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Biomedical subjects

Matthias Schulz

Publications and source records attributed to Matthias Schulz.

8 recordsLinked to original sources

Sensory mapping of lip representation in brass musicians with embouchure dystonia.

Embouchure dystonia is a focal task-specific disorder involving abnormal non-coordinated movements and involuntary muscle contraction around the mouth. In professional brass players it is often so disabling that patients have to limit or give up their occupation. We examined the somatosensory homuncular representation and measured gap detection sensitivity of the lips in eight former professional musicians affected by embouchure dystonia and eight control subjects. Relative to controls, the patients' digit, and especially the thumb, representations were shifted in a lateral direction towards the lip representational zone. Patients' upper lips showed decreased sensitivity compared to their lower lips (p < 0.01). This asymmetry result was absent in controls. Abnormal somatosensory reorganization may contribute to the disorder.

Adult↗

Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases.

Apart from the neoplastic cells, malignant tumours consist of the extracellular matrix (ECM) and normal cells, in particular tumour-associated macrophages (TAM). To understand the mechanisms by which TAM can influence tumour cell invasion we co-cultured the human breast cancer cell lines MCF-7, SK-BR-3 and the benign mammary epithelial cell line hTERT-HME1 with macrophages. Co-incubation enhanced invasiveness of the tumour cells, while hTERT-HME1 remained non-invasive. Addition of the broad-spectrum matrix metalloprotease (MMP)-inhibitor FN 439, neutralizing MMP-9 or tumour necrosis factor-alpha (TNF-alpha) antibodies reduced invasiveness to basal levels. As shown by zymography, all cell lines produced low amounts of MMP-2, -3, -7 and -9 under control conditions. Basal MMP production by macrophages was significantly higher. Upon co-incubation, supernatant levels of MMPs -2, -3, -7 and -9 increased significantly, paralleled by an increase of MMP-2 activation. MMP-2 and -9 induction could be blocked by TNF-alpha antibodies. Co-culture of macrophages and hTERT-HME1 did not lead to MMP induction. In the co-cultures, mRNAs for MMPs and TNF-alpha were significantly up-regulated in macrophages, while the mRNA concentrations in the tumour cells remained unchanged. In summary, we have found that co-cultivation of tumour cells with macrophages leads to enhanced invasiveness of the malignant cells due to TNF-alpha dependent MMP induction in the macrophages.

Breast Neoplasms↗

An integrative MEG-fMRI study of the primary somatosensory cortex using cross-modal correspondence analysis.

We develop a novel approach of cross-modal correspondence analysis (CMCA) to address whether brain activities observed in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) represent a common neuronal subpopulation, and if so, which frequency band obtained by MEG best fits the common brain areas. Fourteen adults were investigated by whole-head MEG using a single equivalent current dipole (ECD) and synthetic aperture magnetometry (SAM) approaches and by fMRI at 1.5 T using linear time-invariant modeling to generate statistical maps. The same somatosensory stimulus sequences consisting of tactile impulses to the right sided: digit 1, digit 4 and lower lip were used in both neuroimaging modalities. To evaluate the reproducibility of MEG and fMRI results, one subject was measured repeatedly. Despite different MEG dipole locations and locations of maximum activation in SAM and fMRI, CMCA revealed a common subpopulation of the primary somatosensory cortex, which displays a clear homuncular organization. MEG activity in the frequency range between 30 and 60 Hz, followed by the ranges of 20-30 and 60-100 Hz, explained best the defined subrepresentation given by both MEG and fMRI. These findings have important implications for improving and understanding of the biophysics underlying both neuroimaging techniques, and for determining the best strategy to combine MEG and fMRI data to study the spatiotemporal nature of brain activity.

Adult↗

Improving permutation test power for group analysis of spatially filtered MEG data.

Non-parametric statistical methods, such as permutation, are flexible tools to analyze data when the population distribution is not known. With minimal assumptions and better statistical power compared to the parametric tests, permutation tests have recently been applied to the spatially filtered magnetoencephalography (MEG) data for group analysis. To perform permutation tests on neuroimaging data, an empirical maximal null distribution has to be found, which is free from any activated voxels, to determine the threshold to classify the voxels as active at a given probability level. An iterative procedure is used to determine the distribution by computing the null distribution, which is recomputed when a possible activated voxel is found within the current distributions. Besides the high computational costs associated with this approach, there is no guarantee that all activated voxels are excluded when constructing the maximal null distribution, which may reduce the statistical power. In this study, we propose a novel way to construct the maximal null distribution from the data of the resting period. The approach is tested on the MEG data from a somatosensory experiment, and demonstrated that the approach could improve the power of the permutation test while reducing the computational cost at the same time.

Adult↗

Evidence for training-induced crossmodal reorganization of cortical functions in trumpet players.

The aim of this study was to compare multimodal information processing in the somatosensory and auditory cortices and related multimodal areas in musicians (trumpet players) and non-musicians. Magnetoencephalographic activity (MEG) was recorded in response to five stimulus conditions from 10 professional trumpet players and nine musically untrained control subjects. Somatosensory and auditory stimuli were presented alone or in combination. Our data suggest that musicians, in general, process multisensory stimuli differently to the control group. When stimulating the lip in professional trumpet players, a multimodal interaction (expressed as difference between the multimodal response and the sum of unimodal responses) in the corresponding somatosensory cortex showed a positive peak at 33 ms, which was not found in the control group. Conversely, the control group shows a significant interaction of opposite polarity around 60-80 ms. We suggest that training-induced reorganization in musicians leads to a qualitatively different way to process multisensory information. It favors an early stage of cortical processing, which is modified by the connections between multimodal and auditory neurons from thalamus to primary somatosensory area.

Acoustic Stimulation↗

Music and learning-induced cortical plasticity.

Auditory stimuli are encoded by frequency-tuned neurons in the auditory cortex. There are a number of tonotopic maps, indicating that there are multiple representations, as in a mosaic. However, the cortical organization is not fixed due to the brain's capacity to adapt to current requirements of the environment. Several experiments on cerebral cortical organization in musicians demonstrate an astonishing plasticity. We used the MEG technique in a number of studies to investigate the changes that occur in the human auditory cortex when a skill is acquired, such as when learning to play a musical instrument. We found enlarged cortical representation of tones of the musical scale as compared to pure tones in skilled musicians. Enlargement was correlated with the age at which musicians began to practice. We also investigated cortical representations for notes of different timbre (violin and trumpet) and found that they are enhanced in violinists and trumpeters, preferentially for the timbre of the instrument on which the musician was trained. In recent studies we extended these findings in three ways. First, we show that we can use MEG to measure the effects of relatively short-term laboratory training involving learning to perceive virtual instead of spectral pitch and that the switch to perceiving virtual pitch is manifested in the gamma band frequency. Second, we show that there is cross-modal plasticity in that when the lips of trumpet players are stimulated (trumpet players assess their auditory performance by monitoring the position and pressure of their lips touching the mouthpiece of their instrument) at the same time as a trumpet tone, activation in the somatosensory cortex is increased more than it is during the sum of the separate lip and trumpet tone stimulation. Third, we show that musicians' automatic encoding and discrimination of pitch contour and interval information in melodies are specifically enhanced compared to those in nonmusicians in that musicians show larger functional mismatch negativity (MMNm) responses to occasional changes in melodic contour or interval, but that the two groups show similar MMNm responses to changes in the frequency of a pure tone.

Auditory Cortex↗

MEG study of long-term cortical reorganization of sensorimotor areas with respect to using chopsticks.

The movements required to use chopsticks are overlearned and routine in Asians. Most non-Asians, on the other hand, typically have difficulty performing this unfamiliar manual activity, and have to focus their attention on the movements required to use chopsticks adequately. Using magnetoencephalography (MEG) we compared the cortical activation of highly trained Asian chopstick users to the activation of Europeans who only occasionally used chopsticks, while they performed the same tasks with chopsticks or a control task of simple tapping of the same fingers. The data were analyzed using the new method of synthetic aperture magnetometry (SAM). In Europeans there was a significantly higher ratio of spectral power in the higher gamma frequency band (60-80 Hz) over the sensorimotor area compared to the Asian subjects. From these results we conclude that the high gamma band activity in the sensorimotor area may reflect focused attention and functional reorganization of the cortical network with respect to sensorimotor experience.

Adult↗

Selective alterations in mast cell subsets and eosinophil infiltration in two complementary types of intestinal inflammation: ascariasis and Crohn's disease.

OBJECTIVE: Numbers of mast cells (MCs) of different subpopulations and the extent of eosinophil infiltration were compared in Crohn's disease and ascariasis. These two types of intestinal inflammation are complementary with regard to T cell response (TH1 versus TH2), prevalence and environmental factors. METHODS: Histochemical, immunohistochemical and ultrastructural tools were applied to biopsies of morphologically uninvolved colon, ileum and duodenum from Crohn's and ascariasis patients, as well as resection margins and tissues from an experimental porcine ascariasis model. MC subsets were defined by their dye-binding properties, and their chymase content was analysed using biochemical tools. RESULTS: The TH2 (IgE-mediated) response in ascariasis was characterised by a dramatic increase in mucosal- type MCs (MMCs) and eosinophils in both the mucosa and the deeper layers of the intestinal wall and a simultaneous decrease of connective tissue-type MCs (CTMCs). Uninvolved intestine of Crohn's patients showed moderate proliferation of CTMCs in the deeper layers of the intestinal wall, but a significant decrease of the MMCs, associated with moderate eosinophilia in all layers of the gut. Similar changes were present in the uninvolved duodenum of Crohn's patients. Comparable amounts of chymase could be extracted from mucosal and submucosal duodenum, with similar proportions of its two principal isoforms in each. CONCLUSIONS: Our results indicate that T cell responses (TH1 or TH2) are associated with different MC subsets in intestinal inflammation. Changes remote from the focus of inflammation point to the systemic nature of the different MC responses.

Adult↗