Reply: Neural detection of complex sound sequences or of statistical regularities in the absence of consciousness?

Tzovara, Athina; Simonin, Alexandre; Oddo, Mauro; Rossetti, Andrea O.; Lucia, Marzia De

doi:10.1093/brain/awv186

Cited by 9 publications

(8 citation statements)

References 12 publications

(23 reference statements)

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“…This study shows that an improvement in auditory discrimination over the first 2 days of coma is predictive of postanoxic patients' chances of awakening, extending our previous findings based on 30 patients 21 to 94 comatose patients (see also Tzovara et al 41,42 ). The above-chance level predictive value of the proposed test for awakening (ie, 82% when including all EEG recordings or 93% when excluding patients with epileptiform EEG activity) should encourage its implementation in clinical practice, to complement other available tests, which are mainly predictive of poor outcome.…”

Section: Discussionsupporting

confidence: 86%

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Prediction of awakening from hypothermic postanoxic coma based on auditory discrimination

Tzovara

Rossetti

Juan

et al. 2016

Annals of Neurology

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 86%

Prediction of awakening from hypothermic postanoxic coma based on auditory discrimination

Tzovara

Rossetti

Juan

et al. 2016

Annals of Neurology

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“…Recent efforts to assess consciousness using neurophysiological data have been limited by the need to interpret data from unresponsive patients by a comparison to healthy controls (Bekinschtein et al, 2009 ; Cruse et al, 2011 ; Goldfine et al, 2012 ; Naccache et al, 2015 ; Tzovara et al, 2015a , b ). The challenges inherent in interpreting the EEG of unresponsive patients are clearly illustrated in this patient.…”

Section: Discussionmentioning

confidence: 99%

“…Machine learning techniques that classify neurophysiological patterns in response to motor imagery commands have been proposed as a means of distinguishing patients with covert consciousness from those with UWS (Cruse et al, 2011 ). However, the ability of these methods to detect covert consciousness has been critiqued on the basis of technical or statistical issues (King et al, 2011 ; Goldfine et al, 2012 ; Naccache et al, 2015 ; Tzovara et al, 2015a , b ). Another issue with current approaches is that neural markers must be compared to those of healthy controls using a between-subject study design, and interpretation of the functional significance of their presence or absence can be controversial.…”

mentioning

confidence: 99%

Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome

Blain-Moraes

Boshra

Kan

et al. 2016

Front. Hum. Neurosci.

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Up to 40% of individuals with unresponsive wakefulness syndrome (UWS) actually might be conscious. Recent attempts to detect covert consciousness in behaviorally unresponsive patients via neurophysiological patterns are limited by the need to compare data from brain-injured patients to healthy controls. In this report, we pilot an alternative within-subject approach by using propofol to perturb the brain state of a patient diagnosed with UWS. An auditory stimulation series was presented to the patient before, during, and after exposure to propofol while high-density electroencephalograph (EEG) was recorded. Baseline analysis revealed residual markers in the continuous EEG and event-related potentials (ERPs) that have been associated with conscious processing. However, these markers were significantly distorted by the patient’s pathology, challenging the interpretation of their functional significance. Upon exposure to propofol, changes in EEG characteristics were similar to what is seen in healthy individuals and ERPs associated with conscious processing disappeared. At the 1-month follow up, the patient had regained consciousness. We offer three alternative explanations for these results: (1) the patient was covertly consciousness, and was anesthetized by propofol administration; (2) the patient was unconscious, and the observed EEG changes were a propofol-specific phenomenon; and (3) the patient was unconscious, but his brain networks responded normally in a way that heralded the possibility of recovery. These alternatives will be tested in a larger study, and raise the intriguing possibility of using a general anesthetic as a probe of brain states in behaviorally unresponsive patients.

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“…In this clinical population, electrophysiological responses to auditory stimuli have been extensively investigated through oddball paradigms allowing to explore the so called mismatch negativity component (MMN) which is typically identified in less than half of the tested patients (Fischer et al, 2004(Fischer et al, , 2000Kotchoubey et al, 2005;Naccache et al, 2005). In more complex auditory paradigms (see for complete paradigm description and related discussion (Bekinschtein et al, 2009a;Faugeras et al, 2012Faugeras et al, , 2011King et al, 2013;Naccache et al, 2015;Tzovara et al, 2015b)), multivariate decoding algorithm showed significant classification performance in response to auditory global deviants in 14% of vegetative state patients (King et al, 2013) and in 25% of recordings in comatose patients (Tzovara et al, 2015a). Evidence of semantic discrimination was also found in acute coma, with 14/38 recordings (37%) showing distinct EEG activity in response to human vs.…”

Section: Discussionmentioning

confidence: 99%

Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds

et al. 2016

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Trace conditioning refers to a learning process occurring after repeated presentation of a neutral conditioned stimulus (CS+) and a salient unconditioned stimulus (UCS) separated by a temporal gap. Recent studies have reported that trace conditioning can occur in humans in reduced levels of consciousness by showing a transfer of the unconditioned autonomic response to the CS+ in healthy sleeping individuals and in vegetative state patients. However, no previous studies have investigated the neural underpinning of trace conditioning in the absence of consciousness in humans. In the present study, we recorded the EEG activity of 29 post-anoxic comatose patients while presenting a trace conditioning paradigm using neutral tones as CS+ and alerting sounds as UCS. Most patients received therapeutic hypothermia and all were deeply unconscious according to standardized clinical scales. After repeated presentation of the CS+ and UCS couple, learning was assessed by measuring the EEG activity during the period where the UCS is omitted after CS+ presentation. Specifically we assessed the 'reactivation' of the neural response to UCS omission by applying a decoding algorithm derived from the statistical model of the EEG activity in response to the UCS presentation. The same procedure was used in a group of 12 awake healthy controls. We found a reactivation of the UCS response in absence of stimulation in eight patients (five under therapeutic hypothermia) and four healthy controls. Additionally, the reactivation effect was temporally specific within trials since it manifested primarily at the specific latency of UCS presentation and significantly less before or after this period. Our results show for the first time that trace conditioning may manifest as a reactivation of the EEG activity related to the UCS and even in the absence of consciousness.

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Reply: Neural detection of complex sound sequences or of statistical regularities in the absence of consciousness?

Cited by 9 publications

References 12 publications

Prediction of awakening from hypothermic postanoxic coma based on auditory discrimination

Prediction of awakening from hypothermic postanoxic coma based on auditory discrimination

Normal Brain Response to Propofol in Advance of Recovery from Unresponsive Wakefulness Syndrome

Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds

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