Waking Up to a New Model for Studying Neural Systems: What Emergence from Unconscious States Can Reveal about Brain Organization

摘要

Each day, anesthesiologists carry out an incredible feat when thousands of individuals are rendered temporarily unconscious by surgical anesthesia. Post-intervention, most of these individuals will “wake up” with their cognitive abilities, their memories, their knowledge of the world, and their sense of continuity of self, intact. The blank spot in the recovered person's conscious awareness is the period of time during which an individual is under anesthesia. What accounts for the ability of the central nervous system (CNS) to maintain a lifetime of information during a period of unconsciousness due to anesthesia when even brief episodes of unconsciousness due to injury or interruptions in cerebral metabolism can cause serious, irreversible losses of function? What makes it possible for the CNS to essentially “reboot” as the anesthetic is withdrawn? Does recovery of function following anesthesia reveal aspects of the organization of neural and cognitive systems? What factors could result in incomplete recovery of neural and cognitive systems and are there underlying clinical conditions that the brain more vulnerable to perturbations and thus make incomplete recovery more likely? Surgical anesthesia provides an opportunity for studying changes in conscious states and a model for seeking the answers to the questions raised above. In a controlled clinical environment, anesthesiologists routinely pharmacologically manipulate a patient's brain activity from consciousness to unconsciousness and back. Within the clinical care setting it is not typical to consider such practices as “experiments” but there is data to be gathered from these situations that could be helpful in advancing our knowledge of brain organization. Anesthesia studies provide an alternative approach to the understanding of brain function that has shared interests with efforts to understand disruptions in emergence from unconsciousness in sleep disorders and coma. Historically speaking, the cardiovascular and respiratory systems have more typically been the focus of anesthesia research than has been the functioning of the CNS—particularly with respect to higher-level, complex cognitive functions. As a result, significant advances have been made in airway techniques and physiologic monitoring, dramatically improving patient safety. Partly in response to these advances, attention is now shifting to the neural and cognitive effects of anesthetic administrations as evidenced by the heightened research interest in possible long-term consequences of commonly administered anesthesia drugs on the elderly and the developing brain. Progress on these issues will continue due to formation of: (1) the International Study of Post-Operative Cognitive Dysfunction (ISPOCD), a study group funded by the European Union (see JSMF, 2011 ) (2) the collaborative effort of the International Anesthesia Research Society (IARS), and (3) the US Food and Drug Administration SmartTots program ( www.smarttots.org ) dedicated to addressing scientific and clinical gaps regarding the safe use of anesthetics in children. Previous to these and other efforts, there were limited attempts for characterizing and monitoring awakening to cognitive and behavioral levels that are indistinguishable from a subject's baseline metrics. In our opinion, quantifying this sequence may have important clinical ramifications while revealing fundamental principles about brain organization. Our aim is to facilitate research investigations focused on this topic especially those that involve neurophysiological measures with strong predictive potential for who willot have full recovery after anesthesia as well as contribute to a more mechanistic understanding by which the brain recovers consciousness. “Neuro-anesthesia” is emerging as an important research direction tackling these questions of fundamental importance to neuroscience and cognitive science. A focused multi-disciplinary effort is now being brought to bear to answer questions raised in the context of emergence from anesthetic unconsciousness, including: In what ways, does anesthesia emergence resemble or depart from what is known about waking from coma or sleep? How does emergence from anesthesia reveal a predictable pattern reflective of anatomical, structural, and/or functional network organizations within the brain and CNS? What opportunities derive from cognitive and systems neuroscience approaches such as combining psychological testing with brain-sensing devices including electroencephalogram, infrared spectroscopy, or other imaging methods (e.g., fMRI, MRS, PET) that make it possible to address these research questions in humans? A multi-disciplinary conversation on these and other questions has been the focus of several international workshops exploring what is and is not known about processes involved in regaining consciousness following surgical anesthesia, coma, and sleep (JSMF, 2011 ). Leading cognitive researchers, biophysicist