Satellite symposium workshops

The concept of consciousness

Adam Zeman
Department of Clinical Neurosciences, University of Edinburgh
Western General Hospital
Edinburgh EH4 2XU, UK

The key question for a 'science of consciousness' is: how can neural processes generate our experiences - how does brain give rise to mind? This question is sometimes referred to as the 'problem of consciousness', and was recently described by EO Wilson as 'the master unsolved problem of biology'. Some contemporary neuroscientists believe that we are approaching a solution using conventional methods, others doubt that the problem will ever be fully amenable to scientific enquiry while a third camp argues that the 'problem' is ill-posed and in need of redefinition. These disagreements stem at least partly from the the complexity of the concept of consciousness, and its hinterland of 'associated beliefs' which remain strongly influenced by religion: a recent survey of Edinburgh students indicates that a majority believe that the mind and the brain are separate, that each of us has a soul which is separate from the body and that some spiritual part of us survives after death. This talk aims to clarify some dimensions of the concept of consciousness which often generate confusion, by way of a series of contrasts. First 'consciousness' comprises two partly distinct functions: 'wakefulness' and 'awareness'. The former, arousal, function has been clarified by studies of the electrical correlates of conscious states  distinguishing wakefulness, slow wave (stages 1-4), rapid eye movement sleep and pathological variants  and of their regulation by the activating systems of the brain stem and thalamus. The neural basis of awareness, the 'content' of consciousness, has been the more or less explicit target of a vast programme of research in neuroscience involving all our major psychological capacities but especially perception (from which I will draw examples). A quite separate, second, set of contrasts is opened up by the distinction between 'consciousness' and 'self-consciousness': the latter is used to refer, among other things, to the 'idea of me' (possession of a concept of self) and the 'awareness of awareness' (possession of a theory of mind). A third contrast, between 'consciousness narrow' and 'consciousness broad' highlights the distinction between the full-blooded adult human expression of consciousness, permitting self-report and the control of action, and a variety of unconscious or preconscious relatives of consciousness: much current research focuses on the 'contrastive analysis' of these two categories. A fourth distinction, between consciousness 'inner' and consciousness 'outer' picks out the distinction between consciousness considered as a fundamentally private, solipsistic phenomenon and consciousness considered as the result of a process of exploration and interaction with our physical, social and cultural surroundings. The strength of our attachment to the 'inner' view is likely to determine our reaction to the final contrast I shall draw, between the 'easy' and 'hard' problems of consciousness. This distinguishes questions amenable to objective science (for example which brain events subserve normal vision and which subserve blindsight?) from a question which some consider to be of a different kind (how do the brain events subserving normal vision give rise to the conscious experience of sight?).
A wide range of disciplines and interests converge on the multi-faceted problem of consciousness: the study of conscious states, content-rich psychological processes, unconscious states, artificial intelligence, religion, the Arts, the philosophy of mind. This convergence creates a rich opportunity for cross-fertilisation - and for cross-purposes. Recent work supplies ample evidence for the feasibility of a science of wakefulness and conscious states, a science of conscious processes, such as perception, and a science of self-awareness (for example of theory of mind). The feasibility of a comprehensive science of consciousness depends on our view of its target: are we studying a private event or an objective set of interactions? To clarify our goal, scientists and philosophers need to renew their old alliance.

Selected references:
Zeman A. Consciousness: A User's Guide. Yale University Press, 2003
Zeman A. Theories of visual awareness. Prog Brain Res. 2004; 144:321-9
Zeman A. Consciousness. Brain. 2001; 124:1263-89

 

Theoretical framework explaining consciousness

Bernard Baars
The Neurosciences Institute
San Diego, CA 92121

Conscious perception, like the sight of a coffee cup, seems to involve the brain's identification of a stimulus. But conscious input activates more brain regions than are needed to identify coffee cups and faces. It spreads beyond sensory cortex to frontal-parietal association areas, which do not serve stimulus identification as such. What is the role of those regions? Parietal cortex may support the "first person perspective" on the visual world, unconsciously framing the visual object stream. Some prefrontal areas may select and interpret conscious events for executive control. Such functions can be viewed as properties of the subject rather than the object of experience, the "observing self" that may be needed to maintain the conscious state.

Selected references:
Baars BJ, Ramsoy TZ, Laureys S. Brain, conscious experience and the observing self. Trends Neurosci. 2003 ; 26 :671-5
Baars BJ. The conscious access hypothesis: origins and recent evidence. Trends Cogn Sci. 2002; 6 :47-52
Baars BJ. A cognitive theory of consciousness. NY: Cambridge University Press, 1988 Available at www.nsi.edu/users/baars

 

Brain death

James Bernat
Neurology Section
Dartmouth-Hitchcock Medical Center
Lebanon, NH 03756, USA

Brain death is the determination of human death by showing the irreversible cessation of the clinical functions of the brain. The concept of brain death is based on death being defined as the irreversible loss of functioning of the organism as a whole. The criterion satisfying this definition is the irreversible cessation of functioning of a critical mass of neurons in the cerebral hemispheres, diencephalon, and brain stem. But how many and which neurons are necessary and sufficient to satisfy the criterion of death remains a point of controversy. I propose that the only test that can confidently satisfy the criterion of death must prove the cessation of all intracranial blood flow. Procedures of contrast angiography, radionuclide angiography, and transcranial Doppler ultrasound reliably demonstrate absent intracranial blood flow and document brain death. The demonstration of absent intracranial blood flow by of these tests should become mandatory in brain death determination.

Selected references:
Bernat JL. The biophilosophical basis of whole-brain death. Soc Philos Policy. 2002; 19:324-42.
Bernat JL. How much of the brain must die in brain death? J Clin Ethics. 1992; 3:21-6
Bernat JL. Ethical issues in neurology. Butterwoth-Heineman, Boston, 2002

 

Evoked Potential Monitoring in Comatose Patients

Jean-Michel Guérit
Clinical Neurophysiology Unit
St. Luc Hospital, Catholic University of Louvain
Brussels, Belgium

Three-modality exogenous evoked potentials (TMEPs) have been used since several years as a prognostic tool in acute anoxic or traumatic coma. The whole information provided by TMEPs can be summarized by means of two indices : the index of global cortical function (IGCF), derived from flash visual and cortical somatosensory EPs, and the index of brain-stem conduction (IBSC), derived from subcortical somatosensory and brainstem auditory EPs. The IGCF is expressed by grades : Grade 0 corresponds to normal (never encountered in comatose patients), Grade 1 and 2 to the variable preservation of associative cortical activities, Grade 3 to the sole preservation of primary cortical activities, and Grade 4 to the loss of all cortical EPs with preservation of brain-stem components. The IBSC is firstly quantitatively determined, and, if abnormal, qualitatively rated in terms of midbrain, pontine or medullar involvement.
Anoxic comas are associated with prognostically relevant IGCF abnormalities while the IBSC remains intact (Pattern 1). For examinations performed between the 1st and the 3d day after the acute episode, Grade 1 and Grade 2 were associated in our series with a 64% and 38% rate of good outcome, respectively, while we never observed any recovery in patients with Grade 4 more than 24 hours after the acute episode.
Head trauma is associated with both IGCF and IBSC alterations and the abnormalities can be clustered into 4 patterns : hemispheric damage without brain-stem involvement (Pattern 1), midbrain dysfunction (Pattern 2), transtentorial herniation (Pattern 3), brain death (Pattern 4). In our series of traumatic patients with Pattern 1, IGCF Grade 1 and Grade 2 observed within the first 3 days were associated with 89% and 78% rates of good outcome, respectively. The outcome of patients with Pattern 2 depended on the extent of hemispheric diffuse axonal lesions (HDAL) associated with the midbrain lesion (67% of good outcome in the absence of HDAL, 20% of good outcome in the presence of HDAL). Therefore, we suggest performing MRI in patients with Pattern 2. Patterns 3 and 4 were always associated with death.
Thus, it appears that strongly altered exogenous EPs are always associated with an ominous prognosis. Mildly altered exogenous EPs were associated with a better prognosis in our series, although 36% of anoxic and 13% of traumatic patients with mildly altered EPs presented a poor evolution. We examined whether the presence of cognitive EPs (oddball paradigm) recorded in passive conditions could be associated with a better prognosis. These were recorded in more than 150 anoxic and traumatic comatose patients (GCS £ 8). Although the P3b component was almost never obtainable, the mismatch negativity (MMN) and the P3a component were recordable in more than 20% of patients, and their persistence was associated in more than 90% of cases with some consciousness recovery. Moreover, the latencies of both the MMN and the P3a were significantly correlated with the GCS (p < 0.006). Thus, while the absence of cognitive EPs in comatose patients doesn't have any prognostic value, their presence implies a very high probability of consciousness recovery. As such, cognitive EPs may very usefully complement exogenous EPs as a prognostic tool in coma.

Selected references:
Guerit JM, Fischer C, Facco E, Tinuper P, Murri L, Ronne-Engstrom E, Nuwer M. Standards of clinical practice of EEG and EPs in comatose and other unresponsive states. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl. 1999;52:117-31
Guerit JM. Medical technology assessment EEG and evoked potentials in the intensive care
unit. Neurophysiol Clin. 1999 Sep;29(4):301-17
Guerit JM, Verougstraete D, de Tourtchaninoff M, Debatisse D, Witdoeckt C. ERPs obtained with the auditory oddball paradigm in coma and altered states of consciousness: clinical relationships, prognostic value, and origin of components. Clin Neurophysiol. 1999 Jul;110(7):1260-9

 

Thought Translation Devices in the Locked-in syndrome

Andrea Kübler
Femke Nijboer, Nicola Neumann
Jürgen Mellinger
Thilo Hinterberger
Niels Birbaumer
Institute of Medical Psychology and Behavioral Neurobiology
University of Tubingen
D-72074 Tubingen, Germany

Real-time interfaces between the brain and a computer (brain-computer interface, BCI) have been used to restore motor functions lost through injury or disease. For example, progressive neurological diseases such as amyotrophic lateral sclerosis (ALS) can lead to severe or total loss of voluntary muscular control due to degeneration of central and peripheral motor neurons. As a result patients are severely or completely paralysed  a condition which is referred to as being 'locked-in'. These patients require alternative non-muscular methods for communication and control. Brain-computer interfaces measure specific features of the electrical activity of the brain and translate them into device commands. These commands do not depend on muscular control and can be used to operate an application. Thus, a BCI can provide communication and control for those who are locked-in. Electrical signals from the brain used for BCI operation can be recorded non-invasively from the scalp or invasively from the cortical surface. These signals include slow cortical potentials (1), P300 evoked potentials (2), and sensorimotor rhythms (3) recorded from the scalp. Some BCIs require self-regulation of the specific brain signal. Then patients are provided with online feedback of their EEG and knowledge of correct responses. In subsequent trials patients have to move a graphic signal (cursor) on a monitor toward targets located at the top or bottom of the screen. We trained severely or totally paralysed patients to regulate their EEG and to use this ability for communication with the aids of a Language Support Program. All patients were trained at home and some communicated extensive messages (4). Brain-computer interfaces for severely paralysed patients have been mainly used for verbal communication. A BCI controlled browser to surf the internet is also available. Furthermore, brain-computer interfaces were used to restore grasping via functional electric stimulation (5). The usefulness of BCIs to maintain or reinstall communication or other lost motor function in locked-in patients has been frequently demonstrated. However, signal analysis has to be improved, training protocols simplified and a better knowledge of the psychosocial factors interacting with BCI use is crucial to make BCI technology ready for routine clinical application.

(1) Kübler A et al. Exp Brain Res 1999;124:223-232.
(2) Donchin E et al. IEEE Trans Neural Syst Rehab Eng 2000;8(2):174-9.
(3) Wolpaw JR et al. IEEE Trans Neural Syst Rehab Eng 2003;11(2):204-7.
(4) Neumann N et al. J Neurol Neurosurg Psychiatry 2003;74(8):1117-21.
(5) Pfurtscheller G et al. Neurosci Lett 2003;351(1):33-6.

 

Brain function in pathological unconsciousness

Steven Laureys
University of Liege
Cyclotron Research Center & Dept. of Neurology
Sart Tilman B30, 4000 Liege, Belgium

Functional neuroimaging techniques represent a useful tool to objectively quantify the residual brain function in patients with altered states of consciousness. We will here compare the cerebral function in patients who survive a severe brain injury (i.e., coma, vegetative state, minimally conscious state and locked in syndrome) with that observed in the resting conscious state, sleep, epilepsy and general anaesthesia. The interest of this work is twofold. First, severely brain injured patients represent a problem in terms of diagnosis, prognosis, treatment and daily management. Second, these patients offer the opportunity to explore human consciousness. Indeed, they present a complete  nearly graded ­ range of conscious states from unconsciousness (coma) to full awareness (locked-in syndrome). In what follows, we will put a special emphasis on the vegetative state. This condition represents a unique and complete dissociation between the two main components of consciousness: wakefulness -which is preserved- and awareness -which is abolished.

Compared to the conscious resting state, global brain metabolism has been shown to be significantly reduced in the vegetative state (approximately 40 to 50% of normal values). Similar values have been observed in coma, slow wave sleep and general anaesthesia. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. In the vegetative state, the most dysfunctional brain regions are bilateral frontal and parieto-temporal associative cortices. Interestingly, a similar fronto-parietal network is the most active during wakefulness and the least active in coma, sleep and general anaesthesia. Despite the metabolic impairment, external stimulation still induces a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both noxious and auditory stimuli.

However, this activation is limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we show that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction. Consciousness seems to rely on the functional integrity of a critical frontal-parietal 'global workspace' network and its intra- and subcortical connections.

Selected references:
Boly M, Faymonville ME, Peigneux P, Lambermont B, Damas P, Del Fiore G, Degueldre C, Franck G, Luxen A, Lamy M, Moonen G, Maquet P, Laureys S. Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state. Arch Neurol. 2004 Feb;61(2):233-8
Laureys S, Faymonville ME, Peigneux P, Damas P, Lambermont B, Del Fiore G, Degueldre C, Aerts J, Luxen A, Franck G, Lamy M, Moonen G, Maquet P. Cortical processing of noxious somatosensory stimuli in the persistent vegetative state. Neuroimage. 2002 Oct;17(2):732-41.
Laureys S, Faymonville ME, Luxen A, Lamy M, Franck G, Maquet P. Restoration of thalamocortical connectivity after recovery from persistent vegetative state. Lancet. 2000 May 20;355:1790-1.

 

Functional imaging in general anesthesia

Pierre Fiset
Department of Anaesthesia
McGill University
Montreal, Quebec, Canada

Brain imaging helps to refine our understanding of anaesthetic effect and is providing novel information that result in the formulation of hypothesis. In the studies that will be shown here as well as in many others in which various anaesthetics were used, a constant finding is that the drugs that we use seem to exert their action on specific sites within the CNS. This is true for a wide variety of drugs like midazolam, anaesthetic vapors and opiates. Although brain imaging can't give precise information on the neurophysiological mechanisms or the anatomical connectivity that underlie anaesthetic effects, it provides an anatomical target for the localization of anaesthetic sensitive neurotransmitters and a framework for the determination of the functional network affected by anaesthetic drugs.

Functional imaging of anaesthetic effects has contributed to the emergence or the reinforcement of some interesting hypothesis on mechanisms of anaesthesia. The thalamus has consistently shown marked deactivation coincident with the anaesthesia-induced loss of consciousness, appearing to be a very important target of anaesthetic effect. This is consistent with findings from other researchers interested in single cell physiology. At the cellular level, anaesthetics have been shown to cause hyper polarization and increased conductance of thalamic ventrobasal relay neurons. This would cause an inhibition of thalamic tonic firing of action potential which, considering the central role of the thalamus in the relay of afferent information and maintenance of consciousness could be well in line with the production of anesthesia.32

Study of the mechanisms of anaesthesia may also reveal the neural substrates of changes in the level of consciousness we experience daily. The use of anaesthetic drugs can be seen as a powerful tool for investigating conscious phenomena. Anaesthetics can be very precisely given to achieve precise states of altered consciousness. Once these conditions are reached, one can look at the functional neural network responsible for that state, gathering information on processes responsible for conscious behaviour.

Selected references:
Fiset P. Functional brain imaging and propofol mechanisms of action.Adv Exp Med Biol. 2003;523:115-21
Backman SB, Fiset P, Plourde G. Cholinergic mechanisms mediating anesthetic induced altered states of consciousness. Prog Brain Res. 2004;145:197-206
Fiset P, Paus T, Daloze T, Plourde G, Meuret P, Bonhomme V, Hajj-Ali N, Backman SB, Evans AC. Brain mechanisms of propofol-induced loss of consciousness in humans: a positron emission tomographic study.J Neurosci. 1999 Jul 1;19(13):5506-13

 

Using functional neuroimaging to detect residual cognitive function in persistent vegetative state

Adrian M. Owen
MRC Cognition and Brain Sciences Unit, 15 Chaucer Road
Cambridge CB2 2EF, UK

Despite converging agreement about the definition of PVS, recent reports have raised concerns about the possibility that, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult in cases where motor responses are inconsistent or may even be undetectable. Here, hypothesis-driven strategies will be described for using H215O PET and fMRI activation studies to assess covert cognitive processing in patients with a clinical diagnosis of PVS. Several recent cases will be described, who have exhibited clear and predicted rCBF and/or BOLD responses during well documented activation paradigms (e.g. face recognition and speech perception) that have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. In spite of the multiple logistic and procedural problems involved, these results provide a strong basis for the systematic study of residual cognitive function in patients diagnosed as being in a PVS.

Selected references:
Ramnani N, Owen AM. Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nat Rev Neurosci. 2004 Mar;5(3):184-94
Brett M, Johnsrude IS, Owen AM. The problem of functional localization in the human brain. Nat Rev Neurosci. 2002 Mar;3(3):243-9
Menon DK, Owen AM, Williams EJ, Minhas PS, Allen CM, Boniface SJ, PickardcJD. Cortical processing in persistent vegetative state. Wolfson Brain Imaging Centre Team. Lancet. 1998 Jul 18;352(9123):200.

 

Characterizing residual cerebral activity following severe brain injuries

Nicholas D. Schiff
Department of Neurology and Neuroscience
Medicine and Psychiatry
Weill Medical College of Cornell University
New York, NY 10021, USA

In order to better characterize residual cerebral activity following severe brain injury recent investigations of severely brain-injured persons using multi-modal neuroimaging techniques will be discussed. Combined evaluations of brain function with positron emission tomography, structural and functional magnetic resonance imaging, and electroencephalography or magnetoencephalography promise to provide greater insight into two parallel issues: 1) the underlying pathophysiological mechanisms separating different disorders of consciousness such as the vegetative state (VS) and minimally conscious state (MCS) and 2) assaying the integrity of functional cerebral networks in the severely brain-injured. The discussion will focus on comparisons of quantitative measurements in patients in the persistent vegetative state and MCS. The results of multi-modal imaging will be used to develop a model of the pathophysiologic basis of MCS and to suggest potential markers for identifying residual functional capacities in some patients.

Selected references:
Schiff ND, Ribary U, Moreno DR, Beattie B, Kronberg E, Blasberg R, Giacino J, McCagg C, Fins JJ, Llinas R, Plum F. Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain. Brain. 2002 Jun;125(Pt 6):1210-34
Schiff ND, Plum F. The role of arousal and "gating" systems in the neurology of impaired
consciousness. J Clin Neurophysiol. 2000 Sep;17(5):438-52
Schiff ND, Plum F. Cortical function in the persistent vegetative state. Trends Cogn Sci. 1999 Feb;3(2):43-44.

 

Personal Identity, Justice and the Regulation of Research in Brain Injury

Joseph J. Fins
Division of Medical Ethics
Departments of Medicine and Public Health
Weill Medical College of Cornell University
New York-Weill Cornell Medical Center, 525 East 68th Street, F-173
New York, NY, USA

Research in severe brain injury is challenging because subjects may be unable to provide informed consent and interventions may alter cognition, memory or affect. This may alter the self and raise fundamental questions about personhood. I will consider these challenges through the prism of the philosopher, Derek Parfit's work on personal identity.

Specifically, I will consider narrative and personal continuity before and after injury and how this should inform our ethical obligations to individuals with severe impairments of consciousness following brain injury. Arguing for narrative and personal continuity, I will reconsider prevailing ethical stances and regulatory norms concerning research on subjects who may lack decision making capacity and suggest novel strategies to engage surrogates. I will assert that our response to research regulation should be cognizant of the connection between the subject's past and current states and the long history of societal neglect sustained by this under-served segment of our population.

Selected references:
Fins JJ. From psychosurgery to neuromodulation and palliation: history's lessons for the ethical conduct and regulation of neuropsychiatric research. Neurosurg Clin N Am. 2003 Apr;14(2):303-19
Fins JJ. Constructing an ethical stereotaxy for severe brain injury: balancing risks, benefits and access. Nat Rev Neurosci. 2003 Apr;4(4):323-7
Fins JJ. A proposed ethical framework for interventional cognitive neuroscience: a consideration of deep brain stimulation in impaired consciousness. Neurol Res. 2000 Apr;22(3):273-8