The Role of Arousal and “Gating” Systems in the Neurology of Impaired Consciousness

Abstract

Summary:A brief taxonomy of neurologic disorders resulting in global impairments of consciousness is presented. Particular emphasis is placed on focal injuries of subcortical structures that may produce disorders that are otherwise associated to large bilateral cortical injuries. A distinction between subcortical arousal and "gating" systems is developed. Both clinical and experimental studies are reviewed in the context of these disorders and their possible underlying mechanisms. Key Words: Awareness-Persistent vegetative state-Intralaminar thalamic nuclei-Akinetic mutism-Reticular formation.Understanding the disorders of human consciousness provides an empirical first step toward understanding mechanisms underlying human awareness. The neurologist's view of consciousness is derived from reliable observations of brain structure and function that lead to implicit hypotheses. These hypotheses represent implied models that may be examined in light of many recent advances in clinical and experimental neuroscience. Impaired consciousness of a variety of kinds may result from focal brain injuries that induce widespread functional changes. Differences in the clinical features of these human disabilities illustrate the interdependent relationships of brain mechanisms underlying arousal, gating, and expression of several specific neuropsychologic traits. In many cases, brain damage is too severe to permit meaningful recovery, as exemplified by the vegetative state. In others, transient or permanent behavioral abnormalities precipitated by focal lesions may reveal the contribution of specific brain systems to the overall conscious state. Global disorders of consciousness include stupor and coma, vegetative states, akinetic mutism, absence and partial complex seizures, hyperkinetic mutism, and others. These disturbances can be acute, and relatively brief, or may persist as protracted states. The authors explore the neurology of impaired consciousness, developing a brief taxonomy of global disorders of consciousness, and placing these neurologic diseases in the context of the underlying anatomy and physiology of arousal and "gating" systems. Definition of consciousness: A definition closely following that of James (1890) is offered for the psychological dimension of consciousness:At its least, normal human consciousness consists of a serially time-ordered, organized, restricted and reflective awareness of self and the environment. Moreover, it is an experience of graded complexity and quantity.

Cortical and Subcortical Connectivity Changes during Decreasing Levels of Consciousness in Humans: A Functional Magnetic Resonance Imaging Study using Propofol

“…A key anatomical specialization of the intralaminar nuclei is that they comprise the largest thalamic efference to the striatum, an important pathway in coordination of thalamocortical signal processing (Schiff and Plum, 2000). Our observations suggest that the putamen is particularly sensitive to propofol and that before the failure of thalamocortical transmission, at the point at which subjects fail to perceive and lose verbal contact, the thalamo-regulatory influence of cortico-striato-thalamo-cortical circuits may be disrupted.…”

“…Minimally conscious states may occur with thalamic strokes affecting the reticular (RT) or intralaminar (ILN) thalamic nuclei or lesions of the reticular formation (Schiff and Plum, 2000). Described formerly as "nonspecific" thalamic nuclei, the anterior and posterior intralaminar nuclei of the thalamus together with the paralaminar portions of the thalamic association nuclei are recognized as central to consciousness (Schiff, 2008).…”

“…The reticular and intralaminar thalamic nuclei have been specifically implicated in both pathologies of consciousness and pharmacodynamic phenomena (Alkire et al, 1999(Alkire et al, , 2007Detsch et al, 1999;Van der Werf et al, 2002;Schiff, 2008). Several authors have suggested, however, that changes within the thalamus could be a consequence of deafferentation rather than necessarily causal to anesthesia (Schiff and Plum, 2000;Alkire, 2008). Alternatively, the unconscious state may arise from uncoupling of corticocortical connections or "cognitive unbinding" (Massimini et al, 2005;Mashour, 2006).…”

Disorders of consciousness after acquired brain injury: the state of the science

“…However, a definition closely following that of William James (1894) 5 is useful for framing DOC across a continuum. 6 According to James, "at its least, normal human consciousness consists of a serially time-ordered, organized, restricted and reflective awareness of self and the environment. Moreover, it is an experience of graded complexity and quantity. "…”

Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of generalized arousal

“…Following anoxia consequent to stroke and other causes such as cardiac failure, drowning, carbon monoxide exposure and various accidents, there is a complex cascade of events in neurons causing cell death and functional neurological damage (Neubauer and Sunderram, 2004;Clarkson et al, 2005;Lo et al, 2005;Rashidian et al, 2005). Altered functional states include arousal, attention, intention, memory and awareness, all observed during global disorders of consciousness (Vexler et al, 1994;Schiff and NY, 10021, Telephone: 212-327-8668, Fax: 212-327-8664, E-mail: iarrieta@mail.rockefeller.edu.2000; Glenn et al, 2003;Dunham et al, 2004;Laureys et al, 2004;Young et al, 2004;Caputa et al, 2005).…”