In the united states, nearly 60,000 patients per day receive general anesthesia for surgery. 1 General anesthesia is a drug-induced, reversible condition that includes specific behavioral and physiological traits -unconsciousness, amnesia, analgesia, and akinesia -with concomitant stability of the autonomic, cardiovascular, respiratory, and thermoregulatory systems. 2 General anesthesia produces distinct patterns on the electroencephalogram (EEG), the most common of which is a progressive increase in low-frequency, high-amplitude activity as the level of general anesthesia deepens 3,4 (Fig. 1). How anesthetic drugs induce and maintain the behavioral states of general anesthesia is an important question in medicine and neuroscience. 6 Substantial insights can be gained by considering the relationship of general anesthesia to sleep and to coma.Humans spend approximately one third of their lives asleep. Sleep, a state of decreased arousal that is actively generated by nuclei in the hypothalamus, brain stem, and basal forebrain, is crucial for the maintenance of health. 7,8 Normal human sleep cycles between two states -rapid-eye-movement (REM) sleep and non-REM sleep -at approximately 90-minute intervals. REM sleep is characterized by rapid eye movements, dreaming, irregularities of respiration and heart rate, penile and clitoral erection, and airway and skeletal-muscle hypotonia. 7 In REM sleep, the EEG shows active high-frequency, lowamplitude rhythms (Fig. 1). Non-REM sleep has three distinct EEG stages, with higheramplitude, lower-frequency rhythms accompanied by waxing and waning muscle tone, decreased body temperature, and decreased heart rate.Coma is a state of profound unresponsiveness, usually the result of a severe brain injury. 9 Comatose patients typically lie with eyes closed and cannot be roused to respond appropriately to vigorous stimulation. A comatose patient may grimace, move limbs, and have stereotypical withdrawal responses to painful stimuli yet make no localizing responses or discrete defensive movements. As the coma deepens, the patient's responsiveness even to painful stimuli may diminish or disappear. Although the patterns of EEG activity observed in comatose patients depend on the extent of the brain injury, they frequently resemble the high-amplitude, low-frequency activity seen in patients under general anesthesia 10 (Fig. 1). General anesthesia is, in fact, a reversible drug-induced coma. Nevertheless, anesthesiologists refer to it as "sleep" to avoid disquieting patients. Unfortunately, anesthesiologists also use the word "sleep" in technical descriptions to refer to Copyright © 2010 CLINICAL SIGNS AND EEG PAT TERNS OF UNCONSCIOUSNESS INDUCED BY GENER AL ANESTHESIAThe clinical signs and EEG patterns of general anesthesia-induced unconsciousness can be described in relation to the three periods in which they appear: induction, maintenance, and emergence. INDUCTION PERIODBefore induction, the patient has a normal, active EEG, with prominent alpha activity (10 Hz) when the eyes are clo...

Nature 414, 173-179 (2001) This Article described patterns of labelling observed in olfactory cortex when a transneuronal tracer was co-expressed with single odorant receptor genes in the mouse olfactory epithelium. During efforts to replicate and extend this work, we have been unable to reproduce the reported findings. Moreover, we have found inconsistencies between some of the figures and data published in the paper and the original data. We have therefore lost confidence in the reported conclusions. We regret any adverse consequences that may have resulted from the paper's publication.

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

We review the nosological criteria and functional neuroanatomical basis for brain death, coma, vegetative state, minimally conscious state and the locked-in state. Functional neuroimaging is providing new insights into cerebral activity in patients with severe brain damage. Measurements of cerebral metabolism and brain activations in response to sensory stimuli using positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and electrophysiological methods have significant potential to provide unique windows on to the presence, degree and location of any residual brain function. However, use of these techniques in severely brain-damaged persons is methodologically complex and requires careful quantitative analysis and interpretation. In addition, ethical frameworks to guide research in these patient populations must be further developed. At present, nosological distinctions confirmed by clinical examinations remain the standard for accurate diagnosis and prognosis. Neuroimaging techniques, while extremely promising, remain important tools for clinical research that should ultimately extend our understanding of the underlying mechanisms of these disorders.3

| The concept of consciousness continues to defy definition and elude the grasp of philosophical and scientific efforts to formulate a testable construct that maps to human experience. Severe acquired brain injury results in the dissolution of consciousness, providing a natural model from which key insights about consciousness may be drawn. In the clinical setting, neurologists and neurorehabilitation specialists are called on to discern the level of consciousness in patients who are unable to communicate through word or gesture, and to project outcomes and recommend approaches to treatment. Standards of care are not available to guide clinical decision-making for this population, often leading to inconsistent, inaccurate and inappropriate care. In this Review, we describe the state of the science with regard to clinical management of patients with prolonged disorders of consciousness. We review consciousness-altering pathophysiological mechanisms, specific clinical syndromes, and novel diagnostic and prognostic applications of advanced neuroimaging and electrophysiological procedures. We conclude with a provocative discussion of bioethical and medicolegal issues that are unique to this population and have a profound impact on care, as well as raising questions of broad societal interest.