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Frieder M Paulus,
Johannes Bedenbender,
Sören Krach,
Martin Pyka,
Axel Krug, Jens Sommer,
Miriam Mette,
Markus M Nöthen,
Stephanie H Witt,
Marcella Rietschel,
Tilo Kircher,
Andreas Jansen
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ABSTRACT: Background: Genome-wide association studies have identified the rs1006737 single nucleotide polymorphism (SNP) in the CACNA1C gene as a susceptibility locus for schizophrenia and bipolar disorder. On the neural systems level this association is explained by altered functioning of the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF), brain regions also affected by mental illness. In the present study we investigated the association of rs1006737 genotype with prefrontal activation and fronto-hippocampal connectivity. Methods: We used functional magnetic resonance imaging to measure neural activation during an n-back working memory task in 94 healthy subjects. All subjects were genotyped for the SNP rs1006737. We tested associations of the rs1006737 genotype with changes in working-memory-related DLPFC activation and functional integration using a seed region functional connectivity approach. Results: Rs1006737 genotype was associated with altered right-hemispheric DLPFC activation. The homozygous A (risk) group showed decreased activation compared to G-allele carriers. Further, the functional connectivity analysis revealed a positive association of fronto-hippocampal connectivity with rs1006737 A alleles. Conclusions: We did not replicate the previous findings of increased right DLPFC activation in CACNA1C rs1006737 A homozygotes. In fact, we found the opposite effect, thus questioning prefrontal inefficiency as rs1006737 genotype-related intermediate phenotype. On the other hand, our results indicate that alterations in the functional coupling between the prefrontal cortex and the medial temporal lobe could represent a neural system phenotype that is mediated by CACNA1C rs1006737 and other genetic susceptibility loci for schizophrenia and bipolar disorder. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
Human Brain Mapping 02/2013; · 5.88 Impact Factor
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Markus Burgmer,
Harald Kugel,
Bettina Pfleiderer,
Adrianna Ewert,
Thomas Lenzen,
Regina Pioch,
Martin Pyka, Jens Sommer,
Volker Arolt,
Gereon Heuft,
Carsten Konrad
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ABSTRACT: INTRODUCTION: The neurobiological basis of non-organic movement impairments is still unknown. As conversion disorder and hypnotic states share many characteristics, we applied an experimental design established in conversion disorder to investigate hypnotic paralysis. METHODS: Movement imitation and observation were investigated by functional magnetic resonance imaging (fMRI) in 19 healthy subjects with and without hypnotically induced paralysis of their left hand. Paralysis-specific activation changes were explored in a multivariate model and functional interdependencies of brain regions by connectivity analysis. RESULTS: Hypnotic paralysis during movement imitation induced hypoactivation of the contralateral sensorimotor cortex (SMC) and ipsilateral cerebellum and increased activation of anterior cingulate cortex (ACC), frontal gyrus and insula. No paralysis-specific effects were revealed during movement observation. CONCLUSIONS: Hyperactivation of ACC, middle frontal gyrus (MFG), and insula might reflect attention (MFG), conflict-detection (ACC) and self-representation processes (insula) during hypnotic paralysis. The lack of effects in movement observation suggests that early motor processes are not disturbed due to the transient nature of the hypnotic impairment.
Cortex 06/2012; · 6.08 Impact Factor
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ABSTRACT: The conceptual notion of the so-called resting state of the brain has been recently challenged by studies indicating a continuing effect of cognitive processes on subsequent rest. In particular, activity in posterior parietal and medial prefrontal areas has been found to be modulated by preceding experimental conditions. In this study, we investigated which brain areas show working memory dependent patterns in subsequent baseline periods and how specific they are for the preceding experimental condition. During functional magnetic resonance imaging, 94 subjects performed a letter-version of the n-back task with the conditions 0-back and 2-back followed by a low-level baseline in which subjects had to passively observe the letters appearing. In a univariate analysis, 2-back served as control condition while 0-back, baseline after 0-back and baseline after 2-back were modeled as regressors to test for activity changes between both baseline conditions. Additionally, we tested, using Gaussian process classifiers, the recognition of task condition from functional images acquired during baseline. Besides the expected activity changes in the precuneus and medial prefrontal cortex, we found differential activity in the thalamus, putamen, and postcentral gyrus that were affected by the preceding task. The multivariate analysis revealed that images of the subsequent baseline block contain task related patterns that yield a recognition rate of 70%. The results suggest that the influence of a cognitive task on subsequent baseline is strong and specific for some areas but not restricted to areas of the so-called default mode network. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 06/2012; · 5.88 Impact Factor
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ABSTRACT: 'Crossed language dominance' is a rare form of language lateralization, characterized by a dissociation of anterior and posterior language regions. We present the case of a healthy subject whose language lateralization pattern, as assessed by functional magnetic resonance imaging, is reliably characterized as crossed language dominance based on a word generation task, but typical left-lateralized when a semantic decision task is applied. A single language task is therefore not sufficient to characterize language lateralization, at least not for subjects with rare forms of language dominance. In the pre-surgical diagnostic of language lateralization, several language tasks tapping into different aspects of language functions should be applied.
Neurocase 04/2012; · 1.11 Impact Factor
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ABSTRACT: Automated gray matter segmentation of magnetic resonance imaging data is essential for morphometric analyses of the brain, particularly when large sample sizes are investigated. However, although detection of small structural brain differences may fundamentally depend on the method used, both accuracy and reliability of different automated segmentation algorithms have rarely been compared. Here, performance of the segmentation algorithms provided by SPM8, VBM8, FSL and FreeSurfer was quantified on simulated and real magnetic resonance imaging data. First, accuracy was assessed by comparing segmentations of twenty simulated and 18 real T1 images with corresponding ground truth images. Second, reliability was determined in ten T1 images from the same subject and in ten T1 images of different subjects scanned twice. Third, the impact of preprocessing steps on segmentation accuracy was investigated. VBM8 showed a very high accuracy and a very high reliability. FSL achieved the highest accuracy but demonstrated poor reliability and FreeSurfer showed the lowest accuracy, but high reliability. An universally valid recommendation on how to implement morphometric analyses is not warranted due to the vast number of scanning and analysis parameters. However, our analysis suggests that researchers can optimize their individual processing procedures with respect to final segmentation quality and exemplifies adequate performance criteria.
PLoS ONE 01/2012; 7(9):e45081. · 4.09 Impact Factor
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Frieder M Paulus,
Sören Krach,
Johannes Bedenbender,
Martin Pyka, Jens Sommer,
Axel Krug,
Susanne Knake,
Markus M Nöthen,
Stephanie H Witt,
Marcella Rietschel,
Tilo Kircher,
Andreas Jansen
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ABSTRACT: Genome-wide association studies identified the single nucleotide polymorphism rs1344706 in ZNF804A as a common risk-variant for schizophrenia and bipolar disorder. Whereas the molecular function of ZNF804A is yet unclear, recent imaging genetics studies have started to characterize the neural systems architecture linking rs1344706 genotype to psychosis. Carring rs1344706 risk-alleles was associated with a decrease in functional connectivity within the dorsolateral prefrontal cortices (DLPFCs) as well as an increase in connectivity between the DLPFC and the hippocampal formation (HF) in the context of a working memory task. The present study aimed at replicating these findings in an independent sample of 94 healthy subjects. Subjects were genotyped for rs1344706 and performed a working memory task during functional magnetic resonance imaging. Results indicate no support for a decrease of functional coupling between the bilateral DLPFCs at higher ZNF804A risk status. However, the current data show the previously described alteration in functional coupling between the right DLPFC and the HFs, albeit with weaker effects. Decoupled by default, the functional connectivity between the right DLPFC and anterior HFs increased with the number of rs1344706 risk alleles. The present data support fronto-hippocampal dysconnectivity as intermediate phenotype linking rs1344706 genotype to psychosis. We discuss the issues in replicating the interhemispheric DLPFC coupling in light of the effect sizes rs1344706 genotype has on brain function, concluding that further independent replication studies are fundamentally needed to ascertain the role of rs1344706 in the functional integration of neural systems. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.
Human Brain Mapping 10/2011; · 5.88 Impact Factor
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ABSTRACT: Distraction from pain reduces pain perception, and imaging studies have suggested that this may at least partially be mediated by activation of descending pain inhibitory systems. Here, we used the nociceptive flexor reflex (RIII reflex) to directly quantify the effects of different distraction strategies on basal spinal nociception and its temporal summation. Twenty-seven healthy subjects participated in 3 distraction tasks (mental imagery, listening to preferred music, spatial discrimination of brush stimuli) and, in a fourth task, concentrated on the painful stimulus. Results show that all 3 distraction tasks reduced pain perception, but only the brush task also reduced the RIII reflex. The concentration-on-pain task increased both pain perception and the RIII reflex. The extent of temporal summation of pain perception and the extent of temporal summation of the RIII reflex were not affected by any of the tasks. These results suggest that some, but not all, forms of pain reduction by distraction rely on descending pain inhibition. In addition, pain reduction by distraction seems to preferentially affect mechanisms of basal nociceptive transmission, not of temporal summation.
Pain 09/2011; 152(11):2662-71. · 5.78 Impact Factor
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ABSTRACT: People vicariously experience embarrassment when observing others' public pratfalls or etiquette violations. In two consecutive studies we investigated the subjective experience and the neural correlates of vicarious embarrassment for others in a broad range of situations. We demonstrated, first, that vicarious embarrassment was experienced regardless of whether the observed protagonist acted accidentally or intentionally and was aware or unaware that he/she was in an embarrassing situation. Second, using functional magnetic resonance imaging (fMRI), we showed that the anterior cingulate cortex and the left anterior insula, two cortical structures typically involved in vicarious feelings of others' pain, are also strongly implicated in experiencing the 'social pain' for others' flaws and pratfalls. This holds true even for situations that engage protagonists not aware of their current predicament. Importantly, the activity in the anterior cingulate cortex and the left anterior insula positively correlated with individual differences in trait empathy. The present findings establish the empathic process as a fundamental prerequisite for vicarious embarrassment experiences, thus connecting affect and cognition to interpersonal processes."When we are living with people who have a delicate sense of propriety, we are in misery on their account when anything unbecoming is committed. So I always feel for and with Charlotte when a person is tipping his chair. She cannot endure it." [Elective Affinities, J. W. Goethe].
PLoS ONE 01/2011; 6(4):e18675. · 4.09 Impact Factor
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Johannes Bedenbender,
Frieder M Paulus,
Sören Krach,
Martin Pyka, Jens Sommer,
Axel Krug,
Stephanie H Witt,
Marcella Rietschel,
Davide Laneri,
Tilo Kircher,
Andreas Jansen
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ABSTRACT: Functional magnetic resonance imaging (fMRI) can be combined with genotype assessment to identify brain systems that mediate genetic vulnerability to mental disorders ("imaging genetics"). A data analysis approach that is widely applied is "functional connectivity". In this approach, the temporal correlation between the fMRI signal from a pre-defined brain region (the so-called "seed point") and other brain voxels is determined. In this technical note, we show how the choice of freely selectable data analysis parameters strongly influences the assessment of the genetic modulation of connectivity features. In our data analysis we exemplarily focus on three methodological parameters: (i) seed voxel selection, (ii) noise reduction algorithms, and (iii) use of additional second level covariates. Our results show that even small variations in the implementation of a functional connectivity analysis can have an impact on the connectivity pattern that is as strong as the potential modulation by genetic allele variants. Some effects of genetic variation can only be found for one specific implementation of the connectivity analysis. A reoccurring difficulty in the field of psychiatric genetics is the non-replication of initially promising findings, partly caused by the small effects of single genes. The replication of imaging genetic results is therefore crucial for the long-term assessment of genetic effects on neural connectivity parameters. For a meaningful comparison of imaging genetics studies however, it is therefore necessary to provide more details on specific methodological parameters (e.g., seed voxel distribution) and to give information how robust effects are across the choice of methodological parameters.
PLoS ONE 01/2011; 6(12):e26354. · 4.09 Impact Factor
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ABSTRACT: A tight link between linguistic functions and activation of motor areas has been consistently reported, indicating that the 2 systems share functional neural resources. Few efforts have been made to explore whether this knowledge could aid the rehabilitation of aphasia.
The authors assessed whether preactivation of the leg motor cortex during standing, compared with sitting, can facilitate language production in patients with chronic aphasia. In a cross-over within-subject design, the authors assessed performance on a picture naming task and controlled for effects on processing speed and simple verbal reaction time.
They found that standing compared with sitting had a beneficial effect on the number of semantic self-corrections that resulted in correct naming. In the absence of effects on motor or general processing speed, this points to a specific effect on lexical retrieval and selection. This was further corroborated by an error pattern analysis. Successful semantic self-corrections during standing were only found when there was already partial activation of the target semantic network-that is, when self-corrections were preceded by an incorrect but semantically associated naming response.
These findings show that preactivation of the motor system, which extends beyond the intrinsic link between manual gestures and language, can facilitate lexical access in chronic aphasia and may open new directions in aphasia rehabilitation.
Neurorehabilitation and neural repair 10/2010; 25(2):178-87. · 4.49 Impact Factor
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ABSTRACT: The medial temporal lobe (MTL) is essential for declarative memory formation, but also a frequent source of seizures. To decrease the risk of amnestic impairments after temporal lobectomy, functional magnetic resonance imaging (fMRI) is increasingly used to establish pre-operative measures for a prognosis of postoperative memory performance. The present study addresses one of the major challenges in clinical fMRI, the interpretation of activation pattern in single subjects. Before investigating patients however, it must be first assessed to which extent the verbal memory paradigm can be used to determine the lateralization and the functional neuroanatomy of MTL-activity. Therefore, this study took a "step backwards" by first examining healthy subjects without known MTL pathology.
An implicit verbal encoding task was applied to a group of ten healthy volunteers using fMRI.
At the group level the MTL activation was strongly left-lateralized and separated into three distinct clusters. At the individual level, the lateralization of MTL-activity could be determined in 9 of 10 subjects. In contrast, its localization was inter-individually highly variable. In each case, only one of the three group activation clusters was detected.
The present study shows that fMRI can be used to assess the lateralization of brain activity related to verbal encoding even in individual subjects. For the routine use in a clinical setting however, the results of verbal memory paradigms must at present be treated with care if they are used to support decisions as to how far the resection of one MTL can be extended.
Clinical neurology and neurosurgery 11/2008; 111(1):57-62. · 1.30 Impact Factor
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ABSTRACT: Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis.
NeuroImage 03/2006; 29(4):1336-43. · 5.89 Impact Factor
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ABSTRACT: To improve the quality of TMS studies by developing a new sham condition.
We describe a novel and easily arranged TMS set-up of two standard TMS coils and a magnetic shield, stacked like a sandwich. In a first step we compare the magnetic field in the sham and verum conditions. In a second step we ask six subjects to rate the stimulation intensity.
The magnetic field in the sham mode is reduced to about one eighth of that during verum stimulation. The attenuation of the magnetic field is not limited to the actual stimulation site but also effective at neighbouring brain areas, avoiding direct and indirect stimulation via connected neural pathways. This also minimizes stimulation of the skin, but as a consequence allows subjects to distinguish between verum and sham conditions when these are contrasted directly. The position of the coil system and the acoustic sensations are indistinguishable between sham and verum condition. Subjects are not able to discriminate TMS position and condition by external cues.
The proposed TMS setup is simple and allows verum and sham TMS without interaction of the researcher. If used with the magnetic shield, the magnetic field in the brain is attenuated most.
With the sandwich TMS coil system it is possible to improve the quality of TMS studies.
Clinical Neurophysiology 03/2006; 117(2):440-6. · 3.41 Impact Factor
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ABSTRACT: The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention.
Journal of Cerebral Blood Flow & Metabolism 10/2005; 25(9):1197-208. · 5.01 Impact Factor
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ABSTRACT: Language proficiency is a key to academic and workplace success for native and non-native speakers. It is largely unknown, however, why some people pick up languages more easily than others. We used event-related functional magnetic resonance imaging (e-fMRI) to elucidate which brain regions are modulated during the acquisition of a novel lexicon and which of these learning-related activity changes correlated with general semantic language knowledge. Fourteen healthy young subjects learned a novel vocabulary of 45 concrete nouns via an associative learning principle over the course of five blocks during e-fMRI. As a control condition, subjects took part in a structurally identical "No-Learning" condition lacking any learning principle. Overall, increasing vocabulary proficiency was associated with (intercorrelated) modulations of activity within the left hippocampus and the left fusiform gyrus, regions involved in the binding and integration of multimodal stimuli, and with an increasing activation of the left inferior parietal cortex, the presumed neural store of phonological associations. None of these activity changes were observed during the control condition. Furthermore, subjects who showed less suppression of hippocampal activity over learning blocks scored higher on semantic knowledge in their native language and learned the novel vocabulary more efficiently. Our findings indicate that (a) the successful acquisition of a new lexicon depends on correlated amplitude changes between the left hippocampus and neocortical regions and (b) learning-related hippocampus activity is a stable marker of individual differences in the ability to acquire and master vocabularies.
NeuroImage 05/2005; 25(3):958-68. · 5.89 Impact Factor
