- Email: [email protected]
The neural correlates of consciousness: Electrophysiological and neuroimaging evidence for conscious processing in vegetative state
Clinical Neurophysiology 122 (2011) 641–642
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
The neural correlates of consciousness: Electrophysiological and neuroimaging evidence for conscious processing in vegetative state See Article, pages 719–724
Consciousness is a puzzling phenomenon. We all know it, but only from a subjective, first-person perspective. For centuries, philosophers, psychologists and scientists have studied the content and the physical basis of consciousness. Most researchers agree that consciousness is not a dichotomic quality. There is convincing evidence that consciousness comprises distinct states, such as consciousness of pain, emotions or language. In addition, there is convincing evidence that conscious experience and behavior is associated with the integrity of specific neural circuits, i.e., the neural correlates of consciousness (Metzinger, 2000). The exact relationship between the subjective experience that constitutes consciousness and these objective neurophysiological phenomena is still unclear. Disorders of consciousness attract growing attention. An increasing number of individuals survive critical brain injury, some with severe disorders of consciousness. For clinical diagnosis, disorders of consciousness have been categorized in terms of awareness and wakefulness (Gawryluk et al., 2010). Wakefulness refers to a state in which individuals can open their eyes and exhibit some degree of motor arousal. Awareness refers to a state in which individuals have experiences of any kind, such as thoughts, memories, emotions and pain. Applying these qualities, three distinct disorders of consciousness have been defined: coma (absence of both wakefulness and awareness), persistent vegetative state (VS; wakefulness without awareness) and locked-in syndrome (wakefulness and awareness). More recently, clinical experience motivated the definition of another disorder of consciousness, the minimally conscious state (MCS, Giacino et al., 2002). These individuals demonstrate wakefulness but, in contrast to patients in VS, inconsistent but discernible evidence of awareness. Patients in MCS may reach for objects or visually fixate or speak a word or gesture in response to a command. The diagnosis of MCS is difficult, time-consuming and fallible, because there is no single clinical sign of awareness. Clinical tests rely on a patient demonstrating awareness and cognitive capabilities by means of overt motor actions, as does the Glasgow Coma Score, which counts eye opening, as well as the best verbal and motor responses (Teasdale and Jennett, 1974). The ability to perform these overt behaviors is often decoupled from consciousness as a direct result of the brain injury. As a matter of fact, we can never exclude the possibility of some form of consciousness in patients thought to be in VS with complete certainty.
In this issue of the journal, Cavinato and co-workers address the question: Is there an electrophysiological marker, which differentiates between MCS and VS? (see Cavinato et al., in this issue). Their results add to the growing corpus of studies exploring the neural correlates of consciousness in individuals with VS and MCS. MCS patients with severe brain injury are frequently misdiagnosed as being in VS. The accurate diagnosis of MCS as opposed to VS affects important decisions concerning care and rehabilitation and is thus of great clinical importance. The authors use the P300 component to study cognitive processing of information. The P300 wave, first reported 45 years ago (Sutton et al., 1965), reflects neural networks that are engaged in information processing, including attention and memory, and are distributed throughout the cerebral cortex and thalamus. Electrophysiological recordings have important advantages compared to other approaches probing human brain function. They are relatively easy to perform, portable and inexpensive. In addition, there are standardized protocols for data acquisition and analysis (Duncan et al., 2009). Probably of greatest importance, electrophysiological studies reveal the time course of brain activity related to cognitive processing with high temporal resolution. In an earlier study, the authors focused on the prediction of consciousness recovery in patients with post-traumatic VS (Cavinato et al., 2009). They used a classical two-stimulus oddball task to elicit the P300 using the patient’s own name as deviant and a pure tone as standard stimulus (‘‘subject’s own name” paradigm). There is evidence that the amplitude of the P300 wave increases when more salient stimuli are used, such as the own first name instead of visual or auditory deviants. The authors found that P300 is a strong predictor of future recovery of consciousness in VS. This finding is in line with several studies that have confirmed the utility of P300 evoked by deviant tones to predict awakening and favourable outcome from coma and VS. In the present study, Cavinato and co-workers continue using the ‘‘subject’s own name” paradigm, but add a pure tone (2000 Hz as deviant, 1000 Hz as standard stimulus) and an ‘‘other first name” paradigm (patient’s own name as deviant and unfamiliar names as standard stimulus). These paradigms represent growing complexity and cognitive demand. To note, the authors instructed their patients to count the occurrence of deviant stimuli to better differentiate between patients in VS and MCS (similar to the paradigm used by Schnakers et al., 2008). The study indicates
1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.10.024
642
Editorial / Clinical Neurophysiology 122 (2011) 641–642
that in 6 out of 11 patients fulfilling the behavioral criteria for VS a reliable P300 component could be observed in all three conditions. These findings corroborate earlier reports showing that 38% of patients in VS generate a P300 wave. Interestingly, patients in MCS exhibit significantly longer P300 latencies for the ‘‘subject’s own name” and the ‘‘other first name” paradigms than patients in VS. This unexpected finding suggests that the cognitive processes associated with the generation of a P300 wave in these paradigms, such as attention, memory and language processing, differ between individuals in VS and MCS. The authors emphasize that the presence of reproducible ERPs in presumably non-conscious patients may indicate the ability of severely damaged brains to execute spared modular cognitive functions. They conclude that the increase of P300 latencies for more complex and salient paradigms in MCS but not in VS might help in the difficult differential diagnosis of MCS vs. VS. In summary, Cavinato and co-workers combined a well-studied and established electrophysiological method (recording of P300) with an increasingly used and successful paradigm (the patient’s first name as highly salient stimulus) and found that the generation of P300 waves is preserved in about 50% of VS patients. This finding and the novel observation that the latencies of P300 waves, on average, differ significantly between VS and MCS patients supports the hypothesis that P300 recordings can be used to detect forms of consciousness in patients with severe brain injury. Additional and probably most convincing evidence for conscious behavior in patients thought to be in VS has been obtained using functional magnetic resonance imaging (fMRI) during mental imagery (Owen et al., 2006; Monti et al., 2010). In 2006, Owen et al. published a single-case study on a 23-year-old woman who sustained severe brain injuries, fulfilled the behavioral criteria of VS and was unable to respond to spoken commands with speech or movement. fMRI of mental imagery (imagining playing tennis, imagining visiting her own house), in contrast, provided strong evidence that this patient retained the ability to understand spoken commands and to respond to them through her brain activity (Owen et al., 2006). Building upon this study, functional MRI was used to determine the incidence of undetected awareness in a group of patients with severe brain injuries (Monti et al., 2010). Five of 54 patients with traumatic brain injury were able to modulate their brain activity by generating voluntary, reliable, and repeatable blood-oxygenation-level dependent responses when instructed to perform these imagery tasks (Monti et al., 2010). During clinical assessment, in contrast, these patients remained behaviorally unresponsive. The authors conclude that, in a minority of cases, patients who meet the behavioral criteria for VS have isolated cognitive functions and conscious awareness (Monti et al., 2010). Probably the most spectacular finding of this study was that one MCS patient could use fMRI to establish functional and interactive communication with the researchers. For five of six yes/no questions (e.g., ‘‘Do you have any brothers?”), the patient had a reliable neural response and was able to provide the correct answer with 100% accuracy (Monti et al., 2010). At the bedside, in contrast, this patient was unable to establish any functional communication. The studies of Owen et al. (2006) and Monti et al. (2010) received much attention in the media, reflecting the overwhelming public interest in this matter, but also started a controversy about the fundamental relationship between brain activation and conscious behavior and the interpretation of functional brain imaging data (Nachev and Husain, 2007; Greenberg, 2007). It is fascinating to observe how different electrophysiological and neuroimaging approaches use various paradigms to investigate conscious behavior. These studies support the notion that consciousness is not a single entity, but a construct that encompasses several interrelated functions. These studies have serious limitations, though. Researchers depend on surrogate markers of
brain function, such as changes in neuroelectric potentials (e.g., P300 recordings) and blood-oxygenation-level dependent responses (fMRI) to assess conscious behavior. The relationship between these markers and conscious experiences is not entirely clear yet. A combination of modalities and paradigms may be helpful to study consciousness in patients with severe brain injury (see a related editorial recently published in this journal by Wijnen and Van Boxtel (2010)). Still, there are important caveats: First, the absence of neuroelectric or blood-oxygenation-level dependent responses to the experimental paradigms under investigation does not exclude the possibility of consciousness in its complexity, not even of isolated states of consciousness, in patients with severe brain injury. Second, the interpretation of preserved neuroelectric or blood-oxygenation-level dependent responses in a VS patient, is not always straightforward and uncontroversial. To address these caveats a close collaboration between philosophy of mind, cognitive neuroscience as well as neurophysiology and brain imaging is highly desirable.
References Cavinato M, Freo U, Ori C, Zorzi M, Tonin P, Piccione F, et al. Post-acute P300 predicts recovery of consciousness from traumatic vegetative state. Brain Inj 2009;23:973–80. Cavinato M, Volpato C, Silvoni S, Sacchetto M, Merico A, Piccione F. Event-related brain potential modulation in patients with severe brain damage. Clin Neurophysiol; in this issue. Duncan CC, Barry RJ, Connolly JF, Fischer C, Michie PT, Näätänen R, et al. Eventrelated potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400. Clin Neurophysiol 2009;120:1883–908. Gawryluk JR, D’Arcy RC, Connolly JF, Weaver DF. Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques. BMC Neurol 2010;10:11. Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58:349–53. Greenberg DL. Comment on ‘‘Detecting awareness in the vegetative state”. Science 2007;315:1221. Metzinger T. Neural correlates of consciousness: empirical and conceptual questions. Boston, USA: MIT Press; 2000. Monti MM, Vanhaudenhuyse A, Coleman MR, Boly M, Pickard JD, Tshibanda L, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med 2010;362:579–89. Nachev P, Husain M. Comment on ‘‘Detecting awareness in the vegetative state”. Science 2007;315:1221. Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science 2006;313:1402. Schnakers C, Perrin F, Schabus M, Majerus S, Ledoux D, Damas P, et al. Voluntary brain processing in disorders of consciousness. Neurology 2008;71:1614–20. Sutton S, Braren M, Zubin J, John ER. Evoked-potential correlates of stimulus uncertainty. Science 1965;150:1187–8. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81–4. Wijnen VJ, Van Boxtel GJ. The continuing problem of diagnosing unresponsive patients: searching for neurophysiological correlates of consciousness. Clin Neurophysiol 2010;121:992–3.
Peter Sörös Department of Clinical Neurological Sciences, Schulich School of Medicine & Dentistry, University of Western Ontario, Canada School of Communication Sciences & Disorders, Faculty of Health Sciences, University of Western Ontario, Canada Department of Clinical Neurological Sciences, University Hospital, 339 Windermere Road, London, Canada N6A 5A5 Tel.: +1 519 685 8500x34147; fax: +1 519 663 3196 E-mail address: [email protected] Available online 30 October 2010
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
The neural correlates of consciousness: Electrophysiological and neuroimaging evidence for conscious processing in vegetative state See Article, pages 719–724
Consciousness is a puzzling phenomenon. We all know it, but only from a subjective, first-person perspective. For centuries, philosophers, psychologists and scientists have studied the content and the physical basis of consciousness. Most researchers agree that consciousness is not a dichotomic quality. There is convincing evidence that consciousness comprises distinct states, such as consciousness of pain, emotions or language. In addition, there is convincing evidence that conscious experience and behavior is associated with the integrity of specific neural circuits, i.e., the neural correlates of consciousness (Metzinger, 2000). The exact relationship between the subjective experience that constitutes consciousness and these objective neurophysiological phenomena is still unclear. Disorders of consciousness attract growing attention. An increasing number of individuals survive critical brain injury, some with severe disorders of consciousness. For clinical diagnosis, disorders of consciousness have been categorized in terms of awareness and wakefulness (Gawryluk et al., 2010). Wakefulness refers to a state in which individuals can open their eyes and exhibit some degree of motor arousal. Awareness refers to a state in which individuals have experiences of any kind, such as thoughts, memories, emotions and pain. Applying these qualities, three distinct disorders of consciousness have been defined: coma (absence of both wakefulness and awareness), persistent vegetative state (VS; wakefulness without awareness) and locked-in syndrome (wakefulness and awareness). More recently, clinical experience motivated the definition of another disorder of consciousness, the minimally conscious state (MCS, Giacino et al., 2002). These individuals demonstrate wakefulness but, in contrast to patients in VS, inconsistent but discernible evidence of awareness. Patients in MCS may reach for objects or visually fixate or speak a word or gesture in response to a command. The diagnosis of MCS is difficult, time-consuming and fallible, because there is no single clinical sign of awareness. Clinical tests rely on a patient demonstrating awareness and cognitive capabilities by means of overt motor actions, as does the Glasgow Coma Score, which counts eye opening, as well as the best verbal and motor responses (Teasdale and Jennett, 1974). The ability to perform these overt behaviors is often decoupled from consciousness as a direct result of the brain injury. As a matter of fact, we can never exclude the possibility of some form of consciousness in patients thought to be in VS with complete certainty.
In this issue of the journal, Cavinato and co-workers address the question: Is there an electrophysiological marker, which differentiates between MCS and VS? (see Cavinato et al., in this issue). Their results add to the growing corpus of studies exploring the neural correlates of consciousness in individuals with VS and MCS. MCS patients with severe brain injury are frequently misdiagnosed as being in VS. The accurate diagnosis of MCS as opposed to VS affects important decisions concerning care and rehabilitation and is thus of great clinical importance. The authors use the P300 component to study cognitive processing of information. The P300 wave, first reported 45 years ago (Sutton et al., 1965), reflects neural networks that are engaged in information processing, including attention and memory, and are distributed throughout the cerebral cortex and thalamus. Electrophysiological recordings have important advantages compared to other approaches probing human brain function. They are relatively easy to perform, portable and inexpensive. In addition, there are standardized protocols for data acquisition and analysis (Duncan et al., 2009). Probably of greatest importance, electrophysiological studies reveal the time course of brain activity related to cognitive processing with high temporal resolution. In an earlier study, the authors focused on the prediction of consciousness recovery in patients with post-traumatic VS (Cavinato et al., 2009). They used a classical two-stimulus oddball task to elicit the P300 using the patient’s own name as deviant and a pure tone as standard stimulus (‘‘subject’s own name” paradigm). There is evidence that the amplitude of the P300 wave increases when more salient stimuli are used, such as the own first name instead of visual or auditory deviants. The authors found that P300 is a strong predictor of future recovery of consciousness in VS. This finding is in line with several studies that have confirmed the utility of P300 evoked by deviant tones to predict awakening and favourable outcome from coma and VS. In the present study, Cavinato and co-workers continue using the ‘‘subject’s own name” paradigm, but add a pure tone (2000 Hz as deviant, 1000 Hz as standard stimulus) and an ‘‘other first name” paradigm (patient’s own name as deviant and unfamiliar names as standard stimulus). These paradigms represent growing complexity and cognitive demand. To note, the authors instructed their patients to count the occurrence of deviant stimuli to better differentiate between patients in VS and MCS (similar to the paradigm used by Schnakers et al., 2008). The study indicates
1388-2457/$36.00 Ó 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2010.10.024
642
Editorial / Clinical Neurophysiology 122 (2011) 641–642
that in 6 out of 11 patients fulfilling the behavioral criteria for VS a reliable P300 component could be observed in all three conditions. These findings corroborate earlier reports showing that 38% of patients in VS generate a P300 wave. Interestingly, patients in MCS exhibit significantly longer P300 latencies for the ‘‘subject’s own name” and the ‘‘other first name” paradigms than patients in VS. This unexpected finding suggests that the cognitive processes associated with the generation of a P300 wave in these paradigms, such as attention, memory and language processing, differ between individuals in VS and MCS. The authors emphasize that the presence of reproducible ERPs in presumably non-conscious patients may indicate the ability of severely damaged brains to execute spared modular cognitive functions. They conclude that the increase of P300 latencies for more complex and salient paradigms in MCS but not in VS might help in the difficult differential diagnosis of MCS vs. VS. In summary, Cavinato and co-workers combined a well-studied and established electrophysiological method (recording of P300) with an increasingly used and successful paradigm (the patient’s first name as highly salient stimulus) and found that the generation of P300 waves is preserved in about 50% of VS patients. This finding and the novel observation that the latencies of P300 waves, on average, differ significantly between VS and MCS patients supports the hypothesis that P300 recordings can be used to detect forms of consciousness in patients with severe brain injury. Additional and probably most convincing evidence for conscious behavior in patients thought to be in VS has been obtained using functional magnetic resonance imaging (fMRI) during mental imagery (Owen et al., 2006; Monti et al., 2010). In 2006, Owen et al. published a single-case study on a 23-year-old woman who sustained severe brain injuries, fulfilled the behavioral criteria of VS and was unable to respond to spoken commands with speech or movement. fMRI of mental imagery (imagining playing tennis, imagining visiting her own house), in contrast, provided strong evidence that this patient retained the ability to understand spoken commands and to respond to them through her brain activity (Owen et al., 2006). Building upon this study, functional MRI was used to determine the incidence of undetected awareness in a group of patients with severe brain injuries (Monti et al., 2010). Five of 54 patients with traumatic brain injury were able to modulate their brain activity by generating voluntary, reliable, and repeatable blood-oxygenation-level dependent responses when instructed to perform these imagery tasks (Monti et al., 2010). During clinical assessment, in contrast, these patients remained behaviorally unresponsive. The authors conclude that, in a minority of cases, patients who meet the behavioral criteria for VS have isolated cognitive functions and conscious awareness (Monti et al., 2010). Probably the most spectacular finding of this study was that one MCS patient could use fMRI to establish functional and interactive communication with the researchers. For five of six yes/no questions (e.g., ‘‘Do you have any brothers?”), the patient had a reliable neural response and was able to provide the correct answer with 100% accuracy (Monti et al., 2010). At the bedside, in contrast, this patient was unable to establish any functional communication. The studies of Owen et al. (2006) and Monti et al. (2010) received much attention in the media, reflecting the overwhelming public interest in this matter, but also started a controversy about the fundamental relationship between brain activation and conscious behavior and the interpretation of functional brain imaging data (Nachev and Husain, 2007; Greenberg, 2007). It is fascinating to observe how different electrophysiological and neuroimaging approaches use various paradigms to investigate conscious behavior. These studies support the notion that consciousness is not a single entity, but a construct that encompasses several interrelated functions. These studies have serious limitations, though. Researchers depend on surrogate markers of
brain function, such as changes in neuroelectric potentials (e.g., P300 recordings) and blood-oxygenation-level dependent responses (fMRI) to assess conscious behavior. The relationship between these markers and conscious experiences is not entirely clear yet. A combination of modalities and paradigms may be helpful to study consciousness in patients with severe brain injury (see a related editorial recently published in this journal by Wijnen and Van Boxtel (2010)). Still, there are important caveats: First, the absence of neuroelectric or blood-oxygenation-level dependent responses to the experimental paradigms under investigation does not exclude the possibility of consciousness in its complexity, not even of isolated states of consciousness, in patients with severe brain injury. Second, the interpretation of preserved neuroelectric or blood-oxygenation-level dependent responses in a VS patient, is not always straightforward and uncontroversial. To address these caveats a close collaboration between philosophy of mind, cognitive neuroscience as well as neurophysiology and brain imaging is highly desirable.
References Cavinato M, Freo U, Ori C, Zorzi M, Tonin P, Piccione F, et al. Post-acute P300 predicts recovery of consciousness from traumatic vegetative state. Brain Inj 2009;23:973–80. Cavinato M, Volpato C, Silvoni S, Sacchetto M, Merico A, Piccione F. Event-related brain potential modulation in patients with severe brain damage. Clin Neurophysiol; in this issue. Duncan CC, Barry RJ, Connolly JF, Fischer C, Michie PT, Näätänen R, et al. Eventrelated potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400. Clin Neurophysiol 2009;120:1883–908. Gawryluk JR, D’Arcy RC, Connolly JF, Weaver DF. Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques. BMC Neurol 2010;10:11. Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58:349–53. Greenberg DL. Comment on ‘‘Detecting awareness in the vegetative state”. Science 2007;315:1221. Metzinger T. Neural correlates of consciousness: empirical and conceptual questions. Boston, USA: MIT Press; 2000. Monti MM, Vanhaudenhuyse A, Coleman MR, Boly M, Pickard JD, Tshibanda L, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med 2010;362:579–89. Nachev P, Husain M. Comment on ‘‘Detecting awareness in the vegetative state”. Science 2007;315:1221. Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science 2006;313:1402. Schnakers C, Perrin F, Schabus M, Majerus S, Ledoux D, Damas P, et al. Voluntary brain processing in disorders of consciousness. Neurology 2008;71:1614–20. Sutton S, Braren M, Zubin J, John ER. Evoked-potential correlates of stimulus uncertainty. Science 1965;150:1187–8. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81–4. Wijnen VJ, Van Boxtel GJ. The continuing problem of diagnosing unresponsive patients: searching for neurophysiological correlates of consciousness. Clin Neurophysiol 2010;121:992–3.
Peter Sörös Department of Clinical Neurological Sciences, Schulich School of Medicine & Dentistry, University of Western Ontario, Canada School of Communication Sciences & Disorders, Faculty of Health Sciences, University of Western Ontario, Canada Department of Clinical Neurological Sciences, University Hospital, 339 Windermere Road, London, Canada N6A 5A5 Tel.: +1 519 685 8500x34147; fax: +1 519 663 3196 E-mail address: [email protected] Available online 30 October 2010