Otto W. Witte

YNICL Journal 2022 Journal Article

Cortical and subcortical grey matter atrophy in Amyotrophic Lateral Sclerosis correlates with measures of disease accumulation independent of disease aggressiveness

• Nora Dieckmann
• Annekathrin Roediger
• Tino Prell
• Simon Schuster
• Meret Herdick
• Thomas E. Mayer
• Otto W. Witte
• Robert Steinbach

There is a growing demand for reliable biomarkers to monitor disease progression in Amyotrophic Lateral Sclerosis (ALS) that also take the heterogeneity of ALS into account. In this study, we explored the association between Magnetic Resonance Imaging (MRI)-derived measures of cortical thickness (CT) and subcortical grey matter (GM) volume with D50 model parameters. T1-weighted MRI images of 72 Healthy Controls (HC) and 100 patients with ALS were analyzed using Surface-based Morphometry for cortical structures and Voxel-based Morphometry for subcortical Region-Of-Interest analyses using the Computational Anatomy Toolbox (CAT12). In Inter-group contrasts, these parameters were compared between patients and HC. Further, the D50 model was used to conduct subgroup-analyses, dividing patients by a) Phase of disease covered at the time of MRI-scan and b) individual overall disease aggressiveness. Finally, correlations between GM and D50 model-derived parameters were examined. Inter-group analyses revealed ALS-related cortical thinning compared to HC located mainly in frontotemporal regions and a decrease in GM volume in the left hippocampus and amygdala. A comparison of patients in different phases showed further cortical and subcortical GM atrophy along with disease progression. Correspondingly, regression analyses identified negative correlations between cortical thickness and individual disease covered. However, there were no differences in CT and subcortical GM between patients with low and high disease aggressiveness. By application of the D50 model, we identified correlations between cortical and subcortical GM atrophy and ALS-related functional disability, but not with disease aggressiveness. This qualifies CT and subcortical GM volume as biomarkers representing individual disease covered to monitor therapeutic interventions in ALS.

AIIM Journal 2021 Journal Article

Automated emotion classification in the early stages of cortical processing: An MEG study

• Mina Kheirkhah
• Stefan Brodoehl
• Lutz Leistritz
• Theresa Götz
• Philipp Baumbach
• Ralph Huonker
• Otto W. Witte
• Carsten M. Klingner

Purpose Here we aimed to automatically classify human emotion earlier than is typically attempted. There is increasing evidence that the human brain differentiates emotional categories within 100–300 ms after stimulus onset. Therefore, here we evaluate the possibility of automatically classifying human emotions within the first 300 ms after the stimulus and identify the time-interval of the highest classification performance. Methods To address this issue, MEG signals of 17 healthy volunteers were recorded in response to three different picture stimuli (pleasant, unpleasant, and neutral pictures). Six Linear Discriminant Analysis (LDA) classifiers were used based on two binary comparisons (pleasant versus neutral and unpleasant versus neutral) and three different time-intervals (100–150 ms, 150–200 ms, and 200–300 ms post-stimulus). The selection of the feature subsets was performed by Genetic Algorithm and LDA. Results We demonstrated significant classification performances in both comparisons. The best classification performance was achieved with a median AUC of 0. 83 (95 %- CI [0. 71; 0. 87]) classifying brain responses evoked by unpleasant and neutral stimuli within 100–150 ms, which is at least 850 ms earlier than attempted by other studies. Conclusion Our results indicate that using the proposed algorithm, brain emotional responses can be significantly classified at very early stages of cortical processing (within 300 ms). Moreover, our results suggest that emotional processing in the human brain occurs within the first 100–150 ms.

YNIMG Journal 2021 Journal Article

Experience-dependent structural plasticity in the adult brain: How the learning brain grows

• Silvio Schmidt
• Sidra Gull
• Karl-Heinz Herrmann
• Marcus Boehme
• Andrey Irintchev
• Anja Urbach
• Jürgen R. Reichenbach
• Carsten M. Klingner

Volumetric magnetic resonance imaging studies have shown that intense learning can be associated with grey matter volume increases in the adult brain. The underlying mechanisms are poorly understood. Here we used monocular deprivation in rats to analyze the mechanisms underlying use-dependent grey matter increases. Optometry for quantification of visual acuity was combined with volumetric magnetic resonance imaging and microscopic techniques in longitudinal and cross-sectional studies. We found an increased spatial vision of the open eye which was associated with a transient increase in the volumes of the contralateral visual and lateral entorhinal cortex. In these brain areas dendrites of neurons elongated, and there was a strong increase in the number of spines, the targets of synapses, which was followed by spine maturation and partial pruning. Astrocytes displayed a transient pronounced swelling and underwent a reorganization of their processes. The use-dependent increase in grey matter corresponded predominantly to the swelling of the astrocytes. Experience-dependent increase in brain grey matter volume indicates a gain of structure plasticity with both synaptic and astrocyte remodeling.

YNICL Journal 2021 Journal Article

Patterns of grey and white matter changes differ between bulbar and limb onset amyotrophic lateral sclerosis

• Robert Steinbach
• Tino Prell
• Nayana Gaur
• Annekathrin Roediger
• Christian Gaser
• Thomas E. Mayer
• Otto W. Witte
• Julian Grosskreutz

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a high heterogeneity in patients' disease course. Patients with bulbar onset of symptoms (b-ALS) have a poorer prognosis than patients with limb onset (l-ALS). However, neuroimaging correlates of the assumed biological difference between b-ALS and l-ALS may have been obfuscated by patients' diversity in the disease course. We conducted Voxel-Based-Morphometry (VBM) and Tract-Based-Spatial-Statistics (TBSS) in a group of 76 ALS patients without clinically relevant cognitive deficits. The subgroups of 26 b-ALS and 52 l-ALS patients did not differ in terms of disease Phase or disease aggressiveness according to the D50 progression model. VBM analyses showed widespread ALS-related changes in grey and white matter, that were more pronounced for b-ALS. TBSS analyses revealed that b-ALS was predominantly characterized by frontal fractional anisotropy decreases. This demonstrates a higher degree of neurodegenerative burden for the group of b-ALS patients in comparison to l-ALS. Correspondingly, higher bulbar symptom burden was associated with right-temporal and inferior-frontal grey matter density decreases as well as fractional anisotropy decreases in inter-hemispheric and long association tracts. Contrasts between patients in Phase I and Phase II further revealed that b-ALS was characterized by an early cortical pathology and showed a spread only outside primary motor regions to frontal and temporal areas. In contrast, l-ALS showed ongoing structural integrity loss within primary motor-regions until Phase II. We therefore provide a strong rationale to treat both onset types of disease separately in ALS studies.

YNICL Journal 2020 Journal Article

Applying the D50 disease progression model to gray and white matter pathology in amyotrophic lateral sclerosis

• Robert Steinbach
• Meerim Batyrbekova
• Nayana Gaur
• Annika Voss
• Beatrice Stubendorff
• Thomas E. Mayer
• Christian Gaser
• Otto W. Witte

Therapeutic management and research in Amyotrophic Laterals Sclerosis (ALS) have been limited by the substantial heterogeneity in progression and anatomical spread that are endemic of the disease. Neuroimaging biomarkers represent powerful additions to the current monitoring repertoire but have yielded inconsistent associations with clinical scores like the ALS functional rating scale. The D50 disease progression model was developed to address limitations with clinical indices and the difficulty obtaining longitudinal data in ALS. It yields overall disease aggressiveness as time taken to reach halved functionality (D50); individual disease covered in distinct phases; and calculated functional state and calculated functional loss as acute descriptors of local disease activity. It greatly reduces the noise of the ALS functional rating scale and allows the comparison of highly heterogeneous disease and progression subtypes. In this study, we performed Voxel-Based Morphometry for 85 patients with ALS (60.1 ± 11.5 years, 36 female) and 62 healthy controls. Group-wise comparisons were performed separately for gray matter and white matter using ANCOVA testing with threshold-free cluster enhancement. ALS-related widespread gray and white matter density decreases were observed in the bilateral frontal and temporal lobes (p < 0.001, family-wise error corrected). We observed a progressive spread of structural alterations along the D50-derived phases, that were primarily located in frontal, temporal and occipital gray matter areas, as well as in supratentorial neuronal projections (p < 0.001 family-wise error corrected). ALS patients with higher overall disease aggressiveness (D50 < 30 months) showed a distinct pattern of supratentorial white matter density decreases relative to patients with lower aggressiveness; no significant differences were observed for gray matter density (p < 0.001 family-wise error corrected). The application of the D50 disease progression model separates measures of disease aggressiveness from disease accumulation. It revealed a strong correlation between disease phases and in-vivo measures of cerebral structural integrity. This study underscores the proposed corticofugal spread of cerebral pathology in ALS. We recommend application of the D50 model in studies linking clinical data with neuroimaging correlates.

YNIMG Journal 2016 Journal Article

Column-like Ca2+ clusters in the mouse neonatal neocortex revealed by three-dimensional two-photon Ca2+ imaging in vivo

• Michael Kummer
• Knut Kirmse
• Chuanqiang Zhang
• Jens Haueisen
• Otto W. Witte
• Knut Holthoff

Neuronal network activity in the developing brain is generated in a discontinuous manner. In the visual cortex during the period of physiological blindness of immaturity, this activity mainly comprises retinally triggered spindle bursts or Ca2+ clusters thought to contribute to the activity-dependent construction of cortical circuits. In spite of potentially important developmental functions, the spatial structure of these activity patterns remains largely unclear. In order to address this issue, we here used three-dimensional two-photon Ca2+ imaging in the visual cortex of neonatal mice at postnatal days (P) 3–4 in vivo. Large-scale voxel imaging covering a cortical depth of 200μm revealed that Ca2+ clusters, identified as spindle bursts in simultaneous extracellular recordings, recruit cortical glutamatergic neurons of the upper cortical plate (CP) in a column-like manner. Specifically, the majority of Ca2+ clusters exhibit prominent horizontal confinement and high intra-cluster density of activation involving the entire depth of the upper CP. Moreover, using simultaneous Ca2+ imaging from hundreds of neurons at single-cellular resolution, we demonstrate that the degree of neuronal co-activation within Ca2+ clusters displays substantial heterogeneity. We further provide evidence that co-activated cells within Ca2+ clusters are spatially distributed in a non-stochastic manner. In summary, our data support the conclusion that dense coding in the form of column-like Ca2+ clusters is a characteristic property of network activity in the developing visual neocortex. Such knowledge is expected to be relevant for a refined understanding of how specific spatiotemporal characteristics of early network activity instruct the development of cortical circuits.

YNIMG Journal 2016 Journal Article

Modality-independent reduction mechanisms of primary sensory evoked fields in a one-back task

• David Hanke
• Ralph Huonker
• Thomas Weiss
• Otto W. Witte
• Theresa Götz

Attentional modulation of early, primary sensory components is still a topic of debate, as studies have produced conflicting results concerning the existence of a modulation within the primary somatosensory cortex and its direction. We previously showed that attention to tactile stimuli in a stream with visual stimuli leads to a reduction of primary somatosensory components when discrimination of different stimulus locations is requested. The question arises whether this effect is universal and independent from the distracting or attended modality. To test this, we compared the magnitude of primary somatosensory evoked fields (somatosensory P50m) in a one-back task after tactile finger stimulation during attention to tactile stimuli vs. auditory distraction in 28 volunteers. In comparison to acoustic distraction, we found a significantly decreased primary somatosensory activity when attending to tactile stimuli. Strikingly, similar results were produced within the auditory modality: when attention was focused on acoustic targets, primary auditory (auditory P50m) fields were lower as compared to the situation when attention was directed to the tactile stimulation. Our results clearly indicate that the type of task, independent from the modality, is actually the crucial factor for the direction of modulation of early sensory components by attention. Therefore, our finding of reduced primary sensory components in a discrimination task represents a universal effect independent from the distracting or attended modality.

YNIMG Journal 2015 Journal Article

Parallel processing of somatosensory information: Evidence from dynamic causal modeling of MEG data

• Carsten M. Klingner
• Stefan Brodoehl
• Ralph Huonker
• Theresa Götz
• Lydia Baumann
• Otto W. Witte

The advent of methods to investigate network dynamics has led to discussion of whether somatosensory inputs are processed in serial or in parallel. Both hypotheses are supported by DCM analyses of fMRI studies. In the present study, we revisited this controversy using DCM on magnetoencephalographic (MEG) data during somatosensory stimulation. Bayesian model comparison was used to allow for direct inference on the processing stream. Additionally we varied the duration of the time-window of analyzed data after the somatosensory stimulus. This approach allowed us to explore time dependent changes in the processing stream of somatosensory information and to evaluate the consistency of results. We found that models favoring a parallel processing route best describe neural activities elicited by somatosensory stimuli. This result was consistent for different time-windows. Although it is assumed that the majority of somatosensory information is delivered to the SI, the current results indicate that at least a small part of somatosensory information is delivered in parallel to the SII. These findings emphasize the importance of data analysis with high temporal resolution.

YNICL Journal 2014 Journal Article

Disrupted functional connectivity of the default mode network due to acute vestibular deficit

• Carsten M. Klingner
• Gerd F. Volk
• Stefan Brodoehl
• Otto W. Witte
• Orlando Guntinas-Lichius

Vestibular neuritis is defined as a sudden unilateral partial failure of the vestibular nerve that impairs the forwarding of vestibular information from the labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural instability with a tendency toward ipsilesional falls. Although vestibular neuritis is a common disease, the central mechanisms to compensate for the loss of precise vestibular information remain poorly understood. It was hypothesized that symptoms following acute vestibular neuritis originate from difficulties in the processing of diverging sensory information between the responsible brain networks. Accordingly an altered resting activity was shown in multiple brain areas of the task-positive network. Because of the known balance between the task-positive and task-negative networks (default mode network; DMN) we hypothesize that also the DMN is involved. Here, we employ functional magnetic resonance imaging (fMRI) in the resting state to investigate changes in the functional connectivity between the DMN and task-positive networks, in a longitudinal design combined with measurements of caloric function. We demonstrate an initially disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that the disturbed connectivity between the default mode network and particular parts of the task-positive network might be related to a sustained utilization of processing capacity by diverging sensory information. The current results provide some insights into mechanisms of central compensation following an acute vestibular deficit and the importance of the DMN in this disease.

YNICL Journal 2014 Journal Article

The effects of deefferentation without deafferentation on functional connectivity in patients with facial palsy

• Carsten M. Klingner
• Gerd F. Volk
• Stefan Brodoehl
• Otto W. Witte
• Orlando Guntinas-Lichius

Cerebral plasticity includes the adaptation of anatomical and functional connections between parts of the involved brain network. However, little is known about the network dynamics of these connectivity changes. This study investigates the impact of a pure deefferentation, without deafferentation or brain damage, on the functional connectivity of the brain. To investigate this issue, functional MRI was performed on 31 patients in the acute state of Bell's palsy (idiopathic peripheral facial nerve palsy). All of the patients performed a motor paradigm to identify seed regions involved in motor control. The functional connectivity of the resting state within this network of brain regions was compared to a healthy control group. We found decreased connectivity in patients, mainly in areas responsible for sensorimotor integration and supervision (SII, insula, thalamus and cerebellum). However, we did not find decreased connectivity in areas of the primary or secondary motor cortex. The decreased connectivity for the SII and the insula significantly correlated to the severity of the facial palsy. Our results indicate that a pure deefferentation leads the brain to adapt to the current compromised state during rest. The motor system did not make a major attempt to solve the sensorimotor discrepancy by modulating the motor program.

YNIMG Journal 2014 Journal Article

You’d Better Think Twice: Post-Decision Perceptual Confidence

• Raphael Hirtz
• Thomas Weiss
• Otto W. Witte

Current findings suggest that confidence emerges only after decision making. However, the temporal and neural dynamics of the emergence of post-decision confidence – a metacognitive judgement – are not fully explored. To gain insight into the dynamics of post-decision confidence processing and to disentangle the processes underlying confidence judgements and decision making, we applied a tactile discrimination task during functional magnetic resonance imaging (fMRI). Our results revealed that reaction times to post-decision confidence depend on the level of confidence, suggesting that post-decision confidence in a perceptual choice is not processed in parallel to perceptual decision making. Moreover, we demonstrated by the parametric analysis of fMRI data that post-decisionally modelled confidence processing can be distinguished from processes related to decision making through anatomical location and through the pattern of neural activity. In contrast to perceptual decision making, post-decision confidence appears to be strictly allocated to a prefrontal network of brain regions, primarily the anterior and dorsolateral prefrontal cortex, areas that have been related to metacognition. Moreover, the processes underlying decision making and post-decision confidence may share recruitment of the dorsolateral prefrontal cortex, although the former probably has distinct functions with regard to processing of perceptual choices and post-decision confidence. Thus, this is the first fMRI study to disentangle the processes underlying post-decision confidence and decision making on behavioural, neuroanatomical, and neurofunctional levels. With regard to the temporal evolution of post-decision confidence, results of the present study provide strong support for the most recent theoretical models of human perceptual decision making, and thus provide implications for investigating confidence in perceptual paradigms.

YNICL Journal 2013 Journal Article

Impaired evoked and resting-state brain oscillations in patients with liver cirrhosis as revealed by magnetoencephalography

• Theresa Götz
• Ralph Huonker
• Cornelia Kranczioch
• Philipp Reuken
• Otto W. Witte
• Albrecht Günther
• Stefan Debener

A number of studies suggest that the clinical manifestation of neurological deficits in hepatic encephalopathy results from pathologically synchronized neuronal oscillations and altered oscillatory coupling. In the present study spontaneous and evoked oscillatory brain activities were analyzed jointly with established behavioral measures of altered visual oscillatory processing. Critical flicker and fusion frequencies (CFF, FUF) were measured in 25 patients diagnosed with liver cirrhosis and 30 healthy controls. Magnetoencephalography (MEG) data were collected at rest and during a visual task employing repetitive stimulation. Resting MEG and evoked fields were analyzed. CFF and FUF were found to be reduced in patients, providing behavioral evidence for deficits in visual oscillatory processing. These alterations were found to be related to resting brain activity in patients, namely that the lower the dominant MEG frequency at rest, the lower the CFF and FUF. An analysis of evoked fields at sensor level indicated that in comparison to normal controls, patients were not able to dynamically adapt to flickering visual stimulation. Evoked activity was also analyzed based on independent components (ICs) derived by independent component analysis. The similarity between the shape of each IC and an artificial sine function representing the stimulation frequency was tested via magnitude squared coherence. In controls, we observed a small number of components that correlated strongly with the sine function and a high number of ICs that did not correlate with the sine function. Interestingly, patient data were characterized by a high number of moderately correlating components. Taken together, these results indicate a fundamental divergence of the cerebral resonance activity in cirrhotic patients.

YNIMG Journal 2012 Journal Article

Deformation-based brain morphometry in rats

• Christian Gaser
• Silvio Schmidt
• Martin Metzler
• Karl-Heinz Herrmann
• Ines Krumbein
• Jürgen R. Reichenbach
• Otto W. Witte

Magnetic resonance imaging (MRI)-based morphometry provides in vivo evidence for macro-structural plasticity of the brain. Experiments on small animals using automated morphometric methods usually require expensive measurements with ultra-high field dedicated animal MRI systems. Here, we developed a novel deformation-based morphometry (DBM) tool for automated analyses of rat brain images measured on a 3-Tesla clinical whole body scanner with appropriate coils. A landmark-based transformation of our customized reference brain into the coordinates of the widely used rat brain atlas from Paxinos and Watson (Paxinos Atlas) guarantees the comparability of results to other studies. For cross-sectional data, we warped images onto the reference brain using the low-dimensional nonlinear registration implemented in the MATLAB software package SPM8. For the analysis of longitudinal data sets, we chose high-dimensional registrations of all images of one data set to the first baseline image which facilitate the identification of more subtle structural changes. Because all deformations were finally used to transform the data into the space of the Paxinos Atlas, Jacobian determinants could be used to estimate absolute local volumes of predefined regions-of-interest. Pilot experiments were performed to analyze brain structural changes due to aging or photothrombotically-induced cortical stroke. The results support the utility of DBM based on commonly available clinical whole-body scanners for highly sensitive morphometric studies on rats.

YNIMG Journal 2012 Journal Article

Magnetic resonance imaging of the mouse visual pathway for in vivo studies of degeneration and regeneration in the CNS

• Ronny Haenold
• Karl-Heinz Herrmann
• Silvio Schmidt
• Jürgen R. Reichenbach
• Karl-Friedrich Schmidt
• Siegrid Löwel
• Otto W. Witte
• Falk Weih

Traditionally, depiction of isolated CNS fiber tracts is achieved by histological post mortem studies. As a tracer-dependent strategy, the calcium analog manganese has proved valuable for in vivo imaging of CNS trajectories, particularly in rats. However, adequate protocols in mice are still rare. To take advantage of the numerous genetic mouse mutants that are available to study axonal de- and regeneration processes, a MnCl2-based protocol for high-resolution contrast-enhanced MRI (MEMRI) of the visual pathway in mice acquired on a widely used clinical 3Tesla scanner was established. Intravitreal application of MnCl2 significantly enhanced T1-weighted contrast and signal intensity along the retino-petal projection enabling its reconstruction in a 3D mode from a maximum intensity projection (MIP) calculated dataset. In response to crush injury of the optic nerve, axonal transport of MnCl2 was diminished and completely blocked proximal and distal to the lesion site, respectively. Conditions of Wallerian degeneration after acute optic nerve injury accelerated Mn2+-enhanced signal fading in axotomized projection areas between 12 and 24h post-injury. In long-term regeneration studies 12months after optic nerve injury, the MRI protocol proved highly sensitive and discriminated animals with rare spontaneous axonal regrowth from non-regenerating specimens. Also, structural MRI aspects shared high correlation with histological results in identical animals. Moreover, in a model of chronic neurodegeneration in p50/NF-κB-deficient mice, MnCl2-based neuron-axonal tracing supported by heat map imaging indicated neuropathy of the visual pathway due to atrophy of optic nerve fiber projections. Toxic effects of MnCl2 at MRI contrast-relevant dosages in repetitive administration protocols were ruled out by histological and optometric examinations. At higher dosages, photoreceptors, not retinal ganglion cells, turned out as most susceptible to the well-known toxicity of MnCl2. Our data accentuate in vivo MEMRI of the murine visual system as a highly specific and sensitive strategy to uncover axonal degeneration and restoration processes, even in a functional latent state. We expect MEMRI to be promising for future applications in longitudinal studies on development, aging, or regeneration of CNS projections in mouse models mimicking human CNS pathologies.

YNIMG Journal 2011 Journal Article

Influences of negative BOLD responses on positive BOLD responses

• Carsten M. Klingner
• Kerstin Ebenau
• Caroline Hasler
• Stefan Brodoehl
• Yvonne Görlich
• Otto W. Witte

Understanding possible interactions between blood oxygenation level-dependent (BOLD) responses is critical for model-based analyses and the interpretation of experiments that deal with stimuli presented close together in time. Such interactions are well documented in the case of successive positive BOLD responses. However, the influence that a stimulus-induced, negative BOLD response exerts on a subsequent positive BOLD response has yet to be investigated and is the focus of the current study. We performed functional magnetic resonance imaging on 10 healthy subjects during bilateral electrical median nerve stimulation using five different time intervals between left- and right-sided stimuli. We found an acute interruption of the ongoing negative BOLD response at the onset of the positive BOLD response. Different parameters characterizing the positive BOLD response were estimated. There was no impact of the preceding negative BOLD response on the parameters describing the subsequent positive BOLD response. These findings indicate that the underlying mechanisms for negative and positive BOLD responses do not engage parallel processes. We hypothesize that the negative BOLD response is caused by a decreased release of the same vasodilatative agents that evoke the positive BOLD response. Additionally, our results demonstrate that there is no need to adjust the model of a positive BOLD response due to a preceding negative BOLD response in the same brain area.

YNIMG Journal 2010 Journal Article

Dependence of the negative BOLD response on somatosensory stimulus intensity

• Carsten M. Klingner
• Caroline Hasler
• Stefan Brodoehl
• Otto W. Witte

The primary somatosensory cortex (SI) has been shown to encode the intensity of a stimulus applied to the contralateral side of the body. Recent studies have demonstrated that ipsilateral SI is also involved in the processing of somatosensory information. In this study, we investigated the dependence of the negative BOLD response in ipsilateral SI on the intensity of somatosensory stimulation. Functional MRI was performed in 12 healthy subjects during electrical median nerve stimulation at four different intensities. A monotonic relationship between stimulus intensity and the strength of the negative BOLD response in ipsilateral SI was found. Additionally, a psychophysiological experiment revealed tight coupling between the stimulus intensity applied to one hand and increased perceptual threshold of the other hand. These findings indicate a stimulus intensity-dependent inhibition of ipsilateral SI.

YNIMG Journal 2008 Journal Article

Behavioral correlates of negative BOLD signal changes in the primary somatosensory cortex

• Andreas Kastrup
• Jürgen Baudewig
• Sonja Schnaudigel
• Ralph Huonker
• Lars Becker
• Jan Martin Sohns
• Peter Dechent
• Carsten Klingner

Functional magnetic resonance imaging (fMRI) hypothesis testing based on the blood oxygenation level dependent (BOLD) contrast mechanism typically involves a search for a positive effect during a specific task relative to a control state. However, aside from positive BOLD signal changes there is converging evidence that neuronal responses within various cortical areas also induce negative BOLD signals. Although it is commonly believed that these negative BOLD signal changes reflect suppression of neuronal activity direct evidence for this assumption is sparse. Since the somatosensory system offers the opportunity to quantitatively test sensory function during concomitant activation and has been well-characterized with fMRI in the past, the aim of this study was to determine the functional significance of ipsilateral negative BOLD signal changes during unilateral sensory stimulation. For this, we measured BOLD responses in the somatosensory system during unilateral electric stimulation of the right median nerve and additionally determined the current perception threshold of the left index finger during right-sided electrical median nerve stimulation as a quantitative measure of sensory function. As expected, positive BOLD signal changes were observed in the contralateral primary and bilateral secondary somatosensory areas, whereas a decreased BOLD signal was observed in the ipsilateral primary somatosensory cortex (SI). The negative BOLD signal changes were much more spatially extensive than the representation of the hand area within the ipsilateral SI. The negative BOLD signal changes in the area of the index finger highly correlated with an increase in current perception thresholds of the contralateral, unstimulated finger, thus supporting the notion that the ipsilateral negative BOLD response reflects a functionally effective inhibition in the somatosensory system.

YNIMG Journal 2001 Journal Article

Delayed differential alterations in human brain volume in affected and remote brain areas after cerebral infarction measured intraindividually in vivo by 3D-MRI volumetry

• Matthias Kraemer
• Thorsten Schormann
• Peter Bi
• Georg Hagemann
• Karl Zilles
• Hans-Joachim Freund
• Rüdiger J. Seitz
• Otto W. Witte