ios press epilepsy: the quintessential pathology of consciousness · 2019. 7. 31. · 4 a.e....

Behavioural Neurology 24 (2011) 3–10 3DOI 10.3233/BEN-2011-0311IOS Press

Epilepsy: The quintessential pathology ofconsciousness

Andrea Eugenio Cavannaa,b,∗ and Fizzah AliaaDepartment of Neuropsychiatry, University of Birmingham and BSMHFT, Birmingham, UKbSobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, London, UK

Abstract. Alterations in consciousness are central to epileptic manifestations, and involve changes in both the level of awarenessand subjective content of consciousness. Generalised seizures are characterised by minimal responsiveness and subjectiveexperience whereas simple and complex partial seizures demonstrate more selective disturbances. Despite variationsin ictalorigin, behaviour and electrophysiology, the individual seizure types share common neuroanatomical foundations generatingimpaired consciousness. This article provides a description of the phenomenology of ictal consciousness and reviews theunderlying shared neural network, dubbed the ‘consciousness system’, which overlaps with the ‘default mode’ network.Inaddition, clinical and experimental models for the study ofthe brain correlates of ictal alterations of consciousnessare discussed.It is argued that further investigation into both human and animal models will permit greater understanding of brain mechanismsand associated behavioural consequences, possibly leading to the development of new targeted treatments.

Keywords: Epilepsy, seizures, consciousness

1. Consciousness: A neuroscientific conundrum

Historically examined, analysed and explored froma multitude of perspectives, the multi-faceted conceptof consciousness is the modern day academic enigma.Previously attacked by the realms of philosophy, reli-gion and psychology, recent decades have converselywitnessed renewed interest from a neuroscientific front.Advances in human neuropsychology and functionalimaging have exposed correlations between neural pro-cesses and facets of conscious experience [60]. This,in part, has contributed to the scientific drive for ap-propriate placement of subjective experience alongsideelectro-chemical interactions, into the field of empiricalscrutiny.

Despite a host of controversial definitions and dy-namic components, consciousness is of indisputableclinical relevance; serious acute cerebral involvement

∗Corresponding author: Dr. Andrea Eugenio Cavanna, Depart-ment of Neuropsychiatry, Birmingham and Solihull Mental HealthNHS Foundation Trust, Barberry Building, Birmingham B152FG,UK. E-mail: [email protected].

is inextricably linked with the function of conscious-ness [49]. Progressive injury parallels deterioration inconsciousness ranging from sleep disorders and neu-rodegenerative dementias, steadily culminating in veg-etative states and profound coma [17]. Epilepsy, in par-ticular, has been regarded as providing a key opportuni-ty to illustrate the neural mechanics of altered consciousstates. Current classification regards epilepsy as a spec-trum disorder, characterised by underlying dynamicand reversible brain dysfunction that generates variableand selective impairment of consciousness, rangingfrom minor impairment of attention to total behaviouralunresponsiveness. The principal dichotomy central tocurrent International League Against Epilepsy classifi-cation is the distinction between ‘partial’ seizures (in-volving focal brain regions or confined to one hemi-sphere) and generalised seizures (involving diffuse re-gions throughout both hemispheres) [25]. Within thisdichotomy resides the major definitional criterion: im-pairment of consciousness differentiates between ‘sim-ple’ and ‘complex’ partial seizures [5]. The pathophys-iology of the epilepsies presents an ideal avenue bywhich to scrutinise abnormal neural activity alongside

ISSN 0953-4180/11/$27.50 2011 – IOS Press and the authors. All rights reserved

4 A.E. Cavanna and F. Ali / Epilepsy: The quintessential pathology of consciousnes

associated alterations in consciousness thereby expos-ing brain mechanisms and permitting correlation withimplicated anatomical structures [5,14,44].

This article commences with interpretation of defi-nitional issues surrounding the concept of conscious-ness. A review of a well recognised bi-dimensionalmodel for the study of ictal conscious state follows. Asynopsis of current insights into the neural foundationsunderlying seizure sub-types (generalised tonic-clonic,absence and complex partial seizures) and specific clin-ical phenomenology of ictal consciousness concludesthis review.

1.1. Defining consciousness

Recent decades have delivered an overwhelmingmass of contributions endeavouring to discover, elu-cidate or re-evaluate consciousness. Attempts at def-inition have varied considerably over time as offer-ings have concurrently ranged a multitude of academicdomains. The quintessentially subjective experienceof consciousness, therein, evades unequivocal defini-tion. Indeed, the use of the term may be regardedas context-dependent [60]. It is pertinent to empha-sise, however, the distinction between consciousnessand self-consciousness; the latter conversely embodiesnotions such as a propensity to embarrassment, self-detection, self-recognition, self-knowledge and aware-ness of awareness [60].

Within clinical practice physicians regularly applyterminology such as ‘dwindling’, ‘lapsing’ and ‘cloud-ing’ of consciousness, rendering consciousness akin tothe waking state. In other words, consciousness maybe regarded as the ability to perceive, interact and en-gage with the environment and with other individu-als [23,42,60]. Specifically, from the clinical perspec-tive of an epileptologist consciousness is considered asthe patient’s responsiveness during the ictal state, orconversely as ‘loss of contact’ with the surrounding en-vironment. Yet this definition is far from all-inclusive,initially failing to account for alternative origins ofsub-optimal responsiveness; whether ictal disturbanceof speech, attention or other transient disturbances ofmemory and sensory processes [44,59]. This limitationis particularly crucial when considering seizure type.Generalised seizures are characterised by complete lossof consciousness, whereas complex partial seizures of-ten cause selective and limited disturbances that mayculminate into motor/sensory aphasia or transient inat-tention [27,41]; end-points that are open to misinter-pretation as loss of consciousness. This simplistic def-

inition further fails to consider variations in the subjec-tive content component of consciousness. Therein, liesthe concept of a bi-dimensional consciousness.

1.2. Level and contents of consciousness

Conventionally, neurology has widely employed theterm consciousness to mean alertness or responsive-ness [36], conversely theoretical approaches have re-garded subjective experience central to the concept ofconsciousness [46]. An amalgamation of neurophysio-logical and neuroimaging studies indicate the divisionof the neural correlates of consciousness into structuresnecessary for the maintenance of the quantitative (lev-el) of consciousness and those responsible for generat-ing the qualitative (content) features of conscious ex-perience [5,16,17]. Epileptic seizures involve changesto both the objective level of awareness and subjectivecontent of consciousness.

The first element, the level of consciousness, maybe considered loosely akin to the conventional mean-ing of consciousness i.e. arousal or vigilance. Specif-ically, it is a matter of ‘degree’ along a spectrum ex-tending through a range of consciousness and uncon-scious states, from alertness continuing through intosleep and terminating in coma [38,58]. The level ofconsciousness may be further compartmentalised intomultiple synergistic systems necessary for the mainte-nance of (1) alert state (2) attention (3) awareness ofself and environment. The role of the ascending ac-tivating pontomesodiencephalic reticular formation inassociation with its thalamic projections is fundamen-tal to the neurobiological basis of vigilance [45]. Func-tional imaging reports have further demonstrated sub-cortical spread of ictal discharge to consume the normalactivity of thalamocortical networks, in turn generatingcomplete loss of consciousness [40].

The second element, the content of consciousness,includes an array of multimodal perceptions (emo-tions, sensations, memories and intentions) and in itselfmay be regarded as a mutli-faceted dimension encir-cling sensorimotor, emotional and memory systems [5].Subjective experiences are manufactured through in-teraction between exogenous environmental input andendogenous factors such as internal attention, and aregoverned by temporo-limbic activity [21,22,37]. Ac-cordingly, the depth and the emotional salience of suchexperience demonstrates great variability, ranging fromfringe phenomena to intense experiences. Previous in-vestigations have noted the significance of the temporalcortex in inducing changes in the contents of conscious-

A.E. Cavanna and F. Ali / Epilepsy: The quintessential pathology of consciousnes 5

ness [35], with further observations about the role ofmedial temporal lobe structures in the conscious recallof past events [29].

Consciousness is not a unitary phenomenonand hav-ing provided discourse on its individual dimensions, itis pertinent to comment on the extent to which the com-ponents are separable. The content of consciousnessmay be deemed the substrate system upon which levelof consciousness acts [10]. The level of arousal holdsconsiderable control over the contents of conscious-ness; in most instances an increase in arousal is ac-companied by more vibrant conscious experience. Ex-ceptional states such as limbic status epilepticus mustbe acknowledged, whereby high levels of arousal arecoupled with depleted contents of consciousness. Theunion between level and content of consciousness is in-completely determined; disruption of either, however,engenders loss of consciousness. Cortical dysfunctionis a mutual player in the disruption of consciousness:involvement of higher order association cortex yieldsimpairment in the level of consciousness, and specif-ic regions of the sensory or motor cortex induce alter-ations in the content of consciousness [10]. In the ab-sence of generalised cerebral dysfunction, the contentsof consciousness indicate the specialised function ofparticular brain structures.

Traditionally, evaluation of the ictal conscious statehas involved observer interpretation and individual vo-cabulary, riddled with poor inter-rater and test-retest re-liability and aggravated by an absence of standardisedtools. Over recent years an integrated bi-dimensionalmodel of consciousness has been proposed, reconcil-ing qualitative and quantitative aspects of conscious-ness and allowing the comprehensive assessment of theictal conscious state in accordance with these two keycomponent elements.

1.3. The bi-dimensional model of consciousness

Comprehensive assessment of ictal clinical alter-ations requires combined assessment of both the leveland contents of consciousness. Graphical representa-tion of the level of consciousness plotted against thecontent of consciousness allows delineation of bothpathological and physiological conscious states [14,44]and provides a valuable framework for the comprehen-sive and systematic assessment of seizure-specific ictalconscious state. The waking state in a healthy subjectis characterised by an almost invariably high level ofarousal but less predictable contents of consciousness.Accordingly, generalised seizures are characterised by

total absence of both responsiveness and subjective ex-perience. Complex partial seizures are characterisedby more selective disturbances to sensory processes,attention or memory and demonstrate variable impacton both the level and content of consciousness [17].Seizures of temporal lobe origin display heightenedsubjective experiences as a result of experiential phe-nomena, typically combining elements of perception,memory and affect [19,28]. Simple partial seizuresare accompanied by visual, auditory and somatosenso-ry features that selectively impact on the contents ofconsciousness, preserving levels of awareness [17].

Within this paradigm a twenty-item self-report scale,the Ictal Consciousness Inventory (ICI) has been devel-oped permitting quantitative analysis of the ictal state asper the established bi-dimensional representation. Pa-tients with epilepsy complete one questionnaire per wit-nessed seizure recalled. The first ten items of the scaleassess the level of general awareness/responsiveness;including general awareness of time, place and oth-ers; comprehension and responsiveness; gaze control;forced attention and voluntary initiative. The secondset of items assess vividness of ictal subjective expe-rience (content of consciousness), including dreamystates and derealisation, illusions and hallucinations,and ictal emotions. Each item is rated on a 0–2 Lik-ert type scale and the scale yields two sub-scores foreach dimension of consciousness each ranging from0 to 20. The ICI reveals the nature of impairment inconsciousness, allowing differentiation between thoseseizure types principally generating a deficit in the levelof awareness (generalised seizures, including absence(petit mal) or tonic-clonic (grand mal)) and those mod-ifying the contents of consciousness (focal seizures).Despite the intrinsic limitations of user compliance andictal amnesia generating recall bias, the ICI features asa user-friendly tool permitting description of the ictalstate in a systematic and standardised fashion [18].

Regardless of evident variations in ictal origin, be-haviour and electrophysiology, the underlying neuralfoundations of impaired consciousness are bound bycommon anatomical structures.

2. A common foundation

Core to the pathology of epilepsy is the anomalousincrease or decrease in neural activity that provokes ab-normal brain function. Regional increases or decreasesin neuronal activity tend to vary between absence, gen-eralised tonic-clonic and complex partial seizures [5].


Though physiologically distinct, the seizure types areanatomically bound. Investigation into both normalstates of arousal and circumstances of impaired con-sciousness (anaesthesia, sleep and brain lesions) hasexposed a common network of cortical and sub-corticalstructures involved in the generation of consciousness.This ‘consciousness system’ comprises regions of theupper brainstem (midbrain and upper pons),medial tha-lamus, cingulate gyrus, medial prefrontal cortex, pre-cuneus, as well as lateral frontal and parietal associa-tion cortex. Additionally the significance of midlineand intralaminar thalamic nuclei and hypothalamus aswell as activating systems located in the basal forebrainhave been noted [5]. The basal ganglia and cerebellum,implicated in the control of attention, may be cautiouslyincluded.

The following sections are designed to provide thereader with insight into the neuroanatomical archi-tecture generating seizure specific alterations in con-sciousness.

2.1. Consciousness in generalised seizures

2.1.1. Generalised tonic clonic seizuresGeneralised tonic-clonic seizures (GTCS) or grand

mal seizures are characterised by abnormal bi-hemisph-eric neuronal discharge generating complete unrespon-siveness and convulsions. The sudden tonic phase ofthese seizures comprises sustained axial muscle con-traction, upward eye deviation and pupillary dilatation,in association with 10–20 seconds of high frequen-cy electroencephalographic (EEG) activity. The en-suing clonic portion refers to rhythmic limb contrac-tion with EEG demonstrating poly-spike-and-wavedis-charges [5]. GTCS can be primarily generalised withno clear focal onset. Alternatively, discharges originat-ing from a single focus may propagate to form secon-darily generalised seizures (i.e. secondary generalisa-tion of partial seizures). Nonetheless, both primary andsecondary generalised seizures are typically accompa-nied by a ‘black-out’ of both awareness and subjectiveexperience of consciousness.

Investigations into the neural correlates of impairedconsciousness in GTCS signal the involvement of spe-cific brain regions more intensely rejecting the ideaof homogenous participation of the whole brain. Al-though initial neuroimaging studies indicated homoge-nous involvement of the entire brain [26] and ani-mal studies based on electrophysiological, blood flowand metabolic mapping of GTCS have produced vari-able findings, other investigations have demonstrated

more regional changes [5,17]. Single photon emis-sion CT (SPECT) studies of cerebral blood flow insecondary GTCS have demonstrated focal involvementof the brain, frequently in the region of seizure on-set [6,11,39,54]. Additionally, SPECT inter-ictal dif-ference imaging of secondary GTCS as part of epilep-sy and GTCS provoked by electro-convulsive therapyin patients with treatment refractory-depression has re-vealed cerebral blood flow increases during the seizurein particular brain regions. Those brain regions har-nessed by the ‘consciousness system’ are implicated.Increased blood flow was seen in the thalamus and up-per brainstem as well as lateral frontal and parietal cor-tex. Conversely, decreases in cerebral blood flow wereseen during the seizure period in the cingulate gyrus.Post-ictal unconsciousness was accompanied, also, bydiminished blood flow in the anterior and posterior cin-gulate gyrus as well as the lateral frontal and parietalcortex. Inhibitory cerebellar outputs are potential play-ers in seizure termination and in diminished conscious-ness post-ictally; increases in cerebral blood flow arecoupled with increased flow in the thalamus and withsubstantial decrease in blood flow in frontal and parietalcortex [5,17,48].

The bilateral frontal and parietal association corticesare associated with greatest increases in cerebral bloodflow during GTCS. The focal disruption in GTCS ofthese loci together with effects on related sub-corticalstructures yields the intense and persevering impairedconsciousness typical of GTCS. Conversely, there isrelative sparing of the intervening regions of the pri-mary sensory and motor cortices. Additionally, rareseizures limited to the bilateral sensorimotor areas [47]and secondary GTCS following spread from a temporallobe focus [4] exhibit total preservation of conscious-ness.

2.1.2. Absence seizuresAbsence seizures are typified by sudden onset of

blank staring and unresponsiveness, usually lasting 5–10 seconds. Interruption or cessation of voluntary be-haviour, as well as a variety of mild motor manifesta-tions ranging clonic, atonic, tonic, or myotonic activitymay also feature. Typically eyelid fluttering or my-oclonic jerks are witnessed, yet, the motor manifesta-tions of absence seizures are subtle; allowing absenceseizures to pose as the most ‘transparent’ form of ic-tal impaired consciousness. Recovery is sudden withprevious activity resuming and no significant post-ictaldeficit [17]. Absences are generated through abnormalcortico-thalamic network oscillations whereby the tha-


lamus acts as the generator of the 3Hz oscillation andthe cortex generator of the spike and wave patterns.In combination the characteristic bilateral and frontalpre-dominant 3–4 Hz large amplitude spike-and-wavedischarges result [56]. Although absences are regard-ed as essentially ‘generalised’, both human and animalstudies indicate the specific involvement of particularcortico-thalamic networks with relative sparing of oth-er regions. Earlier human imaging studies, marred bytechnical limitation of method and the intrinsic vari-ability of absence seizures themselves [10], yielded in-congruent findings. Some investigations demonstrat-ed global increases in cerebral blood flow, whilst oth-ers have shown no change or alternatively increasedor decreased blood flow in either focal or generalisedpatterns [5,17].

Preliminary investigation through functional MRI(fMRI) with simultaneous EEG recordings (EEG-fMRI) has verified that generalised spike-wave seizuresselectively involve particular networks, whilst sparingothers. The improved spatial and temporal resolutionhas further allowed identification of bilateral thalam-ic activation, and cortical signal decrease in the ante-rior and posterior midline regions, and lateral frontaland parietal association areas [1,30,33,53]. A numberof these studies also noted signal increases in the lat-eral frontal and parietal cortical regions. According-ly, various authors have discounted the impaired con-sciousness of absence seizures as a whole brain phe-nomenon. Alternatively it has been postulated that dis-ruption of normal information processing in specificbrain regions, namely the bilateral fronto-parietal asso-ciation cortex as well as related sub-cortical structuresis implicated [5,17].

2.2. Consciousness in complex partial seizures

Partial epileptic seizures are of focal origin; abnor-mal discharges may remain localised to the originalsource or can secondarily generalise. Partial epilep-tic seizures can be further classified into simple partialseizures whereby consciousness is retained, or alterna-tively complex partial seizures which are defined by aloss of consciousness. Clinical manifestation is depen-dent on cortical origin, extent of seizure propagationand duration.

Complex partial seizures usually last between 15 sec-onds and 3 minutes and demonstrate variable alterationsin the consciousness state. Characteristically, con-sciousness is initially spared, seizure progression how-ever brings variable loss of contact with the environ-

ment with most profound impairment typically late inthe seizure, persisting for several minutes post-ictally.The temporal lobe is the original seizure focus in ap-proximately 80% of patients with partial seizures [13]and mesial temporal lobe sclerosis features as a fre-quent neuropathological association [57]. Focal pre-monitory phenomena such as fear, rising abdominalsensation or lip smacking automatisms (epileptic aura)mark seizure onset [2]. As the seizure evolves, clinicalmanifestations ranging affective, mnemonic and com-posite perceptual phenomena are experienced. Affec-tive components of experiential phenomena (‘epilep-tic qualia’) [44], include pleasant (joy, excitement, eu-phoria) and unpleasant (sadness, fear, guilt) subjectivefeelings, symptoms of depersonalisation (altered senseof self) and derealisation (altered experience of the ex-ternal world). Cognitive and psychosensory subjec-tive experiences may feature [3,34] as well as auditorydistortions, metamorphopsias, olfactory and gustatoryhallucinations. Automatisms (stereotyped behaviouralpatterns) including oral activities such as lip smack-ing, chewing, swallowing, as well as postural changeswhich can accompany or follow experiential phenom-ena. The limbic components of the medial temporallobe, in particular the amygdala, have been related tothe affective component of experiential phenomena [17,44]. However, the vast array of experiential phenomenaindicates recruitment of wider neural networks beyondthe temporal lobe.

SPECT and EEG studies indicate the requirementof bilateral temporal lobe involvement for loss of con-sciousness (general level of awareness) in complexpartial seizures [3]. Although bilateral temporal lobedysfunction generates amnesia, we resort to the ‘net-work inhibition hypothesis’ to fully explain the as-sociation between impaired consciousness and focaltemporal lobe seizures [48]. In accordance with thismodel, medial temporal lobe seizures propagate tomidline sub-cortical structures (medial diencephalonand ponto-mesencephalic reticular formation), inter-rupting their normal activating function, in turn spawn-ing widespread inhibition of non-seizing regions of thefrontal and parietal association cortex. Fronto-parietalnetwork inhibition may be ultimately accountable forthe impaired level of consciousness in the late ictaland immediate post-ictal phase. It is pertinent to notethat the structures listed in this hypothesis are thosecomprising the consciousness system. SPECT has fur-ther shown complex partial seizures with impairmentof consciousness to exhibit increases in cerebral bloodflow in the upper brain stem and medial thalamus, and


hypoperfusion in the fronto-parietal association cor-tex and the anterior and posterior inter-hemisphericregions. This model was scrutinised through ictal-interictal investigation of 24 subjects with surgicallyconfirmed mesial temporal lobe epilepsy through anal-ysis of cerebral blood flow changes whilst perform-ing continuous video-EEG monitoring [8]. Complexpartial seizures (associated with loss of consciousness)displayed widespread changes; increases in cerebralblood flow in the temporal lobe and in midbrain sub-cortical structures (including mediodorsal thalamus andupper brainstem), alongside decreases in the frontal andparietal association cortex bilaterally (including lateralprefrontal, anterior cingulate, orbitofrontal and lateralparietal cortex). Simple partial seizures (characterisedby sparing of consciousness) in contrast, were accom-panied by more focal changes limited to the temporallobes. Furthermore, EEG recordings obtained duringtemporal lobe seizures with impaired responsivenessshow marked slowing in bilateral frontal and parietal as-sociation cortices, noted to be particularly prominent inthe late ictal phase and extending into the early postic-tal period [9]. Thus supporting the hypothesis that ab-normal activity in the midline cortical structures (upperbrainstem–diencephalic activating systems),which dis-seminates into diffuse inhibition of the fronto-parietalcortex, causes loss of consciousness during temporallobe seizures.

2.3. Epilepsy and the brain ‘default mode’

A higher order associative network consisting ofthe lateral parietal, ventromedial prefrontal, mid-dorsolateral prefrontal and anterior temporal corticesalong with the postero-medial parietal region is highlymetabolically active during the resting state (lying qui-etly awake with eyes closed). The posteromedial cortexcomprises retrosplenial cortices, the posterior cingulategyrus as well as the precuneus [51]. The precuneusacts as an integral component in four general functions:body movements in space, episodic memory retrieval,visuo-spatial imagery, self-awareness and, pertinent inthis instance, consciousness. It is of particular inter-est as it is the most active of the three regions, con-suming approximately 35% more glucose [32]. Thetonic level of activity of this neural network decreaseswith engagement in goal-directed cognitive or percep-tual tasks, otherwise termed task-induced deactivations(TIDS). These findings may be translated into the ‘de-fault mode’ of brain function, whereby the demand offocused attention on a particular task heralds curtailing

of baseline brain processes such that deactivations in theregions serving the broad information gathering of thebaseline state are observed [32,43]. Functional imag-ing studies have further demonstrated significant deac-tivation of ‘default mode’ network of activity in alteredstates of consciousness including slow wave as well asrapid-eye movement sleep, general anaesthetic inducedsedation and the persistent vegetative state [15,19].Likewise, several neuropsychiatric conditions includ-ing Alzheimer’s disease, schizophrenia and attention-deficit hyperactivity disorder have also been linked todeactivations in ‘default mode’ zones [15,31]. Whol-ly, these findings suggest the existence of this multi-modal associative network, to which the precuneus isintegral, to function as part of greater neural machinerysub-serving self-awareness and conscious experiencei.e. baseline backdrop processes running during a quietresting state [15,19,52,55].

3. Conclusion

Seizure activity has been long associated with al-terations in consciousness, indeed, transient impair-ment in consciousness has been heralded as indica-tive of generalised seizure activity [27,59]. Epilepticseizures form a spectrum of disorders that generate se-lective, variable and transient impairment of conscious-ness, ranging from minor impairment of attention to to-tal behavioural unresponsiveness. The immense vari-ability in ictal semiology offers an ideal opportunityby which to examine the associated underlying patho-logical neurological function. Through an establishedbi-dimensional model, evidenced by neurophysiolog-ical and neuroimaging studies, this article has soughtinitially to delineate this spectrum of seizure-specificconsciousness alterations and secondly to clarify theunderlying neural correlates. The level of awarenessand contents of consciousness are variably affected bydifferent epileptic seizure types.

A collection of neuro-imaging studies demonstratethat generalised seizures do not encompass all brain ar-eas homogenously. Likewise, complex partial seizureshave been noted to be less focally active than previouslyrecognised [7,8,10,12]. Moreover, an accumulation ofevidence indicates a common network, the ‘conscious-ness system’, overlapping with the ‘default mode’ net-work, between all seizure sub-types. The upper brain-stem and medial thalamus, the anterior and posteriorcingulate, lateral and orbital frontal cortex and lateralparietal cortex as well as the medial frontal cortex and


precuneus are mutually implicated. Investigation intospecific neurobiological correlates allows further de-velopment of targeted treatment, including new phar-macological therapy as well as deep brain stimulators.It is imperative that such new treatments aim to pre-serve consciousness as it is within this impairment thatthe negative outcomes of seizures (accidents, trauma,driving and occupational sanctions) flourish.

References

[1] Y. Aghakhani, A.P. Bagshaw, C.G. Benar et al., fMRI activa-tion during spike and wave discharges in idiopathic general-ized epilepsy,Brain 127(2004), 1127–1144.

[2] S. Alvarez-Silva, I. Alvarez-Silva, J. Alvarez-Rodriguez etal., Epileptic consciousness: concept and meaning of aura,Epilepsy Behav8 (2006), 527–533.

[3] J. Bancaud, F. Brunet-Bourgin, P. Chauvel and E. Halgren,Anatomical origin of deja vu and vivid ‘memories’ in humantemporal lobe epilepsy,Brain 117(1994), 71–90.

[4] W.L. Bell, T.S. Walczak, C. Shin and R.A. Radtke, Painfulgeneralised clonic and tonic-clonic seizures with retained con-sciousness,J Neurol Neurosurg Psychiatry63 (1997), 792–795.

[5] H. Blumenfeld, Epilepsy and consciousness, in:The Neurol-ogy of Consciousness, S Laureys and G Tononi, eds, Amster-dam, Elsevier, 2009 pp. 247–260.

[6] H. Blumenfeld, From molecules to networks: corti-cal/subcortical interactions in the pathophysiology of idiopath-ic generalised epilepsy,Epilepsia44 (2003), 7–15.

[7] H. Blumenfeld. Consciousness and epilepsy: why are patientswith absence seizures absent?Prog Brain Res150 (2005),271–286.

[8] H. Blumenfeld, K.A. McNally, S.D. Vanderhill et al., Positiveand negative network correlations in temporal lobe epilepsy,Cereb Cortex14 (2004), 892–902.

[9] H. Blumenfeld, M. Rivera, K.A. McNally et al., Ictal neocor-tical slowing in temporal lobe epilepsy,Neurology63 (2004),1015–1021.

[10] H. Blumenfeld and J. Taylor, Why do seizures cause loss ofconsciousness?The Neuroscientist9 (2003), 301–310.

[11] H. Blumenfeld, G.I. Varghese, M.J. Purcaro et al., Corticaland subcortical networks in human secondarily generalizedtonic-clonic seizures,Brain 132(2009), 999–1012.

[12] H. Blumenfeld, M. Westerveld, R.B. Ostroff et al., Selec-tive frontal, parietal, and temporal networks in generalisedseizures,Neuroimage19 (2003), 1556–1566.

[13] G.D. Cascino, Use of routine and video electroencephalogra-phy,Neurol Clin19 (2001), 271–287.

[14] A.E. Cavanna, Seizures and consciousness, in:BehavioralAspects of Epilepsy: Principles and Practice, S.C. Schachter,G. Holmes and D. Kasteleijn-Nolst Trenite, eds, New York,Demos. 2008, pp. 99–104.

[15] A.E. Cavanna, The precuneus and consciousness,CNS Spec-trums12 (2007) 545–552.

[16] A.E. Cavanna, A.P. Bagshaw and D. McCorry, The neuralcorrelates of consciousness during epileptic seizures,DiscovMed8 (2009), 31–36.

[17] A.E. Cavanna and F. Monaco, Brain mechanisms of alteredconscious states during epileptic seizures,Nature Rev Neurol5 (2009), 267–276.

[18] A.E. Cavanna, M. Mula, S. Servo et al., Measuring the leveland content of consciousness during epileptic seizures: The Ic-tal Consciousness Inventory,Epilepsy Behav13 (2008), 184–188.

[19] A.E. Cavanna and M.R. Trimble, The precuneus: a review ofits functional anatomy and behavioural correlates,Brain 129(2006), 564–583.

[20] Commission on Classification and Terminology of the Interna-tional League Against Epilepsy, Proposal for revised clinicaland electroencephalographic classification of seizures,Epilep-sia 22 (1981), 489–501.

[21] H.B. Coslett, Consciousness and attention,Semin Neurol7(1997), 137–144.

[22] H.D. Critchley, Neural mechanisms of autonomic, affective,and cognitive integration,J Comp Neurol493 (2005), 154–166.

[23] D.C. Dennett, Consciousness, in:The Oxford Companion tothe Mind, R.L. Gregory, ed., Oxford, Oxford University Press,1987 pp. 160–164.

[24] J.C. Dreher and J. Grafman, The roles of the cerebellum andbasal ganglia in timing and error prediction,Eur J Neurosci16 (2002), 1609–1619.

[25] J. Engel, A proposed diagnostic scheme for people with epilep-tic seizures and with epilepsy: report of the ILAE Task Forceon Classification and Terminology,Epilepsia42 (2001), 796–803.

[26] J. Engel, Jr., D.E. Kuhl and M.E. Phelps, Patterns of humanlocal cerebral glucose metabolism during epileptic seizures,Science218(1982), 64–66.

[27] P. Gloor, Consciousness as a neurological concept in epilep-tology: a critical review,Epilepsia27 (1986), 14–26.

[28] P. Gloor, Experiential phenomena of temporal lobe epilepsy:facts and hypotheses,Brain 113(1990), 1673–1694.

[29] P. Gloor, A. Olivier, L.F. Quesney, F. Andermann and S.Horowitz, The role of the limbic system in experiential phe-nomena of temporal lobe epilepsy,Ann Neurol12 (1982),129–144.

[30] J. Gotman, C. Grova, A.P. Bagshaw et al., Generalized epilep-tic discharges show thalamocortical activation and suspensionof the default state of the brain,Proc Natl Acad Sci USA102(2005), 15236–15240.

[31] M. Greicius, Resting-state functional connectivity in neu-ropsychiatric disorders,Curr Opin Neurol21 (2008), 424–430.

[32] D.A. Gusnard and M.E. Raichle, Searching for a baseline:functional imaging and the resting human brain,Nat Rev Neu-rosci2 (2001), 685–694.

[33] K. Hamandi, A. Salek-Haddadi, H. Laufs et al., EEG-fMRIofidiopathic and secondarily generalized epilepsies, Neuroimage31 (2006), 1700–1710.

[34] R.E. Hogan and K. Kaiboriboon, The ‘dreamy state’: John-Hughlings-Jackson’s ideas of epilepsy and consciousness,AmJ Psychiatry160(2003), 1740–1747.

[35] H.H. Jasper, Sensory information and conscious experience,Adv Neurol77 (1998), 33–48.

[36] M. Johanson, A. Revonsuo, J. Chaplin and J.E. Wedlund,Level and contents of consciousness in connection with partialepileptic seizures,Epilepsy and Behavior4 (2003), 279–285.

[37] M. Johanson, K. Valli, A. Revonsuo, J. Chaplin and J.E. Wed-lund, Level and contents of consciousness in connection withpartial epileptic seizures,Epilepsy Behav4 (2003), 279–285.

[38] B.E. Jones, The neural basis of consciousness across the sleep-waking cycle,Adv Neurol77 (1998), 75–94.


[39] B.I. Lee, O.N. Markand, H.N. Wellman t al., HIPDM sin-gle photon emission computed tomography brain imagingin partial onset secondarily generalized tonic-clonic seizures,Epilepsia28 (1987), 305–311.

[40] K.H. Lee, K.J. Meador, Y.D. Park et al., Pathophysiologyof altered consciousness during seizures: subtraction SPECTstudy,Neurology59 (2002), 841–846.

[41] H.O. Luders, R. Burgess and S. Noachtar, Expanding the in-ternational classification of seizures to provide localisationinformation,Neurology43 (1993), 1650–1655.

[42] H.J. Markowitsch, Cerebral basis of consciousness: a histori-cal review,Neuropsychologia33 (1995), 1181–1192.

[43] J.P. Mitchell, T.F. Heatherton and C.N. Macrae, Distinct neuralsystems subserve person and object knowledge,Proc NatlAcad Sci USA99 (2003), 15238–15243.

[44] F. Monaco, M. Mula and A.E. Cavanna, Consciousness,epilepsy and emotional qualia,Epilepsy Behav7 (2005), 150–160.

[45] G. Moruzzi and H.W. Magoun, Brain stem reticular forma-tion and the activation of the EEG,Electroencephalogr ClinNeurophysiol(1949), 455–473.

[46] T. Nagel, What is it like to be a bat?Philos Rev83 (1974),435–450.

[47] R.G. Nogueira, K.N. Sheth, F.H. Duffy, S.L. Helmers andE.B. Bromfield, Bilateral tonic-clonic seizures with temporalonset and preservation of consciousness,Neurology70(2008),2188–2190.

[48] A.D. Norden and H. Blumenfeld, The role of subcortical struc-tures in human epilepsy,Epilepsy Behav3 (2002), 219–231.

[49] E. Niedermeyer, A concept of consciousness,Ital J Neurol Sci20 (1999), 7–15.

[50] F. Plum and J.B. Posner,The Diagnosis of Stupor and Coma,Philadelphia, Davis, 1980.

[51] D.C. Raichle, A.M. MacLeod, A.Z. Snyder et al., A defaultmode of brain function,Proc Natl Acad Sci USA98 (2001),672–682.

[52] M.E. Raichle and A.Z. Snyder, Intrinsic brain activityand con-sciousness, in:The Neurology of Consciousness, S. Laureysand G. Tononi, eds, Elesevier, Amsterdam, 2009.

[53] A. Salek-Haddadi, L. Lemieux, M. Merschhemke et al., Func-tional magnetic resonance imaging of human absence seizures,Ann Neurol20 (2003), 1915–1922.

[54] W.C. Shin, S.B. Hong, W.S. Tae and S.E. Kim, Ictal hyperper-fusion patterns according to the progression of temporal lobeseizures,Neurology58 (2002), 373–380.

[55] B.A. Vogt and S. Laureys, Posterior cingulate, precuneal andretrosplenial cortices: cytology and components of the neu-ral network correlates of consciousness,Prog Brain Res150(2005), 205–217.

[56] B. Weir, The morphology of the spike and wave complex,Electroencephalogr Clin Neurophysiol19 (1965), 284–290.

[57] P.D. Williamson, J.A. French, V.M. Thadani et al., Character-istics of medial temporal lobe epilepsy: II. Interictal andic-tal scalp electroencephalography, neuropsychological testing,neuroimaging, surgical results, and pathology,Ann Neurol34(1993), 781–787.

[58] G.B. Young, Coma and impaired consciousness: a clinicalperspective, New York: McGraw-Hill, 1998.

[59] R.A. Zappulla, Epilepsy and consciousness,Semin Neurol17(1997), 113–119.

[60] A. Zeman, Consciousness,Brain 124(2001), 1263–1289.

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

ios press epilepsy: the quintessential pathology of consciousness · 2019. 7. 31. · 4 a.e....

Documents