Andrea Eugenio Cavanna

Epilepsy and Disorders of Consciousness

The default mode network has been hypothesized based on the observation that specific regions of the brain are consistently activated during the resting state and deactivated during engagement with task. The primary nodes of this network, which typically include the precuneus/posterior cingulate, the medial frontal and lateral parietal cortices, are thought to be involved in introspective and social cognitive functions. Interestingly, this same network has been shown to be selectively impaired during epileptic seizures associated with loss of consciousness. Using a wide range of neuroimaging and electrophysiological modalities, decreased activity in the default mode network has been confirmed during complex partial, generalized tonic-clonic, and absence seizures. In this review we will discuss these three seizure types and will focus on possible mechanisms by which decreased default mode network activity occurs. Although the specific mechanisms of onset and propagation differ considerably across these seizure types, we propose that the resulting loss of consciousness in all three types of seizures is due to active inhibition of subcortical arousal systems that normally maintain default mode network activity in the awake state. Further, we suggest that these findings support a general &#x201C;network inhibition hypothesis&#x201D;, by which active inhibition of arousal systems by seizures in certain cortical regions leads to cortical deactivation in other cortical areas. This may represent a push-pull mechanism similar to that seen operating between cortical networks under normal conditions.

Nathan B. Danielson

Jennifer N. Guo

Hal Blumenfeld

The Default Mode Network and Altered Consciousness in Epilepsy

Alterations in consciousness are central to epileptic manifestations, and involve changes in both the level of awareness and subjective content of consciousness. Generalised seizures are characterised by minimal responsiveness and subjective experience whereas simple and complex partial seizures demonstrate more selective disturbances. Despite variations in ictal origin, behaviour and electrophysiology, the individual seizure types share common neuroanatomical foundations generating impaired consciousness. This article provides a description of the phenomenology of ictal consciousness and reviews the underlying shared neural network, dubbed the 'consciousness system', which overlaps with the 'default mode' network. In addition, clinical and experimental models for the study of the brain correlates of ictal alterations of consciousness are discussed. It is argued that further investigation into both human and animal models will permit greater understanding of brain mechanisms and associated behavioural consequences, possibly leading to the development of new targeted treatments.

Fizzah Ali

Epilepsy: The Quintessential Pathology of Consciousness

Consciousness is often disrupted in epilepsy. This may involve altered responsiveness or changes in awareness of self and subjective experiences. Subcortical arousal systems and paralimbic fronto-parietal association cortices are thought to underpin current concepts of consciousness. The Network Inhibition Hypothesis proposes a common neuroanatomical substrate for impaired consciousness during absence, complex partial and tonic-clonic seizures.Neurostimulation in epilepsy remains in its infancy with vagal nerve stimulation (VNS) as the only firmly established technique
and a series of other methods under investigation including deep brain stimulation (DBS), intracranial cortical stimulation and
repetitive transcranial magnetic stimulation (rTMS). Many of these systems impact on the neural systems thought to be involved
in consciousness as a continuous duty cycle although some adaptive (seizure triggered) techniques have been developed.Theoretically, fixed duty cycle neurostimulation could have profound effects on responsiveness, awareness of self and subjective
experience. Animal studies suggest vagal nerve stimulation positively influences hippocampal long term potentiation. In humans,
a chronic effect of increased alertness in VNS implanted subjects and acute effect on memory consolidation have been reported
but convincing data on either improvements or deterioration in attention and memory is lacking. Thalamic deep brain stimulation
(DBS) is perhaps the most interesting neurostimulation technique in the context of consciousness. Neither bilateral anterior
or centromedian thalamic nucleus DBS seem to affect cognition. Unilateral globus pallidus internus DBS caused transient
wakefulness in an anaesthetised individual.As intracranial neurostimulation, particularly thalamic DBS, becomes more established as a clinical intervention, the effects on
consciousness and cognition with variations in stimulus parameters will need to be studied to understand whether these secondary
effects of neurostimulation make a significant positive (or adverse) contribution to quality of life.

Manny Bagary

Epilepsy, Consciousness and Neurostimulation

In spite of the inherent difficulties in achieving a biologically meaningful definition of consciousness, recent neurophysiological studies are starting to provide some insight in fundamental mechanisms associated with impaired consciousness in neurological disorders. Generalised seizures are associated with disruption of the default state network, a functional network of discrete brain areas, which include the fronto-parietal cortices. Subcortical contribution through activation of thalamocortical structures, as well as striate nuclei are also crucial to produce impaired consciousness in generalised seizures.

Stefano Seri

Daniela Brazzo

Ngoc J. Thai

Antonella Cerquiglini

Brain Mechanisms of Altered Consciousness in Generalised Seizures

The impact of epilepsy on Quality of Life (QoL) is well-documented. The ability of epileptic seizures to alter the conscious states of patients is also well established. Although there is much research on the QoL of people with epilepsy, few researchers have looked specifically at the effect of sudden, unanticipated alterations of consciousness on QoL. This lack of systematic studies of consciousness alterations and QoL in epilepsy limits our ability to shed light on this interrelation. In this article, with these limitations in mind, we focus on studies of newer AEDs. We review the evidence as to whether a significant reduction (typically more than 50&#x25;) in seizures that induce alterations of consciousness, as a result of switching to one of the newer AEDs, leads to improvements in QoL. We draw on this literature to speculate on the relationship between ictal consciousness alterations and poor QoL in epilepsy, to identify contributory and confounding factors and to highlight implications for future research. We suggest that an understanding of how factors associated with consciousness impairment affect QoL could help the treatment and management of these patients.

Andreas Charidimou

Caroline Selai

The Effect of Alterations in Consciousness on Quality of Life (QoL) in Epilepsy: Searching for Evidence

Disturbances in cognitive function, particularly memory, are a common complaint of patients with epilepsy. Factors contributing to cognitive dysfunction are the type of epilepsy, type and frequency of seizures, anti-epileptic drugs and the location of underlying brain lesions. Whilst a great deal of attention has been paid to permanent cognitive impairment, the nature and underlying mechanisms of ictal and peri-ictal cognitive changes are poorly understood. In-depth investigation of seizure related cognitive dysfunction is of great clinical relevance, as these changes are potentially reversible and treatable, thus reducing the cumulative effect of frequent seizures Greater knowledge of peri-ictal and ictal cognitive dysfunction would improve seizure prediction, localization of seizure focus and assessment of treatment effectiveness, greatly reducing distress and disability. This paper will review current understanding of peri-ictal and ictal cognitive dysfunction and discuss future directions for research.

Lavanya Vijayaraghavan

Subbulakshmy Natarajan

Ennapadam Srinivas Krishnamoorthy

Peri-Ictal and Ictal Cognitive Dysfunction in Epilepsy

This paper examines three respects in which the study of epileptic absence seizures promises to inform our understanding of consciousness. Firstly, it has the potential to bear on debates concerning the behavioural and cognitive functions associated with consciousness. Secondly, it has the potential to illuminate the relationship between background states (or &#x2018;levels&#x2019;) of consciousness and the contents of consciousness. Thirdly, it has the potential to bear on our understanding of the unity of consciousness.

Tim Bayne

The Presence of Consciousness in Absence Seizures

Non-epileptic attack disorder (NEAD) is one of the most important differential diagnoses of epilepsy. Impairment of consciousness is the key feature of non-epileptic attacks (NEAs). The first half of this review summarises the clinical research literature featuring observations relating to consciousness in NEAD. The second half places this evidence in the wider context of the recent discourse on consciousness in neuroscience and the philosophy of mind. We argue that studies of consciousness should not only distinguish between the &#x2018;level&#x2019; and &#x2018;content&#x2019; of consciousness but also between &#x2018;phenomenal consciousness&#x2019; (consciousness of states it somehow &#x201C;feels to be like&#x201D;) and &#x2018;access consciousness&#x2019; (having certain &#x2018;higher&#x2019; cognitive processes at one&#x2019;s disposal). The existing evidence shows that there is a great intra- and interindividual variability of NEA experience. However, in most NEAs phenomenal experience &#x2013; and, as a precondition for that experience, vigilance or wakefulness &#x2013; is reduced to a lesser degree than in those epileptic seizures involving impairment of consciousness. In fact, complete loss of &#x201C;consciousness&#x201D; is the exception rather than the rule in NEAs. Patients, as well as external observers, may have a tendency to overestimate impairments of consciousness during the seizures.

M. Reuber

M. Kurthen

Consciousness in Non-Epileptic Attack Disorder

Consciousness is a central concept in epileptology, relevant to the understanding of both focal and generalized seizures. Within focal seizures, impairment of consciousness has long been considered as the main criterion differentiating complex partial seizures (CPS) from simple partial seizures With the development of improved tools for investigating human brain function, new insights into the brain mechanisms of altered consciousness in CPS have become available. This paper reviews the existing literature on how the currently available methods can be used to address the fundamental issue of how CPS alter consciousness.

Andrew P. Bagshaw

Andrea E. Cavanna

Brain Mechanisms of Altered Consciousness in Focal Seizures

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Epilepsy and Disorders of Consciousness

Epilepsy and Disorders of Consciousness

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