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S Koelsch

Publications and source records attributed to S Koelsch.

13 recordsLinked to original sources

Cognitive priming in sung and instrumental music: activation of inferior frontal cortex.

Neural correlates of the processing of musical syntax-like structures have been investigated via expectancy violation due to musically unrelated (i.e., unexpected) events in musical contexts. Previous studies reported the implication of inferior frontal cortex in musical structure processing. However - due to the strong musical manipulations - activations might be explained by sensory deviance detection or repetition priming. Our present study investigated neural correlates of musical structure processing with subtle musical violations in a musical priming paradigm. Instrumental and sung sequences ended on related and less-related musical targets. The material controlled sensory priming components, and differences in target processing required listeners' knowledge on musical structures. Participants were scanned with functional Magnetic Resonance Imaging (fMRI) while performing speeded phoneme and timbre identification judgments on the targets. Behavioral results acquired in the scanner replicated the facilitation effect of related over less-related targets. The blood oxygen level-dependent (BOLD) signal linked to target processing revealed activation of right inferior frontal areas (i.e., inferior frontal gyrus, frontal operculum, anterior insula) that was stronger for less-related than for related targets, and this was independent of the material carrying the musical structures. This outcome points to the implication of inferior frontal cortex in the processing of syntactic relations also for musical material and to its role in the processing and integration of sequential information over time. In addition to inferior frontal activation, increased activation was observed in orbital gyrus, temporal areas (anterior superior temporal gyrus, posterior superior temporal gyrus and sulcus, posterior middle temporal gyrus) and supramarginal gyrus.

Adult↗

Age-related differences in parameters of feline immune status.

In order to assess age-related differences in feline immune status, 101 domestic short haired cats were assigned to two groups, adult (2-5 years, n=50) and senior (10-14 years, n=51). Analyses of leucocyte populations, lymphocyte subsets, complement activity, serum immunoglobulins and acute-phase proteins were undertaken and revealed significant differences between the two groups. The senior group had significantly lower WBC, lymphocyte and eosinophil counts than the adult group. Neutrophil, monocyte and basophil counts did not differ between the groups. Flow cytometry analysis, in combination with differential WBC data, revealed that the absolute values (cells/l) of T-cells, B-cells and natural killer (NK) cells were significantly lower in the older animals. While serum immunoglobulins IgA and IgM were higher in the senior group when compared with the adult group, no significant differences were observed in complement activity or in serum acute-phase proteins. Our findings suggest that age-related changes to parameters of immune status in the feline model are likely to follow a similar pattern to those observed in other long-lived mammalian species.

Age Factors↗

Differentiating ERAN and MMN: an ERP study.

In the present study, the early right-anterior negativity (ERAN) elicited by harmonically inappropriate chords during listening to music was compared to the frequency mismatch negativity (MMN) and the abstract-feature MMN. Results revealed that the amplitude of the ERAN, in contrast to the MMN, is specifically dependent on the degree of harmonic appropriateness. Thus, the ERAN is correlated with the cognitive processing of complex rule-based information, i.e. with the application of music-syntactic rules. Moreover, results showed that the ERAN, compared to the abstract-feature MMN, had both a longer latency, and a larger amplitude. The combined findings indicate that ERAN and MMN reflect different mechanisms of pre-attentive irregularity detection, and that, although both components have several features in common, the ERAN does not easily fit into the classical MMN framework. The present ERPs thus provide evidence for a differentiation of cognitive processes underlying the fast and pre-attentive processing of auditory information.

Acoustic Stimulation↗

Musical syntax is processed in Broca's area: an MEG study.

The present experiment was designed to localize the neural substrates that process music-syntactic incongruities, using magnetoencephalography (MEG). Electrically, such processing has been proposed to be indicated by early right-anterior negativity (ERAN), which is elicited by harmonically inappropriate chords occurring within a major-minor tonal context. In the present experiment, such chords elicited an early effect, taken as the magnetic equivalent of the ERAN (termed mERAN). The source of mERAN activity was localized in Broca's area and its right-hemisphere homologue, areas involved in syntactic analysis during auditory language comprehension. We find that these areas are also responsible for an analysis of incoming harmonic sequences, indicating that these regions process syntactic information that is less language-specific than previously believed.

Acoustic Stimulation↗

Brain indices of music processing: "nonmusicians" are musical.

Only little systematic research has examined event-related brain potentials (ERPs) elicited by the cognitive processing of music. The present study investigated how music processing is influenced by a preceding musical context, affected by the task relevance of unexpected chords, and influenced by the degree and the probability of violation. Four experiments were conducted in which "nonmusicians" listened to chord sequences, which infrequently contained a chord violating the sound expectancy of listeners. Integration of in-key chords into the musical context was reflected as a late negative-frontal deflection in the ERPs. This negative deflection declined towards the end of a chord sequence, reflecting normal buildup of musical context. Brain waves elicited by chords with unexpected notes revealed two ERP effects: an early right-hemispheric preponderant-anterior negativity, which was taken to reflect the violation of sound expectancy; and a late bilateral-frontal negativity. The late negativity was larger compared to in-key chords and taken to reflect the higher degree of integration needed for unexpected chords. The early right-anterior negativity (ERAN) was unaffected by the task relevance of unexpected chords. The amplitudes of both early and late negativities were found to be sensitive to the degree of musical expectancy induced by the preceding harmonic context, and to the probability for deviant acoustic events. The employed experimental design opens a new field for the investigation of music processing. Results strengthen the hypothesis of an implicit musical ability of the human brain.

Acoustic Stimulation↗

Superior pre-attentive auditory processing in musicians.

The present study focuses on influences of long-term experience on auditory processing, providing the first evidence for pre-attentively superior auditory processing in musicians. This was revealed by the brain's automatic change-detection response, which is reflected electrically as the mismatch negativity (MMN) and generated by the operation of sensoric (echoic) memory, the earliest cognitive memory system. Major chords and single tones were presented to both professional violinists and non-musicians under ignore and attend conditions. Slightly impure chords, presented among perfect major chords elicited a distinct MMN in professional musicians, but not in non-musicians. This demonstrates that compared to non-musicians, musicians are superior in pre-attentively extracting more information out of musically relevant stimuli. Since effects of long-term experience on pre-attentive auditory processing have so far been reported for language-specific phonemes only, results indicate that sensory memory mechanisms can be modulated by training on a more general level.

Acoustic Stimulation↗

IL-4 in combination with TGF-beta favors an alternative pathway of Th1 development independent of IL-12.

IL-4 was found to be the essential differentiation factor for Th2 cells and simultaneously to be a potent inhibitor of Th1 development that is induced by IFN-gamma and IL-12. Furthermore, it was demonstrated that TGF-beta can also inhibit Thl development. In this work, we demonstrate that polyclonal activation of Mel-14highCD4+ T cells by immobilized anti-alphabetaTCR mAb together with a mixture of IL-4 and TGF-beta can lead to the development of both Th1 and Th2 cells, depending on the concentration of these cytokines. Additional experiments revealed that Th1 induction by a combination of IL-4 and TGF-beta depends on the presence of endogenous IFN-gamma, and that this alternative Th1 development is further enhanced by IL-12, but is not dependent on this cytokine. Moreover, naive OVA323-339-specific Th cells that were stimulated by APCs and OVA323-339 peptide differentiated toward Th1 cells after priming in the presence of IL-4 in combination with TGF-beta. Hence, this finding confirmed the results obtained by polyclonal activation of naive CD4+ Th cells and implicates that this alternative Th1 development may also occur in vivo under the influence of TGF-beta and IL-4 independently of the Th1-promoting effect of IL-12.

Animals↗

Th1 development of naive CD4+ T cells is inhibited by co-activation with anti-CD4 monoclonal antibodies.

Co-activation of CD4+ T cells by anti-CD4 mAb strongly enhances the proliferation of these T cells. We have analyzed the influence of CD4-mediated co-activation on Th cell differentiation. Our data demonstrate that activation of high density (HD)-CD4+ T cells by immobilized anti-CD3 mAb in combination with immobilized anti-CD4 mAb led to a strong inhibition of Th1 differentiation and to a variable but significant induction of Th2 development. Priming of highly enriched Mel-14highCD4+ T cells in the presence of anti-CD4 mAb also resulted in a pronounced suppression of secondary IFN-gamma production, indicating that the Th1 development of naive CD4+ T cells is inhibited by co-activation via CD4. In contrast to HD-CD4+ T cells, CD4-induced costimulation of MEL-14highCD4+ T cells did not result in a primary and secondary IL-4 production. Hence, these results suggest that a MEL-14low population within the HD-CD4+ T cell fraction was the source of the endogenous IL-4 and imply, in addition, that co-activation via CD4 inhibits the development of Th1 cells from naive CD4+ T cells independently from endogenous IL-4. This assumption is further corroborated by the fact that neither the application of neutralizing anti-IL-4 mAb nor the use of T cells from IL-4 knockout mice could prevent CD4-mediated inhibition of Th1 development. The Th1-inhibiting effect of anti-CD4 mAb could not be reversed by the application of the Th1 inducer IL-12. On the contrary, the secondary IL-4 production of HD-CD4+ T cells as an indicator of Th2 differentiation, which was promoted by anti-CD4 mAb, was enhanced even in the presence of IL-12. Therefore, our results suggest that co-activation of naive CD4+ T cells by anti-CD4 mAb directly and selectively inhibits Th1 differentiation of naive dense CD4+ T cells.

Animals↗

Opposing effects of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells isolated from different mouse strains.

The development of naive dense CD4+ T cells from different mouse strains toward Th1 cells, as monitored by measuring secondary IFN-gamma production, was affected by TGF-beta 2 in a differential way. Th1 cell development of naive CD4+ T cells from strains C57Bl/6, BALB/c, and NMRI primed by immobilized anti-CD3 mAb was strongly inhibited in the presence of TGF-beta 2. Even when the Th1 cell-inducer IL-12 was added, the same effect of TGF-beta 2 was observed. In contrast, Th1 development was substantially promoted by TGF-beta 2 with T cells from C3H/He and CBA/J mice. Further analyses using CD4+ T cells from (C57Bl/6xCBA/J)F1 hybrids or DBA/1 mice showed that Th1 development was inhibited by TGF-beta 2 if the T cells were activated by anti-CD3 mAb, but it was enhanced upon costimulation with anti-CD28 mAb. Determination of primary IL-2 production revealed that T cells from (C57Bl/6xCBA/J)F1 and DBA/1 mice produced low amounts of IL-2 following stimulation by anti-CD3 mAb alone and comparatively high amounts after coactivation by anti-CD28 mAb. In the presence of TGF-beta 2, the production of IL-2 was completely suppressed if such T cells were activated solely by anti-CD3 mAb, but it was only partially inhibited after costimulation by anti-CD28 mAb. Furthermore, TGF-beta 2-promoted Th1 development of such T cells was strongly inhibited after neutralization of endogenously produced IL-2 and completely restored by the addition of human IL-2. Thus, our results indicate that the TGF-beta 2-mediated stimulation of Th1 cell development requires the presence of relatively high concentrations of IL-2. Therefore, the opposing effect of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells from different mouse strains appears to be the result of the variable potency of the respective CD4+ T cells to produce IL-2 in the presence of TGF-beta 2.

Animals↗

Co-activation of naive CD4+ T cells and bone marrow-derived mast cells results in the development of Th2 cells.

Activation of naive dense CD4+ T cells by plate-bound anti-CD3 antibodies favors the development of Th1 cells which, upon re-stimulation, produce significant amounts of IFN-gamma but no IL-4. However, co-activation of such naive T cells in the presence of IgE [anti-dinitrophenyl (DNP)]-loaded bone marrow-derived mast cells (BMMC) on plates coated with anti-CD3 antibodies and DNP-BSA led to the development of IL-4-producing Th2 cells. The same result could be observed if irradiated (800 rad) BMMC were applied as co-stimulators. Moreover, BMMC could be replaced by the supernatant of IgE-activated BMMC suggesting that a soluble mediator, presumably IL-4, was responsible for this effect. This assumption was substantiated using neutralizing anti-IL-4 antibodies which abolished the BMMC-mediated Th2 development in all cases. Addition of IL-12, a cytokine that was shown to antagonize the Th2-promoting effect of IL-4 in vivo, could not inhibit the development of IL-4-producing T cells, but gave rise to a T cell population which produced relatively high amounts of IL-4 and IFN-gamma. Since BMMC represent the in vitro equivalent of mucosal mast cells these data suggest that IgE-activated mucosal mast cells can bias an emerging T cell dependent immune response towards a Th2 dominated reaction by the initial production of IL-4.

Animals↗

IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF-beta and IL-4, and is inhibited by IFN-gamma.

Dense CD4+ T cells isolated from naive mice produce only trace amounts of IL-9 when stimulated by immobilized anti-CD3 in combination with anti-CD28 Abs. In this situation, IL-9 production is significantly stimulated by TGF-beta and further enhanced by the addition of IL-4, which, by itself, has only a minimal influence. IFN-gamma was found to inhibit the enhancing effect of IL-4. However, increasing amounts of IL-4 in the presence of a constant concentration of IFN-gamma could overcome the inhibitory activity of IFN-gamma. The application of CD4+ T cells isolated from IL-2 knockout mice unequivocally revealed that IL-2 is essential for the production of IL-9 by T cells. In addition, the use of T cells from IL-4 knockout mice elucidated that the basic (IL-2 + TGF-beta) mediated IL-9 production is independent of IL-4. Therefore, our results demonstrate that optimal IL-9 production of naive dense CD4+ T cells is positively regulated at different levels: 1) by IL-2, which is essential for IL-9 secretion; 2) followed by TGF-beta, which promotes a considerable increase in IL-9 production above the level induced by IL-2; and 3) finally, by IL-4, which requires the presence of IL-2 and TGF-beta to strongly enhance the production of IL-9. IFN-gamma inhibits the production of IL-9 mainly at the level of IL-4 by neutralizing the effect of this cytokine.

Animals↗

Co-development of naive CD4+ cells towards T helper type 1 or T helper type 2 cells induced by a combination of IL-12 and IL-4.

Cytokines were found to play a key role in Th cell differentiation. Among them IL-12 was shown to be a potent differentiation factor for Th1 cells, whereas IL-4 is the only known cytokine that promotes the development of Th2 cells. Upon addition of comparable amounts of IL-4 and IL-12 to a primary culture of naive CD4+ T cells activated by immobilized anti-CD3 mAb, it was found that the Th1-inducing capacity of IL-12 is dominated by the Th2-promoting effect of IL-4. However, high amounts of IL-12 (10,000 U/ml) in combination with low amounts of IL-4 (100 U/ml) led to the development of a Th cell population that, upon rechallenge, showed a substantial secondary IFN-gamma (Th1 cytokine) production concomitantly with the production of high amounts of IL-4 (Th2 cytokine). This can be due to the coexistence of Th1 and Th2 cells or to the development of Th0 cells producing a mixed pattern of cytokines. Immunofluorescence double staining of intracellular IL-4 and IFN-gamma in combination with flow cytometry (FACS) revealed that most of the emerging Th cells produced either IL-4 or IFN-gamma. Only a few double producers could be detected. This finding indicates that individual naive CD4+ T cells can differentiate under the same conditions towards Th1 or Th2 cells and implicates that the development of Th1 and Th2 cells is not necessarily mutually exclusive.

Animals↗