF, providing new insight into the temporal dynamics of plasticity, necessary to exploit the therapeutic potential of exercise

A qualitative study of Telehealth patient information leaflets (TILs) : are we giving patients enough information?

BACKGROUND: The provision of patient information leaflets regarding telehealth has been perceived by potential consumers as a strategy to promote awareness and adoption of telehealth services. However, such leaflets need to be designed carefully if adoption and awareness among potential users is to be promoted. Therefore, the aims of this study were: first, to see how telehealth was portrayed in some of the existing telehealth leaflets (THLs). Second, to explore patients' perceptions of the existing THLs and their engagement with the concept and how THLs can be optimised. METHODS: A two-step approach was employed to address the aims of this study. The first phase involved the use of discourse analysis to compare 12 electronically and publically available THLs, with the existing THL guidance "Involve Yorkshire and Humber". The second phase involved conducting 14 semi-structured interviews with potential telehealth users/patients to gauge their perception and engagement with the concept, using the two leaflets that were mostly matching with the guidance used. Six interviews were audio-recorded and eight had detailed jotted notes. The interviews were transcribed and thematically analysed to identify key themes. RESULTS: The discourse analysis showed certain gaps and variations within the screened leaflets when addressing the following aspects: cost of the telehealth service, confidentiality, patients' choices in addition to equipment use and technical support. Analysis of the interviews revealed patients' need for having clear and sufficient information about the telehealth service within the THLs; in addition to, patients' preference for the use of simpler terminologies for telehealth description and the provision of clear simple texts with pictorial presentations. The interviews also revealed certain limitations against adoption of telehealth by the participants, such as: lack of privacy and confidentiality of information, fear of technology breakdown and equipment failure, loss of face-to-face contact with healthcare professionals and being too dependent on the telehealth service. CONCLUSION: The current study showed a great variation among the screened THLs and highlighted certain gaps within the content and presentation of these leaflets. However, the study also highlighted certain key issues to be considered when designing THLs in the future to enhance telehealth uptake and use by patients

Surveillance Technology in Dementia Care: Implicit Assumptions and Unresolved Tensions

This paper examines the concept of “Surveillance Technology [ST]” as it is used in ageing and dementia research but which suffers from poor definition. We attempt to clarify this imprecision by contextualizing a brief history of the development of ST and provide a summary of the research in this area. We contrast this with the responses provided by a public and patient involvement group of people living with a dementia diagnosis, or experience of supporting people with dementia. ST operates in multiple interacting ways, all of which need to be taken into account in research, public and policy debate. As a technology it is often seen as a way of assisting individuals and therefore classified as an Assistive Technology [AT]. However, the meaning of ST used in dementia care has pragmatic implications beyond the meeting of the needs for “safety and independence”; ideas which is often used to justify its use. We argue that there is need to interrogate the terms “Surveillance” and “Technology” more carefully if ST is to be considered as empowering for people with dementia. This tension is brought out in the accounts present in a group discussion on ST and its use. This paper argues that there needs to be an acknowledgement that the purposes of such technologies need to be regularly reviewed in order for society to keep up with the rapidly changing pace of technology and the changing needs of users

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI

One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10−3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application

A Src-Tks5 Pathway Is Required for Neural Crest Cell Migration during Embryonic Development

In the adult organism, cell migration is required for physiological processes such as angiogenesis and immune surveillance, as well as pathological events such as tumor metastasis. The adaptor protein and Src substrate Tks5 is necessary for cancer cell migration through extracellular matrix in vitro and tumorigenicity in vivo. However, a role for Tks5 during embryonic development, where cell migration is essential, has not been examined. We used morpholinos to reduce Tks5 expression in zebrafish embryos, and observed developmental defects, most prominently in neural crest-derived tissues such as craniofacial structures and pigmentation. The Tks5 morphant phenotype was rescued by expression of mammalian Tks5, but not by a variant of Tks5 in which the Src phosphorylation sites have been mutated. We further evaluated the role of Tks5 in neural crest cells and neural crest-derived tissues and found that loss of Tks5 impaired their ventral migration. Inhibition of Src family kinases also led to abnormal ventral patterning of neural crest cells and their derivatives. We confirmed that these effects were likely to be cell autonomous by shRNA-mediated knockdown of Tks5 in a murine neural crest stem cell line. Tks5 was required for neural crest cell migration in vitro, and both Src and Tks5 were required for the formation of actin-rich structures with similarity to podosomes. Additionally, we observed that neural crest cells formed Src-Tks5-dependent cell protrusions in 3-D culture conditions and in vivo. These results reveal an important and novel role for the Src-Tks5 pathway in neural crest cell migration during embryonic development. Furthermore, our data suggests that this pathway regulates neural crest cell migration through the generation of actin-rich pro-migratory structures, implying that similar mechanisms are used to control cell migration during embryogenesis and cancer metastasis