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Cornelius Weiller

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25 papers
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25

YNICL Journal 2024 Journal Article

The connection of motor improvement after deep brain stimulation in Parkinson’s disease and microstructural integrity of the substantia nigra and subthalamic nucleus

  • Marco G. Hermann
  • Nils Schröter
  • Alexander Rau
  • Marco Reisert
  • Nadja Jarc
  • Michel Rijntjes
  • Jonas A. Hosp
  • Peter C. Reinacher

BACKGROUND: Nigrostriatal microstructural integrity has been suggested as a biomarker for levodopa response in Parkinson's disease (PD), which is a strong predictor for motor response to deep brain stimulation (DBS) of the subthalamic nucleus (STN). This study aimed to explore the impact of microstructural integrity of the substantia nigra (SN), STN, and putamen on motor response to STN-DBS using diffusion microstructure imaging. METHODS: and records of motor improvement available. RESULTS: The association between a poorer DBS-response and increased free interstitial fluid showed notable effect sizes (rho > |0.4|) in SN and STN, but not in putamen. However, this did not reach significance after Bonferroni correction and controlling for sex and age. CONCLUSION: Microstructural integrity of SN and STN are potential biomarkers for the prediction of therapy efficacy following STN-DBS, but further studies are required to confirm these associations.

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.

YNIMG Journal 2022 Journal Article

The dual-loop model for combining external and internal worlds in our brain

  • Cornelius Weiller
  • Marco Reisert
  • Volkmar Glauche
  • Mariachristina Musso
  • Michel Rijntjes

Intelligible communication with others as well as covert conscious thought requires us to combine a representation of the external world with inner abstract concepts. Interaction with the external world through sensory perception and motor execution is arranged as sequences in time and space, whereas abstract thought and invariant categories are independent of the moment. Using advanced MRI-based fibre tracking on high resolution data from 183 participants in the Human Connectome Project, we identified two large supramodal systems comprising specific cortical regions and their connecting fibre tracts; a dorsal one for processing of sequences in time and space, and a ventral one for concepts and categories. We found that two hub regions exist in the executive front and the perceptive back of the brain where these two cognitive processes converge, constituting a dual-loop model. The hubs are located in the onto- and phylogenetically youngest regions of the cortex. We propose that this hub feature serves as the neural substrate for the more abstract sense of syntax in humans, i.e. for the system populating sequences with content in all cognitive domains. The hubs bring together two separate systems (dorsal and ventral) at the front and the back of the brain and create a closed-loop. The closed-loop facilitates recursivity and forethought, which we use twice; namely, for communication with others about things that are not there and for covert thought.

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.

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.

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.

YNICL Journal 2017 Journal Article

Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder

  • Thomas Hassa
  • Alexandra Sebastian
  • Joachim Liepert
  • Cornelius Weiller
  • Roger Schmidt
  • Oliver Tüscher

Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

YNIMG Journal 2016 Journal Article

Age differences in behavioral and neural correlates of proactive interference: Disentangling the role of overall working memory performance

  • Sandra V. Loosli
  • Benjamin Rahm
  • Josef M. Unterrainer
  • Irina Mader
  • Cornelius Weiller
  • Christoph P. Kaller

Reliable performance in working memory (WM) critically depends on the ability to resist proactive interference (PI) from previously relevant WM contents. Both WM performance and PI susceptibility are subject to cognitive decline at older adult age. However, the behavioral and neural processes underlying these co-evolving developmental changes and their potential interdependencies are not yet understood. Here, we investigated PI using a recent-probes WM paradigm and functional MRI in a cross-sectional sample of younger (n=18, 10 female, 23. 4±2. 7years) and older adults (n=18, 10 female, 70. 2±2. 7years). As expected, older adults showed lower WM performance and higher PI susceptibility than younger adults. Resolution of PI activated a mainly bilateral frontal network across all participants. Significant interactions with age indicated reduced neural activation in older adults for PI resolution. A second analysis in a selection of younger and older adults (n=12 each) with matched WM performance also revealed significant differences in PI between both age groups and – on a descriptive level – again a hypo-activation of the older adults' PI network. But the differential effect of age on the neural PI effects did not reach significance in this smaller sample most likely to the reduced statistical power. However, given the highly similar patterns in both the overall and the WM-matched samples, we propose that the hypo-activation of the PI network in the older adults may not be attributable to age-related differences in overall WM performance, hence suggesting that higher PI susceptibility in older adult age does not directly depend on their lower WM performance.

YNIMG Journal 2015 Journal Article

A single dual-stream framework for syntactic computations in music and language

  • Mariacristina Musso
  • Cornelius Weiller
  • Andreas Horn
  • Volkmer Glauche
  • Roza Umarova
  • Jürgen Hennig
  • Albrecht Schneider
  • Michel Rijntjes

This study is the first to compare in the same subjects the specific spatial distribution and the functional and anatomical connectivity of the neuronal resources that activate and integrate syntactic representations during music and language processing. Combining functional magnetic resonance imaging with functional connectivity and diffusion tensor imaging-based probabilistic tractography, we examined the brain network involved in the recognition and integration of words and chords that were not hierarchically related to the preceding syntax; that is, those deviating from the universal principles of grammar and tonal relatedness. This kind of syntactic processing in both domains was found to rely on a shared network in the left hemisphere centered on the inferior part of the inferior frontal gyrus (IFG), including pars opercularis and pars triangularis, and on dorsal and ventral long association tracts connecting this brain area with temporo-parietal regions. Language processing utilized some adjacent left hemispheric IFG and middle temporal regions more than music processing, and music processing also involved right hemisphere regions not activated in language processing. Our data indicate that a dual-stream system with dorsal and ventral long association tracts centered on a functionally and structurally highly differentiated left IFG is pivotal for domain–general syntactic competence over a broad range of elements including words and chords.

YNIMG Journal 2015 Journal Article

The ventral fiber pathway for pantomime of object use

  • Magnus-Sebastian Vry
  • Linda C. Tritschler
  • Farsin Hamzei
  • Michel Rijntjes
  • Christoph P. Kaller
  • Markus Hoeren
  • Roza Umarova
  • Volkmar Glauche

The current concept of a dual loop system of brain organization predicts a domain-general dual-pathway architecture involving dorsal and ventral fiber connections. We investigated if a similar dichotomy of brain network organization applies for pantomime (P) and imitation of meaningless gestures (I). Impairments of these tasks occur after left hemispheric brain lesions causing apraxia. Isolated impairments and double-dissociations point towards an anatomical segregation. Frontal and parietal areas seem to contribute differently. A special role of the inferior frontal gyrus and underlying fiber pathways was suggested recently. Using a combined fMRI/DTI-approach, we compared the fiber pathway architecture of left hemispheric frontal, temporal and parietal network components of pantomime and imitation. Thereby, we separated object effects from pantomime-specific effects. P and I both engage a fronto-temporo-parietal network of cortical areas interconnected by a dorsal fiber system (superior longitudinal fascicle) for direct sensory–motor interactions. The pantomime-specific effect additionally involved the triangular part of the inferior frontal gyrus, the middle temporal gyrus, the inferior parietal cortex and the intraparietal sulcus, interconnected by ventral fibers of the extreme capsule, likely related to higher-order conceptual and semantic operations. We discuss this finding in the context of the dual loop model and recent anatomical concepts.

YNIMG Journal 2012 Journal Article

Linking planning performance and gray matter density in mid-dorsolateral prefrontal cortex: Moderating effects of age and sex

  • Christoph P. Kaller
  • Katharina Heinze
  • Irina Mader
  • Josef M. Unterrainer
  • Benjamin Rahm
  • Cornelius Weiller
  • Lena Köstering

Planning of behavior relies on the integrity of the mid-dorsolateral prefrontal cortex (mid-dlPFC). Yet, only indirect evidence exists on the association of protracted maturation of dlPFC and continuing gains in planning performance post adolescence. Here, gray matter density of mid-dlPFC in young, healthy adults (18–32years) was regressed onto performance on the Tower of London planning task while accounting for moderating effects of age and sex on this interrelation. Multiple regression analysis revealed an association of planning performance and mid-dlPFC gray matter density that was especially strong in late adolescence and early twenties. As expected, for males better planning performance was linked to reduced gray matter density of mid-dlPFC, possibly due to maturational processes such as synaptic pruning. Most surprisingly, females showed an inverted, positive interrelation of planning performance and mid-dlPFC gray matter density, indicating that sexually dimorphic development of dlPFC continues during early adulthood. Age and sex are hence important moderators of the link between planning performance and gray matter density in mid-dlPFC. Consequently, the assessment of moderator effects in regression designs can significantly enhance understanding of brain-behavior relationships.

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.

YNIMG Journal 2009 Journal Article

The separation of processing stages in a lexical interference fMRI-paradigm

  • Stefanie Abel
  • Katharina Dressel
  • Ruth Bitzer
  • Dorothee Kümmerer
  • Irina Mader
  • Cornelius Weiller
  • Walter Huber

In picture–word interference paradigms, the picture naming process is influenced by an additional presentation of linguistic distractors. Naming response times (RTs) are speeded (facilitation) by associatively-related and phonologically-related words when compared to unrelated words, while they are slowed down by categorically-related words (inhibition), given that distractor onsets occur at appropriate stimulus onset asynchronies (SOAs). In the present study with healthy subjects, we for the first time integrated all four auditorily presented distractor types into a single paradigm at an SOA of −200 ms, in order to directly compare behavioral and neural interference effects between them. The behavioral study corroborated results of previous studies and revealed that associatively-related distractors speeded RTs even more than phonologically-related distractors, thereby becoming equally fast as naming without distractors. Distractors were assumed to specifically enhance activation of brain areas corresponding to processing stages as determined in a cognitive model of word production (Indefrey, P. , Levelt, W. J. M. , 2004. The spatial and temporal signatures of word production components. Cognition 92, 101–144.). Functional magnetic resonance imaging (fMRI) at 3 T revealed activation of left superior temporal gyrus exclusively for phonologically-related distractors, and activation of left or right lingual gyrus exclusively for associatively-related and categorically-related distractors, respectively. Moreover, phonologically-related distractors elicited phonological–phonetic networks, and both semantic distractors evoked areas associated with mental imagery, semantics, and episodic memory retrieval and associations. While processes involved in distractor inhibition (e. g. , conflict/competition monitoring) and high articulatory demands were observed for categorically-related distractors, priming of articulatory planning was revealed for associatively-related distractors. We conclude that activations of neural networks as obtained by the fMRI interference paradigm can be predicted from a cognitive model.

YNIMG Journal 2007 Journal Article

The effect of handedness on cortical motor activation during simple bilateral movements

  • Stefan Klöppel
  • Thilo van Eimeren
  • Volkmar Glauche
  • Anna Vongerichten
  • Alexander Münchau
  • Richard S.J. Frackowiak
  • Christian Büchel
  • Cornelius Weiller

The neuronal correlates of handedness are still poorly understood. Here we used event-related functional magnetic resonance imaging to investigate the impact of handedness on neuronal activation of the primary sensorimotor cortex, supplementary motor area and dorsal premotor cortex during simple unilateral and bilateral finger movements. In 16 right-handed and 16 left-handed individuals, we mapped changes in regional neuronal activity while participants responded to four symbolic cues presented in a pseudorandom order. According to pre-specified cues, they pressed a button with their right, left or both index fingers or withheld a response. For unilateral right index finger button presses, reaction times, motor and premotor activity were the same for both right- and left-handers. Compared with right-handers, left-handers had shorter reaction times with unilateral left index finger button presses, along with greater activation of the supplementary motor area and right frontal opercular cortex. Simultaneous bilateral compared with unilateral button presses led to a relative increase of activity in the right and left dorsal premotor cortex and the right primary sensorimotor cortex in right but not left-handers. Neither right nor left-handers showed any tendency during bilateral button presses towards faster responses with the dominant hand and the reaction times were equal in the two groups. Therefore, we conclude that the relative increase of activity in dorsal premotor and right primary sensorimotor cortices in right-handers represents a genuine difference in bimanual motor control related to handedness.

YNIMG Journal 2006 Journal Article

Implementation of visuospatial cues in response selection

  • Thilo van Eimeren
  • Thomas Wolbers
  • Alexander Münchau
  • Christian Büchel
  • Cornelius Weiller
  • Hartwig Roman Siebner

We used functional magnetic resonance imaging to examine neuronal activity reflecting the dynamic interplay of external and internal guidance of action. Participants performed a choice reaction time task based on spatial visual cues with their right and left middle and index finger. In a given trial, the cue either fully determined the motor response (no-selection) or indicated the number and location of alternative responses (selection). Compared with fully determined responses, the selection among (two to four) alternative responses activated a widespread bilateral parieto-premotor-prefrontal cortical network along with the cerebellum. Within this network, task-related activity patterns allowed to delineate two sets of brain areas. In the anterior part of rostral dorsal premotor cortex (PMd), the rostral cingulate and supplementary motor area and the right dorsolateral prefrontal cortex, the increase in activity was independent of spatially defined restrictions. In contrast, there was an additional increase in activity in the posterior part of rostral PMd, superior parietal lobule and parieto-occipital sulcus bilaterally as well as in the right anterior intraparietal sulcus, when the visuospatial cue imposed specific constraints on response selection. We propose that the latter set of dorsal parieto-frontal areas subserves rapid implementation of spatial information during visually guided response selection.

YNIMG Journal 2006 Journal Article

The surround inhibition determines therapy-induced cortical reorganization

  • Joachim Liepert
  • Kerstin Haevernick
  • Cornelius Weiller
  • Anne Barzel

Rehabilitation can induce cortical reorganization in chronic stroke patients. In this study we investigated the mechanisms underlying treatment-associated plasticity. Eight patients with a stroke >6 months earlier participated in a 4-week period of physiotherapy based on a forced use concept. Before and after treatment, focal transcranial magnetic stimulation over the affected hemisphere was used to assess the motor output map of the paretic first dorsal interosseous muscle. Using a paired pulse paradigm, intracortical inhibition was investigated at the center of the cortical output map (CoG) and one cm anterior, posterior, lateral and medial of that position. Motor function was evaluated with the Motor Activity Log and the Wolf Motor Function Test. After therapy, the cortical representation size of the affected hand muscle was increased. In each patient, the CoG moved in the direction where intracortical inhibition had been lowest prior to therapy. Significant correlations were found between motor function tests and changes of output map size and CoG shifts, respectively. We conclude that treatment-associated cortical reorganization is influenced by the distribution of inhibitory properties within the representation area prior to therapy, since the CoG moved in the direction of lowest inhibition. The correlations between motor functions and electrophysiological results indicate a functional relevance of the observed reorganization pattern.

YNIMG Journal 2006 Journal Article

Two different reorganization patterns after rehabilitative therapy: An exploratory study with fMRI and TMS

  • Farsin Hamzei
  • Joachim Liepert
  • Christian Dettmers
  • Cornelius Weiller
  • Michel Rijntjes

We used two complementary methods to investigate cortical reorganization in chronic stroke patients during treatment with a defined motor rehabilitation program. BOLD (“blood oxygenation level dependent”) sensitive functional magnetic resonance imaging (fMRI) and intracortical inhibition (ICI) and facilitation (ICF) measured with transcranial magnetic stimulation (TMS) via paired pulse stimulation were used to investigate cortical reorganization before and after “constraint-induced movement therapy” (CI). The motor hand function improved in all subjects after CI. BOLD signal intensity changes within affected primary sensorimotor cortex (SMC) before and after CI showed a close correlation with ICI (r = 0. 93) and ICF (r = 0. 76) difference before and after therapy. Difference in number of voxels and ICI difference before and after CI also showed a close correlation (r = 0. 92) in the affected SMC over the time period of training. A single subject analysis revealed that patients with intact hand area of M1 (“the hand knob”) and its descending motor fibers (these patients revealed normal motor evoked potentials [MEP] from the affected hand) showed decreasing ipsilesional SMC activation which was paralleled by an increase in intracortical excitability. This pattern putatively reflects increasing synaptic efficiency. When M1 or its descending pyramidal tract was lesioned (MEP from the affected hand was pathologic) ipsilesional SMC activation increased, accompanied by decreased intracortical excitability. We suggest that an increase in synaptic efficiency is not possible here, which leads to reorganization with extension, shift and recruitment of additional cortical areas of the sensorimotor network. The inverse dynamic process between both complementary methods (activation in fMRI and intracortical excitability determined by TMS) over the time period of CI illustrates the value of combining methods for understanding brain reorganization.

YNIMG Journal 2004 Journal Article

Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke

  • Götz Thomalla
  • Volkmar Glauche
  • Martin A Koch
  • Christian Beaulieu
  • Cornelius Weiller
  • Joachim Röther

We used diffusion tensor imaging (DTI) to assess Wallerian degeneration of the pyramidal tract within the first 2 weeks after ischemic stroke, and correlated the extent of Wallerian degeneration with the motor deficit. Nine patients with middle cerebral artery stroke were examined 2–16 days after stroke by DTI and T2-weighted MRI. We measured fractional anisotropy (FA), averaged diffusivity (Dav), eigenvalues of the diffusion tensor and T2-weighted signal in the cerebral peduncle and compared these values between the affected and the unaffected side and between patients and six controls. FA was significantly reduced on the affected side compared to the unaffected side and compared to the control group. The largest eigenvalue was reduced, whereas the smallest eigenvalue was elevated on the affected side. There was no significant difference in T2-weighted signal and Dav. The decrease of anisotropy correlated positively with the motor deficit at the time of DTI study and 90 days after stroke. The reduction of anisotropy mirrors the disintegration of axonal structures, as it occurs in the early phase of Wallerian degeneration. DTI detects changes of water diffusion related to beginning pyramidal tract degeneration within the first 2 weeks after stroke that are not yet visible in conventional T2-weighted or orientationally averaged diffusion weighted MRI. We demonstrated for the first time a correlation of early DTI findings of pyramidal tract damage with the motor deficit. DTI can help prognosing recovery of motor function after stroke within the early subacute phase.

YNIMG Journal 2003 Journal Article

Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans

  • Tobias Bäumer
  • Rüdiger Lange
  • Joachim Liepert
  • Cornelius Weiller
  • Hartwig R Siebner
  • John C Rothwell
  • Alexander Münchau

We explored the aftereffects of two premotor 1 Hz rTMS sessions on motor cortex excitability in healthy humans. In experiment 1, 11 healthy right-handed volunteers received 20-min submotor threshold 1 Hz rTMS trains over the left premotor cortex on 2 consecutive days. Left motor cortex excitability was determined at baseline, immediately after, 30, 60, 120 min, and 24 h after each rTMS session. We measured motor thresholds, amplitudes of motor-evoked potentials, silent periods, and paired-pulse excitability at interstimulus intervals (ISI) of 3–7, 10, and 15 ms. In experiment 2, 5 volunteers received two identical rTMS trains on Days 1 and 7. Measurements were carried out on Day 1 (first rTMS train), Day 2, and Day 7 (second rTMS train). In experiment 1 there was a selective increase of paired pulse facilitation at an ISI of 7 ms after rTMS lasting for less than 30 min on Day 1. This effect was also present after rTMS on Day 2. However, it persisted for at least 2 h. In experiment 2 the same extra facilitation was induced by rTMS on Days 1 and 7 but not on Day 2. It lasted for less than 30 min on both Day 1 and Day 7. We conclude that 1 Hz premotor rTMS leads to cumulative plastic changes of intrinsic motor cortex excitability when repeated within 24 h but not after 1 week, implying the formation of memory after the first rTMS train lasting more than a day but less than a week.

YNIMG Journal 2003 Journal Article

The human action recognition system and its relationship to Broca’s area: an fMRI study

  • Farsin Hamzei
  • Michel Rijntjes
  • Christian Dettmers
  • Volkmar Glauche
  • Cornelius Weiller
  • Christian Büchel

Primate studies have identified populations of neurons that are capable of action recognition. These “mirror neurons” show spiking activity both when the monkey executes or observes a grasping movement. These neurons are located in the ventral premotor cortex, possibly the homologue of “Broca’s area” in human. This led to the speculation that action recognition and language production share a common system [Trends Neurosci. 21 (1998), 188]. To test this hypothesis, we combined an action recognition with a language production (VERB) and a grasping movement task (MOVE) by using functional magnetic resonance imaging. Action recognition-related activation was observed in the left inferior frontal gyrus and on the border between the inferior frontal gyrus and precentral gyrus (defined as IFG/PG), the ventral occipitotemporal junction, the superior and inferior parietal cortex, and in the intraparietal sulcus in the left hemisphere. An overlap of activations due to the language production, movement execution, and action recognition was found in the parietal cortex, the left inferior frontal gyrus, and the IFG-PG border (IFG/PG). The activation peaks of action recognition and verb generation were always different in single subjects, but no consistent spatial relationship was detected, in accord with the hypothesis that action recognition and language production share a common functional architecture.

YNIMG Journal 2003 Journal Article

The influence of extra- and intracranial artery disease on the BOLD signal in FMRI

  • Farsin Hamzei
  • René Knab
  • Cornelius Weiller
  • Joachim Röther

Functional MRI is based on the vascular response due to neuronal activation. The underlying mechanism of fMRI is the blood oxygenation level-dependent (BOLD) effect—a complex interplay between changes in the cerebral metabolisation rate of oxygen (CMRO2), neurovascular coupling, and the resulting hemodynamic response. An intact neurovascular coupling is essential for the detection of the BOLD signal and it seems likely that a disturbed cerebrovascular reserve capacity (CVRC) alters the BOLD response. We tested the hypothesis that extra- or intracranial artery disease influences the BOLD signal. Twenty-one patients with extra- or intracranial stenosis were studied with BOLD sensitive T2*-weighted MRI. All patients presented with transient or prolonged reversible ischemic symptoms ipsilateral to the artery disease but were asymptomatic at the time point of the MRI study. fMRI was performed employing a simple motor task (fist closure right and left). Additionally, the CVRC was assessed applying carbogen gas during serial T2*-weighted MRI for the calculation of CO2 reactivity maps of the relative signal change. Signal differences between both hemispheres were compared in individual subjects and with healthy subjects. Patients with disturbed CVRC in the CO2 reactivity maps showed either a significantly reduced (n = 5) or a negative (n = 1) BOLD signal in the affected compared to the unaffected primary sensorimotor cortex during fist closure. Patients with intact CVRC showed no significant BOLD signal differences between affected and unaffected hemisphere. Extra- or intracranial artery disease influences CVRC and consequently the BOLD signal. This observation is important for the clinical application of fMRI paradigms.

YNIMG Journal 2002 Journal Article

Negative Dip in BOLD fMRI Is Caused by Blood Flow— Oxygen Consumption Uncoupling In Humans

  • Joachim Röther
  • Rene Knab
  • Farsin Hamzei
  • Jens Fiehler
  • Jürgen R. Reichenbach
  • Christian Büchel
  • Cornelius Weiller

The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect.

YNIMG Journal 2002 Journal Article

Reduction of Excitability (“Inhibition”) in the Ipsilateral Primary Motor Cortex Is Mirrored by fMRI Signal Decreases

  • Farsin Hamzei
  • Christian Dettmers
  • Reinhard Rzanny
  • Joachim Liepert
  • Christian Büchel
  • Cornelius Weiller

Functionalmagnetic resonance imaging (fMRI) was used to investigate how focal cortical inhibition affects the blood oxygen level-dependent (BOLD) signal. Phasic low force pinch grip reduces excitability of the ipsilateral primary motor cortex. This task was used to study BOLD signal changes during inhibition. Six right-handed normal volunteers participated in the study. They were asked to perform a right-handed pinch grip repetitively at 1 Hz and 5% of their individual maximal voluntary contraction (MVC). Data were acquired with a 1. 5 Tesla Magnetom and continuous multislice T2*-weighted images. The contralateral primary motor cortex (M1) revealed an activation in the knob-shaped hand representation of the central sulcus area. More importantly, a decreased (often referred to as “negative”) BOLD signal in the ipsilateral M1 was observed. We suggest phasic low force pinch grip as a reproducible, easy model of focal inhibition. Decreased cortical excitability presents as decreased BOLD signal using fMRI.