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Karl Egger

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7 papers

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YNICL Journal 2021 Journal Article

Focal cervical spinal stenosis causes mechanical strain on the entire cervical spinal cord tissue – A prospective controlled, matched-pair analysis based on phase-contrast MRI

Katharina Wolf
Marco Reisert
Saúl Felipe Beltrán
Jan-Helge Klingler
Ulrich Hubbe
Axel J. Krafft
Karl Egger
Marc Hohenhaus

BACKGROUND: Focally increased spinal cord motion at the level of cervical spinal stenosis has been revealed by phase-contrast MRI (PC-MRI). OBJECTIVE: To investigate spinal cord motion among patients suffering of degenerative cervical myelopathy (DCM) across the entire cervical spine applying automated segmentation and standardized PC-MRI post-processing protocols. METHODS: (PTP-amplitude per duration of heartbeat), and, for characterization of intraindividual alterations, the PTP-amplitude index between the cervical segments C3/C4-C7/T1 and C2/C3. RESULTS: Spinal cord motion was increased at C4/C5, C5/C6 and C6/C7 among patients (all parameters, p < 0.001-0.025). The PTP-amplitude index revealed an increase from C3/C4 to C4/C5 (p = 0.002), C4/C5 to C5/C6 (p = 0.037) and a decrease from C5/C6 to C6/C7 and C6/C7 to C7/T1 (p < 0.001, each). This implied an up-building stretch on spinal cord tissue cranial and a mechanical compression caudal of the stenotic level. Furthermore, significant far range effects across the entire cervical spinal cord were observed (e.g. PTP-amplitude C2/C3 vs. C6/C7, p = 0.026) in contrast to controls (p = 1.00). CONCLUSION: This study revealed the nature and extends of mechanical stress on the entire cervical spinal cord tissue due to focal stenosis. These pathophysiological alterations of spinal cord motion can be expected to be clinically relevant.

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YNIMG Journal 2021 Journal Article

The ventral pathway of the human brain: A continuous association tract system

Cornelius Weiller
Marco Reisert
Ivo Peto
Jürgen Hennig
Nikos Makris
Michael Petrides
Michel Rijntjes
Karl Egger

The brain hemispheres can be divided into an upper dorsal and a lower ventral system. Each system consists of distinct cortical regions connected via long association tracts. The tracts cross the central sulcus or the limen insulae to connect the frontal lobe with the posterior brain. The dorsal stream is associated with sensorimotor mapping. The ventral stream serves structural analysis and semantics in different domains, as visual, acoustic or space processing. How does the prefrontal cortex, regarded as the platform for the highest level of integration, incorporate information from these different domains? In the current view, the ventral pathway consists of several separate tracts, related to different modalities. Originally the assumption was that the ventral path is a continuum, covering all modalities. The latter would imply a very different anatomical basis for cognitive and clinical models of processing. To further define the ventral connections, we used cutting-edge in vivo global tractography on high-resolution diffusion tensor imaging (DTI) data from 100 normal subjects from the human connectome project and ex vivo preparation of fiber bundles in the extreme capsule of 8 humans using the Klingler technique. Our data showed that ventral stream tracts, traversing through the extreme capsule, form a continuous band of fibers that fan out anteriorly to the prefrontal cortex, and posteriorly to temporal, occipital and parietal cortical regions. Introduction of additional volumes of interest in temporal and occipital lobes differentiated between the inferior fronto-occipital fascicle (IFOF) and uncinate fascicle (UF). Unequivocally, in both experiments, in all subjects a connection between the inferior frontal and middle-to-posterior temporal cortical region, otherwise known as the temporo-frontal extreme capsule fascicle (ECF) from nonhuman primate brain-tracing experiments was identified. In the human brain, this tract connects the language domains of "Broca's area" and "Wernicke's area". The differentiation in the three tracts, IFOF, UF and ECF seems arbitrary, all three pass through the extreme capsule. Our data show that the ventral pathway represents a continuum. The three tracts merge seamlessly and streamlines showed considerable overlap in their anterior and posterior course. Terminal maps identified prefrontal cortex in the frontal lobe and association cortex in temporal, occipital and parietal lobes as streamline endings. This anatomical substrate potentially facilitates the prefrontal cortex to integrate information across different domains and modalities.

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YNICL Journal 2019 Journal Article

Dissociating frontal and temporal correlates of phonological and semantic fluency in a large sample of left hemisphere stroke patients

Charlotte S.M. Schmidt
Kai Nitschke
Tobias Bormann
Pia Römer
Dorothee Kümmerer
Markus Martin
Roza M. Umarova
Rainer Leonhart

Previous lesion studies suggest that semantic and phonological fluency are differentially subserved by distinct brain regions in the left temporal and the left frontal cortex, respectively. However, as of yet, this often implied double dissociation has not been explicitly investigated due to mainly two reasons: (i) the lack of sufficiently large samples of brain-lesioned patients that underwent assessment of the two fluency variants and (ii) the lack of tools to assess interactions in factorial analyses of non-normally distributed behavioral data. In addition, previous studies did not control for task resource artifacts potentially introduced by the generally higher task difficulty of phonological compared to semantic fluency. We addressed these issues by task-difficulty adjusted assessment of semantic and phonological fluency in 85 chronic patients with ischemic stroke of the left middle cerebral artery. For classical region-based lesion-behavior mapping patients were grouped with respect to their primary lesion location. Building on the extension of the non-parametric Brunner-Munzel rank-order test to multi-factorial designs, ANOVA-type analyses revealed a significant two-way interaction for cue type (semantic vs. phonological) by lesion location (left temporal vs. left frontal vs. other as stroke control group). Subsequent contrast analyses further confirmed the proposed double dissociation by demonstrating that (i) compared to stroke controls, left temporal lesions led to significant impairments in semantic but not in phonological fluency, whereas left frontal lesions led to significant impairments in phonological but not in semantic fluency, and that (ii) patients with frontal lesions showed significantly poorer performance in phonological than in semantic fluency, whereas patients with temporal lesions showed significantly poorer performance in semantic than in phonological fluency. The anatomical specificity of these findings was further assessed in voxel-based lesion-behavior mapping analyses using the multi-factorial extension of the Brunner-Munzel test. Voxel-wise ANOVA-type analyses identified circumscribed parts of left inferior frontal gyrus and left superior and middle temporal gyrus that significantly double-dissociated with respect to their differential contribution to phonological and semantic fluency, respectively. Furthermore, a main effect of lesion with significant impairments in both fluency types was found in left inferior frontal regions adjacent to but not overlapping with those showing the differential effect for phonological fluency. The present study hence not only provides first explicit evidence for the anatomical double dissociation in verbal fluency at the group level but also clearly underlines that its formulation constitutes an oversimplification as parts of left frontal cortex appear to contribute to both semantic and phonological fluency.

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YNIMG Journal 2018 Journal Article

Probing the reproducibility of quantitative estimates of structural connectivity derived from global tractography

Lena V. Schumacher
Marco Reisert
Kai Nitschke
Karl Egger
Horst Urbach
Jürgen Hennig
Cornelius Weiller
Christoph P. Kaller

As quantitative measures derived from fiber tractography are increasingly being used to characterize the structural connectivity of the brain, it is important to establish their reproducibility. However, no such information is as yet available for global tractography. Here we provide the first comprehensive analysis of the reproducibility of streamline counts derived from global tractography as quantitative estimates of structural connectivity. In a sample of healthy young adults scanned twice within one week, within-session and between-session test-retest reproducibility was estimated for streamline counts of connections based on regions of the AAL atlas using the intraclass correlation coefficient (ICC) for absolute agreement. We further evaluated the influence of the type of head-coil (12 versus 32 channels) and the number of reconstruction repetitions (reconstructing streamlines once or aggregated over ten repetitions). Factorial analyses demonstrated that reproducibility was significantly greater for within- than between-session reproducibility and significantly increased by aggregating streamline counts over ten reconstruction repetitions. Using a high-resolution head-coil incurred only small beneficial effects. Overall, ICC values were positively correlated with the streamline count of a connection. Additional analyses assessed the influence of different selection variants (defining fuzzy versus no fuzzy borders of the seed mask; selecting streamlines that end in versus pass through a seed) showing that an endpoint-based variant using fuzzy selection provides the best compromise between reproducibility and anatomical specificity. In sum, aggregating quantitative indices over repeated estimations and higher numbers of streamlines are important determinants of test-retest reproducibility. If these factors are taken into account, streamline counts derived from global tractography provide an adequately reproducible quantitative measure that can be used to gauge the structural connectivity of the brain in health and disease.

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YNICL Journal 2018 Journal Article

The anatomy of the human medial forebrain bundle: Ventral tegmental area connections to reward-associated subcortical and frontal lobe regions

Volker Arnd Coenen
Lena Valerie Schumacher
Christoph Kaller
Thomas Eduard Schlaepfer
Peter Christoph Reinacher
Karl Egger
Horst Urbach
Marco Reisert

Introduction: Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human medial forebrain bundle (MFB) and the connectivity of the ventral tegmental area (VTA). A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB) - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.). This work aims at a normative description of the human MFB (and more detailed the slMFB) anatomy with respect to distant prefrontal connections and microstructural features. Methods and material: = 55; mean age ± SD, 40 ± 10 years; 32 females) underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments) of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB. Results: The MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right) and 98% (left) of the total relative fiber counts of the slMFB. Discussion: The anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and cortical prefrontal regions - but not to emotion-related regions on the medial cortical surface - realized via the superolateral branch of the MFB. Local tractography approaches appear to be inferior in showing these far-reaching projections. Since these local approaches are typically used for surgical targeting of DBS procedures, the here established detailed map might - as a normative template - guide future efforts to target deep brain stimulation of the slMFB in depression and other disorders related to dysfunction of reward and reward-associated learning.

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YNICL Journal 2018 Journal Article

Voxel-wise deviations from healthy aging for the detection of region-specific atrophy

Stefan Klöppel
Shan Yang
Elias Kellner
Marco Reisert
Bernhard Heimbach
Horst Urbach
Jennifer Linn
Stefan Weidauer

The identification of pathological atrophy in MRI scans requires specialized training, which is scarce outside dedicated centers. We sought to investigate the clinical usefulness of computer-generated representations of local grey matter (GM) loss or increased volume of cerebral fluids (CSF) as normalized deviations (z-scores) from healthy aging to either aid human visual readings or directly detect pathological atrophy. Two experienced neuroradiologists rated atrophy in 30 patients with Alzheimer's disease (AD), 30 patients with frontotemporal dementia (FTD), 30 with dementia due to Lewy-body disease (LBD) and 30 healthy controls (HC) on a three-point scale in 10 anatomical regions as reference gold standard. Seven raters, varying in their experience with MRI diagnostics rated all cases on the same scale once with and once without computer-generated volume deviation maps that were overlaid on anatomical slices. In addition, we investigated the predictive value of the computer generated deviation maps on their own for the detection of atrophy as identified by the gold standard raters. Inter and intra-rater agreements of the two gold standard raters were substantial (Cohen's kappa κ > 0.62). The intra-rater agreement of the other raters ranged from fair (κ = 0.37) to substantial (κ = 0.72) and improved on average by 0.13 (0.57 < κ < 0.87) when volume deviation maps were displayed. The seven other raters showed good agreement with the gold standard in regions including the hippocampus but agreement was substantially lower in e.g. the parietal cortex and did not improve with the display of atrophy scores. Rating speed increased over the course of the study and irrespective of the presentation of voxel-wise deviations. Automatically detected large deviations of local volume were consistently associated with gold standard atrophy reading as shown by an area under the receiver operator characteristic of up to 0.95 for the hippocampus region. When applying these test characteristics to prevalences typically found in a memory clinic, we observed a positive or negative predictive value close to or above 0.9 in the hippocampus for almost all of the expected cases. The volume deviation maps derived from CSF volume increase were generally better in detecting atrophy. Our study demonstrates an agreement of visual ratings among non-experts not further increased by displaying, region-specific deviations of volume. The high predictive value of computer generated local deviations independent from human interaction and the consistent advantages of CSF-over GM-based estimations should be considered in the development of diagnostic tools and indicate clinical utility well beyond aiding visual assessments.

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YNIMG Journal 2007 Journal Article

Imaging early practice effects in arithmetic

Anja Ischebeck
Laura Zamarian
Karl Egger
Michael Schocke
Margarete Delazer

A better understanding of learning processes in arithmetic in healthy adults can guide research into learning disabilities such as dyscalculia. The goal of the present functional magnetic resonance imaging study was to investigate the ongoing process of learning itself. No training was provided prior to the scanning session. Training consisted in a higher frequency of repetition for one set of complex multiplication problems (repeated) and a lower frequency for the other set (novel). Repeated and novel problems were presented randomly in an event-related design. We observed activation decreases due to training in fronto-parietal areas and the caudate nucleus, and activation increases in temporo-parietal regions such as the left angular gyrus. Training effects became significant after approximately eight repetitions of a problem and remained stable over the course of the experiment. The change in brain activation patterns observed was similar to the results of previous neuroimaging studies investigating training effects in arithmetic after a week of extensive training. The paradigm employed seems to be a suitably sensitive tool to investigate and compare learning processes on group level for different populations. Furthermore, on a more general level, the early and robust changes in brain activation in healthy adults observed here indicate that repeating stimuli can profoundly and quickly affect fMRI results.

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