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R Goebel

Publications and source records attributed to R Goebel.

At least 19 recordsLinked to original sources

The dynamics of interhemispheric compensatory processes in mental imagery.

The capacity to generate and analyze mental visual images is essential for many cognitive abilities. We combined triple-pulse transcranial magnetic stimulation (tpTMS) and repetitive TMS (rTMS) to determine which distinct aspect of mental imagery is carried out by the left and right parietal lobe and to reveal interhemispheric compensatory interactions. The left parietal lobe was predominant in generating mental images, whereas the right parietal lobe was specialized in the spatial comparison of the imagined content. Furthermore, in case of an rTMS-induced left parietal lesion, the right parietal cortex could immediately compensate such a left parietal disruption by taking over the specific function of the left hemisphere.

Adaptation, Physiological↗

Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: a FMRI study.

BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level-dependent (BOLD) contrasts is a common method for studying sensory or cognitive brain functions. The aim of the present study was to assess the effect of the intravenous anaesthetic propofol on auditory-induced brain activation using BOLD contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were presented binaurally in a block design. Imaging was performed under five conditions: no propofol (or wakefulness) and propofol plasma target concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During wakefulness we found activations in the superior temporal gyrus (STG) corresponding to the primary and secondary auditory cortex as well as in regions of higher functions of auditory information processing. The BOLD response decreased with increasing concentrations of propofol but remained partially preserved in areas of basic auditory processing in the STG during propofol 2.0 microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of central processing of auditory information after propofol administration. These results are consistent with electrophysiological findings measuring neuronal activity directly, thus suggesting a dose-dependent impairment of central processing of auditory information after propofol administration. However, propofol did not totally blunt primary cortical responses to acoustic stimulation, indicating that patients may process auditory information under general anaesthesia.

Acoustic Stimulation↗

Downregulation of CD44v6 in colorectal carcinomas is associated with hypermethylation of the CD44 promoter region.

Overexpression of the cell adhesion protein CD44v6 has been demonstrated in colorectal cancer and other gastrointestinal tumors. While CD44v6 is upregulated in benign colorectal adenomas and well-differentiated colorectal cancer tissues, downregulation frequently occurs during disease progression. The mechanism of downregulation, however, is unknown. Therefore, we evaluated the methylation status of the CD44 promoter as a mechanism for decreased CD44v6 expression in advanced colorectal carcinomas. We demonstrated by methylation-sensitive restriction enzyme digestion that the CpG islands of the CD44 promoter were methylated in 6/21 (28%) of benign colorectal adenomas. Interestingly, in colorectal carcinomas the frequency of promoter methylation was significantly increased (10/19; 53%) compared to 7/21 (33%) in the corresponding normal mucosa. Methylation seems to be associated with a more advanced cancer stage, but the trend did not reach statistical significance. In colorectal carcinomas with CD44 promoter methylation CD44v6 mRNA was detected by reverse transcription-polymerase chain reaction in 3/10 carcinomas, whereas in tumors without CD44 promoter methylation CD44v6 expression was observed in 8/9 (P <or= 0.05). These results demonstrated that methylation of the 5'CpG island of the CD44 gene is closely associated with decreased expression of CD44v6 in human colorectal carcinomas.

Adenocarcinoma↗

Functional imaging of visuospatial processing in Alzheimer's disease.

Alzheimer's disease (AD) is known to cause a variety of disturbances of higher visual functions that are closely related to the neuropathological changes. Visual association areas are more affected than primary visual cortex. Additionally, there is evidence from neuropsychological and imaging studies during rest or passive visual stimulation that the occipitotemporal pathway is less affected than the parietal pathway. Our goal was to investigate functional activation patterns during active visuospatial processing in AD patients and the impact of local cerebral atrophy on the strength of functional activation. Fourteen AD patients and fourteen age-matched controls were measured with functional magnetic resonance imaging (fMRI) while they performed an angle discrimination task. Both groups revealed overlapping networks engaged in angle discrimination including the superior parietal lobule (SPL), frontal and occipitotemporal (OTC) cortical regions, primary visual cortex, basal ganglia, and thalamus. The most pronounced differences between the two groups were found in the SPL (more activity in controls) and OTC (more activity in patients). The differences in functional activation between the AD patients and controls were partly explained by the differences in individual SPL atrophy. These results indicate that parietal dysfunction in mild to moderate AD is compensated by recruitment of the ventral visual pathway. We furthermore suggest that local cerebral atrophy should be considered as a covariate in functional imaging studies of neurodegenerative disorders.

Aged↗

The experimental combination of rTMS and fMRI reveals the functional relevance of parietal cortex for visuospatial functions.

We combined repetitive transcranial magnetic stimulation (rTMS) and functional magnetic resonance imaging (fMRI) to investigate the functional relevance of parietal cortex activation during the performance of visuospatial tasks. fMRI provides information about local transient changes in neuronal activation during behavioural or cognitive tasks. Information on the functional relevance of this activation was obtained by using rTMS to induce temporary regional deactivations. We thereby turned the physiological parameter of brain activity into an independent variable controlled and manipulated by the experimenter and investigated its effect on the performance of the cognitive tasks within a controlled experimental design. We investigated cognitive tasks that were performed on the same visual material but differed in the demand on visuospatial functions. For the visuospatial tasks we found a selective enhancement of fMRI signal in the superior parietal lobule (SPL) and a selective impairment of performance after rTMS to this region in comparison to a control group. We could thus show that the parietal cortex is functionally important for the execution of spatial judgements on visually presented material and that TMS as an experimental tool has the potential to interfere with higher cognitive functions such as visuospatial information processing.

Adult↗

Expression of CD44v6 has no prognostic value in patients with colorectal cancer.

BACKGROUND AND AIMS: In colorectal cancer patients' mortality is largely influenced by spreading of tumour cells from the primary tumour site and subsequent metastasis formation. CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastatic spread and poor prognosis in animal models and several human cancers. Results of immunohistological studies in primary colorectal cancer are mostly retrospective and contradictory. The aim of our prospective study was to assess the controversial role of CD44v6 as a prognostic factor in colorectal cancer. METHODS: In 93 patients we analysed tumour CD44v6 expression in prospectively sampled stage I-IV colorectal adenocarcinomas using RT-PCR and Southern blotting. The prognostic value of the CD44v6 expression was assessed using univariate and multivariate analysis. RESULTS: CD44v6 expression was found in 47 % of the cases. CD44v6 expression failed to show any association with the clinical or histological variables examined. CD44v6 expression did not correlate with survival in long-term follow-up. The most important prognostic factor in this cohort was tumour stage. CONCLUSIONS: Changes in CD446 expression level do not predict tumour spread or patient survival in colorectal cancer.

Adenocarcinoma↗

Synchronization of visual responses in the superior colliculus of awake cats.

Multi-unit responses to moving stimuli were recorded simultaneously from several sites in the superior colliculus of awake cats. Correlation analysis revealed that response synchronization was a prominent feature of visually evoked neural activity in both superficial and deep collicular layers. Responses at about half of the recordings separated by < or = 1 mm showed significant correlations. The synchronized responses oscillated in the gamma frequency range (30-70 Hz) which contrasts to conditions in anaesthetized cats where oscillations predominantly occurred in the alpha and beta frequency range (10-20 Hz). Response synchronization was most pronounced with coherent motion stimuli and broke down with incoherent stimuli. These results agree with previous findings on corticotectal synchronization and support the hypothesis that synchronization in the millisecond range serves to group collicular neurons into functionally coherent assemblies.

Animals↗

7T vs. 4T: RF power, homogeneity, and signal-to-noise comparison in head images.

Signal-to-noise ratio (SNR), RF field (B(1)), and RF power requirement for human head imaging were examined at 7T and 4T magnetic field strengths. The variation in B(1) magnitude was nearly twofold higher at 7T than at 4T ( approximately 42% compared to approximately 23%). The power required for a 90 degrees pulse in the center of the head at 7T was approximately twice that at 4T. The SNR averaged over the brain was at least 1.6 times higher at 7T compared to 4T. These experimental results were consistent with calculations performed using a human head model and Maxwell's equations. Magn Reson Med 46:24-30, 2001.

Brain↗

Stage-specific alternative cplicing of CD44 and alpha 6 beta 1 integrin in colorectal tumorigenesis.

Recent reports suggest that cancerogenesis induces changes in alternative processing of human genes. However, little is known about the regulation of alternative splicing during malignant transformation. Therefore, we examined changes in alternative splicing of two different adhesion molecules, alpha 6 beta 1 integrin and CD44, in multiple stages of colon tumorigenesis. Using semiquantitative RT-PCR it is shown that the alternatively spliced isoforms of both adhesion molecules, alpha 6A and -B and CD44v6, are significantly upregulated in colorectal adenoma (n = 20) compared to normal colon mucosa (n = 32) (P < 0.01). Although beta1 isoforms were expressed in almost all tissues, there was a significant increase in the intensity of gene expression of beta 1A compared to beta 1B (P <0.05) in adenoma tissue. Interestingly, CD44v6 and alpha 6 variant isoforms were downregulated in carcinoma tissue (n = 28) compared to adenoma. These results establish a link between neoplastic transformation and alternative splicing of cell adhesion molecules. Furthermore, these data suggest that colon epithelial cells carrying splice variants of adhesion molecules might acquire a selective growth advantage during early tumorigenesis.

Adenocarcinoma↗

Functional fields in human auditory cortex revealed by time-resolved fMRI without interference of EPI noise.

The gradient switching during fast echoplanar functional magnetic resonance imaging (EPI-fMRI) produces loud noises that may interact with the functional activation of the central auditory system induced by experimental acoustic stimuli. This interaction is unpredictable and is likely to confound the interpretation of functional maps of the auditory cortex. In the present study we used an experimental design which does not require the presentation of stimuli during EPI acquisitions and allows for mapping of the auditory cortex without the interference of scanner noise. The design relies on the physiological delays between the onset, or the end, of stimulation and the corresponding hemodynamic response. Owing to these delays and through a time-resolved acquisition protocol it is possible to analyze the decay of the stimulus-specific signal changes after the cessation of the stimulus itself and before the onset of the EPI-acoustic noise related activation (decay-sampling technique). This experimental design, which might permit a more detailed insight in the auditory cortex, has been applied to the study of the cortical responses to pulsed 1000 Hz sine tones. Distinct activation clusters were detected in the Heschl's gyri and the planum temporale, with an increased extension compared to a conventional block-design paradigm. Furthermore, the comparison of the hemodynamic response of the most anterior and the posterior clusters of activation highlighted differential response patterns to the sound stimulation and to the EPI-noise. These differences, attributable to reciprocal saturation effects unevenly distributed over the superior temporal cortex, provided evidence for functionally distinct auditory fields.

Acoustic Stimulation↗

Is V1 necessary for conscious vision in areas of relative cortical blindness?

Visual field defects result from postgeniculate lesions. It is generally assumed that absolute defects are caused by total destruction or denervation of primary visual cortex (V1) and that the degraded but conscious vision that remains or returns in relative or partial defects is mediated by compromised V1 cortex that retains a sufficiently large population of functional neurons. We here report the results of three patients with long-standing postgeniculate lesions who underwent functional magnetic resonance imaging while their partial defect was stimulated with high-contrast reversing checkerboard stimuli. Although the stimulation evoked conscious visual impressions in all three, in only one patient did it activate perilesional V1. In the other two we found no evidence for perilesional activation, indicating that some conscious vision may return in the absence of functional ipsilesional V1.

Adult↗

An efficient algorithm for topologically correct segmentation of the cortical sheet in anatomical mr volumes.

Polygon-mesh representations of the cortices of individual subjects are of anatomical interest, aid visualization of functional imaging data and provide important constraints for their statistical analysis. Due to noise and partial volume sampling, however, conventional segmentation methods rarely yield a voxel object whose outer boundary represents the folded cortical sheet without topological errors. These errors, called handles, have particularly deleterious effects when the polygon mesh constructed from the segmented voxel representation is inflated or flattened. So far handles had to be removed by cumbersome manual editing, or the computationally more expensive method of reconstruction by morphing had to be used, incorporating the a priori constraint of simple topology into the polygon-mesh model. Here we describe a linear time complexity algorithm that automatically detects and removes handles in presegmentations of the cortex obtained by conventional methods. The algorithm's modifications reflect the true structure of the cortical sheet. The core component of our method is a region growing process that starts deep inside the object, is prioritized by the distance-to-surface of the voxels considered for inclusion and is selftouching-sensitive, i.e., voxels whose inclusion would add a handle are never included. The result is a binary voxel object identical to the initial object except for "cuts" located in the thinnest part of each handle. By applying the same method to the inverse object, an alternative set of solutions is determined, correcting the errors by addition instead of deletion of voxels. For each handle separately, the solution more consistent with the intensities of the original anatomical MR scan is chosen. The accuracy of the resulting polygon-mesh reconstructions has been validated by visual inspection, by quantitative comparison to an expert's manual corrections, and by crossvalidation between reconstructions from different scans of the same subject's cortex.

Algorithms↗

Sustained extrastriate cortical activation without visual awareness revealed by fMRI studies of hemianopic patients.

Patients with lesions in the primary visual cortex (V1) may show processing of visual stimuli presented in their field of cortical blindness even when they report being unaware of the stimuli. To elucidate the neuroanatomical basis of their residual visual functions, we used functional magnetic resonance imaging in two hemianopic patients, FS and GY. In the first experiment, a rotating spiral stimulus was used to assess the responsiveness of dorsal stream areas. Although no response was detectable within denervated or destroyed early visual cortex, motion-sensitive areas (hMT+/V5) ipsilateral to the lesion showed a strong sustained hemodynamic response. In GY, this activation was at least as strong as that of his contralesional hMT+/V5 to the stimulus in the normal hemifield. In the second experiment, coloured images of natural objects were used to assess the responsiveness of ventral stream areas. Again, no activity was detectable in ipsilesional early visual areas, but extrastriate areas in the lateral occipital cortex (hMT+/V5 and LO) and within the posterior fusiform gyrus (V4/V8) showed a robust sustained hemodynamic response. In both experiments, we observed that ipsilesional areas responded to stimuli presented in either hemifield, whereas the normal hemisphere responded preferentially to stimuli in the sighted hemifield. As only one subject occasionally noticed the onset of stimulation in the impaired field, the unexpectedly strong sustained activity in ipsilesional dorsal and ventral cortical areas appears to be insufficient to generate conscious vision.

Adult↗

Rapid feature selective neuronal synchronization through correlated latency shifting.

Spontaneous brain activity could affect processing if it were structured. We show that neuron pairs in cat primary visual cortex exhibited correlated fluctuations in response latency, particularly when they had overlapping receptive fields or similar orientation preferences. Correlations occurred within and across hemispheres, but only when local field potentials (LFPs) oscillated in the gamma-frequency range (40-70 Hz). In this range, LFP fluctuations preceding response onset predicted response latencies; negative (positive) LFPs were associated with early (late) responses. Oscillations below 10 Hz caused covariations in response amplitude, but exhibited no columnar selectivity or coordinating effect on latencies. Thus, during high gamma activity, spontaneous activity exhibits distinct, column-specific correlation patterns. Consequently, cortical cells undergo coherent fluctuations in excitability that enhance temporal coherence of responses to contours that are spatially contiguous or have similar orientation. Because synchronized responses are more likely than dispersed responses to undergo rapid and joint processing, spontaneous activity may be important in early visual processes.

Action Potentials↗

Neural synchrony correlates with surface segregation rules.

To analyse an image, the visual system must decompose the scene into its relevant parts. Identifying distinct surfaces is a basic operation in such analysis, and is believed to precede object recognition. Two superimposed gratings moving in different directions (plaid stimuli) may be perceived either as two surfaces, one being transparent and sliding on top of the other (component motion) or as a single pattern whose direction of motion is intermediate to the component vectors (pattern motion). The degree of transparency, and hence the perception, can be manipulated by changing only the luminance of the grating intersections. Here we show that neurons in two visual cortical areas--A18 and PMLS--synchronize their discharges when responding to contours of the same surface but not when responding to contours belonging to different surfaces. The amplitudes of responses correspond to previously described rate predictions for component and pattern motion, but, in contrast to synchrony, failed to reflect the transition from component to pattern motion induced by manipulating the degree of transparency. Thus, dynamic changes in synchronization could encode, in a context-dependent way, relations among simultaneous responses to spatially superimposed contours and thereby bias their association with distinct surfaces.

Animals↗

Anatomically informed basis functions.

This paper introduces the general framework, concepts, and procedures of anatomically informed basis functions (AIBF), a new method for the analysis of functional magnetic resonance imaging (fMRI) data. In contradistinction to existing voxel-based univariate or multivariate methods the approach described here can incorporate various forms of prior anatomical knowledge to specify sophisticated spatiotemporal models for fMRI time-series. In particular, we focus on anatomical prior knowledge, based on reconstructed gray matter surfaces and assumptions about the location and spatial smoothness of the blood oxygenation level dependent (BOLD) effect. After reconstruction of the grey matter surface from an individual's high-resolution T1-weighted MRI, we specify a set of anatomically informed basis functions, fit the model parameters for a single time point, using a regularized solution, and finally make inferences about the estimated parameters over time. Significant effects, induced by the experimental paradigm, can then be visualized in the native voxel-space or on the reconstructed folded, inflated, or flattened cortical surface. As an example, we apply the approach to a fMRI study (finger opposition task) and compare the results to those of a voxel-based analysis as implemented in the Statistical Parametric Mapping package (SPM99). Additionally, we show, using simulated data, that the approach offers several desirable features particularly in terms of superresolution and localization.

Brain↗