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See detailDisorders of consciousness: coma, vegetative and minimally conscious states
Gosseries, Olivia ULg; Vanhaudenhuyse, Audrey ULg; Bruno, Marie-Aurélie ULg et al

in D. Cvetkovic & I. Cosic (Ed.) States of Consciousness: Experimental Insights into Meditation, Waking, Sleep and Dreams (2011)

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See detailFaisabilité d’une alimentation orale chez les patients avec troubles de la conscience
Maudoux, Audrey ULg; BREUSKIN, Ingrid ULg; Gosseries, Olivia ULg et al

in Schnakers, Caroline (Ed.) Coma et états de conscience altérée (2011)

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See detailDisorders of consciousness: What's in a name?
Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg; Chatelle, Camille ULg et al

in NeuroRehabilitation (2011), 28

Following a coma, some patients may “awaken” without voluntary interaction or communication with the environment. More than 40 years ago this condition was coined coma vigil or apallic syndrome and later ... [more ▼]

Following a coma, some patients may “awaken” without voluntary interaction or communication with the environment. More than 40 years ago this condition was coined coma vigil or apallic syndrome and later became worldwide known as “persistent vegetative state”. About 10 years ago it became clear that some of these patients who failed to recover verbal or nonverbal communication did show some degree of consciousness – a condition called “minimally conscious state”. Some authors questioned the usefulness of differentiating unresponsive “vegetative” from minimally conscious patients but subsequent functional neuroimaging studies have since objectively demonstrated differences in residual cerebral processing and hence, we think, conscious awareness. These neuroimaging studies have also demonstrated that a small subset of unresponsive “vegetative” patients may show unambiguous signs of consciousness and command following inaccessible to bedside clinical examination. These findings, together with negative associations intrinsic to the term “vegetative state” as well as the diagnostic errors and their potential effect on the treatment and care for these patients gave rise to the recent proposal for an alternative neutral and more descriptive name: unresponsive wakefulness syndrome. We here give an overview of PET and (functional) MRI studies performed in these challenging patients and stress the need for a separate ICD9CM diagnosis code and MEDLINEMeSH entry for “minimally conscious state” as the lack of clear distinction between vegetative state/unresponsive wakefulness syndrome and minimally conscious state may encumber scientific studies in the field of disorders of consciousness. [less ▲]

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See detailNear-Death Experiences : Real or imagined memories?
Thonnard, Marie ULg; Laureys, Steven ULg; Brédart, Serge ULg et al

Poster (2010, September)

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See detailBrain-computer interface in disorders of consciousness: answering simple questions with a P3 speller
Noirhomme, Quentin ULg; Chatelle, Camille ULg; Kleih, Sonja et al

Poster (2010, June)

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state (Schnakers et al., 2009). In some patients ... [more ▼]

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state (Schnakers et al., 2009). In some patients, recovery of consciousness may precede motor recovery. Brain-computer interfaces (BCI) might permit these patients to show non-motor dependent signs of awareness and in a next step might enable communication. This study aimed at testing to what extent an EEG-based BCI could help detecting signs of awareness and communication in disorders of consciousness. We employed a P300 based BCI where healthy volunteers and patients with locked-in syndrome and in a minimally conscious state were asked to answer yes or no to simple questions by paying attention to one out of four auditorily presented stimuli (‘yes’, ‘no’, ‘stop’, ‘go’). Methods: We studied 13 patients with a minimally conscious state (MCS, 5 TBI – 8 anoxic, mean time post injury 70±109 months; mean age 42 ± 21) and 2 in pseudo-coma or locked in syndrome (LIS; brainstem stroke, time post injury 26 and 46 months; aged 63 and 29)) and 16 healthy controls (aged 45±19). Patients were evaluated using the Coma Recovery Scale Revised (CRS-R). An auditory P300 four choice speller paradigm (Furdea et al., 2009) based on the BCI2000 system (Schalk et al., 2004) was used. 16-Channel EEG was recorded using a g.tec USBAmp amplifier. A trial constituted of 15 presentation of four sounds the order of presentation being pseudo-randomized (sound duration: ~400ms; inter-stimulus interval: ~600ms). After a training session of 4 trials, patients and healthy subjects were required to answer 10 or 12 questions, respectively. Questions were of the following kind: “Is your name Quentin?”, “Is your mother’s name Dorothée?”. A stepwise linear discriminant analysis based on the training session was used to classify the data and to provide online feedback. Offline, all training and testing sequences were pooled. Sequences with artifacts were discarded and a leave-one-out approach was used to classify the data. Results: Healthy subjects presented a mean correct response rate of 73% online and 93% offline. Note that online classification failed for one control subject due to a presumed change in cognitive strategy between training and testing sessions. LIS patients showed a correct response rate of 30 and 60% (online) and 36 and 79% (offline). Three MCS patients had a correct response rate of ≥50% offline (10, 18, 0% online and 50, 53, 57% offline). Two of these three patients did not show any command following at the bedside. The 10 remaining MCS cases showed online and offline correct answers <50% (mean 33±9% online and 25±13% offline). Conclusion: Our auditory P300-based BCI permitted functional interactive communication in 15/16 controls (online) and in all offline. Our data obtained in patients with locked-in syndrome and disorders of consciousness demonstrate the potential clinical usefulness of the technique following coma but also show lower accuracy in patients as compared to healthy volunteers. This might be due to fluctuating attentional levels and exhaustibility in the MCS and to the suboptimal EEG recording quality due to movement, ocular and respiration artifacts in these challenging patients. Further algorithmic developments should include automatic artifact detection and single trial classification. Despite the need for further improvement in BCI devices adapted to post-coma patients, our results already indicate that MCS patients without any clinical sign of command-following can employ a yes-no speller offering the hope of functional interactive communication and a possibility for decision making and autonomy. Bibliography Furdea A, Halder S, Krusienski DJ, Bross D, Nijboer F, Birbaumer N, Kübler A, 2009, An auditory oddball (P300) spelling system for brain-computer interfaces, Psychophysiology. May; 46(3):617-25. Schalk G., McFarland D.J., Hinterberger T., Birbaumer N., and Wolpaw J.R. 2004, BCI2000: A General-Purpose Brain-Computer Interface (BCI) System, IEEE Trans Biomed Eng, 51(6). Schnakers C, Vanhaudenhuyse A, Giacino J, Ventura; Boly M, Majerus S, Moonen G, Laureys S, 2009, Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment, BMC Neurology, 9 (35). [less ▲]

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See detailProbing command following in patients with disorders of consciousness using a brain-computer interface
Noirhomme, Quentin ULg; Chatelle, Camille ULg; Kleih, Sonja et al

Conference (2010, June)

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state. In some patients, recovery of consciousness ... [more ▼]

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state. In some patients, recovery of consciousness may precede motor recovery. Brain-computer interfaces (BCI) might permit these patients to show non-motor dependent signs of awareness and in a next step might enable communication. This study aimed at testing to what extent an EEG-based BCI could help detecting signs of awareness and communication in disorders of consciousness. Methods: We studied 13 patients with a minimally conscious state (MCS, 5 TBI – 8 anoxic, mean time post injury 70±109 months; mean age 42 ± 21) and 16 healthy controls (aged 45±19). Patients were evaluated using the Coma Recovery Scale Revised. 16-Channel EEG was recorded using a g.tec USBAmp amplifier. An auditory P300 four choice speller paradigm based on the BCI2000 system was used. Subjects were asked to answer yes or no to simple questions by paying attention to one out of four auditorily presented stimuli (‘yes’, ‘no’, ‘stop’, ‘go’). A trial constituted of 15 presentations of each sound the order of presentation being randomized. After a training session, patients and healthy subjects were required to answer 10 to 12 questions. A stepwise linear discriminant analysis based on the training session was used to classify the data. Offline, all training and testing trials were pooled and a leave-one-out approach was used to classify the data. Results: Healthy subjects presented a mean correct response rate of 73% online and 93% offline. Three MCS patients had a correct response rate of ≥50% offline (10, 18, 0% online and 50, 53, 57% offline). Two of these three patients did not show any command following at the bedside. The 10 remaining MCS cases showed online and offline correct answers <50% (mean 33±9% online and 25±13% offline). Conclusion: Our auditory P300-based BCI permitted functional interactive communication in 15/16 controls (online) and in all offline. Our data obtained in patients with disorders of consciousness demonstrate the potential clinical usefulness of the technique following coma but also show lower accuracy in patients as compared to healthy volunteers. This might be due to fluctuating attentional levels and exhaustibility in the MCS and to the suboptimal EEG recording quality due to movement, ocular and respiration artifacts in these challenging patients. [less ▲]

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See detailNear-death experiences: real or imagined?
Thonnard, Marie ULg; Laureys, Steven ULg; Brédart, Serge ULg et al

Conference (2010, June)

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See detailDefault network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.
Vanhaudenhuyse, Audrey ULg; Noirhomme, Quentin ULg; Tshibanda, Luaba ULg et al

in Brain : A Journal of Neurology (2010), 133(Pt 1), 161-71

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than ... [more ▼]

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. [less ▲]

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See detailDisorders of consciousness: Moving from passive to resting state and active paradigms
Bruno, Marie-Aurélie ULg; Soddu, Andrea ULg; Demertzi, Athina ULg et al

in Cognitive Neuroscience (2010), 1(1), 193203

Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e ... [more ▼]

Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e., minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state. The increasing use of fMRI and EEG tools permits the clinical characterization of these patients to be improved. We first discuss “resting metabolism” and “passive activation” paradigms, used in neuroimaging and evoked potential studies, which merely identify neural activation reflecting “automatic” processing—that is, occurring without the patient’s willful intervention. Secondly, we present an alternative approach consisting of instructing subjects to imagine well-defined sensorymotor or cognitive-mental actions. This strategy reflects volitional neural activation and, hence, witnesses awareness. Finally, we present results on blood-oxgen-level-dependent “default mode network”/resting state studies that might be a promising tool in the diagnosis of these challenging patients. [less ▲]

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See detailAuditory P300 and the altered consciousness: detecting altered states of consciousness using the P300 speller
Lulé, D.; Kleih, S.; Chatelle, Camille ULg et al

in Proceedings of TOBI Workshop 2010: Integrating Brain-Computer Interfaces with Conventional Assistive Technology (2010)

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See detailLa Sensory Modality Assessment and Rehabilitation Technique (SMART) : une echelle comportementale d'evaluation et de revalidation pour des etats alteres de conscience.
Chatelle, Camille ULg; Schnakers, Caroline ULg; Bruno, Marie-Aurélie ULg et al

in Revue Neurologique (2010), 166(8-9), 675-82

INTRODUCTION: Difficulties in detecting bedside signs of consciousness in non-communicative patients still lead to a high rate of misdiagnosis illustrating the need to employ standardized behavioral ... [more ▼]

INTRODUCTION: Difficulties in detecting bedside signs of consciousness in non-communicative patients still lead to a high rate of misdiagnosis illustrating the need to employ standardized behavioral assessment scales. STATE OF ART: The Sensory Modality Assessment and Rehabilitation Technique (SMART) is a behavioral assessment scale of consciousness that assesses responses to multimodal sensory stimulation in disorders of consciousness. These stimulations can also be considered to have therapeutic value. PERSPECTIVES: We here review the different components and use of the SMART assessment and discuss its validity, reliability, and robustness in clinical practice. The scale has a high intra- and inter-observer reliability thanks to a detailed procedure description. However, in the absence of objective gold standards in the assessment of consciousness, it is currently difficult to make strong claims about its validity. A comparison between SMART and other standardized and validated coma-scales is proposed. CONCLUSION: In our view, SMART is an interesting tool for monitoring patients with altered states of consciousness subsequent to coma. Currently, we await studies on its concurrent validity as compared to other validated behavioral assessment scales and on the effect of SMART stimulations on patient outcome. [less ▲]

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See detailAssessment and detection of pain in noncommunicative severely brain-injured patients.
Schnakers, Caroline ULg; Chatelle, Camille ULg; Majerus, Steve ULg et al

in Expert Review of Neurotherapeutics (2010), 10(11), 1725-31

Detecting pain in severely brain-injured patients recovering from coma represents a real challenge. Patients with disorders of consciousness are unable to consistently or reliably communicate their ... [more ▼]

Detecting pain in severely brain-injured patients recovering from coma represents a real challenge. Patients with disorders of consciousness are unable to consistently or reliably communicate their feelings and potential perception of pain. However, recent studies suggest that patients in a minimally conscious state can experience pain to some extent. Pain monitoring in these patients is hence of medical and ethical importance. In this article, we will focus on the possible use of behavioral scales for the assessment and detection of pain in noncommunicative patients. [less ▲]

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See detailBreakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness.
Boveroux, Pierre ULg; Vanhaudenhuyse, Audrey ULg; Bruno, Marie-Aurélie ULg et al

in Anesthesiology (2010), 113(5), 1038-53

BACKGROUND: Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes ... [more ▼]

BACKGROUND: Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes during pharmacological modulation of the level of consciousness. METHODS: Low-frequency spontaneous blood oxygen level-dependent fluctuations were measured in 19 healthy volunteers during wakefulness, mild sedation, deep sedation with clinical unconsciousness, and subsequent recovery of consciousness. RESULTS: Propofol-induced decrease in consciousness linearly correlates with decreased corticocortical and thalamocortical connectivity in frontoparietal networks (i.e., default- and executive-control networks). Furthermore, during propofol-induced unconsciousness, a negative correlation was identified between thalamic and cortical activity in these networks. Finally, negative correlations between default network and lateral frontoparietal cortices activity, present during wakefulness, decreased proportionally to propofol-induced loss of consciousness. In contrast, connectivity was globally preserved in low-level sensory cortices, (i.e., in auditory and visual networks across sedation stages). This was paired with preserved thalamocortical connectivity in these networks. Rather, waning of consciousness was associated with a loss of cross-modal interactions between visual and auditory networks. CONCLUSIONS: Our results shed light on the functional significance of spontaneous brain activity fluctuations observed in functional magnetic resonance imaging. They suggest that propofol-induced unconsciousness could be linked to a breakdown of cerebral temporal architecture that modifies both within- and between-network connectivity and thus prevents communication between low-level sensory and higher-order frontoparietal cortices, thought to be necessary for perception of external stimuli. They emphasize the importance of thalamocortical connectivity in higher-order cognitive brain networks in the genesis of conscious perception. [less ▲]

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See detailThe contribution of familiarity to within- and between-domain associative recognition memory: Use of a modified remember/know procedure
Bastin, Christine ULg; Van der Linden, Martial ULg; Schnakers, Caroline ULg et al

in European Journal of Cognitive Psychology (2010), 22(6), 922-943

The purpose of the present study was to determine the extent to which familiarity can support associative recognition memory as a function of whether the associations are within- or between-domain ... [more ▼]

The purpose of the present study was to determine the extent to which familiarity can support associative recognition memory as a function of whether the associations are within- or between-domain. Standard recognition and familiarity only performance were compared in different participants, using a new adaptation of the remember/know procedure. The results indicated that within-domain (face face) associative recognition was mainly supported by familiarity. In contrast, familiarity provided relatively poor support to between-domain (face name) associative recognition for which optimal performance required a major recollection contribution. These findings suggest that familiarity can support associative recognition memory, particularly for within-domain associations, and contrast with the widely held view that associative recognition depends largely on recollection. [less ▲]

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See detailVisual fixation in the vegetative state: an observational case series PET study.
Bruno, Marie-Aurélie ULg; Vanhaudenhuyse, Audrey ULg; Schnakers, Caroline ULg et al

in BMC Neurology (2010), 10

BACKGROUND: Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether ... [more ▼]

BACKGROUND: Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixation is compatible with the diagnosis of the vegetative state (i.e., represents "automatic" subcortical processing) or is a sufficient sign of consciousness and higher order cortical processing. METHODS: We here studied cerebral metabolism in ten patients with chronic post-anoxic encephalopathy and 39 age-matched healthy controls. Five patients were in a vegetative state (without fixation) and five presented visual fixation but otherwise showed all criteria typical of the vegetative state. Patients were matched for age, etiology and time since insult and were followed by repeated Coma Recovery Scale-Revised (CRS-R) assessments for at least 1 year. Sustained visual fixation was considered as present when the eyes refixated a moving target for more than 2 seconds as defined by CRS-R criteria. RESULTS: Patients without fixation showed metabolic dysfunction in a widespread fronto-parietal cortical network (with only sparing of the brainstem and cerebellum) which was not different from the brain function seen in patients with visual fixation. Cortico-cortical functional connectivity with visual cortex showed no difference between both patient groups. Recovery rates did not differ between patients without or with fixation (none of the patients showed good outcome). CONCLUSIONS: Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function. [less ▲]

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See detailFunctional Neuroimaging Approaches to the Changing Borders of Consciousness
Noirhomme, Quentin ULg; Soddu, Andrea ULg; Vanhaudenhuyse, Audrey ULg et al

in Journal of Psychophysiology (2010), 24(2), 68-75

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could ... [more ▼]

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could help disentangle complex cases and offer new prognostic criteria. These methods can be divided into to three categories: First, new anatomical MRI neuroimaging methods, like diffusion tensor imaging (DTI) or spectroscopy, and passive functional imaging methods (looking at the brain’s activation induced by external stimuli), could provide new diagnostic and prognostic markers. Second, neuroimaging methods based on active collaboration from the patient could help to detect clinically unnoticed signs of consciousness. Third, developments in brain-computer interfaces based on EEG, functional MRI, or EMG offer communication possibilities in brain-damaged patients who can neither verbally nor nonverbally express their thoughts or wishes. These new approaches raise important issues not only from a clinical and ethical perspective (i.e., patients’ diagnosis, prognosis and management) but also from a neuroscientific standpoint, as they enrich our current understanding of the emergence and function of the conscious human mind. [less ▲]

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See detailThe nociception coma scale: A new tool to assess nociception in disorders of consciousness.
Schnakers, Caroline ULg; Chatelle, Camille ULg; Vanhaudenhuyse, Audrey ULg et al

in Pain (2010), 148

Assessing behavioral responses to nociception is difficult in severely brain-injured patients recovering from coma. We here propose a new scale developed for assessing nociception in vegetative (VS) and ... [more ▼]

Assessing behavioral responses to nociception is difficult in severely brain-injured patients recovering from coma. We here propose a new scale developed for assessing nociception in vegetative (VS) and minimally conscious (MCS) coma survivors, the Nociception Coma Scale (NCS), and explore its concurrent validity, inter-rater agreement and sensitivity. Concurrent validity was assessed by analyzing behavioral responses of 48 post-comatose patients to a noxious stimulation (pressure applied to the fingernail) (28 VS and 20 MCS; age range 20-82years; 17 of traumatic etiology). Patients' were assessed using the NCS and four other scales employed in non-communicative patients: the 'Neonatal Infant Pain Scale' (NIPS) and the 'Faces, Legs, Activity, Cry, Consolability' (FLACC) used in newborns; and the 'Pain Assessment In Advanced Dementia Scale' (PAINAD) and the 'Checklist of Non-verbal Pain Indicators' (CNPI) used in dementia. For the establishment of inter-rater agreement, fifteen patients were concurrently assessed by two examiners. Concurrent validity, assessed by Spearman rank order correlations between the NCS and the four other validated scales, was good. Cohen's kappa analyses revealed a good to excellent inter-rater agreement for the NCS total and subscore measures, indicating that the scale yields reproducible findings across examiners. Finally, a significant difference between NCS total scores was observed as a function of diagnosis (i.e., VS or MCS). The NCS constitutes a sensitive clinical tool for assessing nociception in severely brain-injured patients. This scale constitutes the first step to a better management of patients recovering from coma. [less ▲]

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See detailEthical implications : pain, coma and related disorders
Schnakers, Caroline ULg; Faymonville, Marie ULg; Laureys, Steven ULg

in Banks, William P. (Ed.) Encyclopedia of Consciousness (2009)

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See detailPain and non-pain processing during hypnosis: a thulium-YAG event-related fMRI study.
Vanhaudenhuyse, Audrey ULg; Boly, Mélanie ULg; Balteau, Evelyne ULg et al

in NeuroImage (2009), 47(3), 1047-54

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and ... [more ▼]

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation. [less ▲]

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