Ictal alterations of consciousness during ecstatic seizures

Ictal alterations of consciousness during ecstatic seizures

Epilepsy & Behavior 30 (2014) 58–61 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh R...

165KB Sizes 4 Downloads 25 Views

Epilepsy & Behavior 30 (2014) 58–61

Contents lists available at ScienceDirect

Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh

Review

Ictal alterations of consciousness during ecstatic seizures Fabienne Picard a,⁎, Florian Kurth b a b

Department of Neurology, University Hospital and Medical School of Geneva, Switzerland Department of Neurology, UCLA School of Medicine, Los Angeles, USA

a r t i c l e

i n f o

Article history: Received 24 September 2013 Accepted 26 September 2013 Available online 26 October 2013 Keywords: Epilepsy Ecstatic Self-awareness Consciousness Insula Meditation

a b s t r a c t Patients with ecstatic epileptic seizures report an altered consciousness, which they describe as a sense of heightened perception of themselves – they “feel very present” – and an increased vividness of sensory perceptions. Recently, the anterior insula has been proposed as the region where these seizures originate, based on the results of ictal nuclear imaging in three patients, the first induction of ecstatic auras by electrical stimulation, and the functional characteristics of the anterior insula in neuroimaging literature. Specifically, the anterior insula is thought to play a key role in integrating information from within the body, the external world, as well as the emotional states. In addition, the anterior insula is thought to convert this integrated information into successive global emotional moments, thus enabling both the construct of a sentient self as well as a mechanism for predictive coding. As part of the salience network, this region is also involved in switching from mind wandering toward attentional and executive processing. In this review, we will summarize previous patient reports and recap how insular functioning may be involved in the phenomenon of ecstatic seizures. Furthermore, we will relate these hypotheses to the results from research on meditation and effects of drug abuse. This article is part of a Special Issue entitled Epilepsy and Consciousness. © 2013 Elsevier Inc. All rights reserved.

1. Introduction

“The feeling of life, of self-awareness, seemed to grow stronger in such lightening moments.” The first description of the state of consciousness observed in ecstatic epileptic seizures was given in the 1860s by Dostoevsky, who described the symptoms of such seizures mainly through the characters in his novels. Prince Mychkine, the main character of “The Idiot”, suffered from such seizures, which were characterized by a sense of bliss. He felt “flashes of lucidity with hyperesthesia of sensory stimuli and of awareness” and “an incredible hitherto unsuspected feeling of bliss and appeasement…”. “My mind grows extraordinarily clear…”. “Such moments represented an incredible effort toward awareness and at the same time the most direct expression of self-awareness.” “Once I returned to normal consciousness, I felt that such illumination, such awareness of a higher consciousness, of a “superior being”, was a kind of illness, a distortion of the normal state. But it was neither mirage nor vain illusions such as those induced by hashish or alcohol that degrade the mind…”. “All my problems, doubts and worries resolved themselves in a limpid subtle Abbreviations: SPECT, single photon emission computed tomography; EEG, electroencephalogram. ⁎ Corresponding author at: Department of Neurology, University Hospital of Geneva, 4 rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland. Fax: +41 22 37 28 340. E-mail address: [email protected] (F. Picard). 1525-5050/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yebeh.2013.09.036

peace, with a feeling of understanding and awareness of the ‘Supreme Principle of life’”. While the majority of patients with ecstatic epileptic seizures report similar feelings, they may find it more difficult than Dostoevsky to describe these surreal symptoms. Most describe a sense of heightened perception of themselves – they “feel very present” – and an increased vividness of sensory perceptions during their seizures. At an initial stage, these ecstatic epileptic seizures are not accompanied by a loss of consciousness. Thus, they correspond to “simple partial seizures” according to the old ILAE Classification of Epilepsies and Epileptic Syndromes [1], a term now replaced by “focal seizures without impairment of consciousness or awareness” [2]. 2. Patients Seven patients have been described, who all reported a state of heightened self-awareness coupled with feelings of enhanced wellbeing and intense positive emotion. Picard and Craig reported five patients with ecstatic seizures, whose descriptions of ecstatic auras were very similar to that of Dostoevsky's [3]. Picard later described two more patients [4]. The heightened awareness actually affected both the internal “self-awareness” (feeling of being “more present”) and, according to some of the patients, the awareness of the external world with a more accurate, more acute perception of external stimuli. Among the descriptions of the ictal symptoms in the first paper, subject 1 reported: “it is as if I were very, very conscious, more aware, and the sensations, everything, seems bigger, overwhelming me.” Subject 2 used these words: “I feel light inside, but far from being empty. I feel really

F. Picard, F. Kurth / Epilepsy & Behavior 30 (2014) 58–61

present…. I feel a stronger consciousness of the body and the mind, but I do not forget what is around me”. Subject 4 described: “I feel more conscious of myself, more concentrated on myself… I feel more present from a psychological point of view, with more sensations…”. “Being very conscious of myself, I feel like discharged from anything else, from any worries”. Subject 5 reported: “It is a feeling of total presence, an absolute integration of myself, a feeling of unbelievable harmony of my whole body and myself with life, with the world, with the ‘All’” [3]. Another subject explained: “This would result in a sense of vividness which derived from the fact that each object in my visual field was emphasized, so to speak, by everything else” [4]. 3. The insula According to Picard and Craig's hypothesis, the symptomatic zone of the ecstatic aura would be the anterior insula, for a variety of reasons. Specifically, the results of ictal nuclear imaging reported in the literature for three patients [3–5] described a maximum of activity in this region. Ictal SPECT showed an increased blood flow in the whole right anterior insula in the first patient [3]; in the left anterior insula and mid-insula on both sides in the second patient [5]; and at the junction of the right dorsal mid-insula and central operculum in the last patient [4]. In addition, ecstatic auras were induced by electrical stimulation of the anterior–dorsal insula in a new patient with ecstatic seizures who underwent a presurgical depth electrode evaluation [52]. Finally, the different physiological roles of this region are abundantly described in literature. The insula is both, segregated into different subregions that are involved in a variety of functional systems, and at the same time a major hub for integrating the information from these different functional systems [6]. Specifically, the insula's functionally defined subregions are involved in interoception, gustation, olfaction, somatosensation, processing of emotions, and cognition. Connectivity studies in animals revealed that the different parts of the insula are extremely well interconnected [7], which enables a rapid flow of information to the anterior insula. In the anterior insula, this incoming interoceptive/ sensory, emotional, and cognitive information is finally integrated into a sense of well-being [8] and emotional regulation [6,9], and used in salience detection, switching between brain states, and predictive coding [10–12]. This integration has been hypothesized to produce self-awareness and the experience of a present moment [9,13]. The rich interconnection between insular subregions [7] may well enable a rapid propagation of seizure activity. This rapid propagation may lead to ecstatic seizures with different attendant symptoms like gustatory, olfactory, or auditory sensations (depending on the exact location of the ictal discharge), which were previously described [3,4]. Interestingly, very close connections also exist between the insula and the temporopolar region [14]. These connections, as well as the observation that ictal discharges can propagate directly from the temporal neocortex to the insula without a mesiotemporal relay [15], may explain how seizures originating in the temporal pole may immediately propagate to the insula [3]. Once ictal activity reaches the anterior insula, it may directly alter its functioning and elicit ecstatic seizures rather than classical temporal lobe epilepsy symptoms [3]. Specifically, changes in well-being, emotional regulation, and awareness of the present moment as reported in ecstatic seizures can be expected. In the following sections, we will discuss alterations in salience detection and switching brain states, changes in “awareness of the present moment”, as well as possible effects on predictive coding. 4. Possible underlying mechanisms of ecstatic seizures The anterior insula shows highly correlated activity with the dorsal anterior cingulate cortex (dACC) during the resting state, constituting a functional network which has been implicated in a broad range of affective and cognitive processes, including interoceptive–autonomic arousal, salience detection (that is, behaviorally relevant stimuli

59

detection), emotional processing, tonic alertness, and decision-making, in order to adequately process high-priority signals [9,16–19]. The most ventral part of this network was referred to as the “salience network” because of its role in the identification of the most salient stimuli and switching between the default mode network (which is activated during mind wandering) and the executive network, which enables the ability to fix attention on the external world and associative interoceptive state/changes [9–11,17,20,21]. It inhibits the default mode network and initiates the executive network (with a consequent activation of other attentional control-related networks). The salience network is implicated in the detection of salient external events as well as internally generated events, such as conscious awareness of errors. Hasenkamp et al. reported robust activations in the bilateral anterior insula and dACC when subjects became aware that their mind had wandered away from the breathing sensations on which they had to maintain attention [22,23]. During ecstatic seizures, the capacity to feel “more present” and have an increased perception of external stimuli could be related to a sustained activation of the salience network despite the absence of salient stimuli. An abnormal (seizure-induced) activation of this network would give rise to a switch away from mind wandering and to an unusual state of sustained high alertness and awareness without cause and without specific aim. Any current internal or external stimulus would then be perceived as if it was salient, giving rise to a feeling of extreme inner and external vividness at any given moment during the ecstatic aura. It has been suggested that the anterior insula is a key structure for the “present-moment awareness” [9], another possible underlying mechanism. Different studies showed that the anterior insula is consistently involved at the moment of perceptual recognition, for example, when subjects become aware that their mind has wandered away from the task [22]. However, this involvement has been particularly shown in conscious error perception or “error awareness”. In a visual saccade task in which it was possible to be either aware or unaware of errors, the anterior insula was activated only when participants could signal awareness of such errors [24,25]. The anterior insula can also analyze intersensory temporal synchrony and is activated during visual–auditory asynchrony detection [26]. According to Craig, the anterior insula integrates internal (interoceptive), external (sensory), and emotional information at each moment, giving rise to an image of ‘the material me’ or the sentient self at the immediate moment of time – ‘now’ – which he calls a “global emotional moment” [9,13,27]. The succession of global emotional moments would produce a cinemascopic ‘image’ of the sentient self that is continuous across a moving window of present time and would constitute the basis of time perception with an approximate frame rate of 8 Hz (i.e., each global emotional moment lasting about 125 ms) [3,13,27]. An important aspect of this model is that the sampling rate is not fixed but is rather dependent on salience. That is, sampling occurs more frequently for salient moments, leading to a subjective dilation of time, thus explaining the strong link between emotions and subjective time perception. The ecstatic seizures could allow a sustained “present-moment awareness” state. Patients all indicate a subjective time dilation [3,4]: their several-second seizures seem to last much longer, as if time had stretched (“I could not say if it lasts one second, hours or months”, Dostoevsky). In the present model, if each stimulus is perceived as salient, the extremely high number of consecutive salient moments would increase the sampling rate to a maximum, leaving the patient subjectively timeless in the ‘here and now’. Finally, a third possible mechanism involves uncertainty. Overall, there is a strong motivation to avoid ambiguity and uncertainty [28], since these have been characterized as aversive states [29]. Generally speaking, uncertainty can be minimized by making inferences about future states with the greatest possible precision [30]. For this purpose, the brain predicts future states and continuously compares these predictions with current states while trying to minimize the prediction

60

F. Picard, F. Kurth / Epilepsy & Behavior 30 (2014) 58–61

error (predictive coding). A mismatch between prediction and actual experience (i.e., prediction error) has been associated with generating negative emotional arousal or anxiety [31–33]. There is accumulating evidence for a role of the anterior insula in predictive coding and eliciting feelings of anxiety and negative emotional arousal in case of prediction errors [10,18,34,35]. As detailed previously, the anterior insula is thought to generate a cinemascopic ‘image’ of the sentient self across time, including the immediate past, present, and anticipated immediate future [9,13,27]. This cinemascopic ‘image’ may provide a means to compare the experienced global moment with its prediction (the anticipated immediate future). A comparison of interoceptive signals and their prediction in this region has recently been proposed as a model of conscious presence [10]. Specifically, an accurate prediction (in other words, a minimized prediction error) was associated with a possible sense of presence in a virtual environment. If we assume that during ecstatic seizures, the sampling rate increases as described above, the cinemascopic image would be ‘filled up’ with present-moment samples. Consequently, at an extremely high sampling rate, the predictive coding would cease to work or at least would not make predictions at the high frequency of actual experience. The nonexisting prediction error may consequently prevent negative emotions and instill the feeling of certainty and the absence of worries and doubts that was reported by patients [4]. 5. Common mechanisms with meditation The peculiarity of the state induced by the ecstatic seizures is a total immersion in the present moment without any intrusion of thoughts regarding the past or the future, without any mind wandering; i.e., the patient is just in a state of contemplation. The sudden immersion into this unusual state of “accordance with the present moment” is so unexpected and powerful that people may have the impression that they have an understanding of “the Supreme Principle of life”, as indicated by Dostoevsky and some of our patients, even if they had no previous religious beliefs. Enhanced awareness of the present moment and the cognitive reappraisal of emotionally salient sensory events, which were described to involve the anterior insula as reported in different studies, are the goals in meditation [36–42]. In functional studies, activity in the anterior–dorsal insula has been reported to be increased during the advanced stage of meditation training [43] and associated with the self-reported intensity of the meditation [38]. In addition, a modulation of the state anxiety by mindfulness meditation was shown to engage a network of brain regions including the anterior insula [36]. Structural studies have likewise indicated more gray matter concentration [41], a thicker cortex [42], and a stronger gyrification [37] in the anterior insula in meditators compared to controls, as well as positive correlations between the number of meditation years and gyrification in this region [37]. The insula's above-discussed role in switching between different brain networks may be important for meditators to achieve and maintain a meditative state. This switch may induce a different brain state away from daydreaming, mind wandering, and projections to the past and the future as mediated by the default mode network, which may then bring meditators into the “present moment”. This role in switching was confirmed during a task in which the subjects had to focus their attention on breath (breath-focused meditation) [22]. The anterior insula was involved in shifting attention back on the “object” (here, the breath), when subjects became aware of mind wandering, confirming the role of the anterior insula in switching to and maintaining a state of “present-moment conscious awareness” [9]. In this context, it is interesting that the anterior insula may be the focus of ecstatic seizures. That is, similar to the willful process of meditation, these seizures may induce a feeling of heightened awareness, similar to the state sought through meditative practice. Moreover, these seizures may alter the brain state by switching away

from the default mode network as discussed above, thus “locking” the patients in a feeling of the “present moment”. 6. Common mechanisms with states induced by drugs of abuse A blissful state can be experienced with some addictive drugs of abuse. Stimulant drugs of abuse, such as amphetamine, cocaine, and ecstasy (3,4-methylene-dioxy-methamphetamine) can induce a feeling of enhanced introspective attention and a heightened awareness of the surroundings, together with extreme bliss and inner peace. Interestingly, neuroimaging studies have shown alterations in the anterior insula when taking stimulant drugs of abuse; in addition, a major role of the anterior insula in addiction is now well recognized [44]. The insula is known to represent the interoceptive effects of drug use, giving rise to “a subjective feeling which includes conscious appreciation of interoceptive effects in addition to pleasure” [45]. A comparison of the emotional effects of nicotine (which acts as a stimulant at small doses) in patients with left insula lesions and in patients with lesions in noninsula regions showed that subjects with left insula lesions failed to find puffs with nicotine more pleasurable and desirable than puffs without nicotine [46]. In rats, a positive correlation was shown between the dose of administered cocaine and the activity within the insula, cingulate cortex, and nucleus accumbens [47]. In nonhuman primates, acute cocaine administration was shown to induce immediate early gene expression in the insula and ventromedial prefrontal cortex [48]. In humans, chronic cocaine abuse is associated with a decreased gray matter concentration in these regions [49]. A longer duration of cocaine dependence was shown to correlate with a greater gray matter volume reduction in the insular, cingulate, and orbitofrontal cortices [50]. A bilateral activation of the anterior insula was also shown under the effect of the psychoactive ayahuasca tea, a central element of Amazonian shamanism which produces enhanced introspective attention and euphoria [51]. The likely involvement of the anterior insula in both ecstatic epileptic seizures and in the use of stimulant addictive drugs could underlie the similarity of symptoms [3]. The activation of the anterior insula observed during the taking of a stimulant drug of abuse could also explain a sustained state of “present-moment conscious awareness” which takes the subject away from mind wandering and projections to the past and the future, all of which can cause doubts and worries. The inner peace could be related to the lack of worries of the past and future. In conclusion, besides the classical impairment of consciousness that often accompanies epileptic seizures and which is one of the most disabling manifestations of epileptic seizures, an almost opposite effect on consciousness may occur in some focal seizures, the ecstatic seizures, with a feeling of heightened consciousness, affecting self-awareness and, possibly, also awareness of external world. This increased awareness seems related to a complete, sustained focus on the present moment, which, according to some arguments, could be caused by an epileptic discharge within the anterior insula, already known for its role in present-moment awareness. Future experiments could explore this issue with functional imaging studies using new paradigms for the investigation of the neural circuits underlying present-moment awareness and, possibly, by studying patients with pharmacoresistant focal epilepsy with ecstatic auras who undergo intracerebral EEG recordings during a presurgical evaluation of their epilepsy. Conflict of interest The authors declare that there are no conflicts of interest. Acknowledgments We would like to thank Dr. Anil Seth (University of Sussex) for helpful comments.

F. Picard, F. Kurth / Epilepsy & Behavior 30 (2014) 58–61

References [1] Epilepsy CoCaTotILA. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30:389–99. [2] Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51:676–85. [3] Picard F, Craig AD. Ecstatic epileptic seizures: a potential window on the neural basis for human self-awareness. Epilepsy Behav 2009;16:539–46. [4] Picard F. State of belief, subjective certainty and bliss as a product of cortical dysfunction. Cortex 2013;49(9):2494–500. [5] Landtblom AM, Lindehammar H, Karlsson H, Craig AD. Insular cortex activation in a patient with “sensed presence”/ecstatic seizures. Epilepsy Behav 2011;20:714–8. [6] Kurth F, Zilles K, Fox PT, Laird AR, Eickhoff SB. A link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis. Brain Struct Funct 2010;214:519–34. [7] Augustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Brain Res Rev 1996;22:229–44. [8] Craig AD. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol 2003;13:500–5. [9] Craig AD. How do you feel—now? The anterior insula and human awareness. Nat Rev Neurosci 2009;10:59–70. [10] Seth AK, Suzuki K, Critchley HD. An interoceptive predictive coding model of conscious presence. Front Psychol 2011;2:395. [11] Sridharan D, Levitin DJ, Menon V. A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc Natl Acad Sci U S A 2008;105:12569–74. [12] Dosenbach NU, Visscher KM, Palmer ED, Miezin FM, Wenger KK, Kang HC, et al. A core system for the implementation of task sets. Neuron 2006;50:799–812. [13] Craig AD. The sentient self. Brain Struct Funct 2010;214:563–77. [14] Mesulam M, Mufson E. The insula of Reil in man and monkey. Architectonics, connectivity and function. In: Peters A, Jones E, editors. Cerebral cortex. New York: Plenum Press; 1985. p. 179–226. [15] Isnard J, Guenot M, Ostrowsky K, Sindou M, Mauguiere F. The role of the insular cortex in temporal lobe epilepsy. Ann Neurol 2000;48:614–23. [16] Sadaghiani S, Scheeringa R, Lehongre K, Morillon B, Giraud AL, Kleinschmidt A. Intrinsic connectivity networks, alpha oscillations, and tonic alertness: a simultaneous electroencephalography/functional magnetic resonance imaging study. J Neurosci 2010;30:10243–50. [17] Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007;27:2349–56. [18] Singer T, Critchley HD, Preuschoff K. A common role of insula in feelings, empathy and uncertainty. Trends Cogn Sci 2009;13:334–40. [19] Medford N, Critchley HD. Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response. Brain Struct Funct 2010;214:535–49. [20] Wiech K, Lin CS, Brodersen KH, Bingel U, Ploner M, Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. J Neurosci 2010;30:16324–31. [21] Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 2010;214:655–67. [22] Hasenkamp W, Wilson-Mendenhall CD, Duncan E, Barsalou LW. Mind wandering and attention during focused meditation: a fine-grained temporal analysis of fluctuating cognitive states. Neuroimage 2012;59:750–60. [23] Hasenkamp W, Barsalou LW. Effects of meditation experience on functional connectivity of distributed brain networks. Front Hum Neurosci 2012;6:38. [24] Klein TA, Endrass T, Kathmann N, Neumann J, von Cramon DY, Ullsperger M. Neural correlates of error awareness. Neuroimage 2007;34:1774–81. [25] Klein TA, Ullsperger M, Danielmeier C. Error awareness and the insula: links to neurological and psychiatric diseases. Front Hum Neurosci 2013;7:14. [26] Bushara KO, Grafman J, Hallett M. Neural correlates of auditory–visual stimulus onset asynchrony detection. J Neurosci 2001;21:300–4.

61

[27] Craig AD. Emotional moments across time: a possible neural basis for time perception in the anterior insula. Philos Trans R Soc Lond B Biol Sci 2009;364:1933–42. [28] Bar-Anan Y, Wilson TD, Gilbert DT. The feeling of uncertainty intensifies affective reactions. Emotion 2009;9:123–7. [29] Sarinopoulos I, Grupe DW, Mackiewicz KL, Herrington JD, Lor M, Steege EE, et al. Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. Cereb Cortex 2010;20:929–40. [30] Friston K, Adams R, Montague R. What is value-accumulated reward or evidence? Front Neurorobot 2012;6:11. [31] Gray MA, Harrison NA, Wiens S, Critchley HD. Modulation of emotional appraisal by false physiological feedback during fMRI. PLoS One 2007;2:e546. [32] Wu CC, Sacchet MD, Knutson B. Toward an affective neuroscience account of financial risk taking. Front Neurosci 2012;6:159. [33] Paulus MP, Stein MB. An insular view of anxiety. Biol Psychiatry 2006;60:383–7. [34] Preuschoff K, Quartz SR, Bossaerts P. Human insula activation reflects risk prediction errors as well as risk. J Neurosci 2008;28:2745–52. [35] Bossaerts P. Risk and risk prediction error signals in anterior insula. Brain Struct Funct 2010;214:645–53. [36] Zeidan F, Martucci KT, Kraft RA, McHaffie JG, Coghill RC. Neural correlates of mindfulness meditation-related anxiety relief. Soc Cogn Affect Neurosci 2013. http://dx.doi.org/10.1093/scan/nst041. [37] Luders E, Kurth F, Mayer EA, Toga AW, Narr KL, Gaser C. The unique brain anatomy of meditation practitioners: alterations in cortical gyrification. Front Hum Neurosci 2012;6:34. [38] Lutz A, Brefczynski-Lewis J, Johnstone T, Davidson RJ. Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise. PLoS One 2008;3:e1897. [39] Baerentsen KB, Stodkilde-Jorgensen H, Sommerlund B, Hartmann T, DamsgaardMadsen J, Fosnaes M, et al. An investigation of brain processes supporting meditation. Cogn Process 2010;11:57–84. [40] Farb NA, Segal ZV, Mayberg H, Bean J, McKeon D, Fatima Z, et al. Attending to the present: mindfulness meditation reveals distinct neural modes of self-reference. Soc Cogn Affect Neurosci 2007;2:313–22. [41] Holzel BK, Ott U, Gard T, Hempel H, Weygandt M, Morgen K, et al. Investigation of mindfulness meditation practitioners with voxel-based morphometry. Soc Cogn Affect Neurosci 2008;3:55–61. [42] Lazar SW, Kerr CE, Wasserman RH, Gray JR, Greve DN, Treadway MT, et al. Meditation experience is associated with increased cortical thickness. Neuroreport 2005;16:1893–7. [43] Tang YY, Rothbart MK, Posner MI. Neural correlates of establishing, maintaining, and switching brain states. Trends Cogn Sci 2012;16:330–7. [44] Noel X, Brevers D, Bechara A. A neurocognitive approach to understanding the neurobiology of addiction. Curr Opin Neurobiol 2013. http://dx.doi.org/10.1016/ j.conb.2013.01.018. [45] Naqvi NH, Bechara A. The hidden island of addiction: the insula. Trends Neurosci 2009;32:56–67. [46] Naqvi NH, Bechara A. The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making. Brain Struct Funct 2010;214:435–50. [47] Lu H, Xi ZX, Gitajn L, Rea W, Yang Y, Stein EA. Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI). Proc Natl Acad Sci U S A 2007;104:2489–94. [48] Porrino LJ, Lyons D. Orbital and medial prefrontal cortex and psychostimulant abuse: studies in animal models. Cereb Cortex 2000;10:326–33. [49] Franklin TR, Acton PD, Maldjian JA, Gray JD, Croft JR, Dackis CA, et al. Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients. Biol Psychiatry 2002;51:134–42. [50] Ersche KD, Barnes A, Jones PS, Morein-Zamir S, Robbins TW, Bullmore ET. Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain 2011;134:2013–24. [51] Riba J, Romero S, Grasa E, Mena E, Carrio I, Barbanoj MJ. Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology (Berl) 2006;186:93–8. [52] Picard F, Scavarda D, Bartolomei F. Induction of a sense of bliss by electrical stimulation of the anterior insula. Cortex 2013. http://dx.doi.org/10.1016/ j.cortex.2013.08.013.