Thesis (M.F.A.)--Georgia State University, 2009. / Title from title page (Digital Archive@GSU, viewed June 16, 2010) Sheri Joseph, committee chair; John Holman Josh Russell, committee members. Includes bibliographical references(p. 210).

This thesis is set in the context of social science’s interest in the generation of expectations, the news media, and neurotechnologies. It is a qualitative case study that examines the nature and impact of news media reporting of some pioneering research, which used functional magnetic resonance imaging in an attempt to diagnose and communicate with severely brain-injured individuals. Previous news media studies exploring neurotechnologies have been quantitative, or have tended to focus on how or why the news media represents neurotechnologies and/or the impact of the reporting, but rarely all three together. My thesis looks at all three aspects of the news media reporting of my case study. I draw on three sets of empirical data. First, those related to the production of the media - the press releases which reported the research; ten semi-structured interviews with science press officers; and the relevant expert comments posted on the Science Media Centre’s website. Second, 51 newspaper articles reporting the research. Third, five semi-structured interviews with relatives of severely brain-injured patients. I show that the mood of excitement and ‘breakthrough’ present in the press release reporting of this research was closely echoed in the news coverage. This excitement influenced the views and beliefs of only some of the relatives I interviewed. I then examine the nature of hype and by drawing on Haraway’s concept of ‘situated knowledges’ (1988) I argue that individuals view hype differently depending on their profession, industry and/or socio-cultural background. Finally, I show how whilst both the news media and the scholarly literature portrayed this research as ethically contentious, the issues most prominently discussed by scholars and/or journalists do not necessarily equate with relatives’ concerns. My findings aim to contribute to the sociology of expectations, media theory, the sociology of bioethics and the public understanding of science.

Disorders of consciousness (DoC) are a group of disorders that can occur after severe brain injury. DOC have been subdivided based on behavioural observations into: Coma, lacking any signs of wakefulness or awareness; the vegetative state, showing signs of wakefulness but lacking any signs of awareness; and the minimally conscious state, showing signs of wakefulness and infrequent and irregular signs of awareness. The so-called locked-in syndrome, a state where both wakefulness and awareness are intact, but no communication is possible due to a lack of muscle function, does not belong to the disorders of consciousness. However, it is difficult to distinguish the locked-in syndrome from DoC diagnostically, because consciousness can only be shown through consistent responses to a command and current methods for assessing consciousness rely on behavioural responses. Patients with locked-in syndrome might not be able to move voluntarily at all in the most severe cases. Behavioural assessment would then classify them as unaware. While this is an extreme and rare case, it illustrates the problem behavioural assessment poses. Such assessments are unable to distinguish the effects of impaired muscular control from impaired awareness, when either has reached an extreme level of severity. Brain damage that does not affect consciousness itself can nevertheless affect the results of the behavioural assessment of consciousness. It is then hardly surprising that the diagnosis of DoC is associated with a high level of uncertainty. The advantage of brain imaging methods is that they do not rely on the patients ability to produce a consistent behavioural response. There have therefore been efforts to use the brain imaging methods electroencephalography, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to aid diagnosis of disorder of consciousness. PET and fMRI have successfully been used to identify regions of difference in some patients in a DoC. Task-based fMRI has been used to identify intact consciousness, using tasks that require explicit understanding of instructions and wilful modulation of brain activity, but no motor control. One of these tasks consists of periods where the participant imagines playing tennis alternated with periods of rest. The ability to follow this paradigm is evidence of consciousness, and a few patients with a diagnosis of DoC have been shown to be able to do this task. However, the tennis task requires high order processing of the tasks requirements and the majority of patients does not respond to this task. fMRI tasks that test sensory modalities instead of consciousness have been used to show retained brain function even in DoC patients that do not respond to the tennis task. In this work the tennis task and a battery of other tasks including tactile, visual and auditory stimulation, were studied on a group of DoC patients. It was found that none of the patients responded to the task of imagining playing tennis, but retained sensory function could be identified in three out of seven patients. This highlights a strength of fMRI, namely that it can identify retained brain function below the level that is necessary for consciousness. However, the results also show that more than half of the patients studied here, did not show retained brain activation during the fMRI scan. For any of the patients that did not show a response, this can be due to an actual lack of retained brain function, but it can also be due to limitations of the task-based fMRI analysis. The fMRI tasks only test one sensory function at a time, for a short time. Thus a visual fMRI task for example, can only provide information about areas of the brain, that are involved in visual processing. And when vigilance is fluctuating, retained brain function can remain undetected, if vigilance is low during the scan. Functional connectivity analysis is a method to study internal connections between brain areas that is not dependent on an external task. It models the brain as a network of interconnected regions and studies the characteristics of this network. Graph theory is a mathematical field that has found application on many other fields using network analysis, like social sciences, metabolic network modelling or gene network modelling. In fMRI analysis, graph theory has been used to study different phenomena and pathologies and global network properties have been shown reproducibly. The work presented here aims to develop new methods based in graph theory aiding the identification of residual brain integrity. To allow an assessment of the brain network topology and its use in the assessment of residual brain integrity, a novel method was designed based on a graph theoretical measure. The method, termed Cortical Hubs And Related network Topology (CHART) is a two stage procedure. The rst stage identifies statistically significant differences in functional connectivity between two groups, using a measure of the average connectivity of each voxel, the weighted global connectivity. The second stage highlights the topology of the networks associated with those differences. Two fMRI datasets, with different underlying tasks and pathologies were used to test the CHART method. The first dataset was acquired from a group of patients with severe depression. It contrasted the state of the brain before and after successful treatment with electroconvulsive therapy. In this patient group the CHART method was able to identify an area of hyperconnectivity in the depressed state, compared to the treated state. This area of hyperconnectivity was connected to areas that had priorly been shown to be overly connected in the depressed state. The second dataset consisted of DoC patients, that had been extensively assessed behaviourally. Half of the patients were diagnosed to be in a vegetative state, the other half was diagnosed to be in a minimally conscious state. The first stage of CHART identified several areas of difference based on the weighted global connectivity. The second stage highlighted that the observed global differences were due to an overall lack of extended functional connectivity in the vegetative state patients. The addition of a healthy control group in stage two allowed comparison not only between the two DoC groups, but also with the healthy group. In summary it was observed that the spatial extent of the connectivity seen in the minimally conscious group resembles the spatial extent of the connectivity seen in the healthy control group, while the spatial extent of connectivity observed in the vegetative state group was minimal, compared to both healthy and minimally conscious group. Thus the spatial extent of connectivity is a distinguishing property for the vegetative state group studied here. However the first stage of the CHART method is a group based method. In disorders of consciousness, where the underlying pathology is different from case to case, this concept is problematic. Finding a meaningful group of interest is difficult or impossible, because lesions differ in location and extent. Individual differences in connectivity can be expected to be large, and a generalisation of the CHART result might not lead to improved diagnosis for every patient. For diagnosis, the patients individual characteristics must be taken into account. An additional objective of this work was therefore to develop a method to compare a single patient to a group of controls. An approach based on regression modelling was tested but failed to provide the necessary statistical sensitivity to detect impaired connectivity. In conclusion the CHART method developed in this work provides insights into the functional connectivity of a group of DoC patients. To assist diagnosis, further development of a method to compare a single subject to a group of controls will be important.

Les états de conscience altérée représentent un réel problème au niveau social, économique et éthique et constituent un défi au niveau diagnostique et thérapeutique. Nos résultats ont permis de montrer que lutilisation dune échelle comportementale standardisée reste indispensable pour éviter lerreur diagnostique et que la Coma Recovery Scale-Revised (Giacino et al, 2004) réprésente loutil diagnostique le plus efficace pour détecter des signes de conscience et donc, distinguer les patients végétatifs des patients en état de conscience minimale. Nos résultats suggérent également que lutilisation de paradigmes actifs électrophysiologiques permet dévaluer les capacités cognitives résiduelles de patients sévèrement cérébro-lésés et de détecter une activité cérébrale consciente, même en présence, au niveau de lévaluation comportementale, de comportements peu complexes tels quune fixation et/ou une poursuite visuelle. Enfin, au niveau du traitement, nous avons pu démontrer, à laide de limagerie fonctionnelle, lefficacité de lamantadine sur la récupération de la conscience chez un patient anoxique chronique en état de conscience minimale. Ainsi, nous pensons que lutilisation combinée de techniques comportementales et de techniques objectives telles que lélectrophysiologie et la neuro-imagerie est primordiale et permettra à lavenir, dune part, de clarifier ce quest un comportement conscient et donc, de mieux caractériser les états de conscience altérée et, dautre part, dinvestiguer lefficacité de thérapeutiques invasives ou non et donc, de mieux traiter les patients sévèrement cérébro-lésés récupérant du coma.

RÉSUMÉ Suite à un accident cérébral grave, quil soit traumatique ou hypoxique-ischémique, les patients peuvent évoluer dun coma (patient non-éveillable et inconscient) vers un état végétatif (patient éveillé mais inconscient), un état de conscience minimale (patient éveillé et conscient, mais non-communiquant), ou un locked-in syndrome (patient éveillé, conscient, mais ne pouvant exprimer cette conscience que par le biais de mouvements oculaires) (Vanhaudenhuyse et al., 2009a). Notre but est de mettre au point des techniques permettant de détecter des signes de conscience chez ces patients incapables de communiquer, que ce soit par des évaluations comportementales, lélectroencéphalographie ou la neuroimagerie. Etudes comportementales : Actuellement, malgré les nouveaux critères de conscience proposés par Giacino et al. en 2002, nous avons pu démontrer que jusquà 40% des patients étaient diagnostiqués comme étant en état végétatif, alors quils étaient en réalité en état de conscience minimale (Schnakers, Vanhaudenhuyse et al., 2009b). Nos travaux ont mis en évidence que labsence doutil dévaluation de la conscience standardisé pouvait expliquer la difficulté à détecter des signes de conscience. Nous avons démontré que la poursuite visuelle, qui est un des premiers signes de conscience réapparaissant chez les patients récupérant de létat végétatif, était significativement mieux détectée lorsquelle était évaluée à laide dun miroir (Vanhaudenhuyse et al., 2008c). Labsence de consensus sur la signification de certains comportements, en termes de conscience, peut également être à la source de problèmes diagnostiques. Nous avons, par exemple, démontré que le clignement à la menace visuelle, comportement ambigu de conscience, était compatible avec le diagnostic détat végétatif et quil navait pas de valeur pronostique de récupération de conscience (Vanhaudenhuyse et al., 2008a). Marqueurs électrophysiologiques : Distinguer un comportement volontaire dun comportement réflexe reste difficile, ce qui nous pousse à étudier dautres techniques permettant dobtenir des marqueurs objectifs de conscience. Nous avons souligné lintérêt des potentiels évoqués de courte latence comme marqueurs dun mauvais pronostic, ainsi que des potentiels évoqués cognitifs pour évaluer la récupération dune conscience et les fonctions cognitives résiduelles des patients en coma et post-coma (Vanhaudenhuyse et al., 2008b). Neuroimagerie fonctionnelle et structurelle : Par lImagerie par Résonance Magnétique fonctionnelle (IRMf), nous avons pu mettre au point différents paradigmes daide au diagnostic détat de conscience altérée de ces patients. Létude du réseau du mode par défaut, cest-à-dire de lensemble des régions cérébrales activées lorsque nous sommes au repos et éveillés (précunéus, cortex mésio-frontal, jonctions temporo-pariétales), nous a permis de développer un outil facile à appliquer en routine clinique. Nous avons mis en évidence une corrélation négative non-linéaire entre la connectivité au sein du réseau du mode par défaut et le degré de conscience des patients (coma, état végétatif, état de conscience minimale et locked-in syndrome Vanhaudenhuyse et al., 2010b). Par ailleurs, en collaboration avec léquipe du MRC Cognition and Brain Sciences Unit de Cambridge, nous avons appliqué des paradigmes actifs en IRMf, durant lesquels 54 patients devaient réaliser activement des tâches cognitives (simaginer jouer au tennis, simaginer visiter sa maison). Sur 23 patients diagnostiqués comme étant en état végétatif, 4 dentre eux (17%) étaient capables de moduler volontairement leur activité neuronale (Monti & Vanhaudenhuyse et al., 2010). De plus, ce paradigme a permis à un de ces patients, chez qui aucune communication nétait possible, de répondre à laide dun code oui (imaginez jouer au tennis) / non (imaginez visiter votre maison) à des questions autobiographiques. Cependant, ce type de méthode est difficilement utilisable au quotidien. Dès lors, nous développons des interfaces cerveau-ordinateur transportables grâce au projet européen WF7 DECODER. Une de ces techniques de communication a pu être proposée par la modulation du pH salivaire chez un sujet sain (Vanhaudenhuyse et al., 2007a). Enfin, dans le cadre détudes multicentriques dirigées par le Pr. Louis Puybasset (Hôpital de la Pitié-Salpétrière, Paris), nous avons mis en évidence lintérêt diagnostique et pronostique de séquences telles que limagerie par tenseur de diffusion et la spectroscopie (Tshibanda & Vanhaudenhuyse et al., 2009 ; 2010). Au terme de ce travail, nous proposons des perspectives de nouvelles études à entreprendre afin daméliorer les évaluations comportementales, mais aussi les paradigmes dacquisition en IRM et en EEG que nous avons à notre disposition. Notre projet est de développer des recherches translationnelles validées pour une application clinique individuelle. Nous espérons que cette approche multimodale permettra daméliorer la prise en charge des patients sévèrement cérébrolésés qui sont toujours un véritable défi pour le corps médical, mais aussi daccroître nos connaissances sur la conscience humaine. SUMMARY Survivors of severe traumatic or hypoxic-ischemic brain damage classically go through different clinical entities such as coma (unarousable unconsciousness), vegetative state (characterized by wakefulness without awareness), minimally conscious state (minimal but definite evidence of awareness without communication) or locked-in syndrome (fully aware but unable to move or speak) (Vanhaudenhuyse et al., 2009a). Our goal is to improve and develop methods to detect consciousness in these non-communicative patients by using bedside behavioral examinations and para-clinical electroencephalography or neuroimaging techniques. Behavioral examination: Bedside assessment is one of the main methods used to detect awareness in severely brain injured patients recovering from coma. However, our prospective multicentric study showed that up to 40% of patients may be diagnosed as vegetative while they are in reality in a minimally conscious state (Schnakers, Vanhaudenhuyse et al., 2009b). The failure to use standardized behavioral assessment tools and the absence of consensus about some clinical behaviors could explain the difficulty to identify signs of consciousness. For example, we showed that clinicians should use a mirror when evaluating visual pursuit, a behavior that is one of the first differentiating minimally conscious from vegetative patients (Vanhaudenhuyse et al., 2008c). Similarly, the blinking to visual threat remains an ambiguous clinical sign of consciousness. We showed that this behavior may be a common clinical feature of the vegetative state and that its presence does not necessarily herald consciousness nor recovery of consciousness in patients with severe brain injury (Vanhaudenhuyse et al., 2008a). Electrophysiological markers: EEG methods offer objective assessment procedures and the possibility to determine whether an unresponsive patient is aware without explicit verbal or motor response. While early evoked-potentials are good prognosticators of bad outcome, cognitive evoked-potentials appear to be good predictors of favourable outcome and may be helpful to estimate the residual cognitive functions of comatose and post-comatose patients (Vanhaudenhuyse et al., 2008b). Functional and structural neuroimaging: By using functional Magnetic Resonance Imaging (fMRI), we first studied the brain spontaneous activity and next used it to identify signs of consciousness and communication in these patients. Studies of default mode network in fMRI, i.e. brain regions encompassing precuneus, medial prefrontal cortex and temporo-parietal junctions which are more active at rest, are easy to perform and could have a potentially broader and faster translation into clinical practice. We showed a negative non-linear correlation between default mode network connectivity and the level of consciousness of brain-damaged patients (ranging from coma, vegetative state, minimally conscious state to locked-in syndrome Vanhaudenhuyse et al., 2010b). In collaboration with the MRC Cognition and Brain Sciences Unit in Cambridge, we applied active paradigms in fMRI (in which patients were asked to imagine playing tennis and visiting their house) in 54 patients. We showed that out of 23 vegetative patients, 4 (17%) were able to voluntary modulate their neuronal brain activity. Moreover, one of these patients, who was not able to behaviorally communicate, showed the ability to apply the imagery technique in order to answer accurately simple yes (imagine playing tennis) / no (imagine visiting your house) questions (Monti & Vanhaudenhuyse et al., 2010). However, this technique will not be useful in the daily life of these patients. Thus, we developed appropriate brain computer interfaces with our European partners of the WF7 DECODER project. For example, we showed that one of these methods could be the mental manipulation of salivary pH as a form of non-motor mediated communication (Vanhaudenhuyse et al., 2007a). Finally, international multi-centric studies leaded by Pr. Louis Puybasset (Pitié-Salpétrière Hospital, Paris) are validating the diagnostic and prognostic interests of MRI sequences such as diffusion tensor and spectroscopy imaging to evaluate the prognosis of recovery of severely brain injured patients (Tshibanda & Vanhaudenhuyse et al., 2009 ; 2010). Future ongoing studies are continuing to improve our actual behavioral assessments, MRI and EEG measurements in disorders of consciousness. Our project is to validate translational research models that can be applied at the individual patient level. We hope that our multimodal and multidisciplinary approach will improve our medical care for brain-damaged patients suffering from disorders of consciousness and additionally shed some light to our understanding of the neural correlates of human consciousness.

This imaginative work of fiction depicts the lives of the Foley family. After a brutal car accident, Kate Foley has lived for the past fourteen years at Gregg Catastrophic Care Center in a persistent vegetative state, leaving her daughter Grace and husband Tom to reconstruct their lives around her. Aside from her mother’s condition, life is relatively normal for Grace; she worries about school, boys, her friends. Then her mother slowly regains consciousness. The family gathers around Kate’s bedside. Grandmother Helen arrives along with Aunt Liz, family that Grace cannot remember, and their stories of her mother’s past are vastly different from the ones her father has told her. Over the next emotional months, secrets are revealed, new alliances forged and others broken as each member of the family grapples with their own issues of memory, self and what it means to be fully present.

Thesis (M.A.)--Catholic Theological Union at Chicago, 1996. / Vita. Includes bibliographical references (leaves 80-85).

Thesis (M. A.)--Trinity Evangelical Divinity School, Deerfield, Ill., 1997. / Abstract. Includes bibliographical references (leaves 108-114).

Thesis (M.A.)--Catholic Theological Union at Chicago, 1996. / Vita. Includes bibliographical references (leaves 80-85).

Thesis (M.A.)--Catholic Theological Union at Chicago, 1996. / Vita. Includes bibliographical references (leaves 80-85).