Transcranial Magnetic Stimulation to the Middle Frontal Gyrus During Attention Modes Induced Dynamic Module Reconfiguration in Brain Networks

The interaction between dorsal and ventral attention networks (VANs) is mediated by the middle frontal gyrus (MFG), which is functionally connected to both networks. However, the direct role of the MFG in selective and sustained attention remains controversial. In the current study, we used transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe the connectivity dynamic changes of MFG-associated regions during different attention modes. The participants underwent visual, selective, and sustained attention tasks to observe TMS-induced network changes. Twenty healthy participants received single-pulse TMS over the left or right MFG during tasks, while synchronous EEG data was acquired. Behavioral results were recorded and time-varying brain network analyses were performed. We found that the MFG is involved in attention processing and that sustained attention was preferentially controlled by the right MFG. Moreover, compared with the right hemisphere, the left hemisphere was associated with selective attention tasks. Visual and selective attention tasks induced MFG-related changes in network nodes were within the left hemisphere; however, sustained attention induced changes in network nodes were in the bilateral posterior MFG. Our findings indicated that the MFG plays a crucial role in regulating attention networks. In particular, TMS-induced MFG alterations influenced key nodes of the time-varying brain network, leading to the reorganization of brain network modules

Identifying Changes of Functional Brain Networks using Graph Theory

This thesis gives an overview on how to estimate changes in functional brain networks using graph theoretical measures. It explains the assessment and definition of functional brain networks derived from fMRI data. More explicitly, this thesis provides examples and newly developed methods on the measurement and visualization of changes due to pathology, external electrical stimulation or ongoing internal thought processes. These changes can occur on long as well as on short time scales and might be a key to understanding brain pathologies and their development. Furthermore, this thesis describes new methods to investigate and visualize these changes on both time scales and provides a more complete picture of the brain as a dynamic and constantly changing network.:1 Introduction 1.1 General Introduction 1.2 Functional Magnetic Resonance Imaging 1.3 Resting-state fMRI 1.4 Brain Networks and Graph Theory 1.5 White-Matter Lesions and Small Vessel Disease 1.6 Transcranial Direct Current Stimulation 1.7 Dynamic Functional Connectivity 2 Publications 2.1 Resting developments: a review of fMRI post-processing methodologies for spontaneous brain activity 2.2 Early small vessel disease affects fronto-parietal and cerebellar hubs in close correlation with clinical symptoms - A resting-state fMRI study 2.3 Dynamic modulation of intrinsic functional connectivity by transcranial direct current stimulation 2.4 Three-dimensional mean-shift edge bundling for the visualization of functional connectivity in the brain 2.5 Dynamic network participation of functional connectivity hubs assessed by resting-state fMRI 3 Summary 4 Bibliography 5. Appendix 5.1 Erklärung über die eigenständige Abfassung der Arbeit 5.2 Curriculum vitae 5.3 Publications 5.4 Acknowledgement

Aberrant brain activation and coupling in Depression – Links between Psychopathology and Neurophysiology

Major Depressive Disorder (MDD) is the most common mental disorder and ranging under the top three of the most disabling diseases worldwide. Although various treatments exist for MDD, about 30 to 40 % of the patients don’t respond. A better understanding of the neurobiological correlates of MDD might lead to the development of new and the improvement of existing treatments. The dissertation at hand is dedicated to the aim of a better understanding of aberrant brain functioning and coupling in MDD. Further, we sought to investigate the behavioral and cognitive-affective underpinnings that lead to aberrant brain functioning and coupling in MDD, in terms of depressive rumination. In total this work comprises four studies. In our first study, we investigated the functional connectivity (FC) during resting state (rsFC) and task performance of the Trail Making Test (TMT) in subjects with late-life depression (LLD) and healthy controls (HC). FC was assessed via functional near-infrared spectroscopy (fNIRS) in areas of the cognitive control network (CCN). While we observed an expected pattern of change in FC in the healthy controls with relatively low FC during resting-state and an increase during task-performance, subjects with LLD showed an opposite pattern, with relatively high FC during resting-state and decreases during task-performance. Further, depressed and non-depressed subjects differed significantly during resting-state (LLD>HC) and the executive demanding condition of the TMT (HC>LLD). While these results were interesting from a standpoint of pathophysiological changes in FC, we couldn’t give a final explanation for the observed FC patterns in LLD. As a possible explanation, we assumed that some kind of depressive cognitive process could lead to hyper-connectivity within the CCN during resting-state that further disturbs cortical coupling during task performance. As depressive rumination is such a cognitive process that is common in depression, we developed a resting-state questionnaire to assess state rumination for subsequent studies. In study two, we investigated rsFC within subjects with MDD and HC with a parietal probeset covering parts of the default mode network (DMN), CCN and dorsal attention network (DAN). Further, we investigated in how far state- and trait rumination explained the differences between depressed and non-depressed subjects in rsFC. In contrast to our first study, we observed an opposite pattern of FC differences between the groups: within the parietal cortex, depressed subjects showed reduced FC in comparison to HC in a widespread bilateral network. While state rumination showed rather restricted effects, the measures of trait rumination showed wide-spread effects. Further, FC was negatively correlated with state- and trait rumination. Since our results so far were restricted to non-experimental between-subject associations, that don’t allow the investigation of causal relationships, we further designed a study in which we sought to induce rumination with the Trier Social Stress Test (TSST). In study three, we investigated the hemodynamic changes during the TSST in high and low trait ruminators in the CCN, further, we examined in how far state rumination would be induced through the TSST. Relationships between hemodynamic responses and state rumination were examined with a mediation analysis. As expected, we found increases in state rumination through the TSST. Further, these increases were higher in the high-trait ruminators. On a cortical level, low ruminators showed higher cortical activation in the stress condition than the high ruminators in the right inferior frontal gyrus (IFG). Further, group differences in post-stress state rumination were mediated by the cortical reactivity in this region. Subject with high IFG reactivity showed less state-rumination following the TSST. In study four, we further investigated in the same study cohort, if rsFC before and after stress would show an expected pattern with higher baseline FC in the high trait ruminators and a higher reactivity in rsFC in subjects with high increases in state rumination. As expected, baseline levels of rsFC were increased in the high-ruminators like in our first study for the LDD group. However, although state rumination increased in the high trait ruminators more strongly than in the low trait ruminators, rsFC only increased in the latter group. Since we didn’t observe a co-variation of change scores between rsFC and state rumination, we concluded that the effect of rumination on FC changes would be an indirect one. In the general discussion of this dissertation, I propose a model of indirect prolonged stress effects in high ruminating subjects that lead to higher stress levels and subsequently to permanent changes in FC. This model would explain the observed effects in our study and is in line with current research of FC alterations in chronic stress. I further outline, in how far the presented results and the research of biological underpinnings could improve the current theory development of mental diseases as well as treatment planning

Identifying the Neurocognitive bases of creativity to increase human and computational creativity

En esta Tesis Doctoral se ha identificado la estructura neurocognitiva que sustenta la creatividad humana a partir del análisis conjunto de más de 800 referencias bibliográficas que muestran las investigaciones más importantes realizadas hasta la fecha. Sobre la base de esta estructura, se ha identificado un paradigma neurocognitivo de la creatividad humana y se ha propuesto un modelo neurocognitivo del proceso creativo. Finalmente, también se ha propuesto un paradigma creativo neurocognitivo computacional y se ha diseñado la estructura de un sistema computacional creativo, basado en una estructura multiagente. La investigación que se ha realizado sobre el tema hasta la fecha es muy especializada y se centra en aspectos muy concretos de la creatividad, y en muchos casos tienen poca relación entre sí. Por ello, y para tener una idea conjunta y holística de los procesos neurocognitivos de la creatividad humana, es necesario estudiar todas estas investigaciones de forma interconectada. Esta idea conjunta permitiría dirigir investigaciones más específicas para ser más efectivos. Por ello, lo primero que se ha hecho ha sido clasificar, agrupar, analizar, entrelazar y estructurar, de forma ordenada, las investigaciones más importantes que se han realizado hasta la fecha. Sin embargo, el trabajo realizado va mucho más allá, ya que estructurando y entrelazando las investigaciones existentes ha sido posible identificar ciertos patrones, correlaciones y paralelismos, y realizar ciertas deducciones, que en su conjunto, han permitido identificar los procesos neurocognitivos fundamentales. bases de la creatividad humana. La Tesis se estructura en los siguientes capítulos: Capitulo 2 Análisis de los principales métodos para estimular la creatividad Se analizan las principales definiciones de creatividad, y se ha decidido que el mejor enfoque para su análisis es estructurarla taxonómicamente, bajo el modelo 4P. Se ha realizado una recopilación y análisis de los métodos más efectivos que estimulan la creatividad humana, mostrando las ventajas y desventajas de cada uno. Capítulo 3 Estructura funcional del cerebro humano y su relación con el proceso creativo Se identifica la estructura neurocognitiva general del cerebro humano que permite generar los procesos fundamentales y básicos de su actividad creativa. Capítulo 4 El papel fundamental de la DMN en el proceso creativo Se ha observado que la red de modo predeterminado (DMN) tiene un papel principal en la creatividad. Por ello, se ha dedicado un capítulo a su estudio, y se han identificado varios factores que la involucran directamente en la actividad creativa del cerebro humano. Capítulo 5 Identificación y análisis de las bases neurocognitivas de la creatividad humana Se ha identificado el conjunto general de factores neurocognitivos que sustentan los procesos creativos en el cerebro humano. Capítulo 6 Paradigma neurocognitivo de la creatividad humana Se ha propuesto un modelo neurocognitivo del proceso creativo que reestructura, completa y detalla todos los modelos conceptuales propuestos hasta el momento. Capítulo 7 Paradigma computacional de la creatividad basado en la estructura neurocognitiva humana Analizando las diferentes bases neurocognitivas que sustentan la creatividad humana, se han establecido paralelismos computacionales y se han realizado diferentes sugerencias para el diseño de un sistema computacional creativo.In this Doctoral Thesis, the neurocognitive structure that supports human creativity has been identified based on the joint analysis of more than 800 bibliographical references that show the most important investigations carried out to date. Based on this structure, a neurocognitive paradigm of human creativity has been described, and a neurocognitive model of creative process has been proposed. Finally, a computational neurocognitive creative paradigm has been also proposed, and the structure of a creative computational multi-agent system has been designed. The research that has been carried out on the subject is very specialized and focuses on very specific aspects of creativity, and in many cases they have little relationship with each other. For this reason, and in order to have a joint and holistic idea of the neurocognitive processes of human creativity, it is necessary to study all these investigations in an interconnected way. This joint idea would allow directing more specific investigations in order to be more effective. For this reason, the first thing that has been done has been to classify, group, analyze, intertwine and structure, in an orderly manner, the most important investigations that have been carried out to date. However, the work carried out goes much further, since by structuring and intertwining the existing research it has been possible to identify certain patterns, correlations and parallelisms, and make certain deductions, which as a whole, have made it possible to identify the fundamental neurocognitive bases of human creativity. Chapter 2 Analysis of the main methods to stimulate creativity The main definitions of creativity are analyzed, and it has been decided that the best approach for its analysis is to structure it taxonomically, under the 4P model. A compilation and analysis of the most effective methods that stimulate human creativity has been carried out, showing the advantages and disadvantages of each one. Chapter 3 Functional structure of the human brain and its relationship with the creative process The general neurocognitive structure of the human brain that allows the generation of the fundamental and basic processes of its creative activity are identified. Chapter 4 The fundamental role of the DMN in the creative process It has been observed that the Default mode network (DMN) has a main role in creativity. For this reason, a chapter has been dedicated to its study, and several factors have been identified that directly involve it in the creative activity of the human brain. Chapter 5 Identification and analysis of the neurocognitive bases of human creativity The general set of neurocognitive factors that underpin creative processes in the human brain has been identified. Chapter 6 Neurocognitive paradigm of human creativity A neurocognitive model of the creative process has been proposed, which restructures, completes and details all the conceptual models proposed so far. Chapter 7 Computational paradigm of creativity based on the human neurocognitive structure Analyzing the different neurocognitive bases that support human creativity, computational parallels have been established and different suggestions have been made for the design of a creative computational system

Modifications de la connectivité cérébrale au sein du réseau attentionnel ventral lors du vieillissement normal

Les capacités attentionnelles sont nécessaires à la plupart des tâches de la vie quotidienne. Au cours du vieillissement normal, ces habiletés se modifient. De même, les études suggèrent que l’activité neurofonctionnelle du réseau fronto-pariétal qui sous-tend les capacités attentionnelles diffère entre les individus âgés et de jeunes adultes. Par contre, les changements en contexte du vieillissement du réseau fronto-pariétal ventral, aussi appelé le réseau attentionnel ventral, ont été peu investigués. Une telle question doit être soulevée dans le contexte où les plus récents modèles décrivant les changements fonctionnels associés au vieillissement rapportent que des possibles transformations neurofonctionnelles peuvent survenir au niveau intrahémisphérique et interhémisphérique. Le but de cet ouvrage est de déterminer comment le vieillissement normal affecte le réseau attentionnel ventral et de décrire la nature des changements qui peuvent survenir sur les axes intra et interhémisphériques. Pour y parvenir, la méthode de connectivité fonctionnelle fut privilégiée puisqu’elle permet de quantifier l’interaction neurofonctionnelle entre diverses régions composant un réseau fonctionnel. La première étude de cette thèse a permis de décrire les modifications de connectivité fonctionelle intrahémisphériques du réseau attentionnel ventral en comparant des adultes jeunes et âgés lorsqu’ils réalisent une tâche d’attention sélective en imagerie par résonance magnétique. Sur le plan comportemental, les individus âgés répondaient significativement plus lentement et commettaient davantage d’erreurs que le groupe composé de jeunes adultes. Les résultats de connectivité fonctionnelle montrent que le degré d’intégration de la connectivité fonctionnelle intrahémisphérique est globalement plus élevé chez les individus âgés dans l’ensemble des régions fronto-pariétales composant ce réseau. De plus, il semble que les aires antérieures du réseau, soit les aires préfrontales et insulaires, sont moins intégrées chez les individus âgés, alors que les zones pariétales, temporales et cérébelleuses le sont davantage. Le degré d’intégration de la connectivité est également plus élevé chez les adultes âgés entre les régions postérieures et antérieures. Ainsi, les résultats de cette étude suggèrent que la dynamique des régions antérieures et postérieures du réseau attentionnel ventral est modifiée au cours du vieillissement normal et que les régions postérieures occupent au sein de ce réseau un rôle plus important avec l’âge. Cette hyperconnectivité des aires pariétales pourrait représenter une stratégie de compensation intrahémisphérique (i.e. recrutement de régions additionnelles en postérieur) qui aurait cependant atteint un certain plateau puisque bien que les âgés réussissent à réaliser la tâche, ils performent significativement plus faiblement que de jeunes adultes. La seconde étude s’est intéressée aux modifications de connectivité interhémisphériques du même réseau fonctionnel en comparant le degré de connectivité fonctionnelle entre des individus jeunes et âgés. De manière similaire à l’étude 1, sur le plan comportemental les individus âgés répondaient significativement plus lentement et commettaient plus d’erreurs que les jeunes adultes. En ce qui concerne la dimension inter-hémisphérique du réseau, les résultats des analyses de connectivité montrent que le degré d’intégration des régions hémisphériques gauches fronto-pariétales et temporales est plus faible pour les participants âgés que pour les participants jeunes. Au contraire, les régions frontales, pariétales, temporales et sous-corticales de l’hémisphère droit sont plus intégrées. Par ailleurs, les résultats montrent également que le degré d’intégration interhémisphérique est plus élevé chez les individus âgés. Ainsi, cette étude suggère que le degré de connectivité fonctionnelle entre les régions hémisphériques droites du réseau attentionnel ventral augmente au cours du vieillissement, suggérant ainsi une amplification de la latéralisation de ce réseau vers l’hémisphère droit avec l’âge. Cette étude montre également que malgré une augmentation de la latéralisation du VAN à droite, celle-ci s’accompagne d’une augmentation du degré de connectivité fonctionnelle interhémisphérique qui pourrait être envisagée comme une tentative de compensation interhémisphérique (i.e. recrutement des régions homologues) qui aurait atteint toutefois un certain plateau car même si les âgés réussissent à réaliser la tâche, leur niveau de performance reste significativement plus faible que les jeunes. En somme, ce travail a permis de contribuer à notre compréhension de l’impact du vieillissement sur le réseau attentionnel ventral sur l’axe intrahémisphérique et interhémisphérique. Cet ouvrage lance de nouvelles pistes d’investigation dans ce domaine et pourrait éventuellement mener à l’élaboration d’interventions susceptibles de promouvoir une santé cognitive optimale lors du vieillissement.Attention is necessary for most of daily life’s tasks. During aging, these cognitive abilities are changed. Studies suggest that the neurofunctional activity of the frontoparietal network, which upholds the attentional capacities, differ between young and older adults. However, age-related changes of the ventral frontoparietal network, also called the ventral attention network, have been less investigated. Such question has to be raised in context of recent models of neurofunctional changes in aging, who report possible functional transformation that could occur both at the intrahemispheric and interhemispheric levels. The goal of the present thesis is to determine how aging affects the ventral attention network and describe the nature of such changes that can occur on the intrahemispheric and interhemispheric axis. To do so, functional connectivity methods were favoured because of their capacity to measure the neurofunctional interaction between the regions of a network. The first study of the present thesis has allowed describing the age-related intrahemispheric modifications of functional connectivity in this network by comparing young and older adults while they respond on a selective attention task during a functional magnetic resonance imagery scan. On the task, aged adults performed significantly slower and made more errors than the young adults. At the functional connectivity level, the results show higher level of the functional connectivity between all frontoparietal regions of this network for the older group. Further, the integration level of functional connectivity in anterior regions of the network seems to be less integrated for the older participants, while posterior regions have more neurofunctional signal dependency. Also, the level of integration of functional connectivity is higher in older adults between anterior and posterior regions. Thus, results from this study suggest that the anterior and posterior regions of the ventral attention network interact differently during aging and that the posterior regions play a more important role with age in this network. This hyperconnectivity in the parietal regions could represent an unsuccessful intrahemispheric compensation attempt (i.e. recruitment of additional regions in posterior part of the brain) since older adults perform significantly less well than younger adults. The second study has investigated interhemispheric alterations of functional connectivity in the same functional network by comparing young and older adults. Like in the first study, younger adults were faster to respond on task and were more accurate. Regarding the neurofunctional lateralization of the network, the degree of functional connectivity is lower in older adults for the left hemisphere’s frontoparietal and temporal regions. However, older adults have a higher degree of functional connectivity in the right frontal, parietal, temporal and subcortical regions of the same network. Also, the results also show that the interhemispheric integration level is superior for the older adults. Thus, this study suggests that the level of functional connectivity with the right hemisphere’s regions of the ventral attention network increases with age, which could suggest an age-related lateralization of this network towards the right hemisphere. In this context, increased interhemispheric functional connectivity could be interpreted as a failed interhemispheric compensation attempt (i.e. recruitment of homologous regions) since the performance of older adults on task was significantly lower than younger adults. In short, this work has allowed contributing to our understanding of the impact of aging on the ventral attention network both on the intrahemispheric and interhemispheric axis. These various results bring up new hypothesis that needs to be investigated in further studies and eventually that could lead to the establishment of intervention that promote an optimal healthy cognitive aging

Characterising the role of the ascending arousal system in facilitating global brain dynamics in health and neurodegeneration

The inherent complexity of the brain can be attributed to countless interacting parts, from microcircuit detail scaled to large oscillatory fluctuations of macroscopic activity. One such structure that has previously been shown to influence dynamic macroscopic fluctuations in brain activity is the ascending arousal system. The ascending arousal system is comprised of multiple nuclei that send diffuse and broad-reaching neuromodulatory inputs across the brain – a function proposed to facilitate global brain activity changes. However, little is known about the exact mechanisms or extent of the influence of the ascending arousal system in facilitating large-scale brain dynamics. Hence, this thesis attempts to reveal the role of the underlying ascending arousal system in facilitating global brain dynamics that are critical for brain function. Specifically, this thesis unpacks the importance of considering the interactions between the cholinergic and noradrenergic system in facilitating global brain state dynamics. We reveal that the structural connections between the noradrenergic and cholinergic systems are critical in constraining global brain-state dynamics. We show a causal role of the cholinergic system in facilitating global brain-state dynamics and demonstrate a microcircuit mechanism of global brain-state dynamics. Next, we discuss the importance of viewing the brain through the lens of a complex system to understand both its function and dysfunction across neurodegenerative diseases. Then, we establish a maladaptive mechanism of the noradrenergic system in the manifestation of freezing of gait in Parkinson’s disease. Lastly, we examine the role of the noradrenergic system in other symptom manifestations in Parkinson’s disease. Ultimately, this thesis characterises the interactions of the cholinergic and noradrenergic systems in facilitating global brain-state dynamics in both healthy and diseased brains

Anesthetic-induced unresponsiveness: Electroencephalographic correlates and subjective experiences

Anesthetic drugs can induce reversible alterations in responsiveness, connectedness and consciousness. The measures based on electroencephalogram (EEG) have marked potential for monitoring the anesthetized state because of their relatively easy use in the operating room. In this study, 79 healthy young men participated in an awake experiment, and 47 participants continued to an anesthesia experiment where they received either dexmedetomidine or propofol as target-controlled infusion with stepwise increments until the loss of responsiveness. The participants were roused during the constant drug infusion and interviewed. The drug dose was increased to 1.5-fold to achieve a deeper unresponsive state. After regaining responsiveness, the participants were interviewed. EEG was measured throughout the experiment and the N400 event-related potential component and functional and directed connectivity were studied. Prefrontal-frontal connectivity in the alpha frequency band discriminated the states that differed with respect to responsiveness or drug concentration. The net direction of connectivity was frontal-to-prefrontal during unresponsiveness and reversed back to prefrontal-to-frontal upon return of responsiveness. The understanding of the meaning of spoken language, as measured with the N400 effect, was lost along with responsiveness but, in the dexmedetomidine group, the N400 component was preserved suggesting partial preservation of the processing of words during anesthetic-induced unresponsiveness. However, the N400 effect could not be detected in all the awake participants and the choice of analysis method had marked impact on its detection rate at the individual-level. Subjective experiences were common during unresponsiveness induced by dexmedetomidine and propofol but the experiences most often suggested disconnectedness from the environment. In conclusion, the doses of dexmedetomidine or propofol minimally sufficient to induce unresponsiveness do not render the participants unconscious and dexmedetomidine does not completely abolish the processing of semantic stimuli. The local anterior EEG connectivity in the alpha frequency band may have potential in monitoring the depth of dexmedetomidine- and propofol-induced anesthesia.Anesteettien aiheuttama vastauskyvyttömyys: aivosähkökäyräpohjaiset korrelaatit ja subjektiiviset kokemukset Anestesialääkkeillä voidaan saada aikaan palautuvia muutoksia vastauskykyisyydessä, kytkeytyneisyydessä ja tajunnassa. Aivosähkökäyrään (EEG) pohjautuvat menetelmät tarjoavat lupaavia mahdollisuuksia mitata anestesian vaikutusta aivoissa, sillä niitä on suhteellisen helppo käyttää leikkaussalissa. Tässä tutkimuksessa 79 tervettä nuorta miestä osallistui valvekokeeseen ja 47 heistä jatkoi anestesiakokeeseen. Anestesiakokeessa koehenkilöille annettiin joko deksmedetomidiinia tai propofolia tavoiteohjattuna infuusiona nousevia annosportaita käyttäen, kunnes he menettivät vastauskykynsä. Koehenkilöt herätettiin tasaisen lääkeinfuusion aikana ja haastateltiin. Koko kokeen ajan mitattiin EEG:tä, josta tutkittiin N400-herätevastetta sekä toiminnallista ja suunnattua konnektiivisuutta. Prefrontaali-frontaalivälillä mitattu konnektiivisuus alfa-taajuuskaistassa erotteli toisistaan tilat, jotka erosivat vastauskykyisyyden tai lääkepitoisuuden suhteen. Konnektiivisuuden vallitseva suunta oli frontaalialueilta prefrontaalialueille vastauskyvyttömyyden aikana, mutta se kääntyi takaisin prefrontaalisesta frontaaliseen kulkevaksi koehenkilöiden vastauskyvyn palatessa. N400-efektillä mitattu puhutun kielen ymmärtäminen katosi vastauskyvyn menettämisen myötä. Deksmedetomidiiniryhmässä N400-komponentti säilyi, mikä viittaa siihen, että anesteettien aiheuttaman vastauskyvyttömyyden aikana sanojen prosessointi voi säilyä osittain. Yksilötasolla N400-efektiä ei kuitenkaan havaittu edes kaikilla hereillä olevilla henkilöillä, ja analyysimenetelmän valinnalla oli suuri vaikutus herätevasteen havaitsemiseen. Subjektiiviset kokemukset olivat yleisiä deksmedetomidiinin ja propofolin aiheuttaman vastauskyvyttömyyden aikana, mutta kokemukset olivat usein ympäristöstä irtikytkeytyneitä. Yhteenvetona voidaan todeta, että deksmedetomidiini- ja propofoliannokset, jotka juuri ja juuri riittävät aikaansaamaan vastauskyvyttömyyden, eivät aiheuta tajuttomuutta. Deksmedetomidiini ei myöskään täysin estä merkityssisällöllisten ärsykkeiden käsittelyä. Frontaalialueen sisällä EEG:llä mitattu konnektiivisuus alfataajuuskaistassa saattaa olla tulevaisuudessa hyödyllinen menetelmä deksmedetomidiini- ja propofolianestesian syvyyden mittaamiseksi

Control Theoretic Analysis of Human Brain Networks

The brain is a complex system with complicated structures and entangled dynamics. Among the various approaches to investigating the brain\u27s mechanics, the graphical method provides a successful framework for understanding the topology of both the structural and functional networks, and discovering efficient diagnostic biomarkers for cognitive behaviors, brain disorders and diseases. Yet it cannot explain how the structure affects the functionality and how the brain tunes its transition among multiple states to manipulate the cognitive control. In my dissertation, I propose a novel framework of modeling the mechanics of the cognitive control, which involves in applying control theory to analyzing the brain networks and conceptually connecting the cognitive control with the engineering control. First, I examine the energy distribution among different states via combining the energetic and structural constraints of the brain\u27s state transition in a free energy model, where the interaction between regions is explicitly informed by structural connectivity. This work enables the possibility of achieving a whole view of the brain\u27s energy landscape and preliminarily indicates the feasibility of control theory to model the dynamics of cognitive control. In the following work, I exploit the network control theory to address two questions about how the large-scale circuitry of the human brain constrains its dynamics. First, is the human brain theoretically controllable? Second, which areas of the brain are most influential in constraining or facilitating changes in brain state trajectories? Further, I seek to examine the structural effect on the control actions through solving the optimal control problem under different boundary conditions. I quantify the efficiency of regions in terms of the energy cost for the brain state transition from the default mode to task modes. This analysis is extended to the perturbation analysis of trajectories and is applied to the comparison between the group with mild traumatic brain injury(mTBI) and the healthy group. My research is the first to demonstrate how control theory can be used to analyze human brain networks