9,260 research outputs found
Pollution-induced community tolerance in freshwater biofilms – from molecular mechanisms to loss of community functions
Exposure to herbicides poses a threat to aquatic biofilms by affecting their community structure, physiology and function. These changes render biofilms to become more tolerant, but on the downside community tolerance has ecologic costs. A concept that addresses induced community tolerance to a pollutant (PICT) was introduced by Blanck and Wängberg (1988). The basic principle of the concept is that microbial communities undergo pollution-induced succession when exposed to a pollutant over a long period of time, which changes communities structurally and functionally and enhancing tolerance to the pollutant exposure. However, the mechanisms of tolerance and the ecologic consequences were hardly studied up to date. This thesis addresses the structural and functional changes in biofilm communities and applies modern molecular methods to unravel molecular tolerance mechanisms.
Two different freshwater biofilm communities were cultivated for a period of five weeks, with one of the communities being contaminated with 4 μg L-1 diuron. Subsequently, the communities were characterized for structural and functional differences, especially focusing on their crucial role of photosynthesis. The community structure of the autotrophs was assessed using HPLC-based pigment analysis and their functional alterations were investigated using Imaging-PAM fluorometry to study photosynthesis and community oxygen profiling to determine net primary production. Then, the molecular fingerprints of the communities were measured with meta-transcriptomics (RNA-Seq) and GC-based community metabolomics approaches and analyzed with respect to changes in their molecular functions. The communities were acute exposed to diuron for one hour in a dose-response design, to reveal a potential PICT and uncover related adaptation to diuron exposure. The combination of apical and molecular methods in a dose-response design enabled the linkage of functional effects of diuron exposure and underlying molecular mechanisms based on a sensitivity analysis.
Chronic exposure to diuron impaired freshwater biofilms in their biomass accrual. The contaminated communities particularly lost autotrophic biomass, reflected by the decrease in specific chlorophyll a content. This loss was associated with a change in the molecular fingerprint of the communities, which substantiates structural and physiological changes. The decline in autotrophic biomass could be due to a primary loss of sensitive autotrophic organisms caused by the selection of better adapted species in the course of chronic exposure. Related to this hypothesis, an increase in diuron tolerance has been detected in the contaminated communities and molecular mechanisms facilitating tolerance have been found. It was shown that genes of the photosystem, reductive-pentose phosphate cycle and arginine metabolism were differentially expressed among the communities and that an increased amount of potential antioxidant degradation products was found in the contaminated communities. This led to the hypothesis that contaminated communities may have adapted to oxidative stress, making them less sensitive to diuron exposure. Moreover, the photosynthetic light harvesting complex was altered and the photoprotective xanthophyll cycle was increased in the contaminated communities. Despite these adaptation strategies, the loss of autotrophic biomass has been shown to impair primary production. This impairment persisted even under repeated short-term exposure, so that the tolerance mechanisms cannot safeguard primary production as a key function in aquatic systems.:1. The effect of chemicals on organisms and their functions .............................. 1
1.1 Welcome to the anthropocene .......................................................................... 1
1.2 From cellular stress responses to ecosystem resilience ................................... 3
1.2.1 The individual pursuit for homeostasis ....................................................... 3
1.2.2 Stability from diversity ................................................................................. 5
1.3 Community ecotoxicology - a step forward in monitoring the effects of chemical
pollution? ................................................................................................................. 6
1.4 Functional ecotoxicological assessment of microbial communities ................... 9
1.5 Molecular tools – the key to a mechanistic understanding of stressor effects
from a functional perspective in microbial communities? ...................................... 12
2. Aims and Hypothesis ......................................................................................... 14
2.1 Research question .......................................................................................... 14
2.2 Hypothesis and outline .................................................................................... 15
2.3 Experimental approach & concept .................................................................. 16
2.3.1 Aquatic freshwater biofilms as model community ..................................... 16
2.3.2 Diuron as model herbicide ........................................................................ 17
2.3.3 Experimental design ................................................................................. 18
3. Structural and physiological changes in microbial communities after chronic
exposure - PICT and altered functional capacity ................................................. 21
3.1 Introduction ..................................................................................................... 21
3.2 Methods .......................................................................................................... 23
3.2.1 Biofilm cultivation ...................................................................................... 23
3.2.2 Dry weight and autotrophic index ............................................................. 23
3.2.4 Pigment analysis of periphyton ................................................................. 23
3.2.4.1 In-vivo pigment analysis for community characterization ....................... 24
3.2.4.2 In-vivo pigment analysis based on Imaging-PAM fluorometry ............... 24
3.2.4.3 In-vivo pigment fluorescence for tolerance detection ............................. 26
3.2.4.4 Ex-vivo pigment analysis by high-pressure liquid-chromatography ....... 27
3.2.5 Community oxygen metabolism measurements ....................................... 28
3.3 Results and discussion ................................................................................... 29
3.3.1 Comparison of the structural community parameters ............................... 29
3.3.2 Photosynthetic activity and primary production of the communities after
selection phase ................................................................................................. 33
3.3.3 Acquisition of photosynthetic tolerance .................................................... 34
3.3.4 Primary production at exposure conditions ............................................... 36
3.3.5 Tolerance detection in primary production ................................................ 37
3.4 Summary and Conclusion ........................................................................... 40
4. Community gene expression analysis by meta-transcriptomics ................... 41
4.1 Introduction to meta-transcriptomics ............................................................... 41
4.2. Methods ......................................................................................................... 43
4.2.1 Sampling and RNA extraction................................................................... 43
4.2.2 RNA sequencing analysis ......................................................................... 44
4.2.3 Data assembly and processing................................................................. 45
4.2.4 Prioritization of contigs and annotation ..................................................... 47
4.2.5 Sensitivity analysis of biological processes .............................................. 48
4.3 Results and discussion ................................................................................... 48
4.3.1 Characterization of the meta-transcriptomic fingerprints .......................... 49
4.3.2 Insights into community stress response mechanisms using trend analysis
(DRomic’s) ......................................................................................................... 51
4.3.3 Response pattern in the isoform PS genes .............................................. 63
4.5 Summary and conclusion ................................................................................ 65
5. Community metabolome analysis ..................................................................... 66
5.1 Introduction to community metabolomics ........................................................ 66
5.2 Methods .......................................................................................................... 68
5.2.1 Sampling, metabolite extraction and derivatisation................................... 68
5.2.2 GC-TOF-MS analysis ............................................................................... 69
5.2.3 Data processing and statistical analysis ................................................... 69
5.3 Results and discussion ................................................................................... 70
5.3.1 Characterization of the metabolic fingerprints .......................................... 70
5.3.2 Difference in the metabolic fingerprints .................................................... 71
5.3.3 Differential metabolic responses of the communities to short-term exposure
of diuron ............................................................................................................ 73
5.4 Summary and conclusion ................................................................................ 78
6. Synthesis ............................................................................................................. 79
6.1 Approaches and challenges for linking molecular data to functional
measurements ...................................................................................................... 79
6.2 Methods .......................................................................................................... 83
6.2.1 Summary on the data ............................................................................... 83
6.2.2 Aggregation of molecular data to index values (TELI and MELI) .............. 83
6.2.3 Functional annotation of contigs and metabolites using KEGG ................ 83
6.3 Results and discussion ................................................................................... 85
6.3.1 Results of aggregation techniques ........................................................... 85
6.3.2 Sensitivity analysis of the different molecular approaches and endpoints 86
6.3.3 Mechanistic view of the molecular stress responses based on KEGG
functions ............................................................................................................ 89
6.4 Consolidation of the results – holistic interpretation and discussion ............... 93
6.4.1 Adaptation to chronic diuron exposure - from molecular changes to
community effects.............................................................................................. 93
6.4.2 Assessment of the ecological costs of Pollution-induced community
tolerance based on primary production ............................................................. 94
6.5 Outlook ............................................................................................................ 9
Examples of works to practice staccato technique in clarinet instrument
Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato
geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı
sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de
durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt
çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham
verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her
aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır.
Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine
yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini
içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin
kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür
taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de
kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt
çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve
güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının
girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken
doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir
kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına
bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği
vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan
çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur.
Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir.
Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır.
Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların
yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve
sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır
The temporality of rhetoric: the spatialization of time in modern criticism
Every conception of criticism conceals a notion of time which informs the manner in which the critic conceives of history, representation and criticism itself. This thesis reveals the philosophies of time inherent in certain key modern critical concepts: allegory, irony and the sublime. Each concept opens a breach in time, a disruption of chronology. In each case this gap or aporia is emphatically closed, elided or denied. Taking the philosophy of time elaborated by Giorgio Agamben as an introductory proposition, my argument turns in Chapter One to the allegorical temporality which Walter Benjamin sees as the time of photography. The second chapter examines the aesthetics of the sublime as melancholic or mournful untimeliness. In Chapter Three, Paul de Man's conception of irony provides an exemplary instance of the denial of this troubling temporal predicament. In opposition to the foreclosure of the disturbing temporalities of criticism, history and representation, the thesis proposes a fundamental rethinking of the philosophy of time as it relates to these categories of reflection. In a reading of an inaugural meditation on the nature of time, and in examining certain key contemporary philosophical and critical texts, I argue for a critical attendance to that which eludes those modes of thought that attempt to map time as a recognizable and essentially spatial field. The Confessions of Augustine provide, in the fourth chapter, a model for thinking through the problems set up earlier: Augustine affords us, precisely, a means of conceiving of the gap or the interim. In the final chapter, this concept is developed with reference to the criticism of Arnold and Eliot, the fiction of Virginia Woolf and the philosophy of cinema derived from Deleuze and Lyotard. In conclusion, the philosophical implications of the thesis are placed in relation to a conception of the untimeliness of death
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Co-design As Healing: Exploring The Experiences Of Participants Facing Mental Health Problems
This thesis is an exploration of the healing role of co-design in mental health. Although co-design projects conducted within mental health settings are rising, existing literature tends to focus on the object of design and its outcomes while the experiences of participants per se remain largely unexplored. The guiding research question of this study is not how we design things that improve mental health, but how co-designing, as an act, might do so.
The thesis presents two projects that were organized in collaboration with the mental health charity Islington Mind and the Psychosis Therapy Project (PTP) in London.
The project at Islington Mind used a structured design process inviting participants to design for wellbeing. A case study analysis provides insights on how participants were impacted, summarizing key challenges and opportunities.
The design at PTP worked towards creating a collective brief in an emergent fashion, finally culminating in a board game. The experiences of participants were explored through Interpretative Phenomenological Analysis (IPA), using semi-structured interview data. The analysis served to identify key themes characterising the experience of co-design such as contributing, connecting, thinking and intentioning. In addition, a mixed-methods analysis of questionnaires and interview data exploring participants' wellbeing, showed that all participants who engaged fairly consistently in the project improved after the project ended, although some participants' scores returned to baseline six months later.
Reflecting on both projects, an approach to facilitation within mental health is outlined, detailing how the dimensions of weaving and layered participation, nurturing mattering and facilitating attitudes interlace. This contribution raises awareness of tacit dimensions in the practice of facilitation, articulating the nuances of how to encourage and sustain meaningful and ethical engagement and offering insights into a range of tools. It highlights the importance of remaining reflexive in relation to attitudes and emotions and discusses practical methodological and ethical challenges and ways to resolve them which can be of benefit to researchers embarking on a similar journey.
The thesis also offers detailed insights on how methodologies from different fields were integrated into a whole, arguing for transparency and reflexivity about epistemological assumptions, and how underlying paradigms shift in an interdisciplinary context.
Based on the overall findings, the thesis makes a case for considering design as healing (or a designerly way of healing), highlighting implications at a systems, social and individual level. It makes an original contribution to our understanding of design, highlighting its healing character, and proposes a new way to support mental health. The participants in this study not only had increased their own wellbeing through co-designing, but were also empowered and contributed towards healing the world. Hence, the thesis argues for a unique, holistic perspective of design and mental health, recognizing the interconnectedness of the individual, social and systemic dimensions of the healing processes that are ignited
Optimising acoustic cavitation for industrial application
The ultrasonic horn is one of the most commonly used acoustic devices in laboratories and industry. For its efficient application to cavitation mediated process, the cavitation generated at its tip as a function of its tip-vibration amplitudes still needed to be studied in detail. High-speed imaging and acoustic detection are used to investigate the cavitation generated at the tip of an ultrasonic horn, operating at a fundamental frequency, f0, of 20 kHz. Tip-vibration amplitudes are sampled at fine increments across the range of input powers available. The primary bubble cluster under the tip is found to undergo subharmonic periodic collapse, with concurrent shock wave emission, at frequencies of f0/m, with m increasing through integer values with increasing tip-vibration amplitude. The contribution of periodic shock waves to the noise spectra of the acoustic emissions is confirmed. Transitional input powers for which the value of m is indistinct, and shock wave emission irregular and inconsistent, are identified through Vrms of the acoustic detector output. For cavitation applications mediated by bubble collapse, sonications at transitional powers may lead to inefficient processing. The ultrasonic horn is also deployed to investigate the role of shock waves in the fragmentation of intermetallic crystals, nominally for ultrasonic treatment of Aluminium melt, and in a novel two-horn configuration for potential cavitation enhancement effects. An experiment investigating nitrogen fixation via cavitation generated by focused ultrasound exposures is also described. Vrms from the acoustic detector is again used to quantify the acoustic emissions for comparison to the sonochemical nitrite yield and for optimisation of sonication protocols at constant input energy. The findings revealed that the acoustic cavitation could be enhanced at constant input energy through optimisation of the pulse duration and pulse interval. Anomalous results may be due to inadequate assessment for the nitrate generated. The studies presented in this thesis have illustrated means of improving the cavitation efficiency of the used acoustic devices, which may be important to some selected industrial processes
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Brain signal recognition using deep learning
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityBrain Computer Interface (BCI) has the potential to offer a new generation of applications independent of
muscular activity and controlled by the human brain. Brain imaging technologies are used to transfer the
cognitive tasks into control commands for a BCI system. The electroencephalography (EEG) technology
serves as the best available non-invasive solution for extracting signals from the brain. On the other hand,
speech is the primary means of communication, but for patients suffering from locked-in syndrome, there
is no easy way to communicate. Therefore, an ideal communication system for locked-in patients is a
thought-to-speech BCI system.
This research aims to investigate methods for the recognition of imagined speech from EEG signals
using deep learning techniques. In order to design an optimal imagined speech recognition BCI, variety
of issues have been solved. These include 1) proposing new feature extraction and classification
framework for recognition of imagined speech from EEG signals, 2) grammatical class recognition of
imagined words from EEG signals, 3) discriminating different cognitive tasks associated with speech in
the brain such as overt speech, covert speech, and visual imagery. In this work machine learning, deep
learning methods were used to analyze EEG signals.
For recognition of imagined speech from EEG signals, a new EEG database was collected while the
participants mentally spoke (imagined speech) the presented words. Along with imagined speech, EEG
data was recorded for visual imagery (imagining a scene or an image) and overt speech (verbal speech).
Spectro-temporal and spatio-temporal domain features were investigated for the classification of imagined
words from EEG signals. Further, a deep learning framework using the convolutional network
and attention mechanism was implemented for learning features in the spatial, temporal, and spectral
domains. The method achieved a recognition rate of 76.6% for three binary word pairs. These experiments
show that deep learning algorithms are ideal for imagined speech recognition from EEG signals
due to their ability to interpret features from non-linear and non-stationary signals. Grammatical classes
of imagined words from EEG signals were also recognized using a multi-channel convolution network
framework. This method was extended to a multi-level recognition system for multi-class classification
of imagined words which achieved an accuracy of 52.9% for 10 words, which is much better in
comparison to previous work.
In order to investigate the difference between imagined speech with verbal speech and visual imagery
from EEG signals, we used multivariate pattern analysis (MVPA). MVPA provided the time segments
when the neural oscillation for the different cognitive tasks was linearly separable. Further, frequencies
that result in most discrimination between the different cognitive tasks were also explored. A framework
was proposed to discriminate two cognitive tasks based on the spatio-temporal patterns in EEG signals.
The proposed method used the K-means clustering algorithm to find the best electrode combination and
convolutional-attention network for feature extraction and classification. The proposed method achieved
a high recognition rate of 82.9% and 77.7%.
The results in this research suggest that a communication based BCI system can be designed using
deep learning methods. Further, this work add knowledge to the existing work in the field of communication
based BCI system
AIUCD 2022 - Proceedings
L’undicesima edizione del Convegno Nazionale dell’AIUCD-Associazione di Informatica Umanistica ha per titolo Culture digitali. Intersezioni: filosofia, arti, media. Nel titolo è presente, in maniera esplicita, la richiesta di una riflessione, metodologica e teorica, sull’interrelazione tra tecnologie digitali, scienze dell’informazione, discipline filosofiche, mondo delle arti e cultural studies
Management Matters : Organizational Storytelling within the Anthroposophical Society in Sweden
The Anthroposophical Society, founded by the Austrian polymath Rudolf Steiner, came to Sweden in 1913, but for the generation of present-day Swedish Anthroposophists whose voices are heard in this study, the great flowering of the movement occurred in the second half of the twentieth century. The movement had by then expanded into a large milieu with many largely independent enterprises and institutions, from the formal organization itself, to various schools, farms, shops, medical facilities, etc., all based on interpretations of Steiner’s legacy. Since then, many members of the movement feel, there has been a decline.
A movement of this size and complexity can be seen as a large organization with a corporate-like structure. Taking its point of departure in ideas from the vast field of organization studies, and specifically in the study of storytelling as part of the creation of a corporate culture where many voices and many perspectives co-exist, this study investigates how Anthroposophists in Sweden, both rank and-file members and some who served in leadership positions, tell the story of the putative Golden Age, decline, and projected future of Anthroposophy in Sweden. Twenty-eight interviews were collected, recurrent themes identified, and the plots of the various individual stories analyzed by means of a version of the actantial model developed by the semioticist Algirdas Greimas.
The basic storyline, of which the interviewees’ individual stories constitute variations, is that the Golden Age, when charismatic leaders could draw crowds of enthusiastic young people and a vibrant Anthroposophical milieu was built up, came to an end with the demise of those leaders. The present, i.e., the time at which the interviews were conducted, is narratively framed as a period of sharp decline. The vistas for the future come across in most stories as quite bleak. An actantial analysis reveals that the past, an epoch that is on one hand held up as a shining example is on the other hand also described as a time characterized by innumerable problems and conflicts. Disagreement is rampant regarding the reasons for the current decline, and a vast number of problems are identified in the individual narratives. The future is for some interviewees impossible to speculate about, whereas others have specific suggestions for change. These suggestions, when held up against each other, show that there is no unified vision of what the necessary changes might be or who must bring them about.
The interviewees agree that Anthroposophy plays a vital role as a spiritual path. When asked how they would describe Anthroposophy and what it more specifically can offer, answers diverge, but substantive descriptions of core concepts or practices are rarely alluded to. Rather, their explanations of what Anthroposophy is are in almost all cases metaphorical or negative, i.e., they represent Anthroposophy as elusive or undefinable. Interviewees can suggest that the lack of a clear Anthroposophical “brand” is a major reason for its current perceived crisis. An analysis of the ways in which Rudolf Steiner is portrayed in the interview material shows that there are a variety of descriptions of him rather than a unified representation of a charismatic leader that members can rally around. This, the study suggests, is because four different forms of charisma can be distinguished on theoretical grounds, and the particular form that permeates the narratives collected for this study does not readily support the dissemination of a centralized, dominant narrative.Antroposofiska Sällskapet, grundat av österrikaren Rudolf Steiner, kom till Sverige redan i 1913, men för den generation av nutida svenska antroposofer vars röster hörs i denna studie inträffade rörelsens stora blomstringstid först under nittonhundratalets andra hälft. Vid det laget hade rörelsen expanderat och blivit till en omfattande miljö med många stort sett oberoende institutioner och verksamheter, från själva det Antroposofiska Sällskapet i strikt mening till olika skolor, lantbruk, butiker, kliniker, osv., som alla byggde på tolkningar av arvet efter Steiner. Många medlemmar i rörelsen menar att det sedan dess har skett en nedgång.
En rörelse med den storlek och komplexitet som det rör sig om i det aktuella fallet kan betraktas som en organisation med en företagsliknande struktur. Denna studie tar därför sin utgångspunkt i ett organisationsteoretiskt perspektiv, i synnerhet i den gren av organisationsteorin som studerar berättande som ett led i hur en organisationskultur med många samexisterande röster skapas. I det aktuella fallet handlar det om berättelser som antroposofer i Sverige, både vanliga medlemmar och personer i ledarställning, framför om den blomstringstid de menar rörelsen en gång hade, den nedgång de säger sig uppleva och den framtid de föreställer sig att antroposofin i Sverige kommer att möta. Tjugoåtta intervjuer genomfördes och de berättelser som förmedlas i dessa intervjuer analyserades med hjälp av en variant av den aktantmodell som utvecklats av semiotikern Algirdas Greimas.
Den grundläggande handling man återfinner i intervjupersonernas olika berättelser är att blomstringstiden var en guldålder då karismatiska ledare kunde samla stora grupper av entusiastiska ungdomar och en levande antroposofisk miljö byggdes upp, men att denna guldålder upphörde när ledarna gick ur tiden. Nuet, alltså den tid då intervjuerna genomfördes, beskrivs i berättelserna som en tid av förfall. Framtidsutsikterna som målas upp i de flesta berättelser är dystra. Aktantanalysen visar att berättelserna om det förflutna både beskriver denna tid i mycket positiva termer och nämner otaliga problem och konflikter. Nuets påstådda förfall återkommer i de flesta berättelser, men åsikterna går vitt isär när det gäller vad nutidens problem är och vad som orsakat dem. Framtiden beskrivs av vissa intervjupersoner som omöjlig att spekulera närmare om, medan andra har specifika förslag till förändringar. Sammantaget visar analysen att det saknas en enhetlig föreställning om vad som behöver göras för att lösa rörelsens problem och vem som ska ta ansvar för dessa förändringar.
Intervjupersonerna är eniga om att antroposofin spelar en viktig roll. Frågan hur de skulle beskriva antroposofin och vad den har att erbjuda besvaras på olika sätt, men sällan i termer av konkreta beskrivningar av för antroposofin centrala föreställningar eller praktiker. Tendensen är snarare att svara i metaforiska eller negativa termer, alltså genom att berätta att de menar att antroposofin inte går att definiera. Samtidigt kan intervjupersonerna förklara att bristen på en tydlig antroposofisk identitet är ett huvudskäl till vad de ser som rörelsens nuvarande kris. En analys av de sätt på vilka Rudolf Steiner beskrivs i intervjumaterialet visar att det också finns en rad divergerande uppfattningar av honom snarare än en sammanhållen beskrivning av en karismatisk ledare som medlemmarna kan samlas kring. Studien konkluderar att karisma på teoretiska grunder kan delas in i fyra olika typer, och att den specifika form av karisma som intervjuerna återspeglar inte harmonierar särskilt väl med spridandet av en centralt utformad dominerande berättelse
Influence of sensorimotor µ rhythm phase and power on motor cortex excitability and plasticity induction, assessed with EEG-triggered TMS
In dieser Arbeit werden zwei Experimente vorgestellt, bei denen EEG-getriggerte
transkranielle Magnetstimulation (TMS) an gesunden Probanden eingesetzt wurde,
um die Rolle des sensomotorischen 8-14Hz µ-Rhythmus auf die kortikospinale
Erregbarkeit (CSE) und die Induktion positiver Plastizität zu untersuchen. Unser
Ziel war es, für Plastizitätsinduktion günstige Zeitpunkte im EEG zu identifizieren,
um in Zukunft die Effektivität solcher zurzeit oft noch unzuverlässigen Anwendungen zu steigern. Unser EEG-TMS System interpretierte Oszillationen im EEG in
Echtzeit und löste einen Stimulus aus, wenn bestimmte, vorher festgelegte Eigenschaften zutrafen. Die ‘Gehirnwellen’ im EEG entstehen durch synchronisierte
Fluktuationen des Membranpotentials kortikaler Neurone, welche aufgrund ihrer
intrakortikalen Kommunikationsfunktion wertvolle Informationen über neuronale
Erregbarkeit vermitteln. Im Gegensatz zu “open-loop” TMS ermöglicht EEG-TMS
nicht nur eine präzisere Erforschung der Funktion von Gehirnwellen, sondern
auch die Umsetzung der gewonnenen Erkenntnisse in effizientere therapeutische Anwendungen. Speziell Oszillationen im Alpha-Frequenzbereich (8-14Hz)
spielen eine bedeutsame Rolle, indem sie den Informationsfluss im Gehirn durch
Hemmung aktuell irrelevanter Areale steuern, und zwar laut einer führenden Theorie als “asymmetrisch gepulste Inhibition” mit einem Maximum der Hemmung
während der Hochpunkte (“Peaks”) und während hoher “Power” (∼ Amplitude).
Der “µ-Rhythmus”, Wellen in alpha-Frequenz über dem sensomotorischen Kortex, scheint für diese Areale eine analoge Rolle wie das okzipitale Alpha für den
visuellen Kortex zu spielen. Die CSE lässt sich durch die Amplitude der ausgelösten kontralateralen Muskelzuckungen (MEPs im EMG) quantifizieren.
Im Vorexperiment erforschten wir den Einfluss der Power der µ-Wellen auf die
CSE. 16 Teilnehmer wurden in einer Sitzung mit Einzelpuls-TMS des linken M1
stimuliert. Die Pulse wurden durch die momentane Power ausgelöst, 10 Dezile
des individuellen µ-Powerspektrums wurden in pseudorandomisierter Reihenfolge angesteuert, verteilt auf 4 Stimulationsblöcke. Nach Berücksichtigung der
“Inter-Trial-Intervalle” (ITIs, bekannter “Confounder”) und Normalisierung pro Block
zeigten unsere Daten eine schwache positiv-lineare Korrelation zwischen µ Power
und MEP-Amplitude, welche somit im Widerspruch zur angenommenen hemmenden Wirkung von µ steht, aber mittlerweile in mehreren anderen Studien
repliziert wurde. Diese Diskrepanz kann z.B. durch eine tatsächlich fazilitatorische
Wirkung erklärt werden, oder auch durch eine anatomisch dem sensorischen
Kortex (S1) zuzuordnende Quelle der angesteuerten µ-Wellen, was über hem-
83mende Interneurone von S1 auf M1 zu einer ‘Vorzeichenumkehrung’ der Effektrichtung führen könnte. Weiterhin wird eine Abhängigkeit der ‘erregbarsten’
Power-Werte von der Stimulusstärke diskutiert.
Im Hauptexperiment sollte mit ‘paarig-assoziativer Stimulation’ (PAS) (intervallsensitive Kombination von Elektrostimulation des rechten Nervus medianus mit TMS
des linken M1) positive Plastizität (die Intervention überdauernde Stärkung von
Synapsen) induziert werden. Dem ging ein umfangreiches “Screening” zur Identifikation geeigneter Probanden mit ausgeprägtem µ-Rhythmus (für präzise EEGTriggerung) voraus. Letztlich absolvierten 16 Teilnehmer je 4 Sitzungen (eine pro
Trigger-Bedingung). Unsere Hypothese war hierbei, mehr Plastizität nach Stimulation während der Tiefpunkte (“Troughs”) als während der Peaks zu erzielen,
also mehr synaptische ‘Formbarkeit’ während höherer Erregbarkeit. In Anbetracht der schwachen Ergebnisse des Vorexperiments sowie einer widersprüchlichen Beweislage bezüglich einer fazilitatorischen oder inhibitorischen Funktion
wurden hohe und niedrige Power nicht explizit miteinander verglichen. TMS
während PAS wurde durch (1) µ-Peaks, (2) µ-Troughs, (3) mittlere µ-Power und
(4) open-loop getriggert. (3) und (4) dienten jeweils als Kontrollbedingung. PAS
konnte, unabhängig von der EEG-Bedingung, keine signifikante Veränderung der
MEP-Amplituden vom Ausgangswert hervorrufen. Die fehlende Wirkung könnte durch intra- und interindividuelle Schwankungen gewisser Parameter zwischen den Sitzungen erklärt werden (z.B. MEP-Ausgangswerte, absolute µ-Power
während PAS), die sich jedoch nicht als systematische Confounder zwischen
EEG-Bedingungen herausstellten.
Die, im Gegensatz zu open-loop-Studien, schwankenden ITIs während der PAS
könnten die Wirkung ebenfalls beeinträchtigt haben. Weiterhin waren zwei verschiedene Kortexareale (S1 und M1) am Protokoll beteiligt, was die Identifikation
einer relevanten EEG-Eigenschaft erschwerte.
Gegenwärtig rufen Plastizitäts-induzierende TMS-Protokolle in der Forschung und
in Studien mit Schlaganfallpatienten schwankende und zeitlich begrenzte Wirkungen hervor. Durch EEG-Triggerung und / oder die Kombination mit klassischer
Physiotherapie könnte eine verbesserte Effektivität und somit eine routinemäßige
Anwendung erreicht werden. Trotz unserer negativen Ergebnisse bleibt EEG-getriggerte TMS ein vielversprechendes Instrument in Forschung und Klinik.This thesis presents two experiments employing real-time EEG-triggered transcranial magnetic stimulation (TMS) on healthy volunteers to investigate the role
of sensorimotor 8-14Hz µ rhythm in EEG at rest on corticospinal excitability and
induction of positive plasticity. We intended to identify brain states favorable to
induction of positive plasticity to inform development of more efficient TMS protocols for clinical application e.g. in stroke patients.
Applying TMS triggered by pre-determined EEG brain states in real time (opposed to open-loop TMS with post-hoc trial sorting) offers not only more precise
research into the role of certain brain waves, but also translation into more efficient therapies. The membrane potential of superficial cortical neurons fluctuates
rhythmically, visible as oscillations in surface EEG. Different brain areas seem to
communicate through these synchronized fluctuations. ‘Brain waves’ therefore
convey valuable information about the excitability of said areas.
Oscillations in the alpha frequency range (8-14Hz) play a crucial role in this, gating information by inhibiting brain areas irrelevant to the current task. According to
an influential hypothesis, this function is exerted as an ‘asymmetric pulsed inhibition’, with a maximum of inhibition during the peaks and during high alpha power
(∼ amplitude). Sensorimotor alpha frequency waves (µ rhythm) play a similar role
as the well-researched occipital alpha does for the visual cortex. The primary motor cortex (M1) provides a quantifiable measure of (corticospinal) excitability, the
amplitude of TMS-elicited contralateral muscle twitches (appearing as MEPs in
the EMG).
The first experiment investigated the role of µ power for M1 excitability. 16 participants underwent one session of single-pulse TMS of the left M1, triggered by
overall 10 individual power deciles in pseudorandomized order, partitioned into
4 ‘blocks’ of stimulation over time. The data revealed, after stratification for confounding inter-trial-intervals (ITIs) and normalization to block average, a weak
positive linear relationship contrary to the proposed inhibitory role of µ, which has
however since been replicated several times in other studies. This discrepancy
can be explained e.g. by an in fact facilitatory nature of µ, by a postcentral and
thus sensory cortical (S1) source of the targeted oscillations, reversing the inhibitory effect in sign to a facilitatory one through S1-to-M1 feedforward inhibition,
or by a shift of most excitable power values dependent on stimulus strength.
For the main experiment, we applied a paired associative stimulation (PAS) pro-
81tocol intended to induce positive plasticity (strengthening of synaptic connection
outlasting the intervention), combining electrical stimulation of the right median
nerve at the wrist with a TMS of the left M1 in a temporally sensitive manner. After an extensive screening to pre-select suitable subjects with a sufficiently strong
µ rhythm (to ensure accurate performance of the real-time EEG targeting), 16
participants completed 4 sessions (one condition each). We expected to induce
more positive plasticity during more excitable brain states, i.e., µ troughs rather
than µ peaks. In light of our findings on µ power from the first experiment (weak
influence as compared to ITIs and intrinsic variability over time) and overall contradictory evidence as to its (facilitatory versus inhibitory) role, high vs. low power
were not explicitly compared. TMS during PAS was applied at (1) µ peaks, (2)
µ troughs, (3) at medium µ powers and (4) open-loop. (3) and (4) both served
as controls. The intervention failed to evoke a significant change in MEP amplitudes from baseline irrespective of condition. Possible explanations can be found
in the intra- and interindividual variability of decisive parameters across sessions
(e.g. baseline amplitudes and absolute µ powers during PAS), which however did
not significantly depend on the targeted condition and were thus not true confounders. The number of sessions might still have introduced a further measure
of variability. Varying PAS ITIs (due to EEG-triggering) could have also impeded
plasticity induction, and the involvement of two cortical regions (S1 and M1) might
have complicated the identification of one relevant brain state.
Currently, plasticity-inducing TMS protocols in research and clinical trials evoke
variable and transient effects. Improvements to enable routine application might
come from EEG-triggering and/or combining with traditional motor training (physiotherapy). Regardless of our nil results in plasticity induction, EEG-triggered
TMS remains a promising instrument in research and therapy
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