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Klaus Fliessbach

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7 papers
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7

YNICL Journal 2023 Journal Article

Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging

  • Leonie Lampe
  • Hans-Jürgen Huppertz
  • Sarah Anderl-Straub
  • Franziska Albrecht
  • Tommaso Ballarini
  • Sandrine Bisenius
  • Karsten Mueller
  • Sebastian Niehaus

INTRODUCTION: Dementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI). METHODS: Atlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer's disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification). RESULTS: The binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration. DISCUSSION: Results suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer's disease.

YNICL Journal 2021 Journal Article

Association between composite scores of domain-specific cognitive functions and regional patterns of atrophy and functional connectivity in the Alzheimer’s disease spectrum

  • Chimezie O. Amaefule
  • Martin Dyrba
  • Steffen Wolfsgruber
  • Alexandra Polcher
  • Anja Schneider
  • Klaus Fliessbach
  • Annika Spottke
  • Dix Meiberth

BACKGROUND: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error. Adopting a multicentric resting state fMRI (rs-fMRI) and cognitive domain approach, we provide a comprehensive description of the structural and functional correlates of the key cognitive domains of AD. METHOD: We analyzed MRI, rs-fMRI and cognitive domain score data of 490 participants from an interim baseline release of the multicenter DELCODE study cohort, including 54 people with AD, 86 with Mild Cognitive Impairment (MCI), 175 with Subjective Cognitive Decline (SCD), and 175 Healthy Controls (HC) in the AD-spectrum. Resulting cognitive domain composite scores (executive, visuo-spatial, memory, working memory and language) from the DELCODE neuropsychological battery (DELCODE-NP), were previously derived using confirmatory factor analysis. Statistical analyses examined the differences between diagnostic groups, and the association of composite scores with regional atrophy and network-specific functional connectivity among the patient subgroup of SCD, MCI and AD. RESULT: Cognitive performance, atrophy patterns and functional connectivity significantly differed between diagnostic groups in the AD-spectrum. Regional gray matter atrophy was positively associated with visuospatial and other cognitive impairments among the patient subgroup in the AD-spectrum. Except for the visual network, patterns of network-specific resting-state functional connectivity were positively associated with distinct cognitive impairments among the patient subgroup in the AD-spectrum. CONCLUSION: Consistent associations between cognitive domain scores and both regional atrophy and network-specific functional connectivity (except for the visual network), support the utility of a multicentric and cognitive domain approach towards explicating the relationship between imaging markers and cognition in the AD-spectrum.

YNICL Journal 2020 Journal Article

Disentangling brain functional network remodeling in corticobasal syndrome – A multimodal MRI study

  • Tommaso Ballarini
  • Franziska Albrecht
  • Karsten Mueller
  • Robert Jech
  • Janine Diehl-Schmid
  • Klaus Fliessbach
  • Jan Kassubek
  • Martin Lauer

OBJECTIVE: The clinical diagnosis of corticobasal syndrome (CBS) represents a challenge for physicians and reliable diagnostic imaging biomarkers would support the diagnostic work-up. We aimed to investigate the neural signatures of CBS using multimodal T1-weighted and resting-state functional magnetic resonance imaging (MRI). METHODS: Nineteen patients with CBS (age 67.0 ± 6.0 years; mean±SD) and 19 matched controls (66.5 ± 6.0) were enrolled from the German Frontotemporal Lobar Degeneration Consortium. Changes in functional connectivity and structure were respectively assessed with eigenvector centrality mapping complemented by seed-based analysis and with voxel-based morphometry. In addition to mass-univariate statistics, multivariate support vector machine (SVM) classification tested the potential of multimodal MRI to differentiate patients and controls. External validity of SVM was assessed on independent CBS data from the 4RTNI database. RESULTS: A decrease in brain interconnectedness was observed in the right central operculum, middle temporal gyrus and posterior insula, while widespread connectivity increases were found in the anterior cingulum, medial superior-frontal gyrus and in the bilateral caudate nuclei. Severe and diffuse gray matter volume reduction, especially in the bilateral insula, putamen and thalamus, characterized CBS. SVM classification revealed that both connectivity (area under the curve 0.81) and structural abnormalities (0.80) distinguished CBS from controls, while their combination led to statistically non-significant improvement in discrimination power, questioning the additional value of functional connectivity over atrophy. SVM analyses based on structural MRI generalized moderately well to new data, which was decisively improved when guided by meta-analytically derived disease-specific regions-of-interest. CONCLUSIONS: Our data-driven results show impairment of functional connectivity and brain structure in CBS and explore their potential as imaging biomarkers.

YNICL Journal 2020 Journal Article

Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer’s disease spectrum

  • Meret Herdick
  • Martin Dyrba
  • Hans-Christian J. Fritz
  • Slawek Altenstein
  • Tommaso Ballarini
  • Frederic Brosseron
  • Katharina Buerger
  • Arda Can Cetindag

BACKGROUND: Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer's disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes. METHODS: Participants included healthy controls, and subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia (ADD) from the multicenter DELCODE study. Resting-state functional MRI (rs-fMRI) and structural MRI data was available for 477 subjects, and a subset of 243 subjects also had DTI data available. Differences between diagnostic groups were investigated using seed-based FC, volumetric, and MD analyses of functionally defined anterior (a-cBF) and posterior (p-cBF) subdivisions of a cytoarchitectonic cBF region-of-interest. In complementary analyses groups were stratified according to amyloid status based on CSF Aβ42/40 biomarker data, which was available in a subset of participants. RESULTS: a-cBF and p-cBF subdivisions showed regional FC profiles that were highly consistent with previously reported patterns, but there were only minimal differences between diagnostic groups. Compared to controls, cBF volumes and MD were significantly different in MCI and ADD but not in SCD. The Aβ42/40 stratified analyses largely matched these results. CONCLUSIONS: We reproduced subregion-specific FC profiles of the cBF in a clinical sample spanning the AD spectrum. At least in this multicentric cohort study, cBF-FC did not show marked changes along the AD spectrum, and multimodal MRI did not provide more sensitive measures of AD-related cBF changes compared to volumetry.

YNIMG Journal 2010 Journal Article

Retest reliability of reward-related BOLD signals

  • Klaus Fliessbach
  • Tim Rohe
  • Nicolas S. Linder
  • Peter Trautner
  • Christian E. Elger
  • Bernd Weber

Reward processing is a central component of learning and decision making. Functional magnetic resonance imaging (fMRI) has contributed essentially to our understanding of reward processing in humans. The strength of reward-related brain responses might prove as a valuable marker for, or correlate of, individual preferences or personality traits. An essential prerequisite for this is a sufficient reliability of individual measures of reward-related brain signals. We therefore determined test–retest reliabilities of BOLD responses to reward prediction, reward receipt and reward prediction errors in the ventral striatum and the orbitofrontal cortex in 25 subjects undergoing three different simple reward paradigms (retest interval 7–13 days). Although on a group level the paradigms consistently led to significant activations of the relevant brain areas in two sessions, across-subject retest reliabilities were only poor to fair (with intraclass correlation coefficients (ICCs) of −0. 15 to 0. 44). ICCs for motor activations were considerably higher (ICCs 0. 32 to 0. 73). Our results reveal the methodological difficulties behind across-subject correlations in fMRI research on reward processing. These results demonstrate the need for studies that address methods to optimize the retest reliability of fMRI.