Nikolaus Weiskopf

Wellcome Trust, Londinium, England, United Kingdom

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Publications (121)622.22 Total impact

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    ABSTRACT: Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer - MT, from healthy subjects (n=96, aged 21 - 88years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* - a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.
    NeuroImage 09/2014; · 6.25 Impact Factor
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    ABSTRACT: Relaxation rates provide important information about tissue microstructure. Multi-parameter mapping (MPM) estimates multiple relaxation parameters from multi-echo FLASH acquisitions with different basic contrasts, i.e., proton density (PD), T1 or magnetization transfer (MT) weighting. Motion can particularly affect maps of the apparent transverse relaxation rate R2(*), which are derived from the signal of PD-weighted images acquired at different echo times. To address the motion artifacts, we introduce ESTATICS, which robustly estimates R2(*) from images even when acquired with different basic contrasts. ESTATICS extends the fitted signal model to account for inherent contrast differences in the PDw, T1w and MTw images. The fit was implemented as a conventional ordinary least squares optimization and as a robust fit with a small or large confidence interval. These three different implementations of ESTATICS were tested on data affected by severe motion artifacts and data with no prominent motion artifacts as determined by visual assessment or fast optical motion tracking. ESTATICS improved the quality of the R2(*) maps and reduced the coefficient of variation for both types of data-with average reductions of 30% when severe motion artifacts were present. ESTATICS can be applied to any protocol comprised of multiple 2D/3D multi-echo FLASH acquisitions as used in the general research and clinical setting.
    Frontiers in Neuroscience 09/2014; 8:278.
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    ABSTRACT: The lateral habenula (LHb) has been shown to respond to cues that predict aversive stimuli in non-human primates (Matsumoto & Hikosaka, 2009, Nat Neurosci, 12 (1), 77-84) and has been implicated in reinforcement processing and the pathophysiology of major depression (MDD) (Roiser et al, Biol Psychiatry, 66 (5), 441-450), possibly via reciprocal connections with monoaminergic nuclei. We report the first high-resolution fMRI investigation of haemodynamic responses during appetitive and aversive conditioning in the LHb in unipolar MDD. Additionally, we report the first assessment of tonic habenula function using quantitative Arterial Spin Labelling (ASL) in MDD.
    Journal of neurology, neurosurgery, and psychiatry. 08/2014; 85(8):e3.
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    ABSTRACT: Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trial-by-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.
    Proceedings of the National Academy of Sciences of the United States of America. 07/2014;
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    ABSTRACT: We present a novel multi-shell position orientation adaptive smoothing (msPOAS) method for diffusion-weighted magnetic resonance data. Smoothing in voxel and diffusion gradient space is embedded in an iterative adaptive multiscale approach. The adaptive character avoids blurring of the inherent structures and preserves discontinuities. The simultaneous treatment of all q-shells improves the stability compared to single shell approaches such as the original POAS method. The msPOAS implementation simplifies and speeds up calculations, compared to POAS, facilitating its practical application. Simulations and heuristics support the face validity of the technique and its rigorousness. The characteristics of msPOAS were evaluated on single and multi-shell diffusion data of the human brain. Significant reduction in noise while preserving the fine structure was demonstrated for diffusion weighted images, standard DTI analysis and advanced diffusion models such as NODDI. MsPOAS effectively improves the poor signal-to-noise ratio in highly diffusion weighted multi-shell diffusion data, which is required by recent advanced diffusion micro-structure models. We demonstrate the superiority of the new method compared to other advanced denoising methods.
    NeuroImage 07/2014; 95:90-105. · 6.25 Impact Factor
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    ABSTRACT: Background / Purpose: Functional and diffusion-weighted MRI are usually performed using echo-planar imaging (EPI). A major problem with EPI are geometric distortions caused by magnetic field inhomogeneities, especially at high field strength. To determine the best way to deal with these, we compared three methods for EPI distortion correction. Main conclusion: Overall, the methods based on opposite phase encoding directions consistently outperform the fieldmap-based method.
    20th Annual Meeting of the Organization for Human Brain Mapping (OHBM) 2014; 07/2014
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    Annual Meeting of the Organization for Human Brain Mapping, Hamburg, Germany; 06/2014
  • Annual Meeting of the Organization for Human Brain Mapping, Hamburg, Germany; 06/2014
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    ABSTRACT: Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2014; · 6.88 Impact Factor
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    ABSTRACT: We present an implementation of a recently developed noise reduction algorithm for dMRI data, called multi-shell position orientation adaptive smoothing (msPOAS), as a toolbox for SPM. The method intrinsically adapts to the structures of different size and shape in dMRI and hence avoids blurring typically observed in non-adaptive smoothing. We give examples for the usage of the toolbox and explain the determination of experiment-dependent parameters for an optimal performance of msPOAS.
    Neuroinformatics 04/2014; · 3.14 Impact Factor
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    ABSTRACT: PurposeThe longitudinal relaxation rate (R1) measured in vivo depends on the local microstructural properties of the tissue, such as macromolecular, iron, and water content. Here, we use whole brain multiparametric in vivo data and a general linear relaxometry model to describe the dependence of R1 on these components. We explore a) the validity of having a single fixed set of model coefficients for the whole brain and b) the stability of the model coefficients in a large cohort.Methods Maps of magnetization transfer (MT) and effective transverse relaxation rate (R2*) were used as surrogates for macromolecular and iron content, respectively. Spatial variations in these parameters reflected variations in underlying tissue microstructure. A linear model was applied to the whole brain, including gray/white matter and deep brain structures, to determine the global model coefficients. Synthetic R1 values were then calculated using these coefficients and compared with the measured R1 maps.ResultsThe model's validity was demonstrated by correspondence between the synthetic and measured R1 values and by high stability of the model coefficients across a large cohort.ConclusionA single set of global coefficients can be used to relate R1, MT, and R2* across the whole brain. Our population study demonstrates the robustness and stability of the model. Magn Reson Med, 2014. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 04/2014; · 3.27 Impact Factor
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    ABSTRACT: A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19-75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.
    Neurobiology of aging 02/2014; · 5.94 Impact Factor
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    ABSTRACT: Neurofeedback based on real-time functional magnetic resonance imaging (fMRI) is a new approach that allows training of voluntary control over regionally specific brain activity. However, the neural basis of successful neurofeedback learning remains poorly understood. Here, we assessed changes in effective brain connectivity associated with neurofeedback training of visual cortex activity. Using dynamic causal modeling (DCM), we found that training participants to increase visual cortex activity was associated with increased effective connectivity between the visual cortex and the superior parietal lobe. Specifically, participants who learned to control activity in their visual cortex showed increased top-down control of the superior parietal lobe over the visual cortex, and at the same time reduced bottom-up processing. These results are consistent with efficient employment of top-down visual attention and imagery, which were the cognitive strategies used by participants to increase their visual cortex activity.
    PLoS ONE 01/2014; 9(3):e91090. · 3.53 Impact Factor
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    ABSTRACT: The aim of this study was to quantify a range of MR parameters [apparent proton density, longitudinal relaxation time T1 , magnetisation transfer (MT) ratio, MT saturation (which represents the additional percentage MT saturation of the longitudinal magnetisation caused by a single MT pulse) and apparent transverse relaxation rate R2 *] in the white matter columns and grey matter of the healthy cervical spinal cord. The cervical cords of 13 healthy volunteers were scanned at 3 T using a protocol optimised for multi-parameter mapping. Intra-subject co-registration was performed using linear registration, and tissue- and column-specific parameter values were calculated. Cervical cord parameter values measured from levels C1-C5 in 13 subjects are: apparent proton density, 4822 ± 718 a.u.; MT ratio, 40.4 ± 1.53 p.u.; MT saturation, 1.40 ± 0.12 p.u.; T1 = 1848 ± 143 ms; R2 * = 22.6 ± 1.53 s(-1) . Inter-subject coefficients of variation were low in both the cervical cord and tissue- and column-specific measurements, illustrating the potential of this method for the investigation of changes in these parameters caused by pathology. In summary, an optimised cervical cord multi-parameter mapping protocol was developed, enabling tissue- and column-specific measurements to be made. This technique has the potential to provide insight into the pathological processes occurring in the cervical cord affected by neurological disorders. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
    NMR in Biomedicine 09/2013; · 3.45 Impact Factor
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    ABSTRACT: In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease.
    Parkinsonism & Related Disorders 08/2013; · 3.27 Impact Factor
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    ABSTRACT: Background In patients with chronic spinal cord injury, imaging of the spinal cord and brain above the level of the lesion provides evidence of neural degeneration; however, the spatial and temporal patterns of progression and their relation to clinical outcomes are uncertain. New interventions targeting acute spinal cord injury have entered clinical trials but neuroimaging outcomes as responsive markers of treatment have yet to be established. We aimed to use MRI to assess neuronal degeneration above the level of the lesion after acute spinal cord injury. Methods In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement. All analyses of brain scans done with statistical parametric mapping were corrected for family-wise error. Findings Between Sept 17, 2010, and Dec 31, 2012, we recruited 13 patients and 18 controls. In the 12 months from baseline, patients recovered by a mean of 5·27 points per log month (95% CI 1·91—8·63) on the international standards for the neurological classification of spinal cord injury (ISNCSCI) motor score (p=0·002) and by 10·93 points per log month (6·20—15·66) on the spinal cord independence measure (SCIM) score (p<0·0001). Compared with controls, patients showed a rapid decline in cross-sectional spinal cord area (patients declined by 0·46 mm per month compared with a stable cord area in controls; p<0·0001). Patients had faster rates than controls of volume decline of white matter in the cranial corticospinal tracts at the level of the internal capsule (right Z score 5·21, p=0·0081; left Z score 4·12, p=0·0004) and right cerebral peduncle (Z score 3·89, p=0·0302) and of grey matter in the left primary motor cortex (Z score 4·23, p=0·041). Volume changes were paralleled by significant reductions of MT and R1 in the same areas and beyond. Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord area over 12 months (Pearson's correlation 0·77, p=0·004) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule (Z score 4·30, p=0·0021), the left internal capsule (Z score 4·27, p=0·0278), and left cerebral peduncle (Z score 4·05, p=0·0316). Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule (Z score 4·01, p<0·0001). Interpretation Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury. Funding SRH Holding, Swiss National Science Foundation, Clinical Research Priority Program “NeuroRehab” University of Zurich, Wellcome Trust.
    The Lancet Neurology 07/2013; · 23.92 Impact Factor
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    ABSTRACT: In patients with chronic spinal cord injury, imaging of the spinal cord and brain above the level of the lesion provides evidence of neural degeneration; however, the spatial and temporal patterns of progression and their relation to clinical outcomes are uncertain. New interventions targeting acute spinal cord injury have entered clinical trials but neuroimaging outcomes as responsive markers of treatment have yet to be established. We aimed to use MRI to assess neuronal degeneration above the level of the lesion after acute spinal cord injury. In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement. All analyses of brain scans done with statistical parametric mapping were corrected for family-wise error. Between Sept 17, 2010, and Dec 31, 2012, we recruited 13 patients and 18 controls. In the 12 months from baseline, patients recovered by a mean of 5·27 points per log month (95% CI 1·91-8·63) on the international standards for the neurological classification of spinal cord injury (ISNCSCI) motor score (p=0·002) and by 10·93 points per log month (6·20-15·66) on the spinal cord independence measure (SCIM) score (p<0·0001). Compared with controls, patients showed a rapid decline in cross-sectional spinal cord area (patients declined by 0·46 mm per month compared with a stable cord area in controls; p<0·0001). Patients had faster rates than controls of volume decline of white matter in the cranial corticospinal tracts at the level of the internal capsule (right Z score 5·21, p=0·0081; left Z score 4·12, p=0·0004) and right cerebral peduncle (Z score 3·89, p=0·0302) and of grey matter in the left primary motor cortex (Z score 4·23, p=0·041). Volume changes were paralleled by significant reductions of MT and R1 in the same areas and beyond. Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord area over 12 months (Pearson's correlation 0·77, p=0·004) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule (Z score 4·30, p=0·0021), the left internal capsule (Z score 4·27, p=0·0278), and left cerebral peduncle (Z score 4·05, p=0·0316). Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule (Z score 4·01, p<0·0001). Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury. SRH Holding, Swiss National Science Foundation, Clinical Research Priority Program "NeuroRehab" University of Zurich, Wellcome Trust.
    The Lancet Neurology 07/2013; · 23.92 Impact Factor
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    ABSTRACT: Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.
    Cerebral Cortex 06/2013; · 8.31 Impact Factor
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    Annual Meeting of the Organization for Human Brain Mapping, Seattle, USA; 06/2013
  • Annual Meeting of the Organization for Human Brain Mapping, Seattle, USA; 06/2013

Publication Stats

4k Citations
622.22 Total Impact Points

Institutions

  • 2014
    • Wellcome Trust
      Londinium, England, United Kingdom
  • 2008–2014
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2007–2014
    • University College London
      • • Wellcome Trust Centre for Neuroimaging
      • • Wellcome Department of Imaging Neuroscience
      • • Institute of Neurology
      • • Institute of Cognitive Neuroscience
      Londinium, England, United Kingdom
  • 2013
    • University of Lausanne
      Lausanne, Vaud, Switzerland
  • 2012
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2011
    • Institut Philippe-Pinel de Montréal
      Montréal, Quebec, Canada
    • University Hospital of Lausanne
      • Département des neurosciences cliniques
      Lausanne, VD, Switzerland
  • 2009
    • Universitätsklinikum Freiburg
      Freiburg an der Elbe, Lower Saxony, Germany
    • University of Liège
      • Cyclotron Research Centre
      Liège, WAL, Belgium
    • Universität Stuttgart
      • Institute for Natural Language Processing
      Stuttgart, Baden-Wuerttemberg, Germany
  • 2003–2009
    • University of Tuebingen
      • Institute of Medical Psychology and Behavioral Neurobiology
      Tübingen, Baden-Württemberg, Germany
  • 2006
    • University of Oxford
      Oxford, England, United Kingdom