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Symposium 2


Saturday June 21, 10:30AM-12:30PM at Alexander Hall

Basic Neuroscientific and Clinical Approaches to Disorders of CNS Arousal


Chair: Donald Pfaff
Laboratory of Neurobiology and Behavior
Rockefeller University


Generalized CNS Arousal in Animal and Human Brains

Donald Pfaff
Laboratory of Neurobiology and Behavior
The Rockefeller University

Donald Pfaff, Laboratory of Neurobiology and Behavior, The Rockefeller University, USA
Isabel Arrieta-Cruz, Laboratory of Neurobiology and Behavior, The Rockefeller University, USA

Generalized CNS arousal has been given an operational definition ("Brain Arousal", Harvard Univ. Press, 2006) that is intended to apply to all vertebrate brains. Using a computer-controlled assay that measures the motoric, sensory and emotional components of generalized CNS arousal in mice, we have detected behavioral deficits due to anoxia that did not appear in a 28 point neurological screen ( Experimental Neurology, 2007). Inspired by the success of Schiff et al (Nature, 2007) in using deep brain to improve the functional ability of a patient who had been in a minimally conscious state, we are now using stimulation of the medial thalamus and/or the basal forebrain to elevate arousal-related behaviors in mice. Included in this effort are mathematically defined trains of pulses designed to conform to the likely non-linear character of CNS arousal systems.

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Neural and Chemical Substrates of Consciousness across Waking and Sleeping

Barbara Jones
Department of Neurology and Neurosurgery
McGill University
Waking and sleeping are actively generated by neuronal systems distributed through the brainstem and forebrain with different projections, discharge patterns, neurotransmitters and receptors. Waking is maintained by systems with ascending projections, which by their discharge stimulate cortical activation, necessary for consciousness. It is also stimulated by neurons with descending projections, which by their discharge stimulate behavioral arousal and responsiveness with muscle tone. Together with predominantly glutamatergic and GABAergic long or locally projecting neurons of the central reticular core, other neurons serve to modulate cortical activity and behavior through diffuse projections, state-regulated discharge and use of modulatory neurotransmitters, including acetylcholine, noradrenaline, and orexin (hypocretin). Cholinergic neurons stimulate cortical activation but not behavioral arousal or muscle tone and discharge in association with cortical activation during both Wake and REM sleep. In contrast, many other modulatory systems stimulate both cortical activation and behavioral arousal and discharge selectively during waking. The modulatory neurotransmitters act upon postsynaptic neurons in different manners according to specific receptors associated with excitatory or inhibitory actions and accordingly recruitment or silencing of other wake or sleep neuronal systems. Sleeping is initiated by inhibition of the activating and arousal systems. This inhibition is effected at multiple levels through particular GABAergic neurons that discharge maximally during sleep. Sleep-active GABAergic neurons are inhibited during waking by noradrenaline through £\2 adrenergic receptors. Some such GABAergic neurons in the preoptic area and basal forebrain discharge with slow wave activity during slow wave sleep (SWS). Such cortical activity is not consonant with conscious perception or cognitive activity. Other GABAergic neurons discharge at progressively increasing rates during SWS and REM sleep potentially promoting behavioral quiescence and inhibition of responsiveness along with diminishing muscle tone. Such GABAergic neurons likely inhibit noradrenergic and orexinergic neurons. During REM sleep, cholinergic systems become active and stimulate cortical activation, while the noradrenergic and orexinergic systems along with other reticular and motor neurons are held under inhibition such as to prevent responsiveness, motor activity and muscle tone during this ¡¥paradoxical¡¦ state of sleep, when dreaming and thus a particular state of consciousness occur.
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Imaging in Disorders of Conscious
Haibo Di
Hangzhou Normal University


  • Learn the difference between coma, vegetative state, minimally conscious state and locked-in syndrome
  • Learn the clinical assessment of consciousness
  • Learn what is the residual brain function and activation in disorders of consciousness
  • Learn about the ethical issues and quality of life measures in these disorders

Financial Disclosure: this presentation will not include discussion of any commercial products or services.

New neuroimaging techniques are giving a better understanding of patients in coma and related conditions. Progress in medical care is increasing the number of people who survive brain damage. We can now save the lives of many patients who suffer trauma or anoxia but if the damage is severe, the victim will slip into a coma. Patients who recover from a coma typically do so within days. Others will die, and still others will awaken but remain unconscious, entering what is called a vegetative state. Even for experts, the vegetative state is very a disturbing condition. It illustrates how the two main components of consciousness can get dissociated: wakefulness remains intact but awareness - encompassing all thoughts and feelings - is abolished. In patients who recover from the vegetative state, the first signs of consciousness are minimal and appear gradually. The patient who starts making non-reflexive movements but remains unable to communicate enters a minimally conscious state. Like the vegetative state, the minimally conscious state may be transient on the way to further recovery, or it may be chronic, sometimes permanent. Making the distinction between vegetative and minimally conscious patients is challenging. Given that conscious awareness is subjective, first-person experience that is inherently difficult to measure in another being; functional neuroimaging offers a unique opportunity to objectively study disorders of consciousness. Positron emission tomography (PET) and functional MRI studies measuring neural activity in brain-damaged patients are disentangling the neural correlates of the vegetative from the minimally conscious state and have major clinical and ethical consequences. More research efforts are awaited so that these new techniques can help in the prognosis and treatment of these devastating medical conditions.

Suggested readings 1-5:

  1. Di HB, Yu SM, Weng XC, Laureys S, Yu D, Li JQ, et al. Cerebral response to patient's own name in the vegetative and minimally conscious states. Neurology 2007;68(12):895-9.
  2. Di H, Boly M, Weng X, Ledoux D, Laureys S. Neuroimaging activation studies in the vegetative state: predictors of recovery? Clinical Medicine in press.
  3. Laureys S, Giacino JT, Schiff ND, Schabus M, Owen AM. How should functional imaging of patients with disorders of consciousness contribute to their clinical rehabilitation needs? Curr Opin Neurol 2006;19(6):520-7.
  4. Laureys S. The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 2005;9(12):556-9.
  5. Laureys S. Science and society: death, unconsciousness and the brain. Nat Rev Neurosci 2005;6(11):899-909.
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Eyes Open, Brain Shut: Consciousness in the Vegetative State
Steven Laureys
Coma Science Group
University of Liege

Haibo Di, Coma Science Group, University of Liege, Liege, BELGIUM
Steven Laureys, Coma Science Group, University of Liege, Liege, BELGIUM

Patients in a vegetative state (VS) and minimally conscious state (MCS) continue to pose problems in terms of their diagnosis, prognosis and treatment. Consciousness is a subjective first-person experience which study has remained the field of philosophy for the past millennia. That time has finally changed and empirical evidence from functional neuroimaging is offering a genuine glimpse on the solution to the infamous mind-body conundrum. New technological and scientific advances offer the neurological community unique ways to improve our understanding and management of severely brain damaged patients.

Good medical management starts by making a correct diagnosis. There is an irreducible limitation in knowing for certain whether any other being is conscious. Vegetative patients can move extensively and clinical studies have shown how difficult it is to differentiate reflex or ¡¥automatic¡¦ from voluntary or ¡¥willed¡¦ movements. This results in an underestimation of behavioural signs of consciousness and hence a misdiagnosis, estimated to occur in about one third to nearly half of chronically vegetative patients.

PET and fMRI studies have not yet shown to be reliable markers of recovery of consciousness. However, they have permitted to reject the ancient view that vegetative patients are neocortically dead or a-pallic. A succession of neuroimaging data has shown cerebral activation in isolated and disconnected islands of ¡§lower level¡¨ cortices or "pallium" in response to auditory, visual, somatosensory and noxious stimuli. Functional neuroimaging studies have also provided scientific evidence that residual brain function in VS is very different from the brain¡¦s integrative capacity in MCS. These studies have confirmed that VS and MCS truly are different physiological entities. However, in the absence of a full understanding of the neural correlates of consciousness, even a normal activation in response to passive sensory stimulation cannot be taken as incontestable proof of consciousness. In contrast, repeated and prolonged activation in response to the instruction to perform a mental imagery task would provide undeniable evidence of voluntary task-dependent brain activity, and hence of consciousness. This ground-breaking approach was recently validated in healthy controls and has been successfully applied to identify conscious perception in a ¡V so far unique - patient behaviourally diagnosed as being in a post-traumatic VS.

Brain computer interfaces (BCI) permit communication via voluntary EEG control, without any motor involvement. Technological improvements in such devices now enable locked-in patients to control their surroundings in ways never possible before. BCI can not only be employed as a communication instrument in LIS but also as a diagnostic tool in disorders of consciousness. It is thrilling to witness the use of this powerful approach in the assessment of possible residual consciousness in patients clinically diagnosed as ¡§VS¡¨ or ¡§MCS¡¨. The question of what it feels like to be minimally conscious has not yet been solved but the technology to at least try to answer the issue is now existing.

Death, unconsciousness and the brain, Laureys S
Nature Reviews Neuroscience, 11 (2005) 899-909

What is it like to be vegetative or minimally conscious ?, Laureys S and Boly M
Current Opinion in Neurology, 20 (2007) 609-13

Self-consciousness in non-communicative patients, Laureys S, Perrin F, Bredart S
Consciousness & Cognition, 16 (2007) 722-741?

Eyes open, brain shut: the vegetative state, Laureys S
Scientific American, 4 (2007) 32-37

What is it like to be vegetative or minimally conscious ?, Laureys S and Boly M
Current Opinion in Neurology, 20 (2007) 609-13

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