title: Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds.
abstract: 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.
authors.affiliation: Laboratoire de Recherche en Neuroimagerie (LREN), Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: elsa.juan@unil.ch.
authors.forename: Elsa
authors.initials: E
authors.lastname: Juan
authors.affiliation: Laboratoire de Recherche en Neuroimagerie (LREN), Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Nathalie Ata
authors.initials: NA
authors.lastname: Nguepnjo Nguissi
authors.affiliation: Neuroscience Centre Zurich and Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, 8032 Zurich, Switzerland; Wellcome Trust Centre for Neuroimaging, University College London, WC1N London, UK.
authors.forename: Athina
authors.initials: A
authors.lastname: Tzovara
authors.affiliation: Neurology Service, Valais Hospital, 1951 Sion, Switzerland.
authors.forename: Dragana
authors.initials: D
authors.lastname: Viceic
authors.affiliation: Department of Intensive Care Medicine, Valais Hospital, 1951 Sion, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Rusca
authors.affiliation: Department of Intensive Care Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Oddo
authors.affiliation: Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Andrea O
authors.initials: AO
authors.lastname: Rossetti
authors.affiliation: Laboratoire de Recherche en Neuroimagerie (LREN), Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Marzia
authors.initials: M
authors.lastname: De Lucia
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000328:Adult; D000368:Aged; D001364:Awareness; D001921:Brain / Q000503:physiopathology*; D003128:Coma / Q000175:diagnosis / Q000503:physiopathology*; D003213:Conditioning, Psychological; D003243:Consciousness; D004569:Electroencephalography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male
keywords: Auditory stimuli; Coma; Consciousness; EEG; Learning; Multivariate analysis; Trace conditioning