Impaired consciousness in epilepsy

ArticleinThe Lancet Neurology 11(9):814-26 · September 2012with15 Reads
DOI: 10.1016/S1474-4422(12)70188-6 · Source: PubMed
Abstract
Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost, which makes it impossible for the individual to experience or respond. These effects have huge consequences for safety, productivity, emotional health, and quality of life. To prevent impaired consciousness in epilepsy, it is necessary to understand the mechanisms that lead to brain dysfunction during seizures. Normally the consciousness system-a specialised set of cortical-subcortical structures-maintains alertness, attention, and awareness. Advances in neuroimaging, electrophysiology, and prospective behavioural testing have shed light on how epileptic seizures disrupt the consciousness system. Diverse seizure types, including absence, generalised tonic-clonic, and complex partial seizures, converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding of these mechanisms could lead to improved treatment strategies to prevent impairment of consciousness and improve the quality of life of people with epilepsy.
    • "Also, TCD is accompanied by a characteristic downward shift of the power spectrum [108]. A similar pattern can occur in epilepsy where pathological dynamics can be observed in fronto-parietal networks and the basal forebrain, thalamus, hypothalamus and upper brainstem, also dubbed the consciousness system [113]. Interestingly, an analysis of the distribution of activity patterns during seizures where consciousness was absent, showed a distinct increase of activity of the fronto-parietal system in the delta range (1– 2 Hz) correlating with seizure activity in the temporal lobe [114]. "
    [Show abstract] [Hide abstract] ABSTRACT: Understanding the nature of consciousness is one of the grand outstanding scientific challenges. The fundamental methodological problem is how phenomenal first person experience can be accounted for in a third person verifiable form, while the conceptual challenge is to both define its function and physical realization. The distributed adaptive control theory of consciousness (DACtoc) proposes answers to these three challenges. The methodological challenge is answered relative to the hard problem and DACtoc proposes that it can be addressed using a convergent synthetic methodology using the analysis of synthetic biologically grounded agents, or quale parsing. DACtoc hypothesizes that consciousness in both its primary and secondary forms serves the ability to deal with the hidden states of the world and emerged during the Cambrian period, affording stable multi-agent environments to emerge. The process of consciousness is an autonomous virtualizationmemory, which serializes and unifies the parallel and subconscious simulations of the hidden states of the world that are largely due to other agents and the self with the objective to extract norms. These norms are in turn projected as value onto the parallel simulation and control systems that are driving action. This functional hypothesis is mapped onto the brainstem, midbrain and the thalamo-cortical and cortico-cortical systems and analysed with respect to our understanding of deficits of consciousness. Subsequently, some of the implications and predictions of DACtoc are outlined, in particular, the prediction that normative bootstrapping of conscious agents is predicated on an intentionality prior. In the view advanced here, human consciousness constitutes the ultimate evolutionary transition by allowing agents to become autonomous with respect to their evolutionary priors leading to a post-biological Anthropocene. © 2016 The Author(s) Published by the Royal Society. All rights reserved.
    Full-text · Article · Aug 2016
    • "For these patients, a strategy aimed at improving quality of life, morbidity, and mortality despite ongoing seizures could be highly beneficial. Consciousness depends on several functions including: 1) specific sensorimotor and other systems constituting the content of consciousness; and 2) systems regulating the overall level of consciousness manifested as awareness, attention, and basic conscious arousal (Posner et al. 2007; Schiff and Laureys 2009; Blumenfeld 2010 Blumenfeld , 2012 Blumenfeld , 2015 Giacino et al. 2014). Importantly, conscious arousal, which distinguishes coma or deep sleep from the alert state, can be assessed by relatively simple behavioral and physiological observations and forms the crucial necessary first step enabling other higher order aspects of consciousness to occur (Posner et al. 2007). "
    [Show abstract] [Hide abstract] ABSTRACT: Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.
    Article · Mar 2016
    • "For these patients, a strategy aimed at improving quality of life, morbidity, and mortality despite ongoing seizures could be highly beneficial. Consciousness depends on several functions including: 1) specific sensorimotor and other systems constituting the content of consciousness; and 2) systems regulating the overall level of consciousness manifested as awareness, attention, and basic conscious arousal (Posner et al. 2007; Schiff and Laureys 2009; Blumenfeld 2010 Blumenfeld , 2012 Blumenfeld , 2015 Giacino et al. 2014). Importantly, conscious arousal, which distinguishes coma or deep sleep from the alert state, can be assessed by relatively simple behavioral and physiological observations and forms the crucial necessary first step enabling other higher order aspects of consciousness to occur (Posner et al. 2007). "
    [Show abstract] [Hide abstract] ABSTRACT: Impaired breathing, cardiac function, and arousal during and after seizures are important causes of morbidity and mortality. Previous work suggests that these changes are associated with depressed brainstem function in the ictal and post-ictal periods. Lower brainstem serotonergic systems are postulated to play an important role in cardiorespiratory changes during and after seizures, whereas upper brainstem serotonergic and other systems regulate arousal. However, direct demonstration of seizure-associated neuronal activity changes in brainstem serotonergic regions has been lacking. Here, we performed multiunit and single-unit recordings from medullary raphe and midbrain dorsal raphe nuclei in an established rat seizure model while measuring changes in breathing rate and depth as well as heart rate. Serotonergic neurons were identified by immunohistochemistry. Respiratory rate, tidal volume, and minute ventilation were all significantly decreased during and after seizures in this model. We found that population firing of neurons in the medullary and midbrain raphe on multiunit recordings was significantly decreased during the ictal and post-ictal periods. Single-unit recordings from identified serotonergic neurons in the medullary raphe revealed highly consistently decreased firing during and after seizures. In contrast, firing of midbrain raphe serotonergic neurons was more variable, with a mixture of increases and decreases. The markedly suppressed firing of medullary serotonergic neurons supports their possible role in simultaneously impaired cardiorespiratory function in seizures. Decreased arousal likely arises from depressed population activity of several neuronal pools in the upper brainstem and forebrain. These findings have important implications for preventing morbidity and mortality in people living with epilepsy.
    Article · Mar 2016
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