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Evoked potentials in the amplitude-time spectrum of the electroencephalogram are commonly used to assess the extent of brain responses to stimulation with noxious contact heat. The magnitude of the N- and P-waves are used as a semi-objective measure of the response to the painful stimulus: the higher the magnitude, the more painful the stimulus has been perceived. The strength of the N-P-wave response is also largely dependent on the chosen reference electrode site. The goal of this study was to examine which reference technique excels both in practical and theoretical terms when analyzing noxious contact heat evoked potentials (CHEPS) in the amplitude-time spectrum. We recruited 21 subjects (10 male, 11 female, mean age of 55.79 years). We applied seven noxious contact heat stimuli using two temperatures, 51°C, and 54°C, to each subject. During EEG analysis, we aimed to identify the referencing technique which produces the highest N-wave and P-wave amplitudes with as little artifactual influence as possible. For this purpose, we applied the following six referencing techniques: mathematically linked A1/A2 (earlobes), average reference, REST, AFz, Pz, and mathematically linked PO7/PO8. We evaluated how these techniques impact the N-P amplitudes of CHEPS based on our data from healthy subjects. Considering all factors, we found that mathematically linked earlobes to be the ideal referencing site to use when displaying and evaluating CHEPS in the amplitude-time spectrum.
Background and objectives: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
Methods: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)–based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).
Results: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = − 0.65; RA patients: g*max = 0.72).
Conclusion: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment.
The scope of this thesis is to elaborate on the use cases of the EEG in pain research. It has been submitted as a cumulative dissertation, meaning that the main part of this thesis has been previously published in international peer-reviewed journals. The first part of this thesis begins with an introduction which describes the general methodoligcal considerations and theoretical background information that is needed to perform pain research using the EEG. Then, I will give a summary of the results of all three studies and the subsequently published manuscripts. The discussion will give an outlook on two ongoing projects and elaborate how the methodology that has been compiled throughout my time as a PhD student can be further applied to scientific problems in pain research. I will conclude with the possibilities and the limitations of the EEG in pain research. The second part of this thesis consists of three publications that cover three individual studies, of which I am the lead/first author. These publications describe different use cases for the EEG in pain research. The first publication lays out the methodological backbone of this thesis, analyzing the exact EEG parameters that are needed to achieve the results in the following projects. Then, I present two additional studies. The first study describes the usefulness of pain-related evoked signatures after standardized noxious stimulation in the EEG in patients undergoing general anesthesia. The second study outlines differences in the pain processing of elite endurance athletes versus a normally active control group. Furthermore, it outlines how the function of the endogenous pain modulatory system can be measured in the EEG using CPM. All studys are discussed individually as per the journal guidelines.
Large-scale genetic census of an elusive carnivore, the European wildcat (Felis s. silvestris)
(2016)
The European wildcat, Felis silvestris silvestris, serves as a prominent target species for the reconnection of central European forest habitats. Monitoring of this species, however, appears difficult due to its elusive behaviour and the ease of confusion with domestic cats. Recently, evidence for multiple wildcat occurrences outside its known distribution has accumulated in several areas across Central Europe, questioning the validity of available distribution data for this species. Our aim was to assess the fine-scale distribution and genetic status of the wildcat in its central European distribution range. We compiled and analysed genetic samples from roadkills and hundreds of recent hair-trapping surveys and applied phylogenetic and genetic clustering methods to discriminate wild and domestic cats and identify population subdivision. 2220 individuals were confirmed as either wildcat (n = 1792) or domestic cat (n = 342), and the remaining 86 (3.9 %) were identified as hybrids between the two. Remarkably, genetic distinction of domestic cats, wildcats and their hybrids was only possible when taking into account the presence of two highly distinct genetic lineages of wildcats, with a suture zone in central Germany. 44 % of the individual wildcats where sampled outside the previously published distribution. Our analyses confirm a relatively continuous spatial presence of wildcats across large parts of the study area in contrast to previous analyses indicating a highly fragmented distribution. Our results suggest that wildcat conservation and management should take advantage of the higher than previously assumed dispersal potential of wildcats, which may use wildlife corridors very efficiently.
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.