Dorothee Saur

YNICL Journal 2022 Journal Article

fMRI informed voxel-based lesion analysis to identify lesions associated with right-hemispheric activation in aphasia recovery

• Hans R. Schneider
• Max Wawrzyniak
• Anika Stockert
• Julian Klingbeil
• Dorothee Saur

Several mechanisms have been attributed to post-stroke loss and recovery of language functions. However, the significance and timing of domain-general and homotopic right-hemispheric activation is controversial. We aimed to examine the effect of left-hemispheric lesion location and time post-stroke on right-hemispheric activation. Voxel-based lesion analyses were informed by auditory language-related fMRI activation of 71 patients with left middle cerebral artery stroke examined longitudinally in the acute, subacute and early chronic phase. Language activation was determined in several right-hemispheric regions of interest and served as regressor of interest for voxel-based lesion analyses. We found that an acute to chronic increase of language activation in the right supplementary motor area was associated with lesions to the left extreme capsule as part of the ventral language pathway. Importantly, this activation increase correlated significantly with improvement of out-of-scanner comprehension abilities. We interpret our findings in terms of successful domain-general compensation in patients with critical left frontotemporal disconnection due to damage to the ventral language pathway but relatively spared cortical language areas.

YNIMG Journal 2022 Journal Article

Resolution of diaschisis contributes to early recovery from post-stroke aphasia

• Max Wawrzyniak
• Hans R. Schneider
• Julian Klingbeil
• Anika Stockert
• Gesa Hartwigsen
• Cornelius Weiller
• Dorothee Saur

Diaschisis is a phenomenon observed in stroke that is defined as neuronal dysfunction in regions spared by the infarction but connected to the lesion site. We combined lesion network mapping and task-based functional MRI in 71 patients with post-stroke aphasia to investigate, whether diaschisis and its resolution contribute to early loss and recovery of language functions. Language activation acquired in the acute, subacute and chronic phase was analyzed in compartments with high and low normative resting-state functional connectivity to the lesion site on an individual basis. Regions with high compared to regions with low lesion connectivity showed a steeper increase in language reactivation from the acute to the subacute phase. This finding is compatible with the assumption of resolution of diaschisis. Additionally, language performance in the subacute phase and improvement from the subacute to the chronic phase significantly correlated with the diaschisis effect and its resolution, respectively, suggesting a behavioral relevance of this effect. We therefore assume that undamaged but functionally connected regions become dysfunctional due to missing input from the lesion contributing to the aphasic deficit. Since these regions are structurally intact, dysfunction resolves over time contributing to the rapid early behavioral improvement observed in aphasic stroke patients. Our results demonstrate that diaschisis and its resolution might be a relevant mechanism of early loss and recovery of language function in acute stroke patients.

YNICL Journal 2022 Journal Article

Voxelwise structural disconnection mapping: Methodological validation and recommendations

• Max Wawrzyniak
• Anika Stockert
• Julian Klingbeil
• Dorothee Saur

Voxelwise disconnection mapping is a novel approach to disclose lesion-symptom relationships for symptoms caused by white matter disconnection. It uses MRI-based fiber tracking in healthy subjects seeded from patient's focal brain lesions. Resulting individual disconnection maps can then be statistically associated with symptoms. Despite increasing use in the recent years, the validity of this approach remains to be investigated. In this study, we validated both, our own implementation and the implementation provided within BCBtoolkit. For technical validation, we used simulated symptoms based on overlap of 70 real stroke lesions with tracts from a white matter atlas. For clinical validation, paresis scores and lesions from 316 patients with stroke were used. We found that voxelwise disconnection mapping is technically valid and outperforms the standard voxel-based lesion-symptom mapping approach for symptoms caused by white matter disconnection. Supporting its clinical validity and utility, we were able to reproduce the known association between corticospinal tract damage and contralateral hemiparesis. In addition, we demonstrate that the validity can be substantially diminished by relatively minor methodological changes. Based on these results, we derive methodological recommendations for the future use of voxelwise disconnection mapping. Our study highlights the importance of validating novel methodological approaches in the rapidly evolving field of neuroimaging.

YNICL Journal 2021 Journal Article

Hippocampal gray matter volume in the long-term course after transient global amnesia

• Mandy Pirlich
• Cathleen Höfer
• Christopher M. Weise
• Anika Stockert
• Angelika Thöne-Otto
• Alexander Garthe
• Stefan Schob
• Joseph Classen

OBJECTIVE: In this retrospective, cross-sectional study we aimed to examine long-term memory deficits and gray matter volumes (GMV) in the hippocampus after transient global amnesia (TGA). METHODS: 20 patients with a history of TGA (TGA+, mean 6.5 years after TGA) and 20 age-matched healthy controls (TGA-) underwent neurocognitive assessment (i.e. Mini-Mental State Examination (MMSE), visuospatial, verbal and episodic autobiographical memory and visuospatial learning/navigation ["human water maze"]) in combination with structural cerebral MRI. Voxel-based morphometry (VBM) was used to detect GMV in the hippocampus in TGA+ versus TGA-. RESULTS: Besides slight differences in MMSE and visuo-spatial learning/navigation measured with a human water maze in TGA+ vs. TGA-, no other tests of visuo-spatial, verbal and autobiographical long-term memory differed between groups. VBM analyses yielded a statistically significant difference in bilateral hippocampal GMV with TGA+ compared to TGA- showing greater GMV in a region corresponding to bilateral CA1. However, none of the hippocampus-dependent cognitive measures correlated with hippocampal GMV. CONCLUSION: In the long-term course after TGA, only subtle neurocognitive deficits without microstructural damage of the hippocampus could be detected. Greater GMV in bilateral hippocampus in TGA+ vs. TGA- may indicate that TGA triggers hippocampal GMV increase rather than atrophy.

YNIMG Journal 2020 Journal Article

Hippocampal diaschisis contributes to anosognosia for hemiplegia: Evidence from lesion network-symptom-mapping

• Julian Klingbeil
• Max Wawrzyniak
• Anika Stockert
• Hans-Otto Karnath
• Dorothee Saur

Anosognosia for hemiplegia (AHP) is known to be associated with lesions to the motor system combined with varying lesions to the right insula, premotor cortex, parietal lobe or hippocampus. Due to this widespread cortical lesion distribution, AHP can be understood best as a network disorder. We used lesion maps and behavioral data (n ​= ​49) from two previous studies on AHP and performed a lesion network-symptom-mapping (LNSM) analysis. This new approach permits the identification of relationships between behavior and regions connected to the lesion site based on normative functional connectome data. In a first step, using ordinary voxel-based lesion-symptom mapping, we found an association of AHP with lesions in the right posterior insula. This is in accordance with previous studies. Applying LNSM, we were able to additionally identify a region in the right posterior hippocampus where AHP was associated with significantly higher normative lesion connectivity. Notably, this region was spared by infarction in all patients. We therefore argue that remote neuronal dysfunction caused by disrupted functional connections between the lesion site and the hippocampus (i. e. diaschisis) contributed to the phenotype of AHP. An indirect affection of the hippocampus may lead to memory deficits which, in turn, impair the stable encoding of updated beliefs on the bodily state thus contributing to the multifactorial phenomenon of AHP.

YNIMG Journal 2019 Journal Article

Neuroimaging of stroke recovery from aphasia – Insights into plasticity of the human language network

• Gesa Hartwigsen
• Dorothee Saur

The role of left and right hemisphere brain regions in language recovery after stroke-induced aphasia remains controversial. Here, we summarize how neuroimaging studies increase the current understanding of functional interactions, reorganization and plasticity in the language network. We first discuss the temporal dynamics across the time course of language recovery, with a main focus on longitudinal studies from the acute to the chronic phase after stroke. These studies show that the functional contribution of perilesional and spared left hemisphere as well as contralesional right hemisphere regions to language recovery changes over time. The second section introduces critical variables and recent advances on early prediction of subsequent outcome. In the third section, we outline how multi-method approaches that combine neuroimaging techniques with non-invasive brain stimulation elucidate mechanisms of plasticity and reorganization in the language network. These approaches provide novel insights into general mechanisms of plasticity in the language network and might ultimately support recovery processes during speech and language therapy. Finally, the neurobiological correlates of therapy-induced plasticity are discussed. We argue that future studies should integrate individualized approaches that might vary the combination of language therapy with specific non-invasive brain stimulation protocols across the time course of recovery. The way forward will include the combination of such approaches with large data sets obtained from multicentre studies.

YNIMG Journal 2019 Journal Article

When less is more: Structural correlates of core executive functions in young adults – A VBM and cortical thickness study

• Christopher M. Weise
• Tobias Bachmann
• Matthias L. Schroeter
• Dorothee Saur

Background The term executive functions (EF) describes a set of higher cognitive abilities/skills needed for goal-oriented and flexible behavior. In contrast to a multitude of functional neuroimaging studies of EF performance, only limited and partially inconclusive data is available for the structural-neuroanatomical underpinnings of EFs, particularly in healthy adults. Methods Here, we applied voxel-based morphometry (VBM) and additional analyses of cortical thickness (CTH; via surface-based morphometry) to a large sample of healthy young adults from the Human Connectome Project (N = 1110; Age 28. 8 ± 3. 7 years) with structural MRI data and test data reflective of three core EFs [i. e. cognitive flexibility (CF), inhibitory control (IC) and working memory (WM)]. Results For CF and IC, VBM analyses yielded a distinct and largely overlapping pattern of exclusively negative associations (CF>IC), most prominently within the medial prefrontal cortex, the insular cortex, central/precentral regions, subcortical and mesotemporal structures. A similar, yet less pronounced pattern of negative associations was found in analyses of CTH. In contrast, both VBM and CTH analyses yielded no significant associations with WM performance. Conclusions Brain regions we found negatively associated with measures of CF and IC have been repeatedly highlighted by functional imaging studies of EF performance. The here observed inverse relationship with brain structural parameters may be related to the young age of our study population and well established neurobiological mechanisms of cortical maturation (i. e. cortical thinning via synaptic pruning and cortical myelination).

YNIMG Journal 2018 Journal Article

The neuronal network involved in self-attribution of an artificial hand: A lesion network-symptom-mapping study

• Max Wawrzyniak
• Julian Klingbeil
• Daniel Zeller
• Dorothee Saur
• Joseph Classen

The feeling of body-ownership can be experimentally manipulated using the rubber hand illusion (RHI) paradigm. Participants experience a sense of ownership over an artificial hand when their hidden real hand and the visible artificial hand are synchronously stroked. Using lesion masks and behavioral data from a previous study on RHI failure in acute stroke patients, we here employed lesion network-symptom-mapping (LNSM) based on normative functional connectome data to identify lesion-dependent network connectivity related to the experience of self-attribution of an artificial hand in the RHI paradigm. We found that failure to experience the RHI was associated with higher normative lesion-dependent network connectivity to the right temporoparietal junction (rTPJ), right anterior Insula (raI) and right inferior frontal gyrus (rIFG). Since these areas were spared by the infarction in most patients with RHI failure (89% for rTPJ and 94% for raI/rIFG), the analysis suggests that remote dysfunction in rTPJ, raI, and rIFG accounted for RHI failure. These results highlight the potential role of rTPJ, raI, and rIFG in bodily self-consciousness. LNSM is a powerful tool capable of delineating the architecture of functional networks underlying complex cognitive function.

YNIMG Journal 2017 Journal Article

Differential spatial representation of precision and power grasps in the human motor system

• Christopher Fricke
• Reinhard Gentner
• Jost-Julian Rumpf
• David Weise
• Dorothee Saur
• Joseph Classen

Power and precision grasps are two interrelated, kinematically distinct types of finger movements. We examined whether these types of motor actions may be spatially differently represented in the human central nervous system. In healthy participants representations of finger movements were mapped by delivering single pulse TMS to multiple scalp regions covering the left primary motor cortex (M1). Finger joint motions were recorded from the right hand using a data glove. Principal component analysis was used to extract local subspaces representing the TMS-evoked movement data from each scalp region. Voluntary power and precision grasps were reconstructed with these subspaces. The spatial properties of these reconstructions were analyzed for each grasp type using a general linear model. We found overlapping, yet distinct spatial representations for precision and power grasps with precision grasps represented slightly posterior compared to a more uniform distribution for power grasps. Differential spatial encoding of both grasp types may point towards a representation of power grasps within a phylogenetically older M1 area at the crown of the precentral gyrus and of precision grasps in a newer area in the depth of the central sulcus. Results also support the idea of separate synergistic movement representations in the human motor system.

YNIMG Journal 2017 Journal Article

Integration demands modulate effective connectivity in a fronto-temporal network for contextual sentence integration

• Gesa Hartwigsen
• Ilona Henseler
• Anika Stockert
• Max Wawrzyniak
• Christin Wendt
• Julian Klingbeil
• Annette Baumgaertner
• Dorothee Saur

Previous neuroimaging studies demonstrated that a network of left-hemispheric frontal and temporal brain regions contributes to the integration of contextual information into a sentence. However, it remains unclear how these cortical areas influence and drive each other during contextual integration. The present study used dynamic causal modeling (DCM) to investigate task-related changes in the effective connectivity within this network. We found increased neural activity in left anterior inferior frontal gyrus (aIFG), posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and anterior superior temporal sulcus/MTG (aSTS/MTG) that probably reflected increased integration demands and restructuring attempts during the processing of unexpected or semantically anomalous relative to expected endings. DCM analyses of this network revealed that unexpected endings increased the inhibitory influence of left aSTS/MTG on pSTS/MTG during contextual integration. In contrast, during the processing of semantically anomalous endings, left aIFG increased its inhibitory drive on pSTS/MTG. Probabilistic fiber tracking showed that effective connectivity between these areas is mediated by distinct ventral and dorsal white matter association tracts. Together, these results suggest that increasing integration demands require an inhibition of the left pSTS/MTG, which presumably reflects the inhibition of the dominant expected sentence ending. These results are important for a better understanding of the neural implementation of sentence comprehension on a large-scale network level and might influence future studies of language in post-stroke aphasia after focal lesions.

YNIMG Journal 2013 Journal Article

Corrigendum to “Neuroimaging in aphasia treatment research: Consensus and practical guidelines for data analysis” [Neuroimage 73 (2013) 215–224]

• Marcus Meinzer
• Pélagie M. Beeson
• Stefano Cappa
• Jenny Crinion
• Swathi Kiran
• Dorothee Saur
• Todd Parrish
• Bruce Crosson

YNIMG Journal 2013 Journal Article

Neuroimaging in aphasia treatment research: Consensus and practical guidelines for data analysis

• Marcus Meinzer
• Pélagie M. Beeson
• Stefano Cappa
• Jenny Crinion
• Swathi Kiran
• Dorothee Saur
• Todd Parrish
• Bruce Crosson

Functional magnetic resonance imaging is the most widely used imaging technique to study treatment-induced recovery in post-stroke aphasia. The longitudinal design of such studies adds to the challenges researchers face when studying patient populations with brain damage in cross-sectional settings. The present review focuses on issues specifically relevant to neuroimaging data analysis in aphasia treatment research identified in discussions among international researchers at the Neuroimaging in Aphasia Treatment Research Workshop held at Northwestern University (Evanston, Illinois, USA). In particular, we aim to provide the reader with a critical review of unique problems related to the pre-processing, statistical modeling and interpretation of such data sets. Despite the fact that data analysis procedures critically depend on specific design features of a given study, we aim to discuss and communicate a basic set of practical guidelines that should be applicable to a wide range of studies and useful as a reference for researchers pursuing this line of research.

YNIMG Journal 2012 Journal Article

Network modulation during complex syntactic processing

• Dirk-Bart den Ouden
• Dorothee Saur
• Wolfgang Mader
• Björn Schelter
• Sladjana Lukic
• Eisha Wali
• Jens Timmer
• Cynthia K. Thompson

Complex sentence processing is supported by a left-lateralized neural network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in an earlier study (Thompson, C. K. , Den Ouden, D. B. , Bonakdarpour, B. , Garibaldi, K. , & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211–3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series extracted from participant-specific activation peaks and showed evidence of functional connectivity between four regions, linearly between premotor cortex, inferior frontal gyrus, posterior superior temporal sulcus and anterior middle temporal gyrus. This pattern served as the basis for Dynamic Causal Modeling of networks with a driving input to posterior superior temporal cortex, which likely supports thematic role assignment, and networks with a driving input to inferior frontal cortex, a core region associated with syntactic computation. The optimal model was determined through both frequentist and Bayesian Model Selection and turned out to reflect a network with a primary drive from inferior frontal cortex and modulation of the connection between inferior frontal cortex and posterior superior temporal cortex by complex sentence processing. The winning model also showed a substantive role for a feedback mechanism from posterior superior temporal cortex back to inferior frontal cortex. We suggest that complex syntactic processing is driven by word-order analysis, supported by inferior frontal cortex, in an interactive relation with posterior superior temporal cortex, which supports verb argument structure processing.

YNIMG Journal 2010 Journal Article

Combining functional and anatomical connectivity reveals brain networks for auditory language comprehension

• Dorothee Saur
• Björn Schelter
• Susanne Schnell
• David Kratochvil
• Hanna Küpper
• Philipp Kellmeyer
• Dorothee Kümmerer
• Stefan Klöppel

Cognitive functions are organized in distributed, overlapping, and interacting brain networks. Investigation of those large-scale brain networks is a major task in neuroimaging research. Here, we introduce a novel combination of functional and anatomical connectivity to study the network topology subserving a cognitive function of interest. (i) In a given network, direct interactions between network nodes are identified by analyzing functional MRI time series with the multivariate method of directed partial correlation (dPC). This method provides important improvements over shortcomings that are typical for ordinary (partial) correlation techniques. (ii) For directly interacting pairs of nodes, a region-to-region probabilistic fiber tracking on diffusion tensor imaging data is performed to identify the most probable anatomical white matter fiber tracts mediating the functional interactions. This combined approach is applied to the language domain to investigate the network topology of two levels of auditory comprehension: lower-level speech perception (i. e. , phonological processing) and higher-level speech recognition (i. e. , semantic processing). For both processing levels, dPC analyses revealed the functional network topology and identified central network nodes by the number of direct interactions with other nodes. Tractography showed that these interactions are mediated by distinct ventral (via the extreme capsule) and dorsal (via the arcuate/superior longitudinal fascicle fiber system) long- and short-distance association tracts as well as commissural fibers. Our findings demonstrate how both processing routines are segregated in the brain on a large-scale network level. Combining dPC with probabilistic tractography is a promising approach to unveil how cognitive functions emerge through interaction of functionally interacting and anatomically interconnected brain regions.