Search

An efficient multi-slice inversion-recovery EPI (MS-IR-EPI) sequence for fast, high spatial resolution, quantitative T 1 mapping is presented, using a segmented simultaneous multi-slice acquisition, combined with slice order shifting across multiple acquisitions. The segmented acquisition minimises the effective TE and readout duration compared to a single-shot EPI scheme, reducing geometric distortions to provide high quality T 1 maps with a narrow point-spread function. The precision and repeatability of MS-IR-EPI T 1 measurements are assessed using both T 1 -calibrated and T 2 -calibrated ISMRM/NIST phantom spheres at 3 and 7 T and compared with single slice IR and MP2RAGE methods. Magnetization transfer (MT) effects of the spectrally-selective fat-suppression (FS) pulses required for in vivo imaging are shown to shorten the measured in-vivo T 1 values. We model the effect of these fat suppression pulses on T 1 measurements and show that the model can remove their MT contribution from the measured T 1 , thus providing accurate T 1 quantification. High spatial resolution T 1 maps of the human brain generated with MS-IR-EPI at 7 T are compared with those generated with the widely implemented MP2RAGE sequence. Our MS-IR-EPI sequence provides high SNR per unit time and sharper T 1 maps than MP2RAGE, demonstrating the potential for ultra-high resolution T 1 mapping and the improved discrimination of functionally relevant cortical areas in the human brain., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: We present the reliability of ultra-high field T 2 * MRI at 7T, as part of the UK7T Network's "Travelling Heads" study. T 2 *-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R 2 * 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 2 * 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 2 * mapping at 7T, in readiness for future multi-site clinical studies., Methods: Ten healthy volunteers were scanned with harmonised single- and multi-echo T 2 *-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 2 * 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 2 * 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 -1 (R 2 *). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R 2 *. The median ICC from within- and cross-site R 2 * data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B 0 inhomogeneity such as the inferior frontal cortex. Across sites, R 2 * values were more consistent than QSM in subcortical structures due to differences in B 0 -shimming. On a between-subject level, our measured χ and R 2 * 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 2 * 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., (Copyright © 2020. Published by Elsevier Inc.)

It is well recognized that in primates, including humans, noxious body stimulation evokes a neural response in the posterior bank of the central sulcus, in Brodmann cytoarchitectonic subdivisions 3b and 1 of the primary somatosensory cortex. This response is associated with the 1st/sharp pain and contributes to sensory discriminative aspects of pain perception and spatial localization of the noxious stimulus. However, neurophysiological studies in New World monkeys predict that in humans noxious stimulation also evokes a separate neural response-mediated by C-afferent drive and associated with the 2nd/burning pain-in the depth of the central sulcus in Brodmann area 3a (BA3a) at the transition between the somatosensory and motor cortices. To evoke such a response, it is necessary to use multi-second duration noxious stimulation, rather than brief laser pulses. Given the limited human pain-imaging literature on cortical responses induced by C-nociceptive input specifically within BA3a, here we used high spatial resolution 7T fMRI to study the response to thermonoxious skin stimulation. We observed the predicted response of BA3a in the depth of the central sulcus in five human volunteers. Review of the available evidence suggests that the nociresponsive region in the depth of the central sulcus is a structurally and functionally distinct cortical area that should not be confused with proprioceptive BA3a. It is most likely engaged in interoception and control of the autonomic nervous system, and contributes to the sympathetic response to noxious stimulation, arguably the most intolerable aspect of pain experience. Ablation of this region has been shown to reduce pain sensibility and might offer an effective means of ameliorating some pathological pain conditions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

With the advent of ultra-high field (7T), high spatial resolution functional MRI (fMRI) has allowed the differentiation of the cortical representations of each of the digits at an individual-subject level in human primary somatosensory cortex (S1). Here we generate a probabilistic atlas of the contralateral SI representations of the digits of both the left and right hand in a group of 22 right-handed individuals. The atlas is generated in both volume and surface standardised spaces from somatotopic maps obtained by delivering vibrotactile stimulation to each distal phalangeal digit using a travelling wave paradigm. Metrics quantify the likelihood of a given position being assigned to a digit (full probability map) and the most probable digit for a given spatial location (maximum probability map). The atlas is validated using a leave-one-out cross validation procedure. Anatomical variance across the somatotopic map is also assessed to investigate whether the functional variability across subjects is coupled to structural differences. This probabilistic atlas quantifies the variability in digit representations in healthy subjects, finding some quantifiable separability between digits 2, 3 and 4, a complex overlapping relationship between digits 1 and 2, and little agreement of digit 5 across subjects. The atlas and constituent subject maps are available online for use as a reference in future neuroimaging studies., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Modulation of beta-band neural oscillations during and following movement is a robust marker of brain function. In particular, the post-movement beta rebound (PMBR), which occurs on movement cessation, has been related to inhibition and connectivity in the healthy brain, and is perturbed in disease. However, to realise the potential of the PMBR as a biomarker, its modulation by task parameters must be characterised and its functional role determined. Here, we used MEG to image brain electrophysiology during and after a grip-force task, with the aim to characterise how task duration, in the form of an isometric contraction, modulates beta responses. Fourteen participants exerted a 30% maximum voluntary grip-force for 2, 5 and 10 s. Our results showed that the amplitude of the PMBR is modulated by task duration, with increasing duration significantly reducing PMBR amplitude and increasing its time-to-peak. No variation in the amplitude of the movement related beta decrease (MRBD) with task duration was observed. To gain insight into what may underlie these trial-averaged results, we used a Hidden Markov Model to identify the individual trial dynamics of a brain network encompassing bilateral sensorimotor areas. The rapidly evolving dynamics of this network demonstrated similar variation with task parameters to the 'classical' rebound, and we show that the modulation of the PMBR can be well-described in terms of increased frequency of beta events on a millisecond timescale rather than modulation of beta amplitude during this time period. Our results add to the emerging picture that, in the case of a carefully controlled paradigm, beta modulation can be systematically controlled by task parameters and such control can reveal new information as to the processes that generate the average beta timecourse. These findings will support design of clinically relevant paradigms and analysis pipelines in future use of the PMBR as a marker of neuropathology., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous work has investigated the electrophysiological origins of the intra-modal (within the stimulated sensory cortex) negative BOLD fMRI response (NBR, decrease from baseline) but little attention has been paid to the origin of cross-modal NBRs, those in a different sensory cortex. In the current study we use simultaneous EEG-fMRI recordings to assess the neural correlates of both intra- and cross-modal responses to left-hemifield visual stimuli and right-hand motor tasks, and evaluate the balance of activation and deactivation between the visual and motor systems. Within- and between-subject covariations of EEG and fMRI responses to both tasks are assessed to determine how patterns of event-related desynchronization/synchronisation (ERD/ERS) of alpha/beta frequency oscillations relate to the NBR in the two sensory cortices. We show that both visual and motor tasks induce intra-modal NBR and cross-modal NBR (e.g. visual stimuli evoked NBRs in both visual and motor cortices). In the EEG data, bilateral intra-modal alpha/beta ERD were consistently observed to both tasks, whilst the cross-modal EEG response varied across subjects between alpha/beta ERD and ERS. Both the mean cross-modal EEG and fMRI response amplitudes showed a small increase in magnitude with increasing task intensity. In response to the visual stimuli, subjects displaying cross-modal ERS of motor beta power displayed a significantly larger magnitude of cross-modal NBR in motor cortex. However, in contrast to the motor stimuli, larger cross-modal ERD of visual alpha power was associated with larger cross-modal visual NBR. Single-trial correlation analysis provided further evidence of relationship between EEG signals and the NBR, motor cortex beta responses to motor tasks were significantly negatively correlated with cross-modal visual cortex NBR amplitude, and positively correlated with intra-modal motor cortex PBR. This study provides a new body of evidence that the coupling between BOLD and low-frequency (alpha/beta) sensory cortex EEG responses extends to cross-modal NBR., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

The sensation of touch in the glabrous skin of the human hand is conveyed by thousands of fast-conducting mechanoreceptive afferents, which can be categorised into four distinct types. The spiking properties of these afferents in the periphery in response to varied tactile stimuli are well-characterised, but relatively little is known about the spatiotemporal properties of the neural representations of these different receptor types in the human cortex. Here, we use the novel methodological combination of single-unit intraneural microstimulation (INMS) with magnetoencephalography (MEG) to localise cortical representations of individual touch afferents in humans, by measuring the extracranial magnetic fields from neural currents. We found that by assessing the modulation of the beta (13-30 Hz) rhythm during single-unit INMS, significant changes in oscillatory amplitude occur in the contralateral primary somatosensory cortex within and across a group of fast adapting type I mechanoreceptive afferents, which corresponded well to the induced response from matched vibrotactile stimulation. Combining the spatiotemporal specificity of MEG with the selective single-unit stimulation of INMS enables the interrogation of the central representations of different aspects of tactile afferent signalling within the human cortices. The fundamental finding that single-unit INMS ERD responses are robust and consistent with natural somatosensory stimuli will permit us to more dynamically probe the central nervous system responses in humans, to address questions about the processing of touch from the different classes of mechanoreceptive afferents and the effects of varying the stimulus frequency and patterning., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The spatial topology of the human motor cortex has been well studied, particularly using functional Magnetic Resonance Imaging (fMRI) which allows spatial separation of haemodynamic responses arising from stimulation of different body parts, individual digits and even spatially separate areas of the same digit. However, the spatial organisation of electrophysiological responses, particularly neural oscillations (rhythmic changes in electrical potential across cellular assemblies) has been less well studied. Mapping the spatial signature of neural oscillations is possible using magnetoencephalography (MEG), however spatial differentiation of responses induced by movement of separate digits is a challenge, because the brain regions involved are separated by only a few millimetres. In this paper we first show, in simulation, how to optimise experimental design and beamformer spatial filtering techniques to increase the spatial specificity of MEG derived functional images. Combining this result with experimental data, we then capture the organisation of the post-movement beta band (13-30 Hz) oscillatory response to movement of digits 2 and 5 of the dominant hand, in individual subjects. By comparing these MEG results to ultra-high field (7T) fMRI, we also show significant spatial agreement between beta modulation and the blood oxygenation level dependent (BOLD) response. Our results show that, when using an optimised inverse solution and controlling subject movement (using custom fitted foam padding) the spatial resolution of MEG can be of order 3-5 mm. The method described offers exciting potential to understand better the cortical organisation of oscillations, and to probe such organisation in patient populations where those oscillations are known to be abnormal., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

In this paper, we present an overview of 7T magnetic resonance imaging (MRI) studies of the detailed function and anatomy of sensory areas of the human brain. We discuss the motivation for the studies, with particular emphasis on increasing the spatial resolution of functional MRI (fMRI) using reduced field-of-view (FOV) data acquisitions. MRI at ultra-high-field (UHF) - defined here as 7T and above - has several advantages over lower field strengths. The intrinsic signal-to-noise ratio (SNR) of images is higher at UHF, and coupled with the increased blood-oxygen-level-dependent (BOLD) signal change, this results in increased BOLD contrast-to-noise ratio (CNR), which can be exploited to improve spatial resolution or detect weaker signals. Additionally, the BOLD signal from the intra-vascular (IV) compartment is relatively diminished compared to lower field strengths. Together, these properties make 7T functional MRI an attractive proposition for high spatial specificity measures. But with the advantages come some challenges. For example, increased vulnerability to susceptibility-induced geometric distortions and signal loss in EPI acquisitions tend to be much larger. Some of these technical issues can be addressed with currently available tools and will be discussed. We highlight the key methodological considerations for high resolution functional and structural imaging at 7 T. We then present recent data using the high spatial resolution available at UHF in studies of the visual and somatosensory cortex to highlight promising developments in this area., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The relationship between venous blood oxygenation and change in transverse relaxation rate (ΔR 2 * ) plays a key role in calibrated BOLD fMRI. This relationship, defined by the parameter β, has previously been determined using theoretical simulations and experimental measures. However, these earlier studies have been confounded by the change in venous cerebral blood volume (CBV) in response to functional tasks. This study used a double-echo gradient echo EPI scheme in conjunction with a graded isocapnic hyperoxic sequence to assess quantitatively the relationship between the fractional venous blood oxygenation (1-Y v ) and transverse relaxation rate of grey matter (ΔR 2⁢GM * ), without inducing a change in vCBV. The results demonstrate that the relationship between ΔR 2 * and fractional venous oxygenation at all magnet field strengths studied was adequately described by a linear relationship. The gradient of this relationship did not increase monotonically with field strength, which may be attributed to the relative contributions of intravascular and extravascular signals which will vary with both field strength and blood oxygenation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Information flow between the thalamus and cerebral cortex is a crucial component of adaptive brain function, but the details of thalamocortical interactions in human subjects remain unclear. The principal aim of this study was to evaluate the agreement between functional thalamic network patterns, derived using seed-based connectivity analysis and independent component analysis (ICA) applied separately to resting state functional MRI (fMRI) data from 21 healthy participants. For the seed-based analysis, functional thalamic parcellation was achieved by computing functional connectivity (FC) between thalamic voxels and a set of pre-defined cortical regions. Thalamus-constrained ICA provided an alternative parcellation. Both FC analyses demonstrated plausible and comparable group-level thalamic subdivisions, in agreement with previous work. Quantitative assessment of the spatial overlap between FC thalamic segmentations, and comparison of each to a histological "gold-standard" thalamic atlas and a structurally-defined thalamic atlas, highlighted variations between them and, most notably, differences with both histological and structural results. Whilst deeper understanding of thalamocortical connectivity rests upon identification of features common to multiple non-invasive neuroimaging techniques (e.g. FC, structural connectivity and anatomical localisation of individual-specific nuclei), this work sheds further light on the functional organisation of the thalamus and the varying sensitivities of complementary analyses to resolve it., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The physiological effect of hyperoxia has been poorly characterize d, with studies reporting conflicting results on the role of hyperoxia as a vasoconstrictor. It is not clear whether hyperoxia is the primary contributor to vasoconstriction or whether induced changes in CO2 that commonly accompany hyperoxia are a factor. As calibrated BOLD fMRI based on hyperoxia becomes more widely used, it is essential to understand the effects of oxygen on resting cerebral physiology. This study used a RespirAct™ system to deliver a repeatable isocapnic hyperoxia stimulus to investigate the independent effect of O2 on cerebral physiology, removing any potential confounds related to altered CO2. T1-independent Phase Contrast MRI was used to demonstrate that isocapnic hyperoxia has no significant effect on carotid blood flow (normoxia 201 ± 11 ml/min, -0.3% ± 0.8% change during hyperoxia, p = 0.8), while Look Locker ASL was used to demonstrate that there is no significant change in arterial cerebral blood volume (normoxia 1.3% ± 0.4%, -0.5 ± 5% change during hyperoxia). These are in contrast to significant changes in carotid blood flow observed for hypercapnia (6.8% ± 1.5%/mm Hg CO2). In addition, magnetoencephalography provided a method to monitor the effect of isocapnic hyperoxia on neuronal oscillatory power. In response to hyperoxia, a significant focal decrease in oscillatory power was observed across the alpha, beta and low gamma bands in the occipital lobe, compared to a more global significant decrease on hypercapnia. This work suggests that isocapnic hyperoxia provides a more reliable stimulus than hypercapnia for calibrated BOLD, and that previous reports of vasoconstriction during hyperoxia probably reflect the effects of hyperoxia-induced changes in CO2. However, hyperoxia does induce changes in oscillatory power consistent with an increase in vigilance, but these changes are smaller than those observed under hypercapnia. The effect of this change in neural activity on calibrated BOLD using hyperoxia or combined hyperoxia and hypercapnia needs further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The measurement of venous cerebral blood oxygenation (Yv) has potential applications in the study of patient groups where oxygen extraction and/or metabolism are compromised. It is also useful for fMRI studies to assess the stimulus-induced changes in Yv, particularly since basal Yv partially accounts for inter-subject variation in the haemodynamic response to a stimulus. A range of MRI-based methods of measuring Yv have been developed recently. Here, we use a method based on the change in phase in the MR image arising from the field perturbation caused by deoxygenated haemoglobin in veins. We build on the existing phase based approach (Method I), where Yv is measured in a large vein (such as the superior sagittal sinus) based on the field shift inside the vein with assumptions as to the vein's shape and orientation. We demonstrate two novel modifications which address limitations of this method. The first modification (Method II), maps the actual form of the vein, rather than assume a given shape and orientation. The second modification (Method III) uses the intra and perivascular phase change in response to a known change in Yv on hyperoxia to measure normoxic Yv in smaller veins. Method III can be applied to veins whose shape, size and orientation are not accurately known, thus allowing more localised measures of venous oxygenation. Results demonstrate that the use of an overly fine spatial filter caused an overestimation in Yv for Method I, whilst the measurement of Yv using Method II was less sensitive to this bias, giving Yv = 0.62 ± 0.03. Method III was applied to mapping of Yv in local veins across the brain, yielding a distribution of values with a mode of Yv = 0.661 ± 0.008., (Copyright © 2014. Published by Elsevier Inc.)

Numerous studies on the tonotopic organisation of auditory cortex in humans have employed a wide range of neuroimaging protocols to assess cortical frequency tuning. In the present functional magnetic resonance imaging (fMRI) study, we made a systematic comparison between acquisition protocols with variable levels of interference from acoustic scanner noise. Using sweep stimuli to evoke travelling waves of activation, we measured sound-evoked response signals using sparse, clustered, and continuous imaging protocols that were characterised by inter-scan intervals of 8.8, 2.2, or 0.0 s, respectively. With regard to sensitivity to sound-evoked activation, the sparse and clustered protocols performed similarly, and both detected more activation than the continuous method. Qualitatively, tonotopic maps in activated areas proved highly similar, in the sense that the overall pattern of tonotopic gradients was reproducible across all three protocols. However, quantitatively, we observed substantial reductions in response amplitudes to moderately low stimulus frequencies that coincided with regions of strong energy in the scanner noise spectrum for the clustered and continuous protocols compared to the sparse protocol. At the same time, extreme frequencies became over-represented for these two protocols, and high best frequencies became relatively more abundant. Our results indicate that although all three scanning protocols are suitable to determine the layout of tonotopic fields, an exact quantitative assessment of the representation of various sound frequencies is substantially confounded by the presence of scanner noise. In addition, we noticed anomalous signal dynamics in response to our travelling wave paradigm that suggest that the assessment of frequency-dependent tuning is non-trivially influenced by time-dependent (hemo)dynamics when using sweep stimuli., (Copyright © 2014. Published by Elsevier Inc.)

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful technique, typically based on the statistical analysis of the magnitude component of the complex time-series. Here, we additionally interrogated the phase data of the fMRI time-series and used quantitative susceptibility mapping (QSM) in order to investigate the potential of functional QSM (fQSM) relative to standard magnitude BOLD fMRI. High spatial resolution data (1mm isotropic) were acquired every 3 seconds using zoomed multi-slice gradient-echo EPI collected at 7 T in single orientation (SO) and multiple orientation (MO) experiments, the latter involving 4 repetitions with the subject's head rotated relative to B0. Statistical parametric maps (SPM) were reconstructed for magnitude, phase and QSM time-series and each was subjected to detailed analysis. Several fQSM pipelines were evaluated and compared based on the relative number of voxels that were coincidentally found to be significant in QSM and magnitude SPMs (common voxels). We found that sensitivity and spatial reliability of fQSM relative to the magnitude data depended strongly on the arbitrary significance threshold defining "activated" voxels in SPMs, and on the efficiency of spatio-temporal filtering of the phase time-series. Sensitivity and spatial reliability depended slightly on whether MO or SO fQSM was performed and on the QSM calculation approach used for SO data. Our results present the potential of fQSM as a quantitative method of mapping BOLD changes. We also critically discuss the technical challenges and issues linked to this intriguing new technique., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ultra-high-field (UHF) MRI is ideally suited for structural and functional imaging of the brain. High-resolution structural MRI can be used to map the anatomical boundaries between functional domains of the brain by identifying changes related to the pattern of myelination within cortical gray matter, opening up the possibility to study the relationship between functional domains and underlying structure in vivo. In a recent study, we demonstrated the correspondence between functional (based on retinotopic mapping) and structural (based on changes in T2(⁎)-weighted images linked to myelination) parcellations of the primary visual cortex (V1) in vivo at 7T (Sanchez-Panchuelo et al., 2012b). Here, we take advantage of the improved BOLD CNR and high spatial resolution achievable at 7T to study regional structural variations across the functionally defined areas within the primary somatosensory cortex (S1) in individual subjects. Using a traveling wave fMRI paradigm to map the internal somatotopic representation of the index, middle, and ring fingers in S1, we were able to identify multiple map reversals at the tip and base, corresponding to the boundaries between Brodmann areas 3a, 3b, 1 and 2. Based on high resolution structural MRI data acquired in the same subjects, we inspected these functionally-parcellated Brodmann areas for differences in cortical thickness and MR contrast measures (magnetization transfer ratio (MTR) and signal intensity in phase sensitive inversion recovery (PSIR) images) that are sensitive to myelination. Consistent area-related differences in cortical thickness and MTR/PSIR measurements were found across subjects. However these measures did not have sufficient sensitivity to allow definition of areal boundaries., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Calibration of the BOLD signal is potentially of great value in providing a closer measure of the underlying changes in brain function related to neuronal activity than the BOLD signal alone, but current approaches rely on an assumed relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF). This is poorly characterised in humans and does not reflect the predominantly venous nature of BOLD contrast, whilst this relationship may vary across brain regions and depend on the structure of the local vascular bed. This work demonstrates a new approach to BOLD calibration which does not require an assumption about the relationship between cerebral blood volume and cerebral blood flow. This method involves repeating the same stimulus both at normoxia and hyperoxia, using hyperoxic BOLD contrast to estimate the relative changes in venous blood oxygenation and venous CBV. To do this the effect of hyperoxia on venous blood oxygenation has to be calculated, which requires an estimate of basal oxygen extraction fraction, and this can be estimated from the phase as an alternative to using a literature estimate. Additional measurement of the relative change in CBF, combined with the blood oxygenation change can be used to calculate the relative change in CMRO(2) due to the stimulus. CMRO(2) changes of 18 ± 8% in response to a motor task were measured without requiring the assumption of a CBV/CBF coupling relationship, and are in agreement with previous approaches., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The simultaneous acquisition and subsequent analysis of EEG and fMRI data is challenging owing to increased noise levels in the EEG data. A common method to integrate data from these two modalities is to use aspects of the EEG data, such as the amplitudes of event-related potentials (ERP) or oscillatory EEG activity, to predict fluctuations in the fMRI data. However, this relies on the acquisition of high quality datasets to ensure that only the correlates of neuronal activity are being studied. In this study, we investigate the effects of head-motion-related artefacts in the EEG signal on the predicted T2*-weighted signal variation. We apply our analyses to two independent datasets: 1) four participants were asked to move their feet in the scanner to generate small head movements, and 2) four participants performed an episodic memory task. We created T2*-weighted signal predictors from indicators of abrupt head motion using derivatives of the realignment parameters, from visually detected artefacts in the EEG as well as from three EEG frequency bands (theta, alpha and beta). In both datasets, we found little correlation between the T2*-weighted signal and EEG predictors that were not convolved with the canonical haemodynamic response function (cHRF). However, all convolved EEG predictors strongly correlated with the T2*-weighted signal variation in various regions including the bilateral superior temporal cortex, supplementary motor area, medial parietal cortex and cerebellum. The finding that movement onset spikes in the EEG predict T2*-weighted signal intensity only when the time course of movements is convolved with the cHRF, suggests that the correlated signal might reflect a BOLD response to neural activity associated with head movement. Furthermore, the observation that broad-spectral EEG spikes tend to occur at the same time as abrupt head movements, together with the finding that abrupt movements and EEG spikes show similar correlations with the T2*-weighted signal, indicates that the EEG spikes are produced by abrupt movement and that continuous regressors of EEG oscillations contain motion-related noise even after stringent correction of the EEG data. If not properly removed, these artefacts complicate the use of EEG data as a predictor of T2*-weighted signal variation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The effect of hypercapnia (an increase in CO(2) concentration in the blood) on the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) haemodynamic response has been well characterised and is commonly used for BOLD calibration. However, relatively little is known of the effect of hypercapnia on the electrical brain processes that underlie the BOLD response. Here, we investigate the effect of hypercapnia on resting and stimulus induced changes in neural oscillations using a feed-forward low gas flow system to deliver a reliable and repeatable level of hypercapnia. Magnetoencephalography (MEG) is used in conjunction with beamformer source localisation algorithms to non-invasively image changes in oscillatory amplitude. At rest, we find robust oscillatory power loss in the alpha (8Hz-13Hz), beta (13Hz-30Hz) and low gamma (30Hz-50Hz) frequency bands in response to hypercapnia. Further, we show that the spatial signature of this power loss differs across frequency bands, with the largest effect being observed for the beta band in sensorimotor cortices. We also measure changes in oscillatory activity induced by visual and motor events, and the effect of hypercapnia on these changes; whilst the percentage change in oscillatory activity on activation was largely unaffected by hypercapnia, the absolute change in oscillatory amplitude differed between normocapnia and hypercapnia. This work supports invasive recordings made in animals, and the results have potential implications for calibrated BOLD studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Functional connectivity (FC) between brain regions is thought to be central to the way in which the brain processes information. Abnormal connectivity is thought to be implicated in a number of diseases. The ability to study FC is therefore a key goal for neuroimaging. Functional connectivity (fc) MRI has become a popular tool to make connectivity measurements but the technique is limited by its indirect nature. A multimodal approach is therefore an attractive means to investigate the electrodynamic mechanisms underlying hemodynamic connectivity. In this paper, we investigate resting state FC using fcMRI and magnetoencephalography (MEG). In fcMRI, we exploit the advantages afforded by ultra high magnetic field. In MEG we apply envelope correlation and coherence techniques to source space projected MEG signals. We show that beamforming provides an excellent means to measure FC in source space using MEG data. However, care must be taken when interpreting these measurements since cross talk between voxels in source space can potentially lead to spurious connectivity and this must be taken into account in all studies of this type. We show good spatial agreement between FC measured independently using MEG and fcMRI; FC between sensorimotor cortices was observed using both modalities, with the best spatial agreement when MEG data are filtered into the β band. This finding helps to reduce the potential confounds associated with each modality alone: while it helps reduce the uncertainties in spatial patterns generated by MEG (brought about by the ill posed inverse problem), addition of electrodynamic metric confirms the neural basis of fcMRI measurements. Finally, we show that multiple MEG based FC metrics allow the potential to move beyond what is possible using fcMRI, and investigate the nature of electrodynamic connectivity. Our results extend those from previous studies and add weight to the argument that neural oscillations are intimately related to functional connectivity and the BOLD response., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mapping cerebrovascular reactivity (CVR) to hypercapnia is important both clinically and for improved understanding of the haemodynamic properties of the BOLD effect. In this work, BOLD/R2 CVR was investigated by using a device which provided small, repeatable and stable steps in PETCO2, whilst maintaining a steady PETO2 level. Significant CVR was observed in both grey and white matter at both 3 and 7 T, whilst an approximately linear relationship found between R2 CVR and field strength has implications for BOLD models and calibration. Grey matter R2 CVR was 0.066+/-0.004 s(-1) mm Hg(-1) at 3 T and 0.141+/-0.008 s(-1) mm Hg(-1) at 7 T. White matter R2 CVR was 0.021+/-0.003 s(-1) mm Hg(-1) at 3 T and 0.040+/-0.007 s(-1) mm Hg(-1) at 7 T., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

The exact relationship between neural activity and BOLD fMRI is unknown. However, several recent findings, recorded invasively in both humans and monkeys, show a positive correlation of BOLD to high-frequency (30-150 Hz) oscillatory power changes and a negative correlation to low-frequency (8-30 Hz) power changes arising from cortical areas. In this study, we computed the time series correlation between BOLD GE-EPI fMRI at 7 T and neural activity measures from noninvasive MEG, using a time-frequency beam former for source localisation. A sinusoidal drifting grating was presented visually for 4 s followed by a 20 s rest period in both recording modalities. The MEG time series were convolved with either a measured or canonical haemodynamic response function (HRF) for comparison with the measured BOLD data, and the BOLD data were deconvolved with either a measured or a canonical HRF for comparison with the measured MEG. In the visual cortex, the higher frequencies (mid-gamma=52-75 Hz and high-gamma=75-98 Hz) were positively correlated with BOLD whilst the lower frequencies (alpha=8-12 Hz and beta=12-25 Hz) were negatively correlated with BOLD. Furthermore, regression including all frequency bands predicted BOLD better than stimulus timing alone, although no individual frequency band predicted BOLD as well as stimulus timing. For this paradigm, there was, in general, no difference between using the SPM canonical HRF compared to the subject-specific measured HRF. In conclusion, MEG replicates findings from invasive recordings with regard to time series correlations with BOLD data. Conversely, deconvolution of BOLD data provides a neural estimate which correlates well with measured neural effects as a function of neural oscillation frequency.

Blood oxygenation level dependent (BOLD) signal changes occurring during execution of a simple motor task were measured at field strengths of 1.5, 3 and 7 T using multi-slice, single-shot, gradient echo EPI at a resolution of 1x1x3 mm(3), to quantify the benefits offered by ultra-high magnetic field for functional MRI. Using four different echo times at each field strength allowed quantification of the relaxation rate, R(2)* and the change in relaxation rate on activation, DeltaR(2)*. This work adds to previous studies of the field strength dependence of BOLD signal characteristics, through its: (i) focus on motor rather than visual cortex; (ii) use of single-shot, multi-slice, gradient echo EPI for data acquisition; (iii) co-registration of images acquired at different field strengths to allow assessment of the BOLD signal changes in the same region at each field strength. DeltaR(2)* was found to increase linearly with field strength (0.51+/-0.06 s(-1) at 1.5 T; 0.98+/-0.08 s(-1) at 3 T; 2.55+/-0.22 s(-1) at 7 T), while the ratio of DeltaR(2)*/R(2), which dictates the accessible BOLD contrast was also found to increase (0.042+/-0.002 at 1.5 T; 0.054+/-0.002 at 3 T; 0.084+/-0.003 at 7 T). The number of pixels classified as active, the t-value calculated over a common region of interest and the percentage signal change in the same region were all found to peak at TE approximately T(2)* and increase significantly with field strength. An earlier onset of the haemodynamic response at higher field provides some evidence for a reduced venous contribution to the BOLD signal at 7 T.

Ankle dorsiflexion (ADF) is an integral component in gait. The objective of this study was to define, using functional magnetic resonance imaging (fMRI) in healthy volunteers (n=12), the brain regions that are activated during Electrical Stimulation (ES)-induced ADF movements, and compare this to the pattern of activation occurring during active and passive ADF. Concurrent electromyography (EMG) was used to monitor the tibialis anterior muscle activity so as to allow EMG-guided fMRI analysis to be performed. Patterns of cortical and sub-cortical activation in response to active, passive and ES-induced ADF movement were identified. EMG-guided fMRI analysis was shown to improve detection and reduce inter-session variance for active and ES tasks. A significantly greater number of voxels were activated during active and ES-induced ADF compared to passive ADF in contralateral primary motor (M1), primary sensory (SI), and secondary somatosensory (SII) areas, as well as in supplementary motor area (SMA) and cingulate motor areas (CMA); bilateral dorsal and ventral premotor areas and cerebellum VI. The contrast of active greater than ES-induced ADF showed increased activation in SMA, contralateral PMdr; bilateral PMvr, dorsolateral prefrontal cortex and CMA; and ipsilateral cerebellum IV. Active ADF generated greater activation in brain areas responsible for motor planning, execution and visuomotor co-ordination. ES-induced activation was greater in bilateral SII and insula than for active ADF, hypothesised to result from increased sensory integration, but also possibly due to a nociceptive component to ES.

This paper introduces a lead field formulation for use in beamformer analysis of MEG data. This 'dual source beamformer' is a technique to image two temporally correlated sources using beamformer methodology. We show that while the standard, single source beamformer suppresses the reconstructed power of two spatially separate but temporally correlated sources, the dual source beamformer allows for their accurate reconstruction. The technique is proven to be accurate using simulations. We also show that it can be used to image accurately the auditory steady state response, which is correlated between the left and right auditory cortices. We suggest that this technique represents a useful way of locating correlated sources, particularly if a seed location can be defined a priori for one of the two sources. Such a priori information could be based on previous studies using similar paradigms, or from other functional neuroimaging techniques.