Automatic EEG processing for the early diagnosis of traumatic brain injury

Traumatic Brain Injury (TBI) is recognized as an important cause of death and disabilities after an accident. The availability a tool for the early diagnosis of brain dysfunctions could greatly improve the quality of life of people affected by TBI and even prevent deaths. The contribution of the paper is a process including several methods for the automatic processing of electroencephalography (EEG) data, in order to provide a fast and reliable diagnosis of TBI. Integrated in a portable decision support system called EmerEEG, the TBI diagnosis is obtained using discriminant analysis based on quantitative EEG (qEEG) features extracted from data recordings after the automatic removal of artifacts. The proposed algorithm computes the TBI diagnosis on the basis of a model extracted from clinically-labelled EEG records. The system evaluations have confirmed the speed and reliability of the processing algorithms as well as the system's ability to deliver accurate diagnosis. The developed algorithms have achieved 79.1% accuracy in removing artifacts, and 87.85% accuracy in TBI diagnosis. Therefore, the developed system enables a short response time in emergency situations and provides a tool the emergency services could base their decision upon, thus preventing possibly miss-diagnosed injuries

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

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

Quantification of EEG reactivity in comatose patients

OBJECTIVE: EEG reactivity is an important predictor of outcome in comatose patients. However, visual analysis of reactivity is prone to subjectivity and may benefit from quantitative approaches. METHODS: In EEG segments recorded during reactivity testing in 59 comatose patients, 13 quantitative EEG parameters were used to compare the spectral characteristics of 1-minute segments before and after the onset of stimulation (spectral temporal symmetry). Reactivity was quantified with probability values estimated using combinations of these parameters. The accuracy of probability values as a reactivity classifier was evaluated against the consensus assessment of three expert clinical electroencephalographers using visual analysis. RESULTS: The binary classifier assessing spectral temporal symmetry in four frequency bands (delta, theta, alpha and beta) showed best accuracy (Median AUC: 0.95) and was accompanied by substantial agreement with the individual opinion of experts (Gwet’s AC1: 65–70%), at least as good as inter-expert agreement (AC1: 55%). Probability values also reflected the degree of reactivity, as measured by the inter-experts’ agreement regarding reactivity for each individual case. CONCLUSION: Automated quantitative EEG approaches based on probabilistic description of spectral temporal symmetry reliably quantify EEG reactivity. SIGNIFICANCE: Quantitative EEG may be useful for evaluating reactivity in comatose patients, offering increased objectivity

Anesthetic-induced unresponsiveness: Electroencephalographic correlates and subjective experiences

Anesthetic drugs can induce reversible alterations in responsiveness, connectedness and consciousness. The measures based on electroencephalogram (EEG) have marked potential for monitoring the anesthetized state because of their relatively easy use in the operating room. In this study, 79 healthy young men participated in an awake experiment, and 47 participants continued to an anesthesia experiment where they received either dexmedetomidine or propofol as target-controlled infusion with stepwise increments until the loss of responsiveness. The participants were roused during the constant drug infusion and interviewed. The drug dose was increased to 1.5-fold to achieve a deeper unresponsive state. After regaining responsiveness, the participants were interviewed. EEG was measured throughout the experiment and the N400 event-related potential component and functional and directed connectivity were studied. Prefrontal-frontal connectivity in the alpha frequency band discriminated the states that differed with respect to responsiveness or drug concentration. The net direction of connectivity was frontal-to-prefrontal during unresponsiveness and reversed back to prefrontal-to-frontal upon return of responsiveness. The understanding of the meaning of spoken language, as measured with the N400 effect, was lost along with responsiveness but, in the dexmedetomidine group, the N400 component was preserved suggesting partial preservation of the processing of words during anesthetic-induced unresponsiveness. However, the N400 effect could not be detected in all the awake participants and the choice of analysis method had marked impact on its detection rate at the individual-level. Subjective experiences were common during unresponsiveness induced by dexmedetomidine and propofol but the experiences most often suggested disconnectedness from the environment. In conclusion, the doses of dexmedetomidine or propofol minimally sufficient to induce unresponsiveness do not render the participants unconscious and dexmedetomidine does not completely abolish the processing of semantic stimuli. The local anterior EEG connectivity in the alpha frequency band may have potential in monitoring the depth of dexmedetomidine- and propofol-induced anesthesia.Anesteettien aiheuttama vastauskyvyttömyys: aivosähkökäyräpohjaiset korrelaatit ja subjektiiviset kokemukset Anestesialääkkeillä voidaan saada aikaan palautuvia muutoksia vastauskykyisyydessä, kytkeytyneisyydessä ja tajunnassa. Aivosähkökäyrään (EEG) pohjautuvat menetelmät tarjoavat lupaavia mahdollisuuksia mitata anestesian vaikutusta aivoissa, sillä niitä on suhteellisen helppo käyttää leikkaussalissa. Tässä tutkimuksessa 79 tervettä nuorta miestä osallistui valvekokeeseen ja 47 heistä jatkoi anestesiakokeeseen. Anestesiakokeessa koehenkilöille annettiin joko deksmedetomidiinia tai propofolia tavoiteohjattuna infuusiona nousevia annosportaita käyttäen, kunnes he menettivät vastauskykynsä. Koehenkilöt herätettiin tasaisen lääkeinfuusion aikana ja haastateltiin. Koko kokeen ajan mitattiin EEG:tä, josta tutkittiin N400-herätevastetta sekä toiminnallista ja suunnattua konnektiivisuutta. Prefrontaali-frontaalivälillä mitattu konnektiivisuus alfa-taajuuskaistassa erotteli toisistaan tilat, jotka erosivat vastauskykyisyyden tai lääkepitoisuuden suhteen. Konnektiivisuuden vallitseva suunta oli frontaalialueilta prefrontaalialueille vastauskyvyttömyyden aikana, mutta se kääntyi takaisin prefrontaalisesta frontaaliseen kulkevaksi koehenkilöiden vastauskyvyn palatessa. N400-efektillä mitattu puhutun kielen ymmärtäminen katosi vastauskyvyn menettämisen myötä. Deksmedetomidiiniryhmässä N400-komponentti säilyi, mikä viittaa siihen, että anesteettien aiheuttaman vastauskyvyttömyyden aikana sanojen prosessointi voi säilyä osittain. Yksilötasolla N400-efektiä ei kuitenkaan havaittu edes kaikilla hereillä olevilla henkilöillä, ja analyysimenetelmän valinnalla oli suuri vaikutus herätevasteen havaitsemiseen. Subjektiiviset kokemukset olivat yleisiä deksmedetomidiinin ja propofolin aiheuttaman vastauskyvyttömyyden aikana, mutta kokemukset olivat usein ympäristöstä irtikytkeytyneitä. Yhteenvetona voidaan todeta, että deksmedetomidiini- ja propofoliannokset, jotka juuri ja juuri riittävät aikaansaamaan vastauskyvyttömyyden, eivät aiheuta tajuttomuutta. Deksmedetomidiini ei myöskään täysin estä merkityssisällöllisten ärsykkeiden käsittelyä. Frontaalialueen sisällä EEG:llä mitattu konnektiivisuus alfataajuuskaistassa saattaa olla tulevaisuudessa hyödyllinen menetelmä deksmedetomidiini- ja propofolianestesian syvyyden mittaamiseksi

From locomotion to dance and back : exploring rhythmic sensorimotor synchronization

Le rythme est un aspect important du mouvement et de la perception de l’environnement. Lorsque l’on danse, la pulsation musicale induit une activité neurale oscillatoire qui permet au système nerveux d’anticiper les évènements musicaux à venir. Le système moteur peut alors s’y synchroniser. Cette thèse développe de nouvelles techniques d’investigation des rythmes neuraux non strictement périodiques, tels que ceux qui régulent le tempo naturellement variable de la marche ou la perception rythmes musicaux. Elle étudie des réponses neurales reflétant la discordance entre ce que le système nerveux anticipe et ce qu’il perçoit, et qui sont nécessaire pour adapter la synchronisation de mouvements à un environnement variable. Elle montre aussi comment l’activité neurale évoquée par un rythme musical complexe est renforcée par les mouvements qui y sont synchronisés. Enfin, elle s’intéresse à ces rythmes neuraux chez des patients ayant des troubles de la marche ou de la conscience.Rhythms are central in human behaviours spanning from locomotion to music performance. In dance, self-sustaining and dynamically adapting neural oscillations entrain to the regular auditory inputs that is the musical beat. This entrainment leads to anticipation of forthcoming sensory events, which in turn allows synchronization of movements to the perceived environment. This dissertation develops novel technical approaches to investigate neural rhythms that are not strictly periodic, such as naturally tempo-varying locomotion movements and rhythms of music. It studies neural responses reflecting the discordance between what the nervous system anticipates and the actual timing of events, and that are critical for synchronizing movements to a changing environment. It also shows how the neural activity elicited by a musical rhythm is shaped by how we move. Finally, it investigates such neural rhythms in patient with gait or consciousness disorders

Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients

Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment

Spectral parameters modulation and source localization of blink-related alpha and low-beta oscillations differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome

Recently, the cortical source of blink-related delta oscillations (delta BROs) in resting healthy subjects has been localized in the posterior cingulate cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode network. This has been interpreted as the electrophysiological signature of the automatic monitoring of the surrounding environment while subjects are immersed in self-reflecting mental activities. Although delta BROs were directly correlated to the degree of consciousness impairment in patients with disorders of consciousness, they failed to differentiate vegetative state/unresponsive wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the present study, we have extended the analysis of BROs to frequency bands other than delta in the attempt to find a biological marker that could support the differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5 patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19-channels EEG recordings during resting conditions. Three-second-lasting EEG epochs centred on each blink instance were submitted to time-frequency analyses in order to extract the normalized Blink-Related Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low-alpha, high-alpha and low-beta) in the time-window of 50-550 ms after the blink-peak and to estimate the corresponding cortical sources of electrical activity. VS/UWS nBRS/BRD levels of all three bands were lower than those related to both CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS. Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital junction and inferior occipito-temporal regions when compared to VS/UWS. This peculiar pattern of activation leads us to hypothesize that resting MCS patients have a bottom-up driven activation of the task positive network and thus are tendentially prone to respond to environmental stimuli, even though in an almost unintentional way