Degenerative disc disease is associated with increased expression of pro-inflammatory cytokines in the intervertebral disc (IVD). However, it is not completely clear how inflammation arises in the IVD and which cellular compartments are involved in this process. Recently, the endoplasmic reticulum (ER) has emerged as a possible modulator of inflammation in age-related disorders. In addition, ER stress has been associated with the microenvironment of degenerated IVDs. Therefore, the aim of this study was to analyze the effects of ER stress on inflammatory responses in degenerated human IVDs and associated molecular mechanisms. Gene expression of ER stress marker GRP78 and pro-inflammatory cytokines IL-6, IL-8, IL-1 beta, and TNF-alpha was analyzed in human surgical IVD samples (n = 51, Pfirrmann grade 2-5). The expression of GRP78 positively correlated with the degeneration grade in lumbar IVDs and IL-6, but not with IL-1 beta and TNF-alpha. Another set of human surgical IVD samples (n = 25) was used to prepare primary cell cultures. ER stress inducer thapsigargin (Tg, 100 and 500 nM) activated gene and protein expression of IL-6 and induced phosphorylation of p38 MAPK. Both inhibition of p38 MAPK by SB203580 (10 mu M) and knockdown of ER stress effector CCAAT-enhancer-binding protein homologous protein (CHOP) reduced gene and protein expression of IL-6 in Tg-treated cells. Furthermore, the effects of an inflammatory microenvironment on ER stress were tested. TNF-alpha (5 and 10 ng/mL) did not activate ER stress, while IL-1 beta (5 and 10 ng/mL) activated gene and protein expression of GRP78, but did not influence [Ca2+](i) flux and expression of CHOP, indicating that pro-inflammatory cytokines alone may not induce ER stress in vivo. This study showed that IL-6 release in the IVD can be initiated following ER stress and that ER stress mediates IL-6 release through p38 MAPK and CHOP. Therapeutic targeting of ER stress response may reduce the consequences of the harsh microenvironment in degenerated IVD.

Introduction: The goal of the present study was to identify the prospective relations between weight/shape and muscularity concerns and emotional problems in adolescents. Methods: Self-report data of 966 German male and female adolescents were analyzed in a cross lagged panel design. Results: Analyses of latent means revealed significant correlations between weight/shape concern and emotional problems as well as between muscularity concern and emotional problems in both genders. Moreover, weight/shape concern predicted emotional problems prospectively, but only in girls. Regarding muscularity concern, we could not find any prospective relation with emotional problems In boys or girls from the general population. Conclusions: It is assumed that as appearance is highly relevant for the self-concept in girls, concerns about the look might promote emotional problems. Thus, weight/shape concern should be addressed in the prevention of emotional problems in adolescent girls, whereas further research is necessary investigating the contribution of muscularity concern in this context.

Conceptual knowledge about objects, people and events in the world is central to human cognition, underlying core cognitive abilities such as object recognition and use, and word comprehension. Previous research indicates that concepts consist of perceptual and motor features represented in modality-specific perceptual-motor brain regions. In addition, cross-modal convergence zones integrate modality-specific features into more abstract conceptual representations. However, several questions remain open: First, to what extent does the retrieval of perceptual-motor features depend on the concurrent task? Second, how do modality-specific and cross-modal regions interact during conceptual knowledge retrieval? Third, which brain regions are causally relevant for conceptually-guided behavior? This thesis addresses these three key issues using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in the healthy human brain. Study 1 - an fMRI activation study - tested to what extent the retrieval of sound and action features of concepts, and the resulting engagement of auditory and somatomotor brain regions depend on the concurrent task. 40 healthy human participants performed three different tasks - lexical decision, sound judgment, and action judgment - on words with a high or low association to sounds and actions. We found that modality-specific regions selectively respond to task-relevant features: Auditory regions selectively responded to sound features during sound judgments, and somatomotor regions selectively responded to action features during action judgments. Unexpectedly, several regions (e.g. the left posterior parietal cortex; PPC) exhibited a task-dependent response to both sound and action features. We propose these regions to be "multimodal", and not "amodal", convergence zones which retain modality-specific information. Study 2 - an fMRI connectivity study - investigated the functional interaction between modality-specific and multimodal areas during conceptual knowledge retrieval. Using the above fMRI data, we asked (1) whether modality-specific and multimodal regions are functionally coupled during sound and action feature retrieval, (2) whether their coupling depends on the task, (3) whether information flows bottom-up, top-down, or bidirectionally, and (4) whether their coupling is behaviorally relevant. We found that functional coupling between multimodal and modality-specific areas is task-dependent, bidirectional, and relevant for conceptually-guided behavior. Left PPC acted as a connectivity "switchboard" that flexibly adapted its coupling to task-relevant modality-specific nodes. Hence, neuroimaging studies 1 and 2 suggested a key role of left PPC as a multimodal convergence zone for conceptual knowledge. However, as neuroimaging is correlational, it remained unknown whether left PPC plays a causal role as a multimodal conceptual hub. Therefore, study 3 - a TMS study - tested the causal relevance of left PPC for sound and action feature retrieval. We found that TMS over left PPC selectively impaired action judgments on low sound-low action words, as compared to sham stimulation. Computational simulations of the TMS-induced electrical field revealed that stronger stimulation of left PPC was associated with worse performance on action, but not sound, judgments. These results indicate that left PPC causally supports conceptual processing when action knowledge is task-relevant and cannot be compensated by sound knowledge. Our findings suggest that left PPC is specialized for action knowledge, challenging the view of left PPC as a multimodal conceptual hub. Overall, our studies support "hybrid theories" which posit that conceptual processing involves both modality-specific perceptual-motor regions and cross-modal convergence zones. In our new model of the conceptual system, we propose conceptual processing to rely on a representational hierarchy from modality-specific to multimodal up to amodal brain regions. Crucially, this hierarchical system is flexible, with different regions and connections being engaged in a task-dependent fashion. Our model not only reconciles the seemingly opposing grounded cognition and amodal theories, it also incorporates task dependency of conceptually-related brain activity and connectivity, thereby resolving several current issues on the neural basis of conceptual knowledge retrieval.

Conceptualisation is the first step of speech production and describes the process by which we map our thoughts onto spoken language. Recent studies suggest that some people with language impairments have conceptualisation deficits manifested by information selection and sequencing difficulties. In this study, we examined conceptualisation in the complex picture descriptions of individuals with and without aphasia. We analysed the number and the order of main concepts (ideas produced by >= 60% of unimpaired speakers) and non-main concepts (e.g. irrelevant details). Half of the individuals with aphasia showed a reduced number of main concepts that could not be fully accounted for by their language production deficits. Moreover, individuals with aphasia produced both a larger amount of marginally relevant information, as well as having greater variability in the order of main concepts. Both findings provide support for the idea that conceptualisation deficits are a relatively common impairment in people with aphasia.

Adaptive Force (AF) reflects the capability of the neuromuscular system to adapt adequately to external forces with the intention of maintaining a position or motion. One specific approach to assessing AF is to measure force and limb position during a pneumatically applied increasing external force. Through this method, the highest (AFmax), the maximal isometric (AFisomax) and the maximal eccentric Adaptive Force (AFeccmax) can be determined. The main question of the study was whether the AFisomax is a specific and independent parameter of muscle function compared to other maximal forces. In 13 healthy subjects (9 male and 4 female), the maximal voluntary isometric contraction (pre- and post-MVIC), the three AF parameters and the MVIC with a prior concentric contraction (MVICpri-con) of the elbow extensors were measured 4 times on two days. Arithmetic mean (M) and maximal (Max) torques of all force types were analyzed. Regarding the reliability of the AF parameters between days, the mean changes were 0.31–1.98 Nm (0.61%–5.47%, p = 0.175–0.552), the standard errors of measurements (SEM) were 1.29–5.68 Nm (2.53%–15.70%) and the ICCs(3,1) = 0.896–0.996. M and Max of AFisomax, AFmax and pre-MVIC correlated highly (r = 0.85–0.98). The M and Max of AFisomax were significantly lower (6.12–14.93 Nm; p ≤ 0.001–0.009) and more variable between trials (coefficient of variation (CVs) ≥ 21.95%) compared to those of pre-MVIC and AFmax (CVs ≤ 5.4%). The results suggest the novel measuring procedure is suitable to reliably quantify the AF, whereby the presented measurement errors should be taken into consideration. The AFisomax seems to reflect its own strength capacity and should be detected separately. It is suggested its normalization to the MVIC or AFmax could serve as an indicator of a neuromuscular function.