A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches

Functional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al

Cortical recovery of swallowing function in wound botulism

<p>Abstract</p> <p>Background</p> <p>Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology.</p> <p>Methods</p> <p>In this study, we applied whole-head magnetoencephalography (MEG) in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM).</p> <p>Results</p> <p>The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC). In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group.</p> <p>Conclusion</p> <p>These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.</p

The CNS Stochastically Selects Motor Plan Utilizing Extrinsic and Intrinsic Representations

Traditionally motor studies have assumed that motor tasks are executed according to a single plan characterized by regular patterns, which corresponds to the minimum of a cost function in extrinsic or intrinsic coordinates. However, the novel via-point task examined in this paper shows distinct planning and execution stages in motion production and demonstrates that subjects randomly select from several available motor plans to perform a task. Examination of the effect of pre-training and via-point orientation on subject behavior reveals that the selection of a plan depends on previous movements and is affected by constraints both intrinsic and extrinsic of the body. These results provide new insights into the hierarchical structure of motion planning in humans, which can only be explained if the current models of motor control integrate an explicit plan selection stage

Resistance to the CCR5 Inhibitor 5P12-RANTES Requires a Difficult Evolution from CCR5 to CXCR4 Coreceptor Use

Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC) or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16–18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a “resistant” variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching

A distinct role for B1b lymphocytes in T cell-independent immunity

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell memory, which requires the formation of germinal centers and T cells, the development of B1b cell-mediated long-lasting antibody responses occurs independent of T cell help. T cell-independent (TI) antigens are important virulence factors expressed by a number of bacterial pathogens, including those associated with biological threats. TI antigens cannot be processed and presented to T cells and therefore are known to possess restricted T cell-dependent (TD) immunogenicity. Nevertheless, specific recognition of TI antigens by B1b cells and the highly protective antibody responses mounted by them clearly indicate a crucial role for this subset of B cells. Understanding the mechanisms of long-term immunity conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI antigens

Measurement of pharyngeal sensory cortical processing: technique and physiologic implications

<p>Abstract</p> <p>Background</p> <p>Dysphagia is a major complication of different diseases affecting both the central and peripheral nervous system. Pharyngeal sensory impairment is one of the main features of neurogenic dysphagia. Therefore an objective technique to examine the cortical processing of pharyngeal sensory input would be a helpful diagnostic tool in this context. We developed a simple paradigm to perform pneumatic stimulation to both sides of the pharyngeal wall. Whole-head MEG was employed to study changes in cortical activation during this pharyngeal stimulation in nine healthy subjects. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test.</p> <p>Results</p> <p>Our results revealed bilateral activation of the caudolateral primary somatosensory cortex following sensory pharyngeal stimulation with a slight lateralization to the side of stimulation.</p> <p>Conclusion</p> <p>The method introduced here is simple and easy to perform and might be applicable in the clinical setting. The results are in keeping with previous findings showing bihemispheric involvement in the complex task of sensory pharyngeal processing. They might also explain changes in deglutition after hemispheric strokes. The ipsilaterally lateralized processing is surprising and needs further investigation.</p

Functional oropharyngeal sensory disruption interferes with the cortical control of swallowing

<p>Abstract</p> <p>Background</p> <p>Sensory input is crucial to the initiation and modulation of swallowing. From a clinical point of view, oropharyngeal sensory deficits have been shown to be an important cause of dysphagia and aspiration in stroke patients. In the present study we therefore investigated effects of functional oropharyngeal disruption on the cortical control of swallowing. We employed whole-head MEG to study cortical activity during self-paced volitional swallowing with and without topical oropharyngeal anesthesia in ten healthy subjects. A simple swallowing screening-test confirmed that anesthesia caused swallowing difficulties with decreased swallowing speed and reduced volume per swallow in all subjects investigated. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of the individual SAM data was performed using a permutation test.</p> <p>Results</p> <p>The analysis of normal swallowing revealed bilateral activation of the mid-lateral primary sensorimotor cortex. Oropharyngeal anesthesia led to a pronounced decrease of both sensory and motor activation.</p> <p>Conclusion</p> <p>Our results suggest that a short-term decrease in oropharyngeal sensory input impedes the cortical control of swallowing. Apart from diminished sensory activity, a reduced activation of the primary motor cortex was found. These findings facilitate our understanding of the pathophysiology of dysphagia.</p

A Compact Representation of Drawing Movements with Sequences of Parabolic Primitives

Some studies suggest that complex arm movements in humans and monkeys may optimize several objective functions, while others claim that arm movements satisfy geometric constraints and are composed of elementary components. However, the ability to unify different constraints has remained an open question. The criterion for a maximally smooth (minimizing jerk) motion is satisfied for parabolic trajectories having constant equi-affine speed, which thus comply with the geometric constraint known as the two-thirds power law. Here we empirically test the hypothesis that parabolic segments provide a compact representation of spontaneous drawing movements. Monkey scribblings performed during a period of practice were recorded. Practiced hand paths could be approximated well by relatively long parabolic segments. Following practice, the orientations and spatial locations of the fitted parabolic segments could be drawn from only 2–4 clusters, and there was less discrepancy between the fitted parabolic segments and the executed paths. This enabled us to show that well-practiced spontaneous scribbling movements can be represented as sequences (“words”) of a small number of elementary parabolic primitives (“letters”). A movement primitive can be defined as a movement entity that cannot be intentionally stopped before its completion. We found that in a well-trained monkey a movement was usually decelerated after receiving a reward, but it stopped only after the completion of a sequence composed of several parabolic segments. Piece-wise parabolic segments can be generated by applying affine geometric transformations to a single parabolic template. Thus, complex movements might be constructed by applying sequences of suitable geometric transformations to a few templates. Our findings therefore suggest that the motor system aims at achieving more parsimonious internal representations through practice, that parabolas serve as geometric primitives and that non-Euclidean variables are employed in internal movement representations (due to the special role of parabolas in equi-affine geometry)

Measured greenhouse gas budgets challenge emission savings from palm-oil biodiesel

Special thanks to our field assistants in Indonesia (Basri, Bayu and Darwis) and to Frank Tiedemann, Edgar Tunsch, Dietmar Fellert and Malte Puhan for technical assistance. We thank PTPN VI and the owner of the plantation at Pompa Air for allowing us to conduct our research at their plantation. We would also like to thank the Spanish national project GEISpain (CGL2014-52838-C2-1-R) and the DAAD (scholarship from the programme ‘Research Stays for University Academics and Scientist 2018, ref. no. 91687130)' for partly financing A. Meijide during the preparation of this paper.The potential of palm-oil biofuels to reduce greenhouse gas (GHG) emissions compared with fossil fuels is increasingly questioned. So far, no measurement-based GHG budgets were available, and plantation age was ignored in Life Cycle Analyses (LCA). Here, we conduct LCA based on measured CO2, CH4 and N2O fluxes in young and mature Indonesian oil palm plantations. CO2 dominates the on-site GHG budgets. The young plantation is a carbon source (1012 ± 51 gC m−2 yr−1), the mature plantation a sink (−754 ± 38 gC m−2 yr−1). LCA considering the measured fluxes shows higher GHG emissions for palm-oil biodiesel than traditional LCA assuming carbon neutrality. Plantation rotation-cycle extension and earlier-yielding varieties potentially decrease GHG emissions. Due to the high emissions associated with forest conversion to oil palm, our results indicate that only biodiesel from second rotation-cycle plantations or plantations established on degraded land has the potential for pronounced GHG emission savings.This study was financed by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)— Project-ID 192626868—in the framework of the collaborative German-Indonesian research project CRC990 (subprojects A03, A04 and A05).Spanish national project GEISpain (CGL2014-52838-C2-1-R) and the DAAD (scholarship from the programme ‘Research Stays for University Academics and Scientist 2018, ref. no. 91687130

Cortical swallowing processing in early subacute stroke

<p>Abstract</p> <p>Background</p> <p>Dysphagia is a major complication in hemispheric as well as brainstem stroke patients causing aspiration pneumonia and increased mortality. Little is known about the recovery from dysphagia after stroke. The aim of the present study was to determine the different patterns of cortical swallowing processing in patients with hemispheric and brainstem stroke with and without dysphagia in the early subacute phase.</p> <p>Methods</p> <p>We measured brain activity by mean of whole-head MEG in 37 patients with different stroke localisation 8.2 +/- 4.8 days after stroke to study changes in cortical activation during self-paced swallowing. An age matched group of healthy subjects served as controls. Data were analyzed by means of synthetic aperture magnetometry and group analyses were performed using a permutation test.</p> <p>Results</p> <p>Our results demonstrate strong bilateral reduction of cortical swallowing activation in dysphagic patients with hemispheric stroke. In hemispheric stroke without dysphagia, bilateral activation was found. In the small group of patients with brainstem stroke we observed a reduction of cortical activation and a right hemispheric lateralization.</p> <p>Conclusion</p> <p>Bulbar central pattern generators coordinate the pharyngeal swallowing phase. The observed right hemispheric lateralization in brainstem stroke can therefore be interpreted as acute cortical compensation of subcortically caused dysphagia. The reduction of activation in brainstem stroke patients and dysphagic patients with cortical stroke could be explained in terms of diaschisis.</p