Publications by authors named "Richard G Wise"

102 Publications

Distinct effects of prematurity on MRI metrics of brain functional connectivity, activity, and structure: Univariate and multivariate analyses.

Hum Brain Mapp 2021 May 6. Epub 2021 May 6.

Department of Neuroscience, Imaging, and Clinical Sciences, University G. D'Annunzio of Chieti-Pescara; Institute for Advanced Biomedical Technologies, Chieti, Italy.

Premature birth affects the developmental trajectory of the brain during a period of intense maturation with possible lifelong consequences. To better understand the effect of prematurity on brain structure and function, we performed blood-oxygen-level dependent (BOLD) and anatomical magnetic resonance imaging (MRI) at 40 weeks of postmenstrual age on 88 newborns with variable gestational age (GA) at birth and no evident radiological alterations. We extracted measures of resting-state functional connectivity and activity in a set of 90 cortical and subcortical brain regions through the evaluation of BOLD correlations between regions and of fractional amplitude of low-frequency fluctuation (fALFF) within regions, respectively. Anatomical information was acquired through the assessment of regional volumes. We performed univariate analyses on each metric to examine the association with GA at birth, the spatial distribution of the effects, and the consistency across metrics. Moreover, a data-driven multivariate analysis (i.e., Machine Learning) framework exploited the high dimensionality of the data to assess the sensitivity of each metric to the effect of premature birth. Prematurity was associated with bidirectional alterations of functional connectivity and regional volume and, to a lesser extent, of fALFF. Notably, the effects of prematurity on functional connectivity were spatially diffuse, mainly within cortical regions, whereas effects on regional volume and fALFF were more focal, involving subcortical structures. While the two analytical approaches delivered consistent results, the multivariate analysis was more sensitive in capturing the complex pattern of prematurity effects. Future studies might apply multivariate frameworks to identify premature infants at risk of a negative neurodevelopmental outcome.
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http://dx.doi.org/10.1002/hbm.25456DOI Listing
May 2021

Evaluation of denoising strategies for task-based functional connectivity: Equalizing residual motion artifacts between rest and cognitively demanding tasks.

Hum Brain Mapp 2021 Apr 2;42(6):1805-1828. Epub 2021 Feb 2.

MARBILab, CREF - Centro Ricerche Enrico Fermi, Roma, 00184, Italy.

In-scanner head motion represents a major confounding factor in functional connectivity studies and it raises particular concerns when motion correlates with the effect of interest. One such instance regards research focused on functional connectivity modulations induced by sustained cognitively demanding tasks. Indeed, cognitive engagement is generally associated with substantially lower in-scanner movement compared with unconstrained, or minimally constrained, conditions. Consequently, the reliability of condition-dependent changes in functional connectivity relies on effective denoising strategies. In this study, we evaluated the ability of common denoising pipelines to minimize and balance residual motion-related artifacts between resting-state and task conditions. Denoising pipelines-including realignment/tissue-based regression, PCA/ICA-based methods (aCompCor and ICA-AROMA, respectively), global signal regression, and censoring of motion-contaminated volumes-were evaluated according to a set of benchmarks designed to assess either residual artifacts or network identifiability. We found a marked heterogeneity in pipeline performance, with many approaches showing a differential efficacy between rest and task conditions. The most effective approaches included aCompCor, optimized to increase the noise prediction power of the extracted confounding signals, and global signal regression, although both strategies performed poorly in mitigating the spurious distance-dependent association between motion and connectivity. Censoring was the only approach that substantially reduced distance-dependent artifacts, yet this came at the great cost of reduced network identifiability. The implications of these findings for best practice in denoising task-based functional connectivity data, and more generally for resting-state data, are discussed.
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http://dx.doi.org/10.1002/hbm.25332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978116PMC
April 2021

Extended-amygdala intrinsic functional connectivity networks: A population study.

Hum Brain Mapp 2021 Apr 12;42(6):1594-1616. Epub 2020 Dec 12.

School of Psychology, University of Bath, Bath, UK.

Pre-clinical and human neuroimaging research implicates the extended-amygdala (ExtA) (including the bed nucleus of the stria terminalis [BST] and central nucleus of the amygdala [CeA]) in networks mediating negative emotional states associated with stress and substance-use behaviours. The extent to which individual ExtA structures form a functionally integrated unit is controversial. We utilised a large sample (n > 1,000 healthy young adult humans) to compare the intrinsic functional connectivity networks (ICNs) of the BST and CeA using task-free functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. We assessed whether inter-individual differences within these ICNs were related to two principal components representing negative disposition and alcohol use. Building on recent primate evidence, we tested whether within BST-CeA intrinsic functional connectivity (iFC) was heritable and further examined co-heritability with our principal components. We demonstrate the BST and CeA to have discrete, but largely overlapping ICNs similar to previous findings. We found no evidence that within BST-CeA iFC was heritable; however, post hoc analyses found significant BST iFC heritability with the broader superficial and centromedial amygdala regions. There were no significant correlations or co-heritability associations with our principal components either across the ICNs or for specific BST-Amygdala iFC. Possible differences in phenotype associations across task-free, task-based, and clinical fMRI are discussed, along with suggestions for more causal investigative paradigms that make use of the now well-established ExtA ICNs.
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http://dx.doi.org/10.1002/hbm.25314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978137PMC
April 2021

Multi-centre, multi-vendor reproducibility of 7T QSM and R* in the human brain: Results from the UK7T study.

Neuroimage 2020 12 9;223:117358. Epub 2020 Sep 9.

Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Box 65, Cambridge Biomedical Campus, Cambridge CB2 0QQ, United Kingdom.

Introduction: We present the reliability of ultra-high field T* MRI at 7T, as part of the UK7T Network's "Travelling Heads" study. T*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5-3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R* mapping at 7T, in readiness for future multi-site clinical studies.

Methods: Ten healthy volunteers were scanned with harmonised single- and multi-echo T*-weighted gradient echo pulse sequences. Participants were scanned five times at each "home" site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space.

Results And Discussion: Mean susceptibility (χ) and R* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001-0.005 ppm (χ) and 0.0005-0.001 ms (R*). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R*. The median ICC from within- and cross-site R* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B inhomogeneity such as the inferior frontal cortex. Across sites, R* values were more consistent than QSM in subcortical structures due to differences in B-shimming. On a between-subject level, our measured χ and R* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol.

Conclusion: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480266PMC
December 2020

Graded fMRI Neurofeedback Training of Motor Imagery in Middle Cerebral Artery Stroke Patients: A Preregistered Proof-of-Concept Study.

Front Hum Neurosci 2020 14;14:226. Epub 2020 Jul 14.

School of Psychology, Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff, United Kingdom.

Ischemic stroke of the middle cerebral artery (MCA), a major brain vessel that supplies the primary motor and premotor cortex, is one of the most common causes for severe upper limb impairment. Currently available motor rehabilitation training largely lacks satisfying efficacy with over 70% of stroke survivors showing residual upper limb dysfunction. Motor imagery-based functional magnetic resonance imaging neurofeedback (fMRI-NF) has been suggested as a potential therapeutic technique to improve motor impairment in stroke survivors. In this preregistered proof-of-concept study (https://osf.io/y69jc/), we translated graded fMRI-NF training, a new paradigm that we have previously studied in healthy participants, to first-time MCA stroke survivors with residual mild to severe impairment of upper limb motor function. Neurofeedback was provided from the supplementary motor area (SMA) targeting two different neurofeedback target levels (low and high). We hypothesized that MCA stroke survivors will show (1) sustained SMA-region of interest (ROI) activation and (2) a difference in SMA-ROI activation between low and high neurofeedback conditions during graded fMRI-NF training. At the group level, we found only anecdotal evidence for these preregistered hypotheses. At the individual level, we found anecdotal to moderate evidence for the absence of the hypothesized graded effect for most subjects. These null findings are relevant for future attempts to employ fMRI-NF training in stroke survivors. The study introduces a Bayesian sequential sampling plan, which incorporates prior knowledge, yielding higher sensitivity. The sampling plan was preregistered together with hypotheses and all planned analysis before data collection to address potential publication/researcher biases. Unforeseen difficulties in the translation of our paradigm to a clinical setting required some deviations from the preregistered protocol. We explicitly detail these changes, discuss the accompanied additional challenges that can arise in clinical neurofeedback studies, and formulate recommendations for how these can be addressed. Taken together, this work provides new insights about the feasibility of motor imagery-based graded fMRI-NF training in MCA stroke survivors and serves as a first example for comprehensive study preregistration of an (fMRI) neurofeedback experiment.
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http://dx.doi.org/10.3389/fnhum.2020.00226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373077PMC
July 2020

Predictors of training-related improvement in visuomotor performance in patients with multiple sclerosis: A behavioural and MRI study.

Mult Scler 2020 Aug 4:1352458520943788. Epub 2020 Aug 4.

Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK/Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK/Helen Durham Centre for Neuroinflammation, University Hospital of Wales, Cardiff, UK/Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University 'G. d'Annunzio' of Chieti-Pescara, Chieti, Italy.

Background: The development of tailored recovery-oriented strategies in multiple sclerosis requires early identification of an individual's potential for functional recovery.

Objective: To identify predictors of visuomotor performance improvements, a proxy of functional recovery, using a predictive statistical model that combines demographic, clinical and magnetic resonance imaging (MRI) data.

Methods: Right-handed multiple sclerosis patients underwent baseline disability assessment and MRI of the brain structure, function and vascular health. They subsequently undertook 4 weeks of right upper limb visuomotor practice. Changes in performance with practice were our outcome measure. We identified predictors of improvement in a of patients using lasso regression; we calculated the best performing model in a and applied this model to a

Results: Patients improved their visuomotor performance with practice. Younger age, better visuomotor abilities, less severe disease burden and concurrent use of preventive treatments predicted improvements. Neuroimaging localised outcome-relevant sensory motor regions, the microstructure and activity of which correlated with performance improvements.

Conclusion: Initial characteristics, including age, disease duration, visuo-spatial abilities, hand dexterity, self-evaluated disease impact and the presence of disease-modifying treatments, can predict functional recovery in individual patients, potentially improving their clinical management and stratification in clinical trials. MRI is a correlate of outcome, potentially supporting individual prognosis.
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http://dx.doi.org/10.1177/1352458520943788DOI Listing
August 2020

Altered cerebrovascular response to acute exercise in patients with Huntington's disease.

Brain Commun 2020 16;2(1):fcaa044. Epub 2020 Apr 16.

Cardiff University Brain Research Imaging Centre, School of Physics and Astronomy, Cardiff University, Cardiff CF24 4HQ, UK.

The objective of this study was to determine whether a single session of exercise was sufficient to induce cerebral adaptations in individuals with Huntington's disease and to explore the time dynamics of any acute cerebrovascular response. In this case-control study, we employed arterial-spin labelling MRI in 19 Huntington's disease gene-positive participants (32-65 years, 13 males) and 19 controls (29-63 years, 10 males) matched for age, gender, body mass index and self-reported activity levels, to measure global and regional perfusion in response to 20 min of moderate-intensity cycling. Cerebral perfusion was measured at baseline and 15, 40 and 60 min after exercise cessation. Relative to baseline, we found that cerebral perfusion increased in patients with Huntington's disease yet was unchanged in control participants in the precentral gyrus ( = 0.016), middle frontal gyrus ( = 0.046) and hippocampus ( = 0.048) 40 min after exercise cessation (+15 to +32.5% change in Huntington's disease participants, -7.7 to 0.8% change in controls). The length of the disease-causing trinucleotide repeat expansion in the huntingtin gene predicted the change in the precentral gyrus ( = 0.03) and the intensity of the exercise intervention predicted hippocampal perfusion change in Huntington's disease participants ( < 0.001). In both groups, exercise increased hippocampal blood flow 60 min after exercise cessation ( = 0.039). These findings demonstrate the utility of acute exercise as a clinically sensitive experimental paradigm to modulate the cerebrovasculature. Twenty minutes of aerobic exercise induced transient cerebrovascular adaptations in the hippocampus and cortex selectively in Huntington's disease participants and likely represents latent neuropathology not evident at rest.
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http://dx.doi.org/10.1093/braincomms/fcaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293798PMC
April 2020

Cerebral Metabolic Changes During Visuomotor Adaptation Assessed Using Quantitative fMRI.

Front Physiol 2020 8;11:428. Epub 2020 May 8.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom.

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 CMRO) 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 CMRO 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 CMRO response as the task progressed. In the cerebellum, there was a sustained positive BOLD response in the absence of a significant CMRO increase from baseline, for all but the first task blocks. This suggests that the brain may continue to elevate the supply energy even after CMRO 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.
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http://dx.doi.org/10.3389/fphys.2020.00428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227432PMC
May 2020

Brain Network Modularity During a Sustained Working-Memory Task.

Front Physiol 2020 8;11:422. Epub 2020 May 8.

Centro Fermi-Museo Storico della Fisica e Centro di Studi e Ricerche Enrico Fermi, Rome, Italy.

Spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal are spatially synchronized within specific brain networks and are thought to reflect synchronized brain activity. Networks are modulated by the performance of a task, even if the exact features and degree of such modulations are still elusive. The presence of networks showing anticorrelated fluctuations lend initially to suppose that a competitive relationship between the default mode network (DMN) and task positive networks (TPNs) supports the efficiency of brain processing. However, more recent results indicate that cooperative and competitive dynamics between networks coexist during task performance. In this study, we used graph analysis to assess the functional relevance of the topological reorganization of brain networks ensuing the execution of a steady state working-memory (WM) task. Our results indicate that the performance of an auditory WM task is associated with a switching between different topological configurations of several regions of specific networks, including frontoparietal, ventral attention, and dorsal attention areas, suggesting segregation of ventral attention regions in the presence of increased overall integration. However, the correct execution of the task requires integration between components belonging to all the involved networks.
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http://dx.doi.org/10.3389/fphys.2020.00422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227445PMC
May 2020

Most Small Cerebral Cortical Veins Demonstrate Significant Flow Pulsatility: A Human Phase Contrast MRI Study at 7T.

Front Neurosci 2020 5;14:415. Epub 2020 May 5.

Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, United Kingdom.

Phase contrast MRI (pcMRI) has been used to investigate flow pulsatility in cerebral arteries, larger cerebral veins, and the cerebrospinal fluid (CSF). Such measurements of intracranial pulsatility and compliance are beginning to inform understanding of the pathophysiology of conditions including normal pressure hydrocephalus, multiple sclerosis, and dementias. We demonstrate the presence of flow pulsatility in small cerebral cortical veins, for the first time using pcMRI at 7 T, with the aim of improving our understanding of the hemodynamics of this little-studied vascular compartment. A method for establishing where venous flow is pulsatile is introduced, revealing significant pulsatility in 116 out of 146 veins, across eight healthy participants, assessed in parietal and frontal regions. Distributions of pulsatility index (PI) and pulse waveform delay were characterized, indicating a small, but statistically significant ( < 0.05), delay of 59 ± 41 ms in cortical veins with respect to the superior sagittal sinus, but no differences between veins draining different arterial supply territories. Measurements of pulsatility in smaller cortical veins, a hitherto unstudied compartment closer to the capillary bed, could lead to a better understanding of intracranial compliance and cerebrovascular (patho)physiology.
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http://dx.doi.org/10.3389/fnins.2020.00415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214844PMC
May 2020

Assessment of the Effects of Aerobic Fitness on Cerebrovascular Function in Young Adults Using Multiple Inversion Time Arterial Spin Labeling MRI.

Front Physiol 2020 21;11:360. Epub 2020 Apr 21.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom.

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 Opeak would be associated with higher GM volume and cognitive performance were also investigated. 20 adults underwent a Opeak 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% CO. Region of interest analysis showed a non-significant inverse correlation between whole-brain gray matter CBF and Opeak; = -0.4, = 0.08, corrected (') = 0.16 and a significant positive correlation between Opeak and whole-brain averaged gray matter CVR; = 0.62, = 0.003, ' = 0.006. Voxel-wise analysis revealed a significant inverse association between Opeak 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.
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http://dx.doi.org/10.3389/fphys.2020.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187806PMC
April 2020

Specific absorption rate implications of within-scan patient head motion for ultra-high field MRI.

Magn Reson Med 2020 11 17;84(5):2724-2738. Epub 2020 Apr 17.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.

Purpose: This study investigates the implications of all degrees of freedom of within-scan patient head motion on patient safety.

Methods: Electromagnetic simulations were performed by displacing and/or rotating a virtual body model inside an 8-channel transmit array to simulate 6 degrees of freedom of motion. Rotations of up to 20° and displacements of up to 20 mm including off-axis axial/coronal translations were investigated, yielding 104 head positions. Quadrature excitation, RF shimming, and multi-spoke parallel-transmit excitation pulses were designed for axial slice-selection at 7T, for seven slices across the head. Variation of whole-head specific absorption rate (SAR) and 10-g averaged local SAR of the designed pulses, as well as the change in the maximum eigenvalue (worst-case pulse) were investigated by comparing off-center positions to the central position.

Results: In their respective worst-cases, patient motion increased the eigenvalue-based local SAR by 42%, whole-head SAR by 60%, and the 10-g averaged local SAR by 210%. Local SAR was observed to be more sensitive to displacements along right-left and anterior-posterior directions than displacement in the superior-inferior direction and rotation.

Conclusion: This is the first study to investigate the effect of all 6 degrees of freedom of motion on safety of practical pulses. Although the results agree with the literature for overlapping cases, the results demonstrate higher increases (up to 3.1-fold) in local SAR for off-axis displacement in the axial plane, which had received less attention in the literature. This increase in local SAR could potentially affect the local SAR compliance of subjects, unless realistic within-scan patient motion is taken into account during pulse design.
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http://dx.doi.org/10.1002/mrm.28276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396298PMC
November 2020

Retrograde blood flow in the internal jugular veins of humans with hypertension may have implications for cerebral arterial blood flow.

Eur Radiol 2020 Jul 10;30(7):3890-3899. Epub 2020 Mar 10.

BHI CardioNomics Research Group, Clinical Research and Imaging Centre-Bristol, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, BS8 1TD, UK.

Objectives: To use multi-parametric magnetic resonance imaging (MRI) to test the hypothesis that hypertensives would have higher retrograde venous blood flow (RVBF) in the internal jugular veins (IJV) vs. normotensives, and that this would inversely correlate with arterial inflow and gray matter, white matter, and cerebrospinal fluid volumes.

Methods: Following local institutional review board approval and written consent, a prospective observational 3-T MRI study of 42 hypertensive patients (53 ± 2 years, BMI 28.2 ± 0.6 kg/m, ambulatory daytime systolic BP 148 ± 2 mmHg, ambulatory daytime diastolic BP 101 ± 2 mmHg) and 35 normotensive patients (48 ± 2 years, BMI 25.2 ± 0.8 kg/m, ambulatory daytime systolic BP 119 ± 3 mmHg, ambulatory daytime diastolic BP 90 ± 2 mmHg) was performed. Phase contrast imaging calculated percentage retrograde venous blood flow (%RVBF), brain segmentation estimated regional brain volumes from 3D T1-weighted images, and pseudo-continuous arterial spin labeling measured regional cerebral blood perfusion. Statistical analysis included two-sample equal variance Student's T tests, two-way analysis of variance with Tukey's post hoc correction, and permutation-based two-group general linear modeling (p < 0.05).

Results: In the left IJV, %RVBF was higher in hypertensives (6.1 ± 1.5%) vs. normotensives (1.1 ± 0.3%, p = 0.003). In hypertensives, there was an inverse relationship of %RVBF (permutation-based general linear modeling) to cerebral blood flow in several brain regions, including the left occipital pole and the cerebellar vermis (p < 0.01). Percentage retrograde flow in the left IJV correlated inversely with the total matter volume (gray plus white matter volume) in hypertensives (r = - 0.49, p = 0.004).

Conclusion: RVBF in the left IJV is greater in hypertensives vs. normotensives and is linked to regional hypoperfusion and brain total matter volume.

Key Points: • Hypertensive humans have higher retrograde cerebral venous blood flow, associated with regional brain hypoperfusion and lower tissue volume, compared with controls. • Cerebral retrograde venous blood flow may add further stress to already hypoperfused tissue in hypertensive patients. • The amount of retrograde venous blood flow in hypertensive patients may predict which patients might be at higher risk of developing cerebral pathologies.
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http://dx.doi.org/10.1007/s00330-020-06752-6DOI Listing
July 2020

Mild Propofol Sedation Reduces Frontal Lobe and Thalamic Cerebral Blood Flow: An Arterial Spin Labeling Study.

Front Physiol 2019 18;10:1541. Epub 2019 Dec 18.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom.

Mechanisms of anesthetic drug-induced sedation and unconsciousness are still incompletely understood. Functional neuroimaging modalities provide a window to study brain function changes during anesthesia allowing us to explore the sequence of neuro-physiological changes associated with anesthesia. Cerebral perfusion change under an assumption of intact neurovascular coupling is an indicator of change in large-scale neural activity. In this experiment, we have investigated resting state cerebral blood flow (CBF) changes in the human brain during mild sedation, with propofol. Arterial spin labeling (ASL) provides a non-invasive, reliable, and robust means of measuring cerebral blood flow (CBF) and can therefore be used to investigate central drug effects. Mild propofol sedation-related CBF changes were studied at rest ( = 15), in a 3 T MR scanner using a PICORE-QUIPSS II ASL technique. CBF was reduced in bilateral paracingulate cortex, premotor cortex, Broca's areas, right superior frontal gyrus and also the thalamus. This cerebral perfusion study demonstrates that propofol induces suppression of key cortical (frontal lobe) and subcortical (thalamus) regions during mild sedation.
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http://dx.doi.org/10.3389/fphys.2019.01541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930185PMC
December 2019

Multi-site harmonization of 7 tesla MRI neuroimaging protocols.

Neuroimage 2020 02 8;206:116335. Epub 2019 Nov 8.

Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom. Electronic address:

Increasing numbers of 7 T (7 T) magnetic resonance imaging (MRI) scanners are in research and clinical use. 7 T MRI can increase the scanning speed, spatial resolution and contrast-to-noise-ratio of many neuroimaging protocols, but technical challenges in implementation have been addressed in a variety of ways across sites. In order to facilitate multi-centre studies and ensure consistency of findings across sites, it is desirable that 7 T MRI sites implement common high-quality neuroimaging protocols that can accommodate different scanner models and software versions. With the installation of several new 7 T MRI scanners in the United Kingdom, the UK7T Network was established with an aim to create a set of harmonized structural and functional neuroimaging sequences and protocols. The Network currently includes five sites, which use three different scanner platforms, provided by two different vendors. Here we describe the harmonization of functional and anatomical imaging protocols across the three different scanner models, detailing the necessary changes to pulse sequences and reconstruction methods. The harmonized sequences are fully described, along with implementation details. Example datasets acquired from the same subject on all Network scanners are made available. Based on these data, an evaluation of the harmonization is provided. In addition, the implementation and validation of a common system calibration process is described.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212005PMC
February 2020

Cardiorespiratory fitness is associated with increased middle cerebral arterial compliance and decreased cerebral blood flow in young healthy adults: A pulsed ASL MRI study.

J Cereb Blood Flow Metab 2020 09 30;40(9):1879-1889. Epub 2019 Sep 30.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.

Cardiorespiratory fitness is thought to have beneficial effects on systemic vascular health, in part, by decreasing arterial stiffness. However, in the absence of non-invasive methods, it remains unknown whether this effect extends to the cerebrovasculature. The present study uses a novel pulsed arterial spin labelling (pASL) technique to explore the relationship between cardiorespiratory fitness and arterial compliance of the middle cerebral arteries (MCAC). Other markers of cerebrovascular health, including resting cerebral blood flow (CBF) and cerebrovascular reactivity to CO (CVR) were also investigated. Eleven healthy males aged 21 ± 2 years with varying levels of cardiorespiratory fitness (maximal oxygen uptake (O) 38-76 ml/min/kg) underwent MRI scanning at 3 Tesla. Higher O was associated with greater MCAC (R= 0.64,  < 0.01) and lower resting grey matter CBF (R= 0.75,  < 0.01). However, O was not predictive of global grey matter BOLD-based CVR (R= 0.47,  = 0.17) or CBF-based CVR (R= 0.19,  = 0.21). The current experiment builds upon the established benefits of exercise on arterial compliance in the systemic vasculature, by showing that increased cardiorespiratory fitness is associated with greater cerebral arterial compliance in early adulthood.
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http://dx.doi.org/10.1177/0271678X19865449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446564PMC
September 2020

Venous contribution to sodium MRI in the human brain.

Magn Reson Med 2020 04 25;83(4):1331-1338. Epub 2019 Sep 25.

Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.

Purpose: Sodium MRI shows great promise as a marker for cerebral metabolic dysfunction in stroke, brain tumor, and neurodegenerative pathologies. However, cerebral blood vessels, whose volume and function are perturbed in these pathologies, have elevated sodium concentrations relative to surrounding tissue. This study aims to assess whether this fluid compartment could bias measurements of tissue sodium using MRI.

Methods: Density-weighted and B corrected sodium MRI of the brain was acquired in 9 healthy participants at 4.7T. Veins were identified using co-registered H -weighted images and venous partial volume estimates were calculated by down-sampling the finer spatial resolution venous maps from the -weighted images to the coarser spatial resolution of the sodium data. Linear regressions of venous partial volume estimates and sodium signal were performed for regions of interest including just gray matter, just white matter, and all brain tissue.

Results: Linear regression demonstrated a significant venous sodium contribution above the underlying tissue signal. The apparent venous sodium concentrations derived from regression were 65.8 ± 4.5 mM (all brain tissue), 71.0 ± 7.4 mM (gray matter), and 55.0 ± 4.7 mM (white matter).

Conclusion: Although the partial vein linear regression did not yield the expected sodium concentration in blood (~87 mM), likely the result of point spread function smearing, this regression highlights that blood compartments may bias brain tissue sodium signals across neurological conditions where blood volumes may differ.
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http://dx.doi.org/10.1002/mrm.27996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972645PMC
April 2020

Whole brain P MRSI at 7T with a dual-tuned receive array.

Magn Reson Med 2020 02 23;83(2):765-775. Epub 2019 Aug 23.

Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, UK.

Purpose: The design and performance of a novel head coil setup for P spectroscopy at ultra-high field strengths (7T) is presented. The described system supports measurements at both the H and P resonance frequencies.

Methods: The novel coil consists of 2, actively detunable, coaxial birdcage coils to give homogeneous transmit, combined with a double resonant 30 channel receive array. This allows for anatomical imaging combined with P acquisitions over the whole head, without changing coils or disturbing the subject. A phosphate buffer phantom and 3 healthy volunteers were scanned with a pulse acquire CSI sequence using both the novel array coil and a conventional transceiver birdcage. Four different methods of combining the array channels were compared at 3 different levels of SNR.

Results: The novel coil setup delivers significantly increased P SNR in the peripheral regions of the brain, reaching up to factor 8, while maintaining comparable performance relative to the birdcage in the center.

Conclusions: The new system offers the potential to acquire whole brain P MRSI with superior signal relative to the standard options.
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http://dx.doi.org/10.1002/mrm.27953DOI Listing
February 2020

Traumatic imagery following glucocorticoid administration in earthquake-related post-traumatic stress disorder: A preliminary functional magnetic resonance imaging study.

Aust N Z J Psychiatry 2019 12 31;53(12):1167-1178. Epub 2019 May 31.

Department of Psychological Medicine, University of Otago, Christchurch, Christchurch, New Zealand.

Objective: Post-traumatic stress disorder involves excessive retrieval of traumatic memories. Glucocorticoids impair declarative memory retrieval. This preliminary study examined the effect of acute hydrocortisone administration on brain activation in individuals with earthquake-related post-traumatic stress disorder compared with earthquake-exposed healthy individuals, during retrieval of traumatic memories.

Method: Participants exposed to earthquakes with ( = 11) and without post-traumatic stress disorder ( = 11) underwent two functional magnetic resonance imaging scans, 1-week apart, in a double-blind, placebo-controlled, counter-balanced design. On one occasion, they received oral hydrocortisone (20 mg), and on the other, placebo, 1 hour before scanning. Symptom provocation involved script-driven imagery (traumatic and neutral scripts) and measures of self-reported anxiety.

Results: Arterial spin labelling showed that both post-traumatic stress disorder and trauma-exposed controls had significantly reduced cerebral blood flow in response to retrieval of traumatic versus neutral memories in the right hippocampus, parahippocampal gyrus, calcarine sulcus, middle and superior temporal gyrus, posterior cingulate, Heschl's gyrus, inferior parietal lobule, angular gyrus, middle occipital gyrus, supramarginal gyrus, lingual gyrus and cuneus, and the left prefrontal cortex. Hydrocortisone resulted in non-significant trends of increasing subjective distress and reduced regional cerebral blood flow in the left inferior frontal gyrus, left anterior cingulate gyrus, middle temporal gyrus, cerebellum, postcentral gyrus and right frontal pole, during the trauma script.

Conclusion: Findings do not fit with some aspects of the accepted neurocircuitry model of post-traumatic stress disorder, i.e., failure of the medial prefrontal cortex to quieten hyperresponsive amygdala activity, and the potential therapeutic benefits of hydrocortisone. They do, however, provide further evidence that exposure to earthquake trauma, regardless of whether post-traumatic stress disorder eventuates, impacts brain activity and highlights the importance of inclusion of trauma-exposed comparisons in studies of post-traumatic stress disorder.
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http://dx.doi.org/10.1177/0004867419851860DOI Listing
December 2019

Regional Cerebral Activation Accompanies Sympathoexcitation in Women With Polycystic Ovary Syndrome.

J Clin Endocrinol Metab 2019 09;104(9):3614-3623

Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.

Context: Polycystic ovary syndrome (PCOS) is associated with increased sympathetic nervous system activation, but the cerebral pathways involved are unclear.

Objective: To compare cerebral [blood oxygen level-dependent (BOLD) functional MRI], pressor [blood pressure (BP), heart rate (HR], and muscle sympathetic nerve activity (MSNA) responses to isometric forearm contraction (IFC) in women with PCOS and matched control subjects.

Design: Case-control study.

Setting: Referral center.

Participants: Patients with PCOS (n = 20; mean ± SD data: age, 29.8 ± 4.8 years; body mass index (BMI), 26.1 ± 4.9 kg/ m2) and 20 age- and BMI-matched control subjects (age, 29.7 ± 5.0 years; BMI, 26.1 ± 4.8 kg/ m2).

Main Outcome Measures: BP, HR, catecholamine, and MSNA responses to 30% IFC. BOLD signal change was modeled for BP response to 30% IFC.

Results: Although HR and BP increased to a similar extent in both groups after IFC, MSNA burst frequency increased by 68% in the PCOS group compared with 11.9% in control subjects (n = 7 in both groups; P = 0.002). Brain activation indexed by the BOLD signal in response to IFC was significantly greater in the PCOS group (n = 15) compared with controls (n = 15) in the right orbitofrontal cortex (P < 0.0001). Adjustment for insulin sensitivity, but not hyperandrogenism, abolished these between-group differences.

Conclusion: Our study confirms enhanced sympathoexcitation in women with PCOS and demonstrates increased regional brain activation in response to IFC. The right orbitofrontal cortex BOLD signal change in women with PCOS is associated with insulin sensitivity. Additional studies are warranted to clarify whether this may offer a novel target for cardiovascular risk reduction.
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http://dx.doi.org/10.1210/jc.2019-00065DOI Listing
September 2019

Comparing MRI metrics to quantify white matter microstructural damage in multiple sclerosis.

Hum Brain Mapp 2019 07 19;40(10):2917-2932. Epub 2019 Mar 19.

Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK.

Quantifying white matter damage in vivo is becoming increasingly important for investigating the effects of neuroprotective and repair strategies in multiple sclerosis (MS). While various approaches are available, the relationship between MRI-based metrics of white matter microstructure in the disease, that is, to what extent the metrics provide complementary versus redundant information, remains largely unexplored. We obtained four microstructural metrics from 123 MS patients: fractional anisotropy (FA), radial diffusivity (RD), myelin water fraction (MWF), and magnetisation transfer ratio (MTR). Coregistration of maps of these four indices allowed quantification of microstructural damage through voxel-wise damage scores relative to healthy tissue, as assessed in a group of 27 controls. We considered three white matter tissue-states, which were expected to vary in microstructural damage: normal appearing white matter (NAWM), T2-weighted hyperintense lesional tissue without T1-weighted hypointensity (T2L), and T1-weighted hypointense lesional tissue with corresponding T2-weighted hyperintensity (T1L). All MRI indices suggested significant damage in all three tissue-states, the greatest damage being in T1L. The correlations between indices ranged from r = 0.18 to r = 0.87. MWF was most sensitive when differentiating T2L from NAWM, while MTR was most sensitive when differentiating T1L from NAWM and from T2L. Combining the four metrics into one, through a principal component analysis, did not yield a measure more sensitive to damage than any single measure. Our findings suggest that the metrics are (at least partially) correlated with each other, but sensitive to the different aspects of pathology. Leveraging these differences could be beneficial in clinical trials testing the effects of therapeutic interventions.
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http://dx.doi.org/10.1002/hbm.24568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563497PMC
July 2019

Polygenic impact of common genetic risk loci for Alzheimer's disease on cerebral blood flow in young individuals.

Sci Rep 2019 01 24;9(1):467. Epub 2019 Jan 24.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, UK.

Genome-wide association studies (GWAS) show that many common alleles confer risk for developing Alzheimer's disease (AD). These risk loci may contribute to MRI alterations in young individuals, preceding the clinical manifestations of AD. Prior evidence identifies vascular dysregulation as the earliest marker of disease progression. However, it remains unclear whether cerebrovascular function (measured via grey-matter cerebral blood flow (gmCBF)) is altered in young individuals with increased AD genetic risk. We establish relationships between gmCBF with APOE and AD polygenic risk score in a young cohort (N = 75; aged: 19-32). Genetic risk was assessed via a) possessing at least one copy of the APOE ɛ4 allele and b) a polygenic risk score (AD-PRS) estimated from AD-GWAS. We observed a reduction in gmCBF in APOE ɛ4 carriers and a negative relationship between AD-PRS and gmCBF. We further found regional reductions in gmCBF in individuals with higher AD-PRS across the frontal cortex (P < 0.05). Our findings suggest that a larger burden of AD common genetic risk alleles is associated with attenuated cerebrovascular function, during young adulthood. These results suggest that cerebral vasculature is a mechanism by which AD risk alleles confer susceptibility.
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http://dx.doi.org/10.1038/s41598-018-36820-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345995PMC
January 2019

Can Blood Oxygenation Level Dependent Functional Magnetic Resonance Imaging Be Used Accurately to Compare Older and Younger Populations? A Mini Literature Review.

Front Aging Neurosci 2018 13;10:371. Epub 2018 Nov 13.

Cardiff University Brain Imaging Research Center, School of Psychology, Cardiff University, Cardiff, United Kingdom.

A wealth of research has investigated the aging brain using blood oxygenation level dependent functional MRI [Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI)]. However, many studies do not consider the aging of the cerebrovascular system, which can influence the BOLD signal independently from neural activity, limiting what can be inferred when comparing age groups. Here, we discuss the ways in which the aging neurovascular system can impact BOLD fMRI, the consequences for age-group comparisons and possible strategies for mitigation. While BOLD fMRI is a valuable tool in this context, this review highlights the importance of consideration of vascular confounds.
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http://dx.doi.org/10.3389/fnagi.2018.00371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243068PMC
November 2018

Modeling of dynamic cerebrovascular reactivity to spontaneous and externally induced CO fluctuations in the human brain using BOLD-fMRI.

Neuroimage 2019 02 10;186:533-548. Epub 2018 Nov 10.

Department of Bioengineering, McGill Univesity, Montreal, QC, H3A 0C3, Canada; Integrated Program in Neuroscience, McGill University, Montreal Neurological Institude, H3A 2B4, QC, Canada. Electronic address:

In this work, we investigate the regional characteristics of the dynamic interactions between arterial CO and BOLD (dynamic cerebrovascular reactivity - dCVR) during normal breathing and hypercapnic, externally induced step CO challenges. To obtain dCVR curves at each voxel, we use a custom set of basis functions based on the Laguerre and gamma basis sets. This allows us to obtain robust dCVR estimates both in larger regions of interest (ROIs), as well as in individual voxels. We also implement classification schemes to identify brain regions with similar dCVR characteristics. Our results reveal considerable variability of dCVR across different brain regions, as well as during different experimental conditions (normal breathing and hypercapnic challenges), suggesting a differential response of cerebral vasculature to spontaneous CO fluctuations and larger, externally induced CO changes that are possibly associated with the underlying differences in mean arterial CO levels. The clustering results suggest that anatomically distinct brain regions are characterized by different dCVR curves that in some cases do not exhibit the standard, positive valued curves that have been previously reported. They also reveal a consistent set of dCVR cluster shapes for resting and forcing conditions, which exhibit different distribution patterns across brain voxels.
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http://dx.doi.org/10.1016/j.neuroimage.2018.10.084DOI Listing
February 2019

The BOLD response in primary motor cortex and supplementary motor area during kinesthetic motor imagery based graded fMRI neurofeedback.

Neuroimage 2019 01 8;184:36-44. Epub 2018 Sep 8.

Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, Cardiff, CF24 4HQ, United Kingdom; School of Physics and Astronomy, Cardiff University, Cardiff, CF24 3AA, United Kingdom. Electronic address:

There is increasing interest in exploring the use of functional MRI neurofeedback (fMRI-NF) as a therapeutic technique for a range of neurological conditions such as stroke and Parkinson's disease (PD). One main therapeutic potential of fMRI-NF is to enhance volitional control of damaged or dysfunctional neural nodes and networks via a closed-loop feedback model using mental imagery as the catalyst of self-regulation. The choice of target node/network and direction of regulation (increase or decrease activity) are central design considerations in fMRI-NF studies. Whilst it remains unclear whether the primary motor cortex (M1) can be activated during motor imagery, the supplementary motor area (SMA) has been robustly activated during motor imagery. Such differences in the regulation potential between primary and supplementary motor cortex are important because these areas can be differentially affected by a stroke or PD, and the choice of fMRI-NF target and grade of self-regulation of activity likely have substantial influence on the clinical effects and cost effectiveness of NF-based interventions. In this study we therefore investigated firstly whether healthy subjects would be able to achieve self-regulation of the hand-representation areas of M1 and the SMA using fMRI-NF training. There was a significant decrease in M1 neural activity during fMRI-NF, whereas SMA neural activity was increased, albeit not with the predicated graded effect. This study has important implications for fMRI-NF protocols that employ motor imagery to modulate activity in specific target regions of the brain and to determine how they may be tailored for neurorehabilitation.
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http://dx.doi.org/10.1016/j.neuroimage.2018.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264383PMC
January 2019

Scale-invariant rearrangement of resting state networks in the human brain under sustained stimulation.

Neuroimage 2018 10 5;179:570-581. Epub 2018 Jul 5.

Centro Fermi - Museo storico della fisica e Centro di studi e ricerche Enrico Fermi, Roma, Italy; Fondazione Santa Lucia IRCCS, Roma, Italy. Electronic address:

Brain activity at rest is characterized by widely distributed and spatially specific patterns of synchronized low-frequency blood-oxygenation level-dependent (BOLD) fluctuations, which correspond to physiologically relevant brain networks. This network behaviour is known to persist also during task execution, yet the details underlying task-associated modulations of within- and between-network connectivity are largely unknown. In this study we exploited a multi-parametric and multi-scale approach to investigate how low-frequency fluctuations adapt to a sustained n-back working memory task. We found that the transition from the resting state to the task state involves a behaviourally relevant and scale-invariant modulation of synchronization patterns within both task-positive and default mode networks. Specifically, decreases of connectivity within networks are accompanied by increases of connectivity between networks. In spite of large and widespread changes of connectivity strength, the overall topology of brain networks is remarkably preserved. We show that these findings are strongly influenced by connectivity at rest, suggesting that the absolute change of connectivity (i.e., disregarding the baseline) may not be the most suitable metric to study dynamic modulations of functional connectivity. Our results indicate that a task can evoke scale-invariant, distributed changes of BOLD fluctuations, further confirming that low frequency BOLD oscillations show a specialized response and are tightly bound to task-evoked activation.
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http://dx.doi.org/10.1016/j.neuroimage.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538940PMC
October 2018

Neurovascular Coupling During Visual Stimulation in Multiple Sclerosis: A MEG-fMRI Study.

Neuroscience 2019 04 23;403:54-69. Epub 2018 Mar 23.

Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University School of Psychology, Maindy Road, Cardiff CF24 4HQ, UK; Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, University Hospital Wales, Heath Park, CF14 4XN, UK. Electronic address:

The process of neurovascular coupling ensures that increases in neuronal activity are fed by increases in cerebral blood flow. Evidence suggests that neurovascular coupling may be impaired in Multiple Sclerosis (MS) due to a combination of brain hypoperfusion, altered cerebrovascular reactivity and oxygen metabolism, and altered levels of vasoactive compounds. Here, we tested the hypothesis that neurovascular coupling is impaired in MS. We characterized neurovascular coupling as the relationship between changes in neuronal oscillatory power within the gamma frequency band (30-80 Hz), as measured by magnetoencephalography (MEG), and associated hemodynamic changes (blood oxygenation level dependent, BOLD, and cerebral blood flow, CBF) as measured by functional MRI. We characterized these responses in the visual cortex in 13 MS patients and in 10 matched healthy controls using a reversing checkerboard stimulus at five visual contrasts. There were no significant group differences in visual acuity, P100 latencies, occipital gray matter (GM) volumes and baseline CBF. However, in the MS patients we found a significant reduction in peak gamma power, BOLD and CBF responses. There were no significant differences in neurovascular coupling between groups, in the visual cortex. Our results suggest that neuronal and vascular responses are altered in MS. Gamma power reduction could be an indicator of GM dysfunction, possibly mediated by GABAergic changes. Altered hemodynamic responses confirm previous reports of a vascular dysfunction in MS. Despite altered neuronal and vascular responses, neurovascular coupling appears to be preserved in MS, at least within the range of damage and disability studied here.
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http://dx.doi.org/10.1016/j.neuroscience.2018.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458991PMC
April 2019

Assessing the repeatability of absolute CMRO, OEF and haemodynamic measurements from calibrated fMRI.

Neuroimage 2018 06 14;173:113-126. Epub 2018 Feb 14.

Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, UK. Electronic address:

As energy metabolism in the brain is largely oxidative, the measurement of cerebral metabolic rate of oxygen consumption (CMRO) is a desirable biomarker for quantifying brain activity and tissue viability. Currently, PET techniques based on oxygen isotopes are the gold standard for obtaining whole brain CMRO maps. Among MRI techniques that have been developed as an alternative are dual calibrated fMRI (dcFMRI) methods, which exploit simultaneous measurements of BOLD and ASL signals during a hypercapnic-hyperoxic experiment to modulate brain blood flow and oxygenation. In this study we quantified the repeatability of a dcFMRI approach developed in our lab, evaluating its limits and informing its application in studies aimed at characterising the metabolic state of human brain tissue over time. Our analysis focussed on the estimates of oxygen extraction fraction (OEF), cerebral blood flow (CBF), CBF-related cerebrovascular reactivity (CVR) and CMRO based on a forward model that describes analytically the acquired dual echo GRE signal. Indices of within- and between-session repeatability are calculated from two different datasets both at a bulk grey matter and at a voxel-wise resolution and finally compared with similar indices obtained from previous MRI and PET measurements. Within- and between-session values of intra-subject coefficient of variation (CV) calculated from bulk grey matter estimates 6.7 ± 6.6% (mean ± std.) and 10.5 ± 9.7% for OEF, 6.9 ± 6% and 5.5 ± 4.7% for CBF, 12 ± 9.7% and 12.3 ± 10% for CMRO. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) maps showed the spatial distribution of the repeatability metrics, informing on the feasibility limits of the method. In conclusion, results show an overall consistency of the estimated physiological parameters with literature reports and a satisfactory level of repeatability considering the higher spatial sensitivity compared to other MRI methods, with varied performance depending on the specific parameter under analysis, on the spatial resolution considered and on the study design.
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http://dx.doi.org/10.1016/j.neuroimage.2018.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503182PMC
June 2018

Calcium channel blockade with nimodipine reverses MRI evidence of cerebral oedema following acute hypoxia.

J Cereb Blood Flow Metab 2019 02 31;39(2):285-301. Epub 2017 Aug 31.

1 Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford, UK.

Acute cerebral hypoxia causes rapid calcium shifts leading to neuronal damage and death. Calcium channel antagonists improve outcomes in some clinical conditions, but mechanisms remain unclear. In 18 healthy participants we: (i) quantified with multiparametric MRI the effect of hypoxia on the thalamus, a region particularly sensitive to hypoxia, and on the whole brain in general; (ii) investigated how calcium channel antagonism with the drug nimodipine affects the brain response to hypoxia. Hypoxia resulted in a significant decrease in apparent diffusion coefficient (ADC), a measure particularly sensitive to cell swelling, in a widespread network of regions across the brain, and the thalamus in particular. In hypoxia, nimodipine significantly increased ADC in the same brain regions, normalizing ADC towards normoxia baseline. There was positive correlation between blood nimodipine levels and ADC change. In the thalamus, there was a significant decrease in the amplitude of low frequency fluctuations (ALFF) in resting state functional MRI and an apparent increase of grey matter volume in hypoxia, with the ALFF partially normalized towards normoxia baseline with nimodipine. This study provides further evidence that the brain response to acute hypoxia is mediated by calcium, and importantly that manipulation of intracellular calcium flux following hypoxia may reduce cerebral cytotoxic oedema.
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http://dx.doi.org/10.1177/0271678X17726624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360646PMC
February 2019

Task-Related Modulations of BOLD Low-Frequency Fluctuations within the Default Mode Network.

Front Phys 2017 Jul 25;5. Epub 2017 Jul 25.

MARBILab, Centro Fermi-Museo Storico Della fisica e Centro Studi e Ricerche Enrico Fermi, Rome, Italy.

Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task.
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http://dx.doi.org/10.3389/fphy.2017.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568127PMC
July 2017