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Project no.: FP6-043457 Project acronym: MindBridge Project title: Measuring Consciousness – Bridging the mind-brain gap Instrument: Specific Targeted Project Thematic Priority: SIXTH FRAMEWORK PROGRAMME NEST Publishable final activity report Period covered: from 01/01 2007 to 31/12 2009 Date of preparation: 30/09 2010 Start date of project: 01/01 2007 Duration: 36 months Project coordinator name: Assoc. prof. Morten Overgaard Project coordinator organisation name: Hammel Neurocenter Research Unita Revision 01 1. Project execution Project objectives Human consciousness as the inner experience of subjective states including perceptions, feelings, beliefs, desires etc. has long been considered as inaccessible to a scientific approach. Recently, however, the increasingly widespread availability of new neuroscience methods (multi-unit recordings in animals and functional neuroimaging in humans, to mention a few) has made it possible to conduct detailed exploration of the correspondences between subjective, conscious states and objective, neural states. As a result, the last few years have witnessed the onset of an enormous worldwide research effort to better characterize the patterns of neural activity associated with consciousness — the so-called search for the “neural correlates of consciousness” (NCC). Research on consciousness, and especially on human consciousness, is extremely diverse and has far reaching consequences on various aspects of human life, including ethics, education, and medicine. Accordingly, characterizing the neural correlates of consciousness is now considered as a high priority topic for most of the leading laboratories in cognitive neuroscience. Thus, efficient research in the domain requires the collaboration of large teams that: • concentrate expertise in various domains of cognitive neuroscience • are able to recruit both normal subjects and various kinds of patients • have access to the latest technology, such as multimodal functional neuroimaging (i.e., EEG, MEG, PET, fMRI). The present project formalizes such a collaboration. Through this project, each team will be able to increase its own research potential as well as benefit from the joint expertise of the whole group. Despite this enormous commitment to the study of consciousness on the part of cognitive scientists covering philosophical, psychological, neuroscientific and modeling approaches, as of now no stable models or strategies for the adequate study of consciousness have emerged. As Crick and Koch wrote in a recent review article: “No one has produced any plausible explanation as to how the experience of the redness of red could arise from the action of the brain”. In this respect, it is worth pointing out that renewed interest in consciousness has triggered what appeared to be unrealistic only decades ago in the scientific community: We continue to expect the discovery of the fundamental neural mechanisms underlying the complex phenomenon of human consciousness in relation to self-consciousness and intersubjectivity. This endeavour clearly needs an interdisciplinary approach that combines psychological, neuroscientific and conceptual expertise. In this light, the overarching goal of this project is to develop tools that make it possible to explore the relationships between conscious and unconscious processing — in other words, to develop a toolbox for the study of the different levels and contents of consciousness. To achieve this goal, the project will, in a multidisciplinary fashion, combine qualitative and quantitative methods to study consciousness in relation to different cognitive functions (e.g. perception, attention, memory or learning), and in different populations and groups of patients (with more or less severe brain injury and psychopathologies). Contractors 1. Hammel Neurorehabilitation and Research Unit (HNRU), PI: Morten Overgaard The Research Unit at Hammel Neurocenter (head: Prof. Dr. Jørgen Feldbæk-Nielsen) and the Cognitive Neuropsychological Laboratory located at HNRU (head: Dr. Morten Overgaard) are interdisciplinary research teams affiliated with Aarhus University, Aarhus University Hospital, and Silkeborg Hospital. Hammel Neurocenter is the largest rehabilitation institute for patients with severe to moderate brain injuries in Scandinavia, and The Research Unit specializes in research relevant to neurorehabilitation, although some related basic research is conducted. The research conducted in the Cognitive Neuroscience Research Unit (CNRU) led by Overgaard tries explicitly to integrate experimental psychological methodology as conducted in basic research with philosophy of consciousness and neurorehabilitation. The argument for this is that even though the three areas today are considered separate, they could be integrated with benefits for each separate approach. Partner 2: Université Libre de Bruxelles (ULB), PI : Axel Cleeremans ULB is represented by CSRU (Cognitive Science Research Unit), a research team affiliated with the Department of Psychology. Its main goal is to contribute to our understanding of the role that consciousness plays in learning. To do so, the lab’s projects involve essentially empirical research with human subjects, computational modelling, and, more recently, neuro-imaging methods in collaboration with the Cyclotron Research Center of the Université de Liège. This combination of computational modeling, empirical research and neuroimaging studies is characteristic of the emerging field of computational cognitive neuroscience, and all of the CSRU lab members are involved to some degree in acquiring expertise in each of the relevant disciplines. Members of the CSRU team are currently involved in about 12 different research projects, many of which are conducted in collaboration with colleagues around Europe. These different projects all aim at contributing to develop a perspective on cognition that is based on the notion that learning is an integral part of human information processing and that the latter is best described in terms of continuous, graded and distributed representation and processing systems. Partner 3: University Medical Center Hamburg-Eppendorf, PI: Andreas Engel The central focus of the research of the Dept. of Neurophysiology is the dynamics of neuronal populations and, specifically, temporal correlations between different neurons leading to the formation of coherent cell assemblies. Since 1987, Andreas Engel's group has investigated these phenomena in sensory and motor systems by means of extracellular recording techniques in carnivores and rodents. Several years ago, the group has begun to address similar question in the human brain. Currently available data suggest that the temporal dynamics of neural activity may be essential to understanding the neural foundations of perceptual, cognitive and motor functions. The projects of the Institute of Neurophysiology therefore investigate neural response patterning in the context of sensory processing, attention, crossmodal and sensorimotor integration, working memory and conscious awareness. Partner 4: University College London, PI: Geraint Rees The Institute of Cognitive Neuroscience is an interdisciplinary institute of University College London bringing together psychologists, neurologists, psychiatrists, anatomists, physiologists and others with a common interest in studying human brain function. It is intimately associated with the Functional Imaging Laboratory and Institute of Neurology, where Dr. Geraint Rees holds joint appointments. All are located in Queen Square adjacent to the National Hospital for Neurology and Neurosurgery. UCL investigated differences in conscious content with use of cutting-edge scanning technologies, with special emphasis on fMRI and MEG research. Partner 5: Cyclotron Research Centre of the University of Liège, PI: Steven Laureys The infrastructure available includes a research dedicated 3-Tesla-MRI (fully equipped with MRI compatible artificial respirator and invasive cardiorespiratory monitoring), MR-compatible 64 channel EEG, cyclotron, chemistry lab, PET-scan; multichannel portable EEG recorders; transcranial magnetic stimulation. – all of which are leading technologies to either do brain scannings, get information about electrophysiological aspects of brain functions, and to stimulate the brain magnetically. The CRC has extensive collaboration with the Dept. of Neurology, Intensive Care, Anaesthesiology and Memory Centre of the University of Liège. The centre organizes regular training for early stage researchers and students on functional imaging data analysis (Statistical Parametric Mapping), neuropsychology, EEG-recording and ERP data analysis. The team conducting research on consciousness consists of 4 neurologists, 1 psychiatrist, 3 anesthesiologists, 3 psychologists, 2 biologists, 1 pharmacist, 1 radiochemist, 2 engineers and 2 Cyclotron operators. Partner 6: Department of Psychiatry, University of Cologne (PUC), PI: Kai Vogeley A major interest of the department lies in the early recognition of psychosis. The department is running an early recognition and therapy centre that was the first of its kind in Germany and is one of the leading institutions in Germany; it has an internationally high reputation in the field. The research conducted in the Neuroimaging Group led by Kai Vogeley is focusing on the pathophysiological study of different psychiatric diseases with a focus on schizophrenia and autism. For this purpose, neuropsychological paradigms are developed that focus on the operationalisation of self-referential and social cognitive capacities with the understanding that psychopathological symptoms can be reconstructed as cognitive dysfunctions. Self-reference and social cognition appear to be the most interesting and fruitful research approaches with respect to psychiatric diseases. Investigations of these issues are carried out under employment of a variety of different neuroimaging and electrophysiological methodologies comprising fMRI, PET and EEG. These studies are carried out in close collaboration with the Brain Imaging Center West (BICW) at the Institute of Medicine at the Research Center Juelich (directors: Prof. Dr. Karl Zilles, Prof. Dr. Gereon Fink). The BICW is one of five national brain imaging competence centres that are funded by the German Ministry of Research and Education (BMBF). Kai Vogeley is member of the BICW. Work performed The work was organized in six workpackages each with a different subgoal, yet all contributing to the overarching project goals. In work package 1, ‘Tools for assessing consciousness’, (WP 1), current approaches to measuring consciousness, "objective" as well as "subjective", are compared in order to arrive at recommendations for future experiments. The problem of measuring consciousness differs from the problem of establishing the absence of consciousness. For instance, in subliminal perception experiments, one desires to know whether or not a stimulus has been consciously perceived, and in implicit learning paradigms one is interested in whether the relationships between different consciously represented stimuli are processed unconsciously. By contrast, the problem of measuring consciousness has to do with tracking the level and contents of consciousness beyond the zero-point of unconsciousness. Furthermore, WP 1 sets out to improve methods in basic neuroscience in order to arrive at more precise suggestions for neural substrates of consciousness in later experiments.Also, work package 1 studies how subjects are able to differentiate themselves from others. The results crucially inform the following work packages with methodological tools to measure consciousness and its related brain activity. From deliverables 1.1 and 1.2 (D 1.1 and D 1.2), we have now new knowledge of how subjective reports can be collected and how they relate to objective performance in different tasks. The methods have already proven relevant for e.g. WP 5 the clinical applications. D 1.3 has given important knowledge of how to find the origins of an EEG signal in the brain, improving knowledge of "linear beamforming". These results have already proven very valuable for research in WP 3. D 1.4 has focussed on implicit and explicit learning of importance to several following tasks, e.g. in WP 2 and 3. Theoretical litterature studies have in themselves given rise to papers important to promoting the over-all idea in MindBridge. D 1.5 studies how people differentiate between "self" and "others", and what happens when this ability fails. As later studies in the clinical WP 5 is about schizophrenia and aspects of WP 4 is about social cognition, this information is crucial. In all significant aspects, goals were achieved. WP 2, entitled "Identifying levels of consciousness", aimed at studying cases of reduced consciousness, e.g. patients in coma or the vegetative state, as well as to explore levels of awareness when engaging in introspection. – the inner “self-monitoring” of conscious experiences. The WP was primarily aimed at documenting the neural mechanisms behind the different levels of consciousness. To do so, it consisted of three tasks: Task 2.1 ("Breakdown of the global workspace under anaesthesia", led by UKE), Task 2.2, ("Delay vs. trace conditioning in PVS and MCS patients", led by ULg), and Task 2.3 ("Identifying the neural correlate of introspection", led by HNRU. The key objective of work package 3 was to perform a series of experiments to investigate the neural correlates of awareness, in particular in respect to their temporal dynamics. Engel and coworkers have argued previously that synchronization may be involved in several processes indispensable for the emergence of conscious mental states, including arousal, perceptual integration, attentional selection, and working memory. Thus, a particular focus of the studies described here was to investigate the relation between neural coherence and fast neuronal oscillations and conscious processing of sensory signals. Here, we report on several behavioural, EEG and MEG studies that were performed to this aim in the second reporting period of Mindbridge. In particular, we conducted: • • • • • An extensive behavioural study on the role of emotion for conscious perception in an attentional blink paradigm (Müsch et al., 2009; see WP 3.1) Two MEG studies to investigate a) neuronal synchronization reflecting the focus of spatial attention (Siegel et al., 2008; see WP 3.1) and b) choice-predictive activity during perceptual decision making (Donner et al., 2009; see WP 3.1). A psychophysical and neurophysiological MEG study on visual awareness and memorization (Hipp et al., 2008; Supp et al., 2008; see WP 3.2) Studies to advance a multilevel approach to the "sense of agency" addressing both consciously reflected and pre-reflective levels of agency (David et al., 2008) and applied this approach to patients with Schizophrenia (see WP 3.3) An EEG study on subjects observing an ambiguous audio-visual stimulus to identify largescale cortical networks in which the degree of synchronization predicts subjects perception (Hipp et al., under review; see WP 3.3) Behavioural work aimed at (1) developing new, reversible sequences for use in the planned MEG experiment, and (2) developing a new, simpler behavioural paradigm aimed at making it possible to track the magnetoencephalographic correlates of conscious and unconscious preparation (see WP3.4) A behavioural study on the temporal dynamics of delay vs. trace conditioning (Destrebecqz et al., 2010) and an fMRI experiment using the same design (see WP 3.5) • • Thus, we successfully continued the work initiated in the first reporting period of Mindbridge and as also demonstrated by the scientific contributions listed above - reached the objectives described for this workpackage in the original proposal through a combination of different methods and a variety of experimental approaches. The key objective of work package 4 was to perform a series of experiments to investigate the patterns of activity associated with awareness in visual cortex, and to delineate new ways in which to decode the contents of awareness from such patterns of activity measured non-invasively with functional MRI and other neuroimaging techniques. This series of experiments has been successfully delivered. We sought to generalise the approach pioneered by partner UCL plus others that initially showed that novel multivariate analysis techniques applied to fMRI signals from human primary visual cortex are sufficient to accurately decode the orientation of a stimulus that a participant is viewing. We have now conducted experiments that show that such approaches can be used to decode: • • • • • spatial frequency of a stimulus (Bahrami et al, under review) the direction of motion of a simple stimulus (Kaul et al, under review) the category of an object (Sterzer et al J Vision 2009) the gender of a human face (Kaul et al under review) the direction of attention (either spatial or feature-based; Kaul et al in prep, Sterzer et al under review)). Thus, the WP has been successful in generalizing the approach to both low and high level features of visual stimuli. A second major objective sought to decode unconscious perception in the ventral visual pathway and we have been successul in showing that even high level features of complex objects are represented in the ventral visual pathway, overturning previous orthodoxy (Sterzer et al 2009). During these studies, we have further refined and disseminated our analytic methods as planned to other partners, enabling some of the work presented in the progress reports to other WPs. We have also made significant progress towards online decoding of dynamic changes in consciousness, conducting several successful fMRI experiments that demonstrate successful online control of visual cortex through biofeedback (Scharnowski et al, in prep). We have overcome a number of technical challenges in this work and are now applying it to decoding spatial attention. Finally, this WP sought to investigate neural correlates of self-reference and social cognition. Partners have successfully conducted a number of fMRI studies and most recently focused on the neural correlates of introspective self-awareness, showing an entirely novel relationship between brain structure in prefrontal cortex and introspective accuracy (Fleming et al in press). This will spark new interactions between the partners and has enabled a new interest by partner UCL in social cognition as a successful networking outcome. Work package 5 studied different diagnostic groups that were clinically and scientifically interesting with respect to the different qualitative and quantitative approaches related to the different levels and contents of consciousness. That is, achievements from other WP’s were put to use in clinical settings. As for the quantitative aspects or levels of consciousness, persons in a coma (i.e. unarousable unawareness), vegetative state (i.e. wakeful unawareness) or minimally conscious states (fluctuating states of awareness without possibility of communication) and healthy volunteers persons during anaesthesia were studied. With respect to qualitative aspects or contents of consciousness, persons suffering from neglect syndrome, schizophrenia, and autism have been examined, both in comparison to normal healthy adults. The grey zone transitions between the different disorders of consciousness in the clinical spectrum following severe brain damage are currently being better defined by adding powerful imaging methodology to bedside behavioural assessment as illustrated by our recently published clinical studies (New England Journal of Medicine 2010 Feb 18;362(7):579-89; 160; British Medical Journal in press; Brain. 2010 Jan;133(Pt 1):161-71; Prog Brain Res. 2009;177:275-9; Neuroimage. 2010 Jun 4. [Epub ahead of print]). However, it should be stressed that these exciting developments are not yet routine clinical reality. The first hurdle to be overcome before the above discussed visions of the future can enter clinical practice relates to the engendered ethical problems. We have proposed a novel ethical framework that emphasizes balancing clear protections for patients with disorders of consciousness alongside access to research and medical progress (Am J Bioeth. 2008 Sep;8(9):3-12). The development of a philosophical framework in WP 6, ‘Towards a theory of consciousness’, was promoted based on a naturalistic intution that proposes that mental phenomena are closely linked (“identical” with) neural phenomena and that mental phenomena can be best and completely explained by applying natural scientific approaches including neurosciences. A considerably important topic has been the relation of temporal dynamics and spatial configurations of neural mechanisms or brain states that are associated with consciousness. This has been an important topic of the whole consortium and is displayed in a wealth of empirical and theoretical studies. End results The overarching goal of Mindbridge was to develop tools that make it possible to explore the relationships between conscious and unconscious processing — in other words, to develop a toolbox for the study of the different levels and contents of consciousness. Other main goals of the project are to further contribute to our understanding of the mechanisms of consciousness first and foremost by developing and integrating different scientific methodologies from the fields of psychology and neuroscience. To do so, the project is focused on the analysis of the qualitative and quantitative characteristics of conscious and unconscious processing (1) in different cognitive functions, such as perception, attention, memory and learning, or language, (2) in different populations, ranging from normal spontaneous or induced conditions (sleep, hypnosis, illiterate subjects) to pathological conditions (neglect, minimally conscious, vegetative or comatose patients with respect to levels of consciousness; psychopathological states with respect to contents of consciousness), and (3) through complementary methods, including behavioural and clinical measurements, structural and functional neuroimaging, and computational modelling methods. Impact Having integrated both the empirical and theoretical account we think that we have made considerable progress in understanding consciousness on neural grounds. Constitutive mechanisms and required brain regions to be recruited during conscious experiences have been detected. A number of studies have dealt with different stages or different degrees of consciousness, others are dealing with contents of consciousness, a special emphasis was here on self-consciousness and social consciousness. These two phenomena of subjectivity and intersubjectivity are classical philosophical topics that are now better understood on empirical grounds. It has been shown in a number of studies and papers of the consortium that this naturalistic approach is a fruitful basis not only for the conception, analysis and interpretation of empirical studies but also for disturbances of consciousness focusing both on disorders of degrees of consciousness and disorders of contents of consciousness. In addition, this framework is also useful to conceptualize the influence of the cultural backgrounds on conscious experience. Combining the different empirical, philosophical and anthropological approaches brought together in this consortium we feel that we have made considerable progress in defining consciousness in a coherent, theoretically sound and neurobiologically grounded framework that will stimulate further research in the field of empirical consciousness research. MindBridge has had a vast impact in several disciplines that usually are considered as clearly distinct. New knowledge about functions of consciousness and methods for how to study subjective states could have important impact in basically any discipline interested in human mental life. Thus, we can expect follow-up studies (by the consortium members or other researchers after the project publications) using the findings in different other areas of research and applications. Theoretical consciousness studies. In state-of-the-art consciousness research, a vast number of theories about mind-brain relations are circulated; some would say that there is one theory per philosopher. The MindBridge project has not just added to this multitude of theories but tried to develop a philosophical framework to grasp empirical and clinical findings and to move towards a theory of consciousness that is directly built on empirical data. Brain sciences. The currently dominating branch within psychology (but which also involves linguistics, robotics, neurophysiology and computer science) is “cognitive neuroscience”. Cognitive neuroscience attempts to unify theories about cognitive processes with neural processes, but has been criticised for leaving out consciousness. Many aspects of the MindBridge project have developed methodologies that will be of importance to several disciplines studying brain processes, also including basic neurophysiology. As most of the project is directly compatible with cognitive neuroscience, the project can also be said to give cognitive neuroscience a set of theories and methods to study consciousness. Neurophysiological and neuropsychological rehabilitation. The project aims to give exact tools for rehabilitating and assessing patients with neurological damage. The impact here will potentially be very important to the involved clinical disciplines. Psychiatry. Although just one experiment in the project used patients with psychopathology as subject group, more aspects will be directly relevant for psychiatry. These are especially developments in knowledge regarding self-consciousness and self-reference, and systematic methods to acquire verbal reports (interviewing or assessing patients). So even though the MindBridge consortium has generated more than 140 publications as a direct result of the grant, the biggest achievement hopefully lies in the inspiration and impact the results may have for future research. 2. Dissemination and use Publishable results N/A Training Exchange of young researchers between partner laboratories (training in specialized techniques) Planned/actual dates Name Purpose of exchange Duration Partner: responsible/involved 08/2007 Bert Timmermans 3 days HNRU, ULB 01/2008 Kristian Sandberg 1 week ULB, HNRU 05/2008 Nicole David 4 weeks PUC, UKE 09/2008 Natallia Lapitskaya Learning about subjective scales for measuring consciousness. Learning of experiment programming software. Collaborative project on the “sense of agency”. Use of TMS in coma 6 months ULg, HNRU September 2008 December 2008 HNRU/UCL ULg, 2 years ULB, PUC 2009/10 Bahador Bahrami MEG training BrainVoyager QX Course Cologne Marie Curie Fellowship Training/project 9 months 2 days December 2009 Kristian Sandberg Audrey Vanhaudenhuyse – Mélanie Boly Bert Timmermans Ongoing UCL/HNRU