Robert Turner

YNIMG Journal 2021 Journal Article

Quantitative T1 mapping using multi-slice multi-shot inversion recovery EPI

• Rosa M. Sanchez Panchuelo
• Olivier Mougin
• Robert Turner
• Susan T. Francis

An efficient multi-slice inversion–recovery EPI (MS-IR-EPI) sequence for fast, high spatial resolution, quantitative T1 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 T1 maps with a narrow point-spread function. The precision and repeatability of MS-IR-EPI T1 measurements are assessed using both T1-calibrated and T2-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 T1 values. We model the effect of these fat suppression pulses on T1 measurements and show that the model can remove their MT contribution from the measured T1, thus providing accurate T1 quantification. High spatial resolution T1 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 T1 maps than MP2RAGE, demonstrating the potential for ultra-high resolution T1 mapping and the improved discrimination of functionally relevant cortical areas in the human brain.

YNIMG Journal 2021 Journal Article

Validating layer-specific VASO across species

• Laurentius (Renzo) Huber
• Benedikt A Poser
• Amanda L Kaas
• Elizabeth J Fear
• Sebastian Dresbach
• Jason Berwick
• Rainer Goebel
• Robert Turner

Cerebral blood volume (CBV) has been shown to be a robust and important physiological parameter for quantitative interpretation of functional (f)MRI, capable of delivering highly localized mapping of neural activity. Indeed, with recent advances in ultra-high-field (≥7T) MRI hardware and associated sequence libraries, it has become possible to capture non-invasive CBV weighted fMRI signals across cortical layers. One of the most widely used approaches to achieve this (in humans) is through vascular-space-occupancy (VASO) fMRI. Unfortunately, the exact contrast mechanisms of layer-dependent VASO fMRI have not been validated for human fMRI and thus interpretation of such data is confounded. Here we validate the signal source of layer-dependent SS-SI VASO fMRI using multi-modal imaging in a rat model in response to neuronal activation (somatosensory cortex) and respiratory challenge (hypercapnia). In particular VASO derived CBV measures are directly compared to concurrent measures of total haemoglobin changes from high resolution intrinsic optical imaging spectroscopy (OIS). Quantified cortical layer profiling is demonstrated to be in agreement between VASO and contrast enhanced fMRI (using monocrystalline iron oxide nanoparticles, MION). Responses show high spatial localisation to layers of cortical processing independent of confounding large draining veins which can hamper BOLD fMRI studies, (depending on slice positioning). Thus, a cross species comparison is enabled using VASO as a common measure. We find increased VASO based CBV reactivity (3.1 ± 1.2 fold increase) in humans compared to rats. Together, our findings confirm that the VASO contrast is indeed a reliable estimate of layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent VASO fMRI as an appropriate method in neuroscience application studies, in which the presence of large draining intracortical and pial veins limits neuroscientific inference with BOLD fMRI.

YNIMG Journal 2018 Journal Article

Somatosensory BOLD fMRI reveals close link between salient blood pressure changes and the murine neuromatrix

• Henning Matthias Reimann
• Mihail Todiras
• Russ Hodge
• Till Huelnhagen
• Jason Michael Millward
• Robert Turner
• Erdmann Seeliger
• Michael Bader

The neuromatrix, or “pain matrix”, is a network of cortical brain areas which is activated by noxious as well as salient somatosensory stimulation. This has been studied in mice and humans using blood oxygenation level-dependent (BOLD) fMRI. Here we demonstrate that BOLD effects observed in the murine neuromatrix in response to salient somatosensory stimuli are prone to reflect mean arterial blood pressure (MABP) changes, rather than neural activity. We show that a standard electrostimulus typically used in murine somatosensory fMRI can induce substantial elevations in MABP. Equivalent drug-induced MABP changes — without somatosensory stimulation — evoked BOLD patterns in the neuromatrix strikingly similar to those evoked by electrostimulation. This constitutes a serious caveat for murine fMRI. The regional specificity of these BOLD patterns can be attributed to the co-localization of the neuromatrix with large draining veins. Based on these findings we propose a cardiovascular support mechanism whereby abrupt elevations in MABP provide additional energy supply to the neuromatrix and other essential brain areas in fight-or-flight situations.

YNIMG Journal 2017 Journal Article

Uncertainty and expectancy deviations require cortico-subcortical cooperation

• Anna Mestres-Missé
• Robert Trampel
• Robert Turner
• Sonja A. Kotz

In a dynamic and uncertain environment it is beneficial to learn the causal structure of the environment in order to minimize uncertainty. This requires determining estimates of probable outcomes, which will guide expectations about incoming information. One key factor in this learning process is to detect whether an unexpected event constitutes a low probability, but valid outcome, or an outright error. The present 7T-fMRI study investigated the role of subcortical structures in regulating this probabilistic inferential learning process. A new task was designed, in which participants learned to calculate the value, and therefore to anticipate the outcome of different visual sequences. Three types of sequences provided unambiguous, ambiguous, and incongruent contextual evidence and each sequence had two outcomes, which differed in their probability of occurrence. We hypothesized that subcortical regions are necessary when expectations are violated, and that their involvement will depend on the nature of the unexpected event. The results show increased dorsomedial striatal and thalamic activation for less probable sequences; in addition, ambiguous sequences also display larger activation in the red nuclei. Incongruent sequences displayed a pattern of subcortical activation restricted to the dorsolateral and the posterior dorsomedial striatum. These results confirm that different subcortical structures regulate uncertainty and expectancy deviations; this is crucial not only for learning to predict events in the environment, but also for flexible cognitive control in general.

YNIMG Journal 2016 Journal Article

A subject-specific framework for in vivo myeloarchitectonic analysis using high resolution quantitative MRI

• Miriam D. Waehnert
• Juliane Dinse
• Andreas Schäfer
• Stefan Geyer
• Pierre-Louis Bazin
• Robert Turner
• Christine Lucas Tardif

Structural magnetic resonance imaging can now resolve laminar features within the cerebral cortex in vivo. A variety of intracortical contrasts have been used to study the cortical myeloarchitecture with the purpose of mapping cortical areas in individual subjects. In this article, we first briefly review recent advances in MRI analysis of cortical microstructure to portray the potential and limitations of the current state-of-the-art. We then present an integrated framework for the analysis of intracortical structure, composed of novel image processing tools designed for high resolution cortical images. The main features of our framework are the segmentation of quantitative T1 maps to delineate the cortical boundaries (Bazin et al. , 2014), and the use of an equivolume layering model to define an intracortical coordinate system that follows the anatomical layers of the cortex (Waehnert et al. , 2014). We evaluate the framework with 150μm isotropic post mortem T2 ∗-weighted images and 0. 5mm isotropic in vivo T1 maps, a quantitative index of myelin content. We study the laminar structure of the primary visual cortex (Brodmann area 17) in the post mortem and in vivo data, as well as the central sulcus region in vivo, in particular Brodmann areas 1, 3b and 4. We also investigate the impact of the layering models on the relationship between T1 and cortical curvature. Our experiments demonstrate that the equivolume intracortical surfaces and transcortical profiles best reflect the laminar structure of the cortex in areas of curvature in comparison to the state-of-the-art equidistant and Laplace implementations. This framework generates a subject specific intracortical coordinate system, the basis for subsequent architectonic analyses of the cortex. Any structural or functional contrast co-registered to the T1 maps, used to segment the cortex, can be sampled on the curved grid for analysis. This work represents an important step towards in vivo structural brain mapping of individual subjects.

YNIMG Journal 2016 Journal Article

Advanced MRI techniques to improve our understanding of experience-induced neuroplasticity

• Christine Lucas Tardif
• Claudine Joëlle Gauthier
• Christopher John Steele
• Pierre-Louis Bazin
• Andreas Schäfer
• Alexander Schaefer
• Robert Turner
• Arno Villringer

Over the last two decades, numerous human MRI studies of neuroplasticity have shown compelling evidence for extensive and rapid experience-induced brain plasticity in vivo. To date, most of these studies have consisted of simply detecting a difference in structural or functional images with little concern for their lack of biological specificity. Recent reviews and public debates have stressed the need for advanced imaging techniques to gain a better understanding of the nature of these differences – characterizing their extent in time and space, their underlying biological and network dynamics. The purpose of this article is to give an overview of advanced imaging techniques for an audience of cognitive neuroscientists that can assist them in the design and interpretation of future MRI studies of neuroplasticity. The review encompasses MRI methods that probe the morphology, microstructure, function, and connectivity of the brain with improved specificity. We underline the possible physiological underpinnings of these techniques and their recent applications within the framework of learning- and experience-induced plasticity in healthy adults. Finally, we discuss the advantages of a multi-modal approach to gain a more nuanced and comprehensive description of the process of learning.

YNIMG Journal 2016 Journal Article

Functional cerebral blood volume mapping with simultaneous multi-slice acquisition

• Laurentius Huber
• Dimo Ivanov
• Maria Guidi
• Robert Turner
• Kâmil Uludağ
• Harald E. Möller
• Benedikt A. Poser

The aim of this study is to overcome the current limits of brain coverage available with multi-slice echo planar imaging (EPI) for vascular space occupancy (VASO) mapping. By incorporating simultaneous multi-slice (SMS) EPI image acquisition into slice-saturation slab-inversion VASO (SS-SI VASO), many more slices can be acquired for non-invasive functional measurements of blood volume responses. Blood-volume-weighted VASO and gradient echo blood oxygenation level-dependent (GE-BOLD) data were acquired in humans at 7T with a 32-channel head coil. SMS-VASO was applied in three scenarios: A) high-resolution acquisition of spatially distant brain areas in the visuo-motor network (V1/V5/M1/S1); B) high-resolution acquisition of an imaging slab covering the entire M1/S1 hand regions; and C) low-resolution acquisition with near whole-brain coverage. The results show that the SMS-VASO sequence provided images enabling robust detection of blood volume changes in up to 20 slices with signal readout durations shorter than 150ms. High-resolution application of SMS-VASO revealed improved specificity of VASO to GM tissue without contamination from large draining veins compared to GE-BOLD in the visual cortex and in the sensory-motor cortex. It is concluded that VASO fMRI with SMS-EPI allows obtaining a reasonable three-dimensional coverage not achievable with standard VASO during the short time period when blood magnetization is approximately nulled. Due to the increased brain coverage and better spatial specificity to GM tissue of VASO compared to GE-BOLD signal, the proposed method may play an important role in high-resolution human fMRI at 7T.

YNIMG Journal 2016 Journal Article

Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain

• Christine Lucas Tardif
• Andreas Schäfer
• Robert Trampel
• Arno Villringer
• Robert Turner
• Pierre-Louis Bazin

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7T, and are now fully available to the entire neuroimaging community.

YNIMG Journal 2016 Journal Article

Temperature dependence of water diffusion pools in brain white matter

• Bibek Dhital
• Christian Labadie
• Frank Stallmach
• Harald E. Möller
• Robert Turner

Water diffusion in brain tissue can now be easily investigated using magnetic resonance (MR) techniques, providing unique insights into cellular level microstructure such as axonal orientation. The diffusive motion in white matter is known to be non-Gaussian, with increasing evidence for more than one water-containing tissue compartment. In this study, freshly excised porcine brain white matter was measured using a 125-MHz MR spectrometer (3T) equipped with gradient coils providing magnetic field gradients of up to 35, 000mT/m. The sample temperature was varied between −14 and +19°C. The hypothesis tested was that white matter contains two slowly exchanging pools of water molecules with different diffusion properties. A Stejskal–Tanner diffusion sequence with very short gradient pulses and b-factors up to 18. 8ms/μm2 was used. The dependence on b-factor of the attenuation due to diffusion was robustly fitted by a biexponential function, with comparable volume fractions for each component. The diffusion coefficient of each component follows Arrhenius behavior, with significantly different activation energies. The measured volume fractions are consistent with the existence of three water-containing compartments, the first comprising relatively free cytoplasmic and extracellular water molecules, the second of water molecules in glial processes, and the third comprising water molecules closely associated with membranes, as for example, in the myelin sheaths and elsewhere. The activation energy of the slow diffusion pool suggests proton hopping at the surface of membranes by a Grotthuss mechanism, mediated by hydrating water molecules.

YNIMG Journal 2015 Journal Article

Cortical lamina-dependent blood volume changes in human brain at 7 T

• Laurentius Huber
• Jozien Goense
• Aneurin J. Kennerley
• Robert Trampel
• Maria Guidi
• Enrico Reimer
• Dimo Ivanov
• Nicole Neef

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0. 8–1. 6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.

YNIMG Journal 2015 Journal Article

Multi-contrast multi-scale surface registration for improved alignment of cortical areas

• Christine Lucas Tardif
• Andreas Schäfer
• Miriam Waehnert
• Juliane Dinse
• Robert Turner
• Pierre-Louis Bazin

The position of cortical areas can be approximately predicted from cortical surface folding patterns. However, there is extensive inter-subject variability in cortical folding patterns, prohibiting a one-to-one mapping of cortical folds in certain areas. In addition, the relationship between cortical area boundaries and the shape of the cortex is variable, and weaker for higher-order cortical areas. Current surface registration techniques align cortical folding patterns using sulcal landmarks or cortical curvature, for instance. The alignment of cortical areas by these techniques is thus inherently limited by the sole use of geometric similarity metrics. Magnetic resonance imaging T1 maps show intra-cortical contrast that reflects myelin content, and thus can be used to improve the alignment of cortical areas. In this article, we present a new symmetric diffeomorphic multi-contrast multi-scale surface registration (MMSR) technique that works with partially inflated surfaces in the level-set framework. MMSR generates a more precise alignment of cortical surface curvature in comparison to two widely recognized surface registration algorithms. The resulting overlap in gyrus labels is comparable to FreeSurfer. Most importantly, MMSR improves the alignment of cortical areas further by including T1 maps. As a first application, we present a group average T1 map at a uniquely high-resolution and multiple cortical depths, which reflects the myeloarchitecture of the cortex. MMSR can also be applied to other MR contrasts, such as functional and connectivity data.

YNIMG Journal 2015 Journal Article

Real diffusion-weighted MRI enabling true signal averaging and increased diffusion contrast

• Cornelius Eichner
• Stephen F. Cauley
• Julien Cohen-Adad
• Harald E. Möller
• Robert Turner
• Kawin Setsompop
• Lawrence L. Wald

This project aims to characterize the impact of underlying noise distributions on diffusion-weighted imaging. The noise floor is a well-known problem for traditional magnitude-based diffusion-weighted MRI (dMRI) data, leading to biased diffusion model fits and inaccurate signal averaging. Here, we introduce a total-variation-based algorithm to eliminate shot-to-shot phase variations of complex-valued diffusion data with the intention to extract real-valued dMRI datasets. The obtained real-valued diffusion data are no longer superimposed by a noise floor but instead by a zero-mean Gaussian noise distribution, yielding dMRI data without signal bias. We acquired high-resolution dMRI data with strong diffusion weighting and, thus, low signal-to-noise ratio. Both the extracted real-valued and traditional magnitude data were compared regarding signal averaging, diffusion model fitting and accuracy in resolving crossing fibers. Our results clearly indicate that real-valued diffusion data enables idealized conditions for signal averaging. Furthermore, the proposed method enables unbiased use of widely employed linear least squares estimators for model fitting and demonstrates an increased sensitivity to detect secondary fiber directions with reduced angular error. The use of phase-corrected, real-valued data for dMRI will therefore help to clear the way for more detailed and accurate studies of white matter microstructure and structural connectivity on a fine scale.

YNIMG Journal 2014 Journal Article

A computational framework for ultra-high resolution cortical segmentation at 7Tesla

• Pierre-Louis Bazin
• Marcel Weiss
• Juliane Dinse
• Andreas Schäfer
• Robert Trampel
• Robert Turner

This paper presents a computational framework for whole brain segmentation of 7Tesla magnetic resonance images able to handle ultra-high resolution data. The approach combines multi-object topology-preserving deformable models with shape and intensity atlases to encode prior anatomical knowledge in a computationally efficient algorithm. Experimental validation on simulated and real brain images shows accuracy and robustness of the method and demonstrates the benefits of an increased processing resolution.

YNIMG Journal 2014 Journal Article

Dorsomedial striatum involvement in regulating conflict between current and presumed outcomes

• Anna Mestres-Missé
• Pierre-Louis Bazin
• Robert Trampel
• Robert Turner
• Sonja A. Kotz

The balance between automatic and controlled processing is essential to human flexible but optimal behavior. On the one hand, the automation of habitual behavior and processing is indispensable, and, on the other hand, strategic processing is needed in light of unexpected, conflicting, or new situations. Using ultra-high-field high-resolution functional magnetic resonance imaging (7T-fMRI), the present study examined the role of subcortical structures in mediating this balance. Participants were asked to judge the congruency of sentences containing a semantically ambiguous or unambiguous word. Ambiguous sentences had three possible resolutions: dominant meaning, subordinate meaning, and incongruent. The dominant interpretation represents the most habitual response, whereas both the subordinate and incongruent options clash with this automatic response, and, hence, require cognitive control. Moreover, the subordinate resolution entails a less expected but correct outcome, while the incongruent condition is simply wrong. The current results reveal the involvement of the anterior dorsomedial striatum in modulating and resolving conflict between actual and expected outcomes, and highlight the importance of cortical and subcortical cooperation in this process.

YNIMG Journal 2014 Journal Article

Introduction to the NeuroImage Special Issue: “In vivo Brodmann mapping of the human brain”

• Robert Turner
• Stefan Geyer

YNIMG Journal 2014 Journal Article

Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T

• Laurentius Huber
• Jozien Goense
• Aneurin J. Kennerley
• Dimo Ivanov
• Steffen N. Krieger
• Jöran Lepsien
• Robert Trampel
• Robert Turner

Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in ‘arterial’ and ‘venous’ blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between ‘arterial’ and ‘venous’ contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms.

YNIMG Journal 2014 Journal Article

Myelin and iron concentration in the human brain: A quantitative study of MRI contrast

• Carsten Stüber
• Markus Morawski
• Andreas Schäfer
• Christian Labadie
• Miriam Wähnert
• Christoph Leuze
• Markus Streicher
• Nirav Barapatre

During the last five years ultra-high-field magnetic resonance imaging (MRI) has enabled an unprecedented view of living human brain. Brain tissue contrast in most MRI sequences is known to reflect mainly the spatial distributions of myelin and iron. These distributions have been shown to overlap significantly in many brain regions, especially in the cortex. It is of increasing interest to distinguish and identify cortical areas by their appearance in MRI, which has been shown to be feasible in vivo. Parcellation can benefit greatly from quantification of the independent contributions of iron and myelin to MRI contrast. Recent studies using susceptibility mapping claim to allow such a separation of the effects of myelin and iron in MRI. We show, using post-mortem human brain tissue, that this goal can be achieved. After MRI scanning of the block with appropriate T 1 mapping and T 2* weighted sequences, we section the block and apply a novel technique, proton induced X-ray emission (PIXE), to spatially map iron, phosphorus and sulfur elemental concentrations, simultaneously with 1μm spatial resolution. Because most brain phosphorus is located in myelin phospholipids, a calibration step utilizing element maps of sulfur enables semi-quantitative ex vivo mapping of myelin concentration. Combining results for iron and myelin concentration in a linear model, we have accurately modeled MRI tissue contrasts. Conversely, iron and myelin concentrations can now be estimated from appropriate MRI measurements in post-mortem brain samples.

YNIMG Journal 2014 Journal Article

Regional reproducibility of calibrated BOLD functional MRI: Implications for the study of cognition and plasticity

• Steffen N. Krieger
• Claudine J. Gauthier
• Dimo Ivanov
• Laurentius Huber
• Elisabeth Roggenhofer
• Bernhard Sehm
• Robert Turner
• Gary F. Egan

Calibrated BOLD fMRI is a promising alternative to the classic BOLD contrast due to its reduced venous sensitivity and greater physiological specificity. The delayed adoption of this technique for cognitive studies may stem partly from a lack of information on the reproducibility of these measures in the context of cognitive tasks. In this study we have explored the applicability and reproducibility of a state-of-the-art calibrated BOLD technique using a complex functional task at 7 tesla. Reproducibility measures of BOLD, CBF, CMRO2 flow-metabolism coupling n and the calibration parameter M were compared and interpreted for three ROIs. We found an averaged intra-subject variation of CMRO2 of 8% across runs and 33% across days. BOLD (46% across runs, 36% across days), CBF (33% across runs, 46% across days) and M (41% across days) showed significantly higher intra-subject variability. Inter-subject variability was found to be high for all quantities, though CMRO2 was the most consistent across brain regions. The results of this study provide evidence that calibrated BOLD may be a viable alternative for longitudinal and cognitive MRI studies.

YNIMG Journal 2014 Journal Article

Using carbogen for calibrated fMRI at 7Tesla: Comparison of direct and modelled estimation of the M parameter

• Steffen N. Krieger
• Dimo Ivanov
• Laurentius Huber
• Elisabeth Roggenhofer
• Bernhard Sehm
• Robert Turner
• Gary F. Egan
• Claudine J. Gauthier

Task-evoked changes in cerebral oxygen metabolism can be measured using calibrated functional Magnetic Resonance Imaging (fMRI). This technique requires the use of breathing manipulations such as hypercapnia, hyperoxia or a combination of both to determine a calibration factor M. The M-value is usually obtained by extrapolating the BOLD signal measured during the gas manipulation to its upper theoretical physiological limit using a biophysical model. However, a recently introduced technique uses a combination of increased inspired concentrations of O2 and CO2 to saturate the BOLD signal completely. In this study, we used this BOLD saturation technique to measure M directly at 7Tesla (T). Simultaneous carbogen-7 (7% CO2 in 93% O2) inhalation and visuo-motor task performance were used to elevate venous oxygen saturation in visual and motor areas close to their maximum, and the BOLD signal measured during this manipulation was used as an estimate of M. As accurate estimation of M is crucial for estimation of valid oxidative metabolism values, these directly estimated M-values were assessed and compared with M-values obtained via extrapolation modelling using the generalized calibration model (GCM) on the same dataset. Average M-values measured using both methods were 10. 4±3. 9% (modelled) and 7. 5±2. 2% (direct) for a visual-related ROI, and 11. 3±5. 2% (modelled) and 8. 1±2. 6% (direct) for a motor-related ROI. Results from this study suggest that, for the CO2 concentration used here, modelling is necessary for the accurate estimation of the M parameter. Neither gas inhalation alone, nor gas inhalation combined with a visuo-motor task, was sufficient to completely saturate venous blood in most subjects. Calibrated fMRI studies should therefore rely on existing models for gas inhalation-based calibration of the BOLD signal.

YNIMG Journal 2013 Journal Article

Optimizing T1-weighted imaging of cortical myelin content at 3.0T

• Nicholas A. Bock
• Eyesha Hashim
• Rafal Janik
• Norman B. Konyer
• Marcel Weiss
• Greg J. Stanisz
• Robert Turner
• Stefan Geyer

With increases in the sensitivity and resolution of anatomical MRI for the brain, methods for mapping the organization of the cerebral cortex by imaging its myelin content have emerged. This identifies major sensory and motor regions and could be used in studies of cortical organization, particularly if patterns of myelination can be visualized over the cortical surface robustly in individual subjects. The imaging problem is difficult, however, because of the relative thinness of the cerebral cortex and the low intracortical tissue contrast. In this paper, we optimize the contrast of T1-weighted MRI to help better visualize patterns of myelination. We measure a small but statistically significant difference in T1 of 171±40ms between cortical regions with low and high myelin contents in the human cortex at 3T, and then perform simulations to choose parameters for an inversion-recovery pulse sequence that utilizes this T1 difference to increase contrast within the cortex. We show that lengthening the delay between signal acquisition and the next inversion pulse in the sequence increases intracortical contrast more effectively than does image averaging. Using the optimized sequence, we show that major myelinated regions that are relatively thick, such as the primary motor and auditory regions, can be visualized well in individuals at 3T using whole-cortex 3D images made at 1mm isotropic resolution, while thinner regions, such as the primary visual cortex, can be visualized using targeted 3D images made at 0. 5mm isotropic resolution. Our findings demonstrate that patterns of myelination can be better visualized in individual subjects when the imaging is optimized to highlight intracortical contrast and can help to pave the way for the creation of matched maps of microanatomy and function in the cortex of living individual humans.

YNIMG Journal 2013 Journal Article

Response to commentaries on our paper: Critical comments on dynamic causal modelling

• Gabriele Lohmann
• Karsten Müller
• Robert Turner

First of all, we would like to state that we are pleased that our paper has spawned a vivid debate about the validity of DCM. Given that DCM has been around for so many years, we think that this was long overdue. In the following, we would like to respond to the comments by Friston et al. and Breakspear.

YNIMG Journal 2013 Journal Article

Statistical inference and multiple testing correction in classification-based multi-voxel pattern analysis (MVPA): Random permutations and cluster size control

• Johannes Stelzer
• Yi Chen
• Robert Turner

An ever-increasing number of functional magnetic resonance imaging (fMRI) studies are now using information-based multi-voxel pattern analysis (MVPA) techniques to decode mental states. In doing so, they achieve a significantly greater sensitivity compared to when they use univariate frameworks. However, the new brain-decoding methods have also posed new challenges for analysis and statistical inference on the group level. We discuss why the usual procedure of performing t-tests on accuracy maps across subjects in order to produce a group statistic is inappropriate. We propose a solution to this problem for local MVPA approaches, which achieves higher sensitivity than other procedures. Our method uses random permutation tests on the single-subject level, and then combines the results on the group level with a bootstrap method. To preserve the spatial dependency induced by local MVPA methods, we generate a random permutation set and keep it fixed across all locations. This enables us to later apply a cluster size control for the multiple testing problem. More specifically, we explicitly compute the distribution of cluster sizes and use this to determine the p-values for each cluster. Using a volumetric searchlight decoding procedure, we demonstrate the validity and sensitivity of our approach using both simulated and real fMRI data sets. In comparison to the standard t-test procedure implemented in SPM8, our results showed a higher sensitivity. We discuss the theoretical applicability and the practical advantages of our approach, and outline its generalization to other local MVPA methods, such as surface decoding techniques.

YNIMG Journal 2013 Journal Article

Toward in vivo histology: A comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2⁎-imaging at ultra-high magnetic field strength

• Andreas Deistung
• Andreas Schäfer
• Ferdinand Schweser
• Uta Biedermann
• Robert Turner
• Jürgen R. Reichenbach

Quantitative magnetic susceptibility mapping (QSM) has recently been introduced to provide a novel quantitative and local MRI contrast. However, the anatomical contrast represented by in vivo susceptibility maps has not yet been compared systematically and comprehensively with gradient (recalled) echo (GRE) magnitude, frequency, and R2 ⁎ images. Therefore, this study compares high-resolution quantitative susceptibility maps with conventional GRE imaging approaches (magnitude, frequency, R2 ⁎) in healthy individuals at 7T with respect to anatomic tissue contrast. Volumes-of-interest were analyzed in deep and cortical gray matter (GM) as well as in white matter (WM) on R2 ⁎ and susceptibility maps. High-resolution magnetic susceptibility maps of the human brain exhibited superb contrast that allowed the identification of substructures of the thalamus, midbrain and basal ganglia, as well as of the cerebral cortex. These were consistent with histology but not generally visible on magnitude, frequency or R2 ⁎-maps. Common target structures for deep brain stimulation, including substantia nigra pars reticulata, ventral intermediate nucleus, subthalamic nucleus, and the substructure of the internal globus pallidus, were clearly distinguishable from surrounding tissue on magnetic susceptibility maps. The laminar substructure of the cortical GM differed depending on the anatomical region, i. e. , a cortical layer with increased magnetic susceptibility, corresponding to the Stria of Gennari, was found in the GM of the primary visual cortex, V1, whereas a layer with reduced magnetic susceptibility was observed in the GM of the temporal cortex. Both magnetic susceptibility and R2 ⁎ values differed substantially in cortical GM depending on the anatomic regions. Regression analysis between magnetic susceptibility and R2 ⁎ values of WM and GM structures suggested that variations in myelin content cause the overall contrast between gray and white matter on susceptibility maps and that both R2 ⁎ and susceptibility values provide linear measures for iron content in GM. In conclusion, quantitative magnetic susceptibility mapping provides a non-invasive and spatially specific contrast that opens the door to the assessment of diseases characterized by variation in iron and/or myelin concentrations. Its ability to reflect anatomy of deep GM structures with superb delineation may be useful for neurosurgical applications.

YNIMG Journal 2013 Journal Article

White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI

• Derek K. Jones
• Thomas R. Knösche
• Robert Turner

Diffusion-weighted MRI (DW-MRI) has been increasingly used in imaging neuroscience over the last decade. An early form of this technique, diffusion tensor imaging (DTI) was rapidly implemented by major MRI scanner companies as a scanner selling point. Due to the ease of use of such implementations, and the plausibility of some of their results, DTI was leapt on by imaging neuroscientists who saw it as a powerful and unique new tool for exploring the structural connectivity of human brain. However, DTI is a rather approximate technique, and its results have frequently been given implausible interpretations that have escaped proper critique and have appeared misleadingly in journals of high reputation. In order to encourage the use of improved DW-MRI methods, which have a better chance of characterizing the actual fiber structure of white matter, and to warn against the misuse and misinterpretation of DTI, we review the physics of DW-MRI, indicate currently preferred methodology, and explain the limits of interpretation of its results. We conclude with a list of ‘Do's and Don'ts’ which define good practice in this expanding area of imaging neuroscience.

YNIMG Journal 2012 Journal Article

An anterior–posterior gradient of cognitive control within the dorsomedial striatum

• Anna Mestres-Missé
• Robert Turner
• Angela D. Friederici

Lateral prefrontal cortex and basal ganglia work together to mediate working memory and top-down regulation of cognition. This circuit regulates the balance and interactions between automatic and high-order control responses. Using ultra-high-field high-resolution functional magnetic resonance imaging (7T-fMRI), the present study examined the role of subcortical structures in cognitive control during language processing. Participants were asked to judge the grammaticality of unambiguous, ungrammatical and ambiguous sentences. Grammatical unambiguous sentences should elicit an automatic response, while ambiguous and ungrammatical sentences should conflict with the automatic response and, hence, require a high-order control response. Within the control response domain, ambiguity and ungrammaticality represent two different dimensions of conflict resolution, while for a temporarily ambiguous sentence a correct interpretation is available, that is not the case for ungrammatical sentences. Our results reveal an anterior–posterior axis in the dorsomedial striatum with more rostral regions supporting higher levels of cognitive processing. This functional architecture mirrors the rostrocaudal hierarchical organization evidenced within the lateral prefrontal cortex.

YNIMG Journal 2012 Journal Article

Cortico-subthalamic white matter tract strength predicts interindividual efficacy in stopping a motor response

• Birte U. Forstmann
• Max C. Keuken
• Sara Jahfari
• Pierre-Louis Bazin
• Jane Neumann
• Andreas Schäfer
• Alfred Anwander
• Robert Turner

The subthalamic nucleus (STN) is a small but vitally important structure in the basal ganglia. Because of its small volume, and its localization in the basal ganglia, the STN can best be visualized using ultra-high resolution 7 Tesla (T) magnetic resonance imaging (MRI). In the present study, first we individually segmented 7T MRI STN masks to generate atlas probability maps. Secondly, the individually segmented STN masks and the probability maps were used to derive cortico-subthalamic white matter tract strength. Tract strength measures were then taken to test two functional STN hypotheses which account for the efficiency in stopping a motor response: the right inferior fronto-subthalamic (rIFC-STN) hypothesis and the posterior medial frontal cortex-subthalamic (pMFC-STN) hypothesis. Results of two independent experiments show that increased white matter tract strength between the pMFC and STN results in better stopping behaviour.

YNIMG Journal 2012 Journal Article

Critical comments on dynamic causal modelling

• Gabriele Lohmann
• Kerstin Erfurth
• Karsten Müller
• Robert Turner

Dynamic causal modelling (DCM) (Friston et al. , 2003) is a technique designed to investigate the influence between brain areas using time series data obtained by EEG/MEG or functional magnetic resonance imaging (fMRI). The basic idea is to fit various models to time series data, and select one of those models using Bayesian model comparison. Here, we present a critical evaluation of DCM in which we show that DCM can be challenged on several grounds. We will discuss three main points relating to combinatorial explosion, the validity of the model selection procedure, and problems with respect to model validation.

YNIMG Journal 2012 Journal Article

k-space and q-space: Combining ultra-high spatial and angular resolution in diffusion imaging using ZOOPPA at 7T

• Robin M. Heidemann
• Alfred Anwander
• Thorsten Feiweier
• Thomas R. Knösche
• Robert Turner

There is ongoing debate whether using a higher spatial resolution (sampling k-space) or a higher angular resolution (sampling q-space angles) is the better way to improve diffusion MRI (dMRI) based tractography results in living humans. In both cases, the limiting factor is the signal-to-noise ratio (SNR), due to the restricted acquisition time. One possible way to increase the spatial resolution without sacrificing either SNR or angular resolution is to move to a higher magnetic field strength. Nevertheless, dMRI has not been the preferred application for ultra-high field strength (7T). This is because single-shot echo-planar imaging (EPI) has been the method of choice for human in vivo dMRI. EPI faces several challenges related to the use of a high resolution at high field strength, for example, distortions and image blurring. These problems can easily compromise the expected SNR gain with field strength. In the current study, we introduce an adapted EPI sequence in conjunction with a combination of ZOOmed imaging and Partially Parallel Acquisition (ZOOPPA). We demonstrate that the method can produce high quality diffusion-weighted images with high spatial and angular resolution at 7T. We provide examples of in vivo human dMRI with isotropic resolutions of 1mm and 800μm. These data sets are particularly suitable for resolving complex and subtle fiber architectures, including fiber crossings in the white matter, anisotropy in the cortex and fibers entering the cortex.

YNIMG Journal 2012 Journal Article

The NIH experience in first advancing fMRI

• Robert Turner

The introduction of functional MRI at NIH in 1992 was the outcome of research goals first formulated by Turner in 1983. Between 1988 and 1990, Turner worked at NIH on actively-shielded gradient coils and the implementation of EPI-based techniques, especially diffusion-weighted EPI. His work on hypoxia in cat brain in 1990 directly inspired Ken Kwong's demonstration of BOLD contrast in humans at MGH in May 1991. Turner collaborated actively with this MGH team, the first group to map entirely noninvasively human brain activity due to visual stimulation. He introduced BOLD fMRI at NIH in February 1992. This paper reviews the steps that led up to BOLD EPI, and Turner's initial applications of BOLD fMRI at NIH.

YNIMG Journal 2011 Journal Article

Exploring functional relations between brain regions from fMRI meta-analysis data: Comments on Ramsey, Spirtes, and Glymour

• Jane Neumann
• Robert Turner
• Peter T. Fox
• Gabriele Lohmann

In this paper, we address the critical assessment of Ramsey et al. of our method for learning partially directed graphs from meta-analysis imaging data (Neumann et al. , 2010). We argue that our method provides valid and interpretable results when applied to data representing a single experimental paradigm. Simulations further suggest that, despite theoretical limitations, the application of our method to mixed probability distributions yields reliable results with error rates at acceptable levels. Finally, we discuss the nature of meta-analysis data and the notion of causality in the context of functional neuroimaging.

YNIMG Journal 2011 Journal Article

How the brain tissue shapes the electric field induced by transcranial magnetic stimulation

• Alexander Opitz
• Mirko Windhoff
• Robin M. Heidemann
• Robert Turner
• Axel Thielscher

In transcranial magnetic stimulation (TMS), knowledge of the distribution of the induced electric field is fundamental for a better understanding of the position and extent of the stimulated brain region. However, the different tissue types and the varying fibre orientation in the brain tissue result in an inhomogeneous and anisotropic conductivity distribution and distort the electric field in a non-trivial way. Here, the field induced by a figure-8 coil is characterized in detail using finite element calculations and a geometrically accurate model of an individual head combined with high-resolution diffusion-weighted imaging for conductivity mapping. It is demonstrated that the field strength is significantly enhanced when the currents run approximately perpendicular to the local gyral orientation. Importantly, the spatial distribution of this effect differs distinctly between gray matter (GM) and white matter (WM): While the field in GM is selectively enhanced at the gyral crowns and lips, high field strengths can still occur rather deep in WM. Taking the anisotropy of brain tissue into account tends to further boost this effect in WM, but not in GM. Spatial variations in the WM anisotropy affect the local field strength in a systematic way and result in localized increases of up to 40% (on average ~7% for coil orientations perpendicular to the underlying gyri). We suggest that these effects might create hot spots in WM that might contribute to the excitation of WM structures by TMS. However, our results also demonstrate the necessity of using realistic nerve models in the future to allow for more definitive conclusions.

YNIMG Journal 2011 Journal Article

Parcellation of human amygdala in vivo using ultra high field structural MRI

• Eugenia Solano-Castiella
• Andreas Schäfer
• Enrico Reimer
• Erik Türke
• Thomas Pröger
• Gabriele Lohmann
• Robert Trampel
• Robert Turner

Histological studies show that human amygdala is subdivided into several nuclei with specific connections to other brain areas. One such study has been recently used as the basis of a probabilistic amygdala map, to enable in vivo identification of specifically located functions within the amygdala and connections to it. The involvement of the amygdala in cognition, emotion and action, which may underlie several psychiatric disorders, points to a need for discrimination of these nuclei in living human brains using different techniques. Structural MRI scans of the human amygdala at standard field strengths (≤3T) have shown a region of generally featureless gray matter. Apparently homogeneous regions may reveal internal structure, however, when improved imaging strategies and better SNR are available. The goal of this study is the in vivo anatomical segmentation of the amygdala using high resolution structural MR data. The use of different MRI tissue contrast mechanisms at high field strengths has been little explored so far. Combining two different contrasts, and using cutting-edge image analysis, the following study provides a robust clustering of three amygdala components in vivo using 7T structural imaging.

YNIMG Journal 2010 Journal Article

Diffusion tensor imaging segments the human amygdala in vivo

• Eugenia Solano-Castiella
• Alfred Anwander
• Gabriele Lohmann
• Marcel Weiss
• Carol Docherty
• Stefan Geyer
• Enrico Reimer
• Angela D. Friederici

The amygdala plays an important role in emotion, learning, and memory. It would be highly advantageous to understand more precisely its internal structure and connectivity for individual human subjects in vivo. Earlier cytoarchitectural research in post-mortem human and animal brains has revealed multiple subdivisions and connectivity patterns, probably related to different functions. With standard magnetic resonance imaging (MRI) techniques, however, the amygdala appears as an undifferentiated area of grey matter. Using high-quality diffusion tensor imaging (DTI) at 3 Tesla, we show diffusion anisotropy in this grey matter area. Such data allowed us to subdivide the amygdala for the first time in vivo. In 15 living subjects, we applied a spectral clustering algorithm to the principal diffusion direction in each amygdala voxel and found a consistent subdivision of the amygdala into a medial and a lateral region. The topography of these regions is in good agreement with the fibre architecture visible in myelin-stained sections through the amygdala of a human post-mortem brain. From these in vivo results we derived a probabilistic map of amygdalar fibre orientations. This segmentation technique has important implications for functional studies in the processing of emotions, cognitive function, and psychiatric disorders and in studying morphometry and volumetry of amygdala subdivisions.

YNIMG Journal 2010 Journal Article

Learning partially directed functional networks from meta-analysis imaging data

• Jane Neumann
• Peter T. Fox
• Robert Turner
• Gabriele Lohmann

We propose a new exploratory method for the discovery of partially directed functional networks from fMRI meta-analysis data. The method performs structure learning of Bayesian networks in search of directed probabilistic dependencies between brain regions. Learning is based on the co-activation of brain regions observed across several independent imaging experiments. In a series of simulations, we first demonstrate the reliability of the method. We then present the application of our approach in an extensive meta-analysis including several thousand activation coordinates from more than 500 imaging studies. Results show that our method is able to automatically infer Bayesian networks that capture both directed and undirected probabilistic dependencies between a number of brain regions, including regions that are frequently observed in motor-related and cognitive control tasks.

YNIMG Journal 2010 Journal Article

Whole-brain mapping of venous vessel size in humans using the hypercapnia-induced BOLD effect

• Thies H. Jochimsen
• Dimo Ivanov
• Derek V.M. Ott
• Wolfgang Heinke
• Robert Turner
• Harald E. Möller
• Jürgen R. Reichenbach

Measuring the morphology of the cerebral microvasculature by vessel-size imaging (VSI) is a promising approach for clinical applications, such as the characterization of tumor angiogenesis and stroke. Despite the great potential of VSI, this method has not yet found widespread use in practice due to the lack of experience in testing it on healthy humans. Since this limitation derives mainly from the need for an invasive injection of a contrast agent, this work explores the possibility to employ instead the easily accessible blood oxygenation level dependent (BOLD) effect for VSI of the venous microstructure. It is demonstrated that BOLD-VSI in humans can be realized by a hypercapnic challenge using a fast gradient-echo (GE) and spin-echo (SE) sequence at 7T. Reproducible maps of the mean venous vessel radius, based on the BOLD-induced changes in GE and SE relaxation rates, could be obtained within a scan time of 10min. Moreover, the method yields maps of venous blood volume and vessel density. Owing to its non-invasive character, BOLD-VSI provides a low-risk method to analyze the venous microstructure, which will not only be useful in clinical applications, but also provide a better understanding of BOLD effect.

YNIMG Journal 2008 Journal Article

Voxel-based cortical thickness measurements in MRI

• Chloe Hutton
• Enrico De Vita
• John Ashburner
• Ralf Deichmann
• Robert Turner

The thickness of the cerebral cortex can provide valuable information about normal and abnormal neuroanatomy. High resolution MRI together with powerful image processing techniques has made it possible to perform these measurements automatically over the whole brain. Here we present a method for automatically generating voxel-based cortical thickness (VBCT) maps. This technique results in maps where each voxel in the grey matter is assigned a thickness value. Sub-voxel measurements of thickness are possible using sub-sampling and interpolation of the image information. The method is applied to repeated MRI scans of a single subject from two MRI scanners to demonstrate its robustness and reproducibility. A simulated data set is used to show that small focal differences in thickness between two groups of subjects can be detected. We propose that the analysis of VBCT maps can provide results that are complementary to other anatomical analyses such as voxel-based morphometry.

YNIMG Journal 2006 Journal Article

BOLD correlates of EMG spectral density in cortical myoclonus: Description of method and case report

• Mark P. Richardson
• Pascal Grosse
• Philip J. Allen
• Robert Turner
• Peter Brown

The recording of electrophysiological data during BOLD fMRI is highly challenging but provides the opportunity to develop a more thorough account of brain function than either modality alone. To develop new techniques in this area has often required the study of pathological electrophysiological measures because such measures can be unusually strong (e. g. , epileptic EEG spikes) and hence more easily detectable during fMRI than weaker normal phenomena. In this paper, we have studied pathologically strong EMG signals in a patient with cortical myoclonus. First, we studied the patient outside of scanning: The pathological corticospinal drive to muscle was concentrated over 6–30 Hz so that EMG components at higher frequency could be used to control for non-corticospinal contributions to the EMG during scanning. Additionally, there was very strong EMG–EMG and EMG–EEG coherence in this frequency band. Furthermore, analysis of spectral phase showed that this exaggerated coherence was produced by efferent drive from brain to muscle. Hence, the exaggerated peak in distal muscle EMG power spectrum reflected brain activity producing the efferent drive. Subsequently, we modified equipment and data analysis techniques previously developed for simultaneous EEG–fMRI to record polychannel EMG from distal upper limbs during simultaneous BOLD fMRI. After artefact reduction, the EMG recorded during fMRI retained the essential frequency and phase characteristics of EMG recorded outside of scanning. The BOLD signal was significantly correlated with time-varying 6- to 30-Hz power in a frontoparietal network compatible with the neurophysiological characteristics of our patient and compatible with prior hypotheses explaining the origin of cortical myoclonus.

YNIMG Journal 2006 Journal Article

Improving whole brain structural MRI at 4.7 Tesla using 4 irregularly shaped receiver coils

• David W. Carmichael
• David L. Thomas
• Enrico De Vita
• Maria A. Fernández-Seara
• Navjeet Chhina
• Mark Cooper
• Colin Sunderland
• Chris Randell

Both higher magnetic field strengths (≥3 T) and multiple receiver ‘array coils’ can provide increased signal-to-noise ratio (SNR) for MRI. This increase in SNR can be used to obtain images with higher resolution, enabling better visualisation of structures within the human brain. However, high field strength systems also suffer from increased B1 non-uniformity and increased power deposition, reaching specific absorption rate (SAR) limits more quickly. For these problems to be mitigated, a careful choice of both the pulse sequence design and transmit RF coil is required. This paper describes the use of a prototype array coil consisting of 4 irregularly shaped coils within a standard configuration for neuroimaging at 4. 7 T (a head transmit/receive volume coil to minimise SAR and a head gradient insert for maximum gradient performance). With a fast spin echo (FSE) pulse sequence optimised for 4. 7 T, this provides dramatically increased quality and resolution over a large brain volume. Using the array coil, a SNR improvement relative to the volume coil of 1–1. 5 times in central brain areas and 2–3 times in cortical regions was obtained. Array coil images with a resolution of 352 × 352 × 2000 μm had a SNR of 16. 0 to 26. 2 in central regions and 19. 9 to 34. 8 in cortical areas. Such images easily demonstrate cortical myeloarchitecture, while still covering most of the brain in a ∼12 min scan.

YNIMG Journal 2006 Journal Article

Song and speech: Brain regions involved with perception and covert production

• Daniel E. Callan
• Vassiliy Tsytsarev
• Takashi Hanakawa
• Akiko M. Callan
• Maya Katsuhara
• Hidenao Fukuyama
• Robert Turner

This 3-T fMRI study investigates brain regions similarly and differentially involved with listening and covert production of singing relative to speech. Given the greater use of auditory–motor self-monitoring and imagery with respect to consonance in singing, brain regions involved with these processes are predicted to be differentially active for singing more than for speech. The stimuli consisted of six Japanese songs. A block design was employed in which the tasks for the subject were to listen passively to singing of the song lyrics, passively listen to speaking of the song lyrics, covertly sing the song lyrics visually presented, covertly speak the song lyrics visually presented, and to rest. The conjunction of passive listening and covert production tasks used in this study allow for general neural processes underlying both perception and production to be discerned that are not exclusively a result of stimulus induced auditory processing nor to low level articulatory motor control. Brain regions involved with both perception and production for singing as well as speech were found to include the left planum temporale/superior temporal parietal region, as well as left and right premotor cortex, lateral aspect of the VI lobule of posterior cerebellum, anterior superior temporal gyrus, and planum polare. Greater activity for the singing over the speech condition for both the listening and covert production tasks was found in the right planum temporale. Greater activity in brain regions involved with consonance, orbitofrontal cortex (listening task), subcallosal cingulate (covert production task) were also present for singing over speech. The results are consistent with the PT mediating representational transformation across auditory and motor domains in response to consonance for singing over that of speech. Hemispheric laterality was assessed by paired t tests between active voxels in the contrast of interest relative to the left–right flipped contrast of interest calculated from images normalized to the left–right reflected template. Consistent with some hypotheses regarding hemispheric specialization, a pattern of differential laterality for speech over singing (both covert production and listening tasks) occurs in the left temporal lobe, whereas, singing over speech (listening task only) occurs in right temporal lobe.

YNIMG Journal 2003 Journal Article

Brain changes after learning to read and play music

• Lauren Stewart
• Rik Henson
• Knut Kampe
• Vincent Walsh
• Robert Turner
• Uta Frith

Musically naive participants were scanned before and after a period of 15 weeks during which they were taught to read music and play the keyboard. When participants played melodies from musical notation after training, activation was seen in a cluster of voxels within the bilateral superior parietal cortex. A subset of these voxels were activated in a second experiment in which musical notation was present, but irrelevant for task performance. These activations suggest that music reading involves the automatic sensorimotor translation of a spatial code (written music) into a series of motor responses (keypresses).

YNIMG Journal 2002 Journal Article

Echo Time Dependence of BOLD Contrast and Susceptibility Artifacts

• Maria Luisa Gorno-Tempini
• Chloe Hutton
• Oliver Josephs
• Ralf Deichmann
• Cathy Price
• Robert Turner

Echo-planar imaging with gradient echo allows whole-brain images to be rapidly acquired. However, its main limitation is that magnetic field inhomogeneities in regions of the brain close to bone and air-filled sinuses result in reduced signal-to-noise ratio and signal loss. In particular this is a problem for imaging the temporal lobes, and can therefore affect the results of some language-related studies. Decreasing the echo time (TE) increases the signal-to-noise ratio and reduces the amount of signal loss in susceptible regions. In this study we investigate the TE dependence of BOLD (blood oxygenation level-dependent) contrast and, in particular, how it is influenced in regions with susceptibility artifacts. We use a dual echo-time sequence to compare brain activations measured with two different TEs, TE = 40 ms and TE = 27 ms. The paradigm involves comparing famous faces to scrambled faces, a low-level control condition. It was chosen because famous faces have been repeatedly shown to activate the fusiform gyri and anterior temporal lobes in both PET and fMRI. Our results show that it is possible to detect robust activations at a lower TE in brain regions not affected by susceptibility artifacts (i. e. , fusiform gyri), allowing for faster scanning times. However, although the amount of signal loss is reduced at the lower TE, this does not appear to be sufficient to recover the BOLD signal in regions affected by susceptibility artifacts (i. e. , anterior temporal lobes).

YNIMG Journal 2002 Journal Article

Image Distortion Correction in fMRI: A Quantitative Evaluation

• Chloe Hutton
• Andreas Bork
• Oliver Josephs
• Ralf Deichmann
• John Ashburner
• Robert Turner

A well-recognized problem with the echo-planar imaging (EPI) technique most commonly used for functional magnetic resonance imaging (fMRI) studies is geometric distortion caused by magnetic field inhomogeneity. This makes it difficult to achieve an accurate registration between a functional activation map calculated from an EPI time series and an undistorted, high resolution anatomical image. A correction method based on mapping the spatial distribution of field inhomogeneities can be used to reduce these distortions. This approach is attractive in its simplicity but requires postprocessing to improve the robustness of the acquired field map and reduce any secondary artifacts. Furthermore, the distribution of the internal magnetic field throughout the head is position dependent resulting in an interaction between distortion and head motion. Therefore, a single field map may not be sufficient to correct for the distortions throughout a whole fMRI time series. In this paper we present a quantitative evaluation of image distortion correction for fMRI at 2T. We assess (i) methods for the acquisition and calculation of field maps, (ii) the effect of image distortion correction on the coregistration between anatomical and functional images, and (iii) the interaction between distortion and head motion, assessing the feasibility of using field maps to reduce this effect. We propose that field maps with acceptable noise levels can be generated easily using a dual echo-time EPI sequence and demonstrate the importance of distortion correction for anatomical coregistration, even for small distortions. Using a dual echo-time series to generate a unique field map at each time point, we characterize the interaction between head motion and geometric distortion. However, we suggest that the variance between successively measured field maps introduces additional unwanted variance in the voxel time-series and is therefore not adequate to correct for time-varying distortions.

YNIMG Journal 2002 Journal Article

Initial Demonstration of in Vivo Tracing of Axonal Projections in the Macaque Brain and Comparison with the Human Brain Using Diffusion Tensor Imaging and Fast Marching Tractography

• Geoffrey J.M. Parker
• Klaas E. Stephan
• Gareth J. Barker
• James B. Rowe
• David G. MacManus
• Claudia A.M. Wheeler-Kingshott
• Olga Ciccarelli
• Richard E. Passingham

Diffusion tensor imaging (DTI), a magnetic resonance imaging technique, is used to infer major axonal projections in the macaque and human brain. This study investigates the feasibility of using known macaque anatomical connectivity as a “gold-standard” for the evaluation of DTI tractography methods. Connectivity information is determined from the DTI data using fast marching tractography (FMT), a novel tract-tracing (tractography) method. We show for the first time that it is possible to determine, in an entirely noninvasive manner, anatomical connection pathways and maps of an anatomical connectivity metric in the macaque brain using a standard clinical scanner and that these pathways are consistent with known anatomy. Analogous human anatomical connectivity is also presented for the first time using the FMT method, and the results are compared. The current limitations of the methodology and possibilities available for further studies are discussed.

YNIMG Journal 2001 Journal Article

Are fMRI realignment parameters contaminated by task-induced activation?

• Dmitry Laptev
• Chloe Hutton
• Ralf Deichmann
• Oliver Josephs
• Robert Turner

YNIMG Journal 2001 Journal Article

BOLD localization: the implications of vascular architecture

• Robert Turner

YNIMG Journal 2001 Journal Article

Brain-behavior correlates of continuous and step tracking using partial-least squares analysis

• Scott Grafton
• Michel Desmurget
• Helena Grea
• Randy McIntosh
• Robert Turner

YNIMG Journal 2001 Journal Article

Compensation of susceptibility induced BOLD sensitivity losses in echo-planar fMRI imaging

• Ralf Deichmann
• Robert Turner

YNIMG Journal 2001 Journal Article

Echo time dependence of BOLD contrast and susceptibility artefacts

• Chloe Hutton
• Maria Luisa Gorno-Tempini
• Oliver Josephs
• Ralf Deichmann
• Cathy Price
• Robert Turner

YNIMG Journal 2001 Journal Article

Event-Related fMRI with Simultaneous and Continuous EEG: Description of the Method and Initial Case Report

• Louis Lemieux
• Afraim Salek-Haddadi
• Oliver Josephs
• Philip Allen
• Nathan Toms
• Catherine Scott
• Karsten Krakow
• Robert Turner

We report on the initial imaging findings with a new technique for the simultaneous and continuous acquisition of functional MRI data and EEG recording. Thirty-seven stereotyped interictal epileptiform discharges (spikes) were identified on EEG recorded continuously during the fMRI acquisition on a patient with epilepsy. Localization of the BOLD activation associated with the EEG events was consistent with previous findings and EEG source modeling. The time course of activation was comparable with the physiological hemodynamic response function (HRF). The new methodology could lead to novel and important applications in many areas of neuroscience.

YNIMG Journal 2001 Journal Article

High spatial resolution diffusion tensor imaging without cardiac gating: Comparison between Segmented EPI and Half Fourier Acquisition

• Jiun-Jie Wang
• Ralf Deichmann
• Robert Turner
• Roger Ordidge

YNIMG Journal 2001 Journal Article

In vivo tracing of anatomical fibre tracts in the Macaque monkey brain by diffusion tensor imaging (DTI)

• Klaas E Stephan
• Geoffrey J.M. Parker
• Gareth J. Barker
• James B. Rowe
• David G. MacManus
• Richard E. Passingham
• Roger N. Lemon
• Robert Turner

YNIMG Journal 2001 Journal Article

Modeling Geometric Deformations in EPI Time Series

• Jesper L.R. Andersson
• Chloe Hutton
• John Ashburner
• Robert Turner
• Karl Friston

Even after realignment there is residual movement-related variance present in fMRI time-series, causing loss of sensitivity and, potentially, also specificity. One cause is the differential deformation of the sampling matrix, by field inhomogeneities, at different object positions, i. e. , a movement-by-inhomogeneity interaction. This has been addressed previously by using empirical field measurements. In the present paper we suggest a forward model of how data is affected by an inhomogeneous field at different object positions. From this model we derive a method to solve the inverse problem of estimating the field inhomogeneities and their derivatives with respect to object position, directly from the EPI data and estimated realignment parameters. The field is modeled as a linear combination of cosine basis fields, which facilitates a fast way of implementing the necessary matrix operations. Simulations suggest that the solution is tractable and that the fields are estimable given the deformed images and knowledge of the relative positions at which they have been acquired. An experiment on a subject performing voluntary movements in the scanner yielded plausible estimates of the deformation fields and their application to “unwarp” the time series significantly reduced movement-related variance.

YNIMG Journal 2000 Journal Article

A Method for Removing Imaging Artifact from Continuous EEG Recorded during Functional MRI

• Philip J. Allen
• Oliver Josephs
• Robert Turner

Combined EEG/fMRI recording has been used to localize the generators of EEG events and to identify subject state in cognitive studies and is of increasing interest. However, the large EEG artifacts induced during fMRI have precluded simultaneous EEG and fMRI recording, restricting study design. Removing this artifact is difficult, as it normally exceeds EEG significantly and contains components in the EEG frequency range. We have developed a recording system and an artifact reduction method that reduce this artifact effectively. The recording system has large dynamic range to capture both low-amplitude EEG and large imaging artifact without distortion (resolution 2 μV, range 33. 3 mV), 5-kHz sampling, and low-pass filtering prior to the main gain stage. Imaging artifact is reduced by subtracting an averaged artifact waveform, followed by adaptive noise cancellation to reduce any residual artifact. This method was validated in recordings from five subjects using periodic and continuous fMRI sequences. Spectral analysis revealed differences of only 10 to 18% between EEG recorded in the scanner without fMRI and the corrected EEG. Ninety-nine percent of spike waves (median 74 μV) added to the recordings were identified in the corrected EEG compared to 12% in the uncorrected EEG. The median noise after artifact reduction was 8 μV. All these measures indicate that most of the artifact was removed, with minimal EEG distortion. Using this recording system and artifact reduction method, we have demonstrated that simultaneous EEG/fMRI studies are for the first time possible, extending the scope of EEG/fMRI studies considerably.

YNIMG Journal 2000 Journal Article

Diffusion tensor imaging with high spatial resolution

• Jiun-Jie Wang
• Ralf Deichmann
• John Ashburner
• Robert Turner
• Roger Ordidge

YNIMG Journal 2000 Journal Article

Effect of head motion and non-linear distortions on fMRI time series

• Chloe Hutton
• Andreas Bork
• Oliver Josephs
• John Ashburner
• Robert Turner

YNIMG Journal 2000 Journal Article

Trajectory measurement and generalised reconstruction in rectilinear EPI

• Oliver Josephs
• Ralf Deichmann
• Robert Turner

YNIMG Journal 1999 Journal Article

The Effect of Slice Order and Thickness on fMRI Activation Data Using Multislice Echo-Planar Imaging

• Alistair M. Howseman
• Sylke Grootoonk
• David A. Porter
• Joann Ramdeen
• Andrew P. Holmes
• Robert Turner

Multislice echo-planar imaging (EPI) is a commonly used technique for fMRI studies. Brain activation images acquired using fMRI are sensitive to T2* changes, reflecting the level of blood oxygenation (BOLD contrast), and may also contain an element of T1contrast which detects blood flow changes in large vessels. If slice inflow (T1) effects are significant in multislice EPI, then as the order in which the slices are acquired is changed, differences in the activation maps are predicted. However, in experiments presented here using visual stimulation, the data demonstrate that highly consistent results can be achieved for repetition times (TR) of 6. 0, 3. 0, and 1. 5 s. This suggests that, for whole-brain multislice EPI, fMRI activation is dominated by T2*, BOLD contrast. The thickness of the imaging slice is also an important parameter in these studies, having implications for spatial resolution, sensitivity, and acquisition time. In separate visual cortex experiments the effect on the values of the fMRIZscores and the number of activated voxels is investigated as a function of slice thickness (from 1 to 8 mm). The maximumZscores in the data are similar for all slice thicknesses and, after resampling to allow a direct comparison to be made, the volume of visual cortex detected as significantly activated increases with slice thickness.

YNIMG Journal 1998 Journal Article

An Adaptive MRI Gradient Noise Filter

• Oliver Josephs
• Robert Turner

YNIMG Journal 1998 Journal Article

The Time Course of Changes during Motor Sequence Learning: A Whole-Brain fMRI Study

• Ivan Toni
• Michael Krams
• Robert Turner
• Richard E. Passingham

There is a discrepancy between the results of imaging studies in which subjects learn motor sequences. Some experiments have shown decreases in the activation of some areas as learning increased, whereas others have reported learning-related increases as learning progressed. We have exploited fMRI to measure changes in blood oxygen level-dependent (BOLD) signal throughout the course of learning. T2*-weighted echo-planar images were acquired over the whole brain for 40 min while the subjects learned a sequence eight moves long by trial and error. The movements were visually paced every 3. 2 s and visual feedback was provided to the subjects. A baseline period followed each activation period. The effect due to the experimental conditions was modeled using a square-wave function, time locked to their occurrence. Changes over time in the difference between activation and baseline signal were modeled using a set of polynomial basis functions. This allowed us to take into account linear as well as nonlinear changes over time. Low-frequency changes over time common to both activation and baseline conditions (and thus not learning related) were modeled and removed. Linear and nonlinear changes of BOLD signal over time were found in prefrontal, premotor, and parietal cortex and in neostriatal and cerebellar areas. Single-unit recordings in nonhuman primates during the learning of motor tasks have clearly shown increased activity early in learning, followed by a decrease as learning progressed. Both phenomena can be observed at the population level in the present study.

YNIMG Journal 1997 Journal Article

Simultaneous Measurement of ΔR2 and ΔR2* in Cat Brain during Hypoxia and Hypercapnia

• Anna Prinster
• Carlo Pierpaoli
• Robert Turner
• Peter Jezzard

One of the most important issues in blood-oxygen-level-dependent (BOLD)-based brain functional magnetic resonance imaging is the understanding of the vascular structures that are responsible for the signal changes observed. The T2*-related signal changes observed during variations in susceptibility-induced magnetic field gradients are a function both of non-refocusable mechanisms, such as diffusion, and of refocusable effects such as field inhomogeneities. Conversely, T2-related signal changes are only a function of non-refocusable effects. It has been suggested that T2-weighted images could be less sensitive to blood susceptibility changes in a macrovascular environment than T2*-weighted images and could thus be more accurate in identifying the “activation” of the parenchyma rather than “draining vein” effects. In this study we use hypoxia and hypercapnia challenges in cats to provide a change in blood deoxyhemoglobin concentration (as a model for classic BOLD changes and not as a model for neuronal activation). A combined gradient echo and spin echo echo-planar-imaging (EPI) pulse sequence was used to map ΔR2 (i. e. , Δ(1/T2)) and ΔR2* (i. e. , Δ(1/T2*)) changes during the challenges. Our experiments demonstrate that: (i) the acquisition of T2-weighted EPI data does not in itself differentiate signal changes in the parenchyma from those occurring in regions around larger vessels, but that (ii) the simultaneous acquisition of T2- and T2*-weighted images could be useful in identifying microvascular regions in gray matter by analyzing the ratio ΔR2/ΔR2*. This value seems independent of the degree of deoxyhemoglobin concentration change, but is related to properties of the vascular environment. We suggest a possible application of the results to the study of brain function in humans.

YNIMG Journal 1996 Journal Article

Analysis of fMRI data using the general linear statistical model

• Robert Turner
• Karl Friston
• John Ashburner
• Oliver Josephs
• Alistair Howseman

YNIMG Journal 1996 Journal Article

Quantitative Comparison of Functional Magnetic Resonance Imaging with Positron Emission Tomography Using a Force-Related Paradigm

• Christian Dettmers
• Alan Connelly
• Klaus M Stephan
• Robert Turner
• Karl J Friston
• Richard S.J Frackowiak
• David G Gadian

The intention of our study was to compare functional magnetic resonance imaging (fMRI) with positron emission tomography (PET). We used the same force-related motor paradigm for both techniques, which allows for quantification of stimulus intensity. Regional cerebral blood flow (rCBF) was determined with PET in six male subjects (age 30±3) using the slow bolus injection technique and oxygen-15-labeled water. Scans were collected during six different conditions: at rest and during repetitive Morse key press at 1 Hz, with the right index finger at a range of different forces. In a second series of experiments fMRI data were acquired under similar conditions in six volunteers in a single slice parallel to and 51 ± 3 mm dorsal to the anterior and posterior commissure (AC–PC). A conventional 1. 5-T clinical magnetic resonance (MR) system and the FLASH technique were used. The data obtained in both series of experiments were subjected to the same statistical analyses. Statistical parametric maps (SPM) were generated by two different approaches: a correlation between peak force and rCBF or fMRI signal and using a categorical comparison of force exerted with rest. SPMs were coregistered with anatomical MR images. PET and fMRI measurements demonstrated activation in the primary motor cortex (M1) and posterior supplementary motor cortex in all subjects. Correlation analysis demonstrated foci in the M1 in four subjects with PET and in only one subject with fMRI. Locations of activation peaks differed by 2 to 8 mm between imaging methods. The relationship between fMRI signal or rCBF and peak force was logarithmic. The maximum increase in fMRI signal was 5. 0% ± 0. 9 at 60% of the maximum voluntary contraction while the corresponding increase in rCBF was 13. 7% ± 1. 2. The ratio of percentage rCBF change to percentage fMRI signal change was very similar across all force levels. The high degree of correspondence between PET and fMRI data provides good cross-validation for the two techniques.

YNIMG Journal 1995 Journal Article

Activation of Prefrontal Cortex in Children during a Nonspatial Working Memory Task with Functional MRI

• B.J. Casey
• Jonathan D. Cohen
• Peter Jezzard
• Robert Turner
• Douglas C. Noll
• Rolf J. Trainor
• Jay Giedd
• Debra Kaysen

Functional magnetic resonance imaging (fMR1) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed.