Biology subjects

Karnath, H.-O.

Publications and source records attributed to Karnath, H.-O..

At least 19 recordsLinked to original sources

bioRxiv2025

Minimizing the influence of magnetic vestibular stimulation inside MRI-scanners by adjusting head position

Magnetic resonance imaging (MRI) offers detailed diagnostic insights but also unintentionally induces vestibular side effects by its static magnetic field. Magnetic vestibular stimulation (MVS) may cause dizziness and confound behavioral and physiological measures in fMRI by introducing an unavoidable mixture of neural activation in vestibular projection areas, driven both by the signal of interest and by vestibular system activation. This study investigated how different head orientations within a 3T MRI scanner influence the MVS-induced vestibulo-ocular reflex (VOR) in complete darkness, with the goal of identifying a head position that minimizes or eliminates MVS effects. Results revealed a linear relationship between head pitch and the horizontal VOR (Experiment 1), as well as between head roll and the vertical VOR (Experiment 2). Across participants, the horizontal VOR was eliminated at an average forward head pitch of 24.4{degrees}, while the vertical VOR was nullified at an average roll angle of 15.9{degrees} towards the right shoulder. A head position combining this forward pitch with this rightward roll effectively minimized both horizontal and vertical VOR components across subjects (Experiment 3). The findings provide a practical solution to reduce the impact of MVS effects in MRI with important implications for improving data quality in neuroscientific fMRI studies and patient comfort during clinical imaging.

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bioRxiv2025

Galvanic vestibular stimulation alters the sense of upright

Given the vestibular systems important role in the perception of upright, we investigated the possible effects of galvanic vestibular stimulation (GVS) on the perception of ones own upright body orientation in relation to gravity, the so-called Subjective Postural Vertical (SPV). Two groups of healthy participants with an average age of 25.4 years and 64.5 years respectively, each consisting of 28 healthy participants, sat (blindfolded) on a tilting chair. The subjects feeling of being upright was tested under three different conditions of GVS: right-sided anodal stimulation, left-sided anodal stimulation, and sham stimulation. Our findings revealed that right-sided anodal GVS significantly altered the SPV in both age groups, whereas left-sided anodal GVS did not. The observed effect of GVS on perceived upright body posture was numerically small (up to 0.87{degrees} on average) and not due to a loss of sensitivity to the perception of body verticality. The unexpected asymmetry of the behavioral effects of GVS could be related to the known right hemispheric asymmetry of cortical activation in vestibular projection areas, which would need to be further clarified in future studies.

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bioRxiv2025

Optic Ataxia in Patients with Thalamic Lesions

Lesions in parietal cortex can strongly impair visually guided reach-grasping behaviour. A specific reaching deficit termed Optic Ataxia (OA) occurs when eye and hand position are dissociated. Optic ataxia has typically been studied in patients with lesions in parietal cortex, neglecting potential thalamic contributions. We here examined 28 acute stroke patients (age 58.9 {+/-} 12.6 years) with circumscribed thalamic lesions for the presence of optic ataxia. We leveraged MRI-based lesion-symptom mapping to address the contributions of specific thalamic nuclei to visually-guided reaching deficits under foveal and peripheral viewing conditions. Based on the cortical literature, we hypothesized that lesions in thalamic nuclei with strong connections to the inferior and superior parietal cortex, such as the ventrolateral nucleus and pulvinar might lead to optic ataxia. In comparison with aged-matched healthy subjects (n = 40, age 60.6 {+/-} 9.1 years), we identified five thalamic patients with optic ataxia, most pronounced for reaches with the contralesional hand into the contralesional space. While motor and grasping deficits and optic ataxia occurred frequently together, they did not always co-occur, and visual attention deficits could not account for the optic ataxia either. Comparing the lesion maps of patients with and without optic ataxia, the critical lesion site for optic ataxia was not restricted to one circumscribed thalamic region within the Morel atlas. Instead, it encompassed several medial and lateral nuclei within and around the internal medullary laminar (IML) complex. Interestingly, this region matches the so-called central thalamus, a functionally defined thalamic region that is considered a higher-order nucleus complex. It receives afferent inputs from the cerebellum and brainstem regions and connects to fronto-parietal regions involved in eye movement control. Taken together, our results suggest the critical importance of thalamic nuclei for the spatial transformation from eye-into body-centered coordinates.

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bioRxiv2024

Structural disconnections caused by white matter hyperintensities in post-stroke spatial neglect

White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, affect a wide range of cognitive dysfunctions, including spatial neglect. The latter is a disorder of spatial attention and exploration typically after right hemisphere brain damage. To explore the impact of WMH on neglect-related structural disconnections, the present study investigated the indirectly quantified structural disconnectome induced by either stroke lesion alone, WMH alone, or their combination. Further, we compared different measures of structural disconnections - voxel-wise, pairwise, tract-wise, and parcel-wise - to identify neural correlates and predict acute neglect severity. We observed that WMH-derived disconnections alone were not associated to neglect behavior. However, when combined with disconnections derived from individual stroke lesions, pre-stroke WMH contributed to post-stroke neglect severity by affecting right frontal and subcortical substrates, like the middle frontal gyrus, basal ganglia, thalamus, and the fronto-pontine tract. Predictive modeling demonstrated that voxel-wise disconnection data outperformed other measures of structural disconnection, explaining 42% of the total variance. Compared to using stroke lesion anatomy, prediction performance can be improved by either estimating stroke-based structural disconnections or delineating the combined anatomy of stroke lesion and WMH. We conclude that pre-stroke alterations in the white matter microstructure due to WMH contribute to post-stroke deficits in spatial attention, likely by impairing the integrity of human attention networks.

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bioRxiv2024

Spatial neglect after subcortical stroke: sometimes a cortico-cortical disconnection syndrome

Background and ObjectivesSpatial neglect is commonly attributed to lesions of a predominantly right-hemispheric cortical network. Although spatial neglect was also repeatedly observed after lesions to the basal ganglia and the thalamus, many anatomical network models omit these structures. We investigated if disruption of functional or structural connectivity can explain spatial neglect in subcortical stroke. MethodsWe retrospectively investigated data of first-ever, acute stroke patients with right-sided lesions of the basal ganglia (n = 27) or the thalamus (n = 16). Based on lesion location, we estimated i) functional connectivity via lesion-network mapping with normative resting state fMRI data, ii) structural white matter disconnection and iii) tract-wise disconnection of association fibres based on normative tractography data to investigate the association of spatial neglect and disconnection measures. ResultsApart from very small clusters of functional disconnection observed in inferior/middle frontal regions in lesion-network symptom mapping for basal ganglia lesions, our analyses found no evidence of functional or structural subcortico-cortical disconnection. Instead, the multivariate consideration of lesion load to several association fibres predicted the occurrence of spatial neglect (p = 0.0048; AUC = 0.76), which were the superior longitudinal fasciculus, inferior occipitofrontal fasciculus, superior occipitofrontal fasciculus, and the uncinate fasciculus. ConclusionDisconnection of long (cortico-cortical) association fibres can explain spatial neglect in subcortical stroke. Like the competing theory of remote cortical hypoperfusion, this mechanism does not require the assumption of a genuine role for subcortical grey matter structures in spatial neglect.

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bioRxiv2024

Sustained bias of spatial attention in a 3T MRI scanner

The static magnetic field of MRI scanners induces magneto-hydrodynamic stimulation of the vestibular organ (MVS) in the inner ear. This not only causes a horizontal vestibular nystagmus but also induces a horizontal bias in spatial attention. In this study, we aimed to determine the time course of MVS-induced biases in both VOR and spatial attention inside a 3T MRI-scanner as well as their respective aftereffects after participants left the scanner. Eye movements and overt spatial attention in a visual search task were assessed in healthy volunteers before, during and after a one-hour MVS period. All participants exhibited a VOR inside the scanner, which declined over time but never vanished completely. Importantly, there was also an MVS-induced horizontal bias in spatial attention and exploration, which persisted throughout the entire hour within the scanner. Upon exiting the scanner, we observed aftereffects in the opposite direction manifested in both the VOR and in spatial attention, lasting for about 6 minutes. Sustained MVS effects on spatial attention have important implications for the design and interpretation of fMRI-studies and for the development of therapeutic interventions counteracting spatial neglect.

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bioRxiv2024

Bayesian evidence for the neural dissociation between finger and hand imitation skills

IntroductionFor limb apraxia - a heterogeneous disorder of higher motor cognition following stroke - an enduring debate has arisen regarding the existence of dissociating neural correlates for finger and hand gestures in the left hemisphere. We re-assessed this question asking whether previous attempts analysing pooled samples of patients with deficits in only one and patients with deficits in both imitation types might have led to systematically biased results. MethodsWe conducted frequentist and Bayesian, voxelwise and regionwise lesion symptom mappings on a pooled sample (N=96) and subsamples containing only shared and only isolated hand and finger imitation deficits and respective controls. ResultsAnatomical analyses on the isolated sample reinforced a cortical dissociation of finger deficits (located more anteriorly) and hand deficits (located more posteriorly). The presence of patients with shared deficits did indeed dilute associations that appeared stronger in the respective isolated samples. Also, brain regions truly associated with hand imitation deficits showed a positive bias for finger imitation deficits, when the sample contained patients with shared deficits. In addition, our frequentist parameters uncovered that some of our Bayesian evidence supported reverse associations (damage protecting from rather than increasing the deficit). DiscussionJoint analyses of patients with shared and isolated imitation deficits do indeed lead to biases, which may explain why some previous studies have failed to detect the actual neural dissociation between hand and finger imitation deficits.

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bioRxiv2023

The need for hemispheric separation in pairwise structural disconnection studies

The development of new approaches indirectly measuring the structural disconnectome has recently led to an increase in studies investigating pairwise structural disconnections following brain damage. Previous studies jointly analyzed patients with left hemispheric and patients with right hemispheric lesions when investigating a behavior of interest. An alternative approach would be to perform analyses separated by hemisphere, which has been applied in only a minority of studies to date. The present simulation study investigated whether joint or separate analyses (or both equally) are appropriate to reveal the ground truth disconnections. In fact, both approaches resulted in very different patterns of disconnection. In contrast to analyses separated by hemisphere, joint analyses introduced a bias to the disadvantage of intra-hemispheric disconnections. Intra-hemispheric disconnections were statistically underpowered in the joint analysis and thus surpassed the significance threshold with more difficulty compared to inter-hemispheric disconnections. This statistical imbalance was also shown by a greater number of significant inter-hemispheric than significant intra-hemispheric disconnections. This bias from joint analyses is based on mechanisms similar to those underlying the partial injury problem. We therefore conclude that pairwise structural disconnections in patients with unilateral left hemispheric and with unilateral right hemispheric lesions exhibiting a specific behavior (or disorder) of interest should be studied separately by hemisphere rather than in a joint analysis.

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bioRxiv2022

Thalamocortical networks involved in Pusher Syndrome

Indirect quantification of functional and structural disconnection increases the knowledge derived from focal brain lesions by inferring subsequent brain network damage from the respective lesion. We applied both measures to a sample of 124 stroke patients to investigate brain disconnection in pusher syndrome - a disorder characterized by a disturbed perception of ones own upright body posture. Our results suggest a hub-like function of the posterior and lateral portions of the thalamus in the perception of ones own postural upright and identified dysfunction in a thalamo-cortical network as one likely cause of pusher syndrome. Lesion network-symptom-mapping investigating functional disconnection indicated cortical diaschisis in cerebellar, frontal, parietal, occipital, and temporal areas in patients with thalamic lesions suffering from pusher syndrome, but there was no evidence for functional diaschisis in cortical stroke and no evidence for the convergence of thalamic and cortical lesions onto a common functional network. Structural disconnectivity mapping identified several thalamo-cortical disconnections. Many of the thalamic and cortical regions disconnected by lesions that lead to pusher behavior correspond to previously reported lesion sites associated with pusher syndrome. Thus, while the presence of both, isolated thalamic and cortical lesions in context with pusher behavior has been reported previously and led to the conclusion that the correct estimation of ones own postural upright might depend on a thalamo-cortical network, our analyses offer the first evidence for a direct thalamo-cortical (or cortico-thalamic) interconnection and, more importantly, shed light on the location of the respective thalamo-cortical disconnections.

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bioRxiv2022

Spatial neglect after stroke is reduced when lying inside a 3T MRI scanner

Recently, it was discovered that the static magnetic field of an MRI scanner not only causes horizontal vestibular nystagmus in healthy individuals but, in addition, leads to a horizontal bias of spatial orienting and exploration that closely resembles the one observed in stroke patients with spatial neglect (a disorder of spatial attention and exploration). The present study asked whether the behavioral effects of this magnetic vestibular stimulation (MVS) can be inverted and thus be used to reduce the pathological bias of stroke patients with spatial neglect. Indeed, when patients with left-sided spatial neglect entered the scanner with their feet first, i.e., with the magnetic field vector pointing from head to toes, MVS inside the scanner reduced the ipsilesionally biased distribution of overt attention and the corresponding neglect of the left parts of the search-space. Thus, an intervention as simple as lying in a 3T MRI scanner bears the potential to become an integral part of a future strategy for treating spatial neglect.

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bioRxiv2021

Left angular gyrus disconnection impairs multiplication fact retrieval

Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and subcortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n=73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct grey-to-grey matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.

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bioRxiv2021

The role of posterior ventral stream areas for viewpoint-invariant object recognition

Object constancy is one of the most crucial mechanisms of the human visual system enabling viewpoint invariant object recognition. However, the neuronal foundations of object constancy are widely unknown. Research has shown that the ventral visual stream is involved in processing of various kinds of object stimuli and that several regions along the ventral stream are possibly sensitive to the orientation of an object in space. To systematically address the question of viewpoint sensitive object perception, we conducted a study with stroke patients as well as an fMRI experiment with healthy participants applying object stimuli in several spatial orientations, for example in typical and atypical viewing conditions. In the fMRI experiment, we found stronger BOLD signals and above-chance classification accuracies for objects presented in atypical viewing conditions in fusiform face sensitive and lateral occipito-temporal object preferring areas. In the behavioral patient study, we observed that lesions of the right fusiform gyrus were associated with lower performance in object recognition for atypical views. The complementary results from both experiments emphasize the contributions of fusiform and lateral-occipital areas to visual object constancy and indicate that visual object constancy is particularly enabled through increased neuronal activity and specific activation patterns for objects in demanding viewing conditions.

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bioRxiv2021

Spatial neglect in the digital age - Influence of presentation format on patients' test behavior

Computerization of diagnostic neglect tests can deepen our knowledge of neglect specific abnormalities, by effortlessly providing additional behavioral markers that are hardly extractable from existing paper-and-pencil versions. However, so far it is not known whether the digitization and/or a change in size format impact neglect patients search behavior and test scores and thus require adjustments of cut-off criteria. We compared the Center of cancellation (CoC) measure of right hemisphere stroke patients with spatial neglect in two cancellation tasks across different modalities (paper-and-pencil vs. digital) and display sizes (small, medium, large). We found that the CoC measure did neither vary considerably between paper-and-pencil versus digital versions, nor between different digital size formats. The CoC derived from cancellation tasks thus seems robust to test digitization. A further aim of the present study was to evaluate three additional parameters of search behavior which became available through digitization. We observed slower search behavior, increased distance between two consecutively identified items, and signs of a more strategic search for neglect patients than control patients without neglect. Machine learning classifications indicated that - beyond the CoC measure - the latter three variables can help to differentiate stroke patients with spatial neglect from thosewithout.

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bioRxiv2021

Lying in a 3T MRI Scanner Induces Neglect-Like Spatial Attention Bias

The static magnetic field of MRI scanners can induce a magneto-hydrodynamic stimulation of the vestibular organ (MVS). In common fMRI settings, this MVS effect leads to a vestibular ocular reflex (VOR). We asked whether - beyond inducing a VOR - putting a healthy subject in a 3T MRI scanner would also alter goal-directed spatial behavior, as is known from other types of vestibular stimulation. We investigated 17 healthy volunteers, all of which exhibited a rightward VOR inside the MRI-scanner as compared to outside-MRI conditions. More importantly, when probing the distribution of overt spatial attention inside the MRI using a visual search task, subjects scanned a region of space that was significantly shifted towards the right. An additional estimate of subjective straight-ahead orientation likewise exhibited an MVC-induced rightward shift. Hence, putting a subject in a 3T MRI-scanner induces a bias of spatial attention, which closely mimics that of stroke patients with spatial neglect.

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bioRxiv2020

Neural correlates of imaging biomarkers for primary motor deficits after stroke - more than just the primary motor system?

Hemiparesis is a common consequence of stroke to the primary motor system. Previous studies suggested that damage to additional brain areas might play a causal role in the occurrence and severity of hemiparesis and its recovery. Knowledge of these regions might be applied in the creation of imaging biomarkers for motor outcome prediction if lesion information from such areas carries predictive value. We assessed acute and chronic paresis of the upper limb in 102 patients with unilateral stroke. In a first experiment, the neural correlates of acute and chronic upper limb paresis were mapped by lesion behaviour mapping. Following the same approach, a lesion biomarker of corticospinal tract (CST) damage was mapped. This analysis served as an artificial control condition as the biomarker, by definition, is only causally related to damage of the CST. Mapping acute or chronic upper limb paresis implicated areas outside of the primary motor system. Likewise, mapping the CST lesion biomarker implicated several areas outside of the CST with high correspondence to areas associated with upper limb paresis. Damage to areas outside of the primary motor system thus might, to some degree, not play a causal role in hemiparesis. In a second experiment, we showed that lesion information from these areas outside of the primary motor system can be used to predict motor outcome. This was even the case for the CST lesion biomarker. Although the only causal source underlying the CST lesion biomarker was damage to the CST, lesion information that mainly included non-CST regions was able to predict the biomarker (non-significantly) better than information taken from only the CST itself. These findings suggest that simple theory-based biomarkers or qualitative rules to infer post-stroke outcome from imaging data might perform sub-optimally, as they do not consider the complexity of lesion data. Instead, high-dimensional models with data-driven feature selection strategies might be required.

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bioRxiv2020

Mapping the human praxis network: an investigation of white matter disconnection in limb apraxia

Left hemispheric cerebral stroke can cause apraxia, a motor-cognitive disorder characterised by deficits of higher-order motor skills such as the failure to accurately produce meaningful gestures. This disorder provides unique insights into the anatomical and cognitive architecture of the human praxis system. The present study aimed to map the structural brain network that is damaged in apraxia. We assessed the ability to perform meaningful gestures with the hand in 101 patients with chronic left hemisphere stroke. Structural white matter fibre damage was directly assessed by diffusion tensor imaging and fractional anisotropy mapping. We used multivariate topographical inference on tract-based fractional anisotropy topographies to identify white matter disconnection associated with apraxia. We found relevant pathological white matter alterations in a densely connected fronto-temporo-parietal network of short and long association fibres. Hence, the findings suggest that heterogeneous topographical results in previous lesion mapping studies might not only result from differences in study design, but also from the general methodological limitations of univariate topographical mapping in uncovering the structural praxis network. A striking role of middle and superior temporal lobe disconnection, including temporo-temporal short association fibres, was found, suggesting strong involvement of the temporal lobe in the praxis network. Further, the results stressed the importance of subcortical disconnections for the emergence of apractic symptoms. Our study provides a fine-grain view into the structural connectivity of the human praxis network and suggests a potential value of disconnection measures in the clinical prediction of behavioural post-stroke outcome.

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bioRxiv2020

Temporo-parietal brain regions are involved in higher order object perception

Lesions to posterior temporo-parietal brain regions are associated with deficits in perception of global, hierarchical shapes, but also impairments in the processing of objects presented under demanding viewing conditions. Evidence from neuroimaging studies and lesion patterns observed in patients with simultanagnosia and agnosia for object orientation suggest similar brain regions to be involved in perception of global shapes and processing of objects in atypical ( non-canonical) orientation. In a localizer experiment, we identified individual temporoparietal brain areas involved in global shape perception and found significantly higher BOLD signals during the processing of non-canonical compared to canonical objects. In a multivariate approach, we demonstrated that posterior temporo-parietal brain areas show distinct voxel patterns for non-canonical and canonical objects and that voxel patterns of global shapes are more similar to those of objects in non-canonical compared to canonical viewing conditions. These results suggest that temporo-parietal brain areas are not only involved in global shape perception but might serve a more general mechanism of complex object perception. Our results challenge a strict attribution of object processing to the ventral visual stream by suggesting specific dorsal contributions in more demanding viewing conditions. HighlightsO_LIPosterior temporo-parietal brain areas in the TPJ region that are involved in global shape perception are significantly involved in object perception C_LIO_LIIndividual global shape TPJ ROIs identified with a specific localizer experiment prefer objects in non-canonical over objects in canonical orientations C_LIO_LIUnivariate activations and multivariate voxel patterns in global shape TPJ ROIs distinguish canonical and non-canonical object presentations C_LI

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bioRxiv2020

Disconnection somewhere down the line: Multivariate lesion-symptom mapping of the line bisection error

Line Bisection is a simple task frequently used in stroke patients to diagnose disorders of spatial perception characterized by a directional bisection bias to the ipsilesional side. However, previous anatomical and behavioural findings are contradictory, and the diagnostic validity of the line bisection task has been challenged. We hereby aimed to re-analyse the anatomical basis of pathological line bisection by using multivariate lesion-symptom mapping and disconnection-symptom mapping based on support vector regression in a sample of 163 right hemispheric acute stroke patients. In line with some previous studies, we observed that pathological line bisection was related to more than a single focal lesion location. Cortical damage primarily to right parietal areas, particularly the inferior parietal lobe, including the angular gyrus, as well as damage to the right basal ganglia contributed to the pathology. In contrast to some previous studies, an involvement of frontal cortical brain areas in the line bisection task was not observed. Subcortically, damage to the right superior longitudinal fasciculus (I, II and III) and arcuate fasciculus as well as the internal capsule was associated with line bisection errors. Moreover, white matter damage of interhemispheric fibre bundles, such as the anterior commissure and posterior parts of the corpus callosum projecting into the left hemisphere, was predictive of pathological deviation in the line bisection task.

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