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Grand average event-related brain potential waveforms for the 2 semantic paradigms (WP: left column; SP: right column) in coma patients. The solid line stands for semantically incongruent words and the thin line for semantically congruent words. Top: session 1, N = 42. Bottom: session 2, N = 8. Note the similarity of the SP waveforms, particularly in session 2, with those in healthy controls presented in Figure 1. SP indicates Sentence Priming; WP, Word Priming.
Source publication
To evaluate cortical information processing (particularly, semantic processing) in acute nontraumatic coma by means of event-related brain potentials (ERPs).
The tests included measures of obligatory auditory processing (N100), automatic (Mismatch Negativity) and controlled (P300) detection of stimulus deviance, and semantic processing (ERP effects...
Context in source publication
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Citations
... One of the most commonly used approaches when investigating cognitive function and coma outcome are event-related potentials (ERPs), which are time-locked electrophysiological brain responses elicited typically by auditory, visual or tactile stimuli. Particularly, the mismatch negativity (MMN) has been considered a useful predictor of emergence from coma (10)(11)(12)(13), and a key early biomarker in the information processing hierarchy leading up to conscious perception (14). ...
... As expected, most of the blocks where the MMN was confirmed to be present, corresponded to the duration-deviant condition in two comatose patients (Patient 1 and 2). Multivariate analysis has demonstrated a better discrimination between standard and duration deviants than other types of deviant-stimuli in comatose patients (54), which is in line with the choice of using duration deviants in previous coma studies (11,24). Similar to controls, the Bayesian analysis was more sensitive in capturing more blocks with reliable MMN and P3a responses than the permutation t-test in the comatose patients in both testing days. ...
The mismatch negativity (MMN) is considered the electrophysiological change-detection response of the brain, and therefore a valuable clinical tool for monitoring functional changes associated with return to consciousness after severe brain injury. Using an auditory multi-deviant oddball paradigm, we tracked auditory MMN responses in seventeen healthy controls over a 12-h period, and in three comatose patients assessed over 24 h at two time points. We investigated whether the MMN responses show fluctuations in detectability over time in full conscious awareness, or whether such fluctuations are rather a feature of coma. Three methods of analysis were utilized to determine whether the MMN and subsequent event-related potential (ERP) components could be identified: traditional visual analysis, permutation t-test, and Bayesian analysis. The results showed that the MMN responses elicited to the duration deviant-stimuli are elicited and reliably detected over the course of several hours in healthy controls, at both group and single-subject levels. Preliminary findings in three comatose patients provide further evidence that the MMN is often present in coma, varying within a single patient from easily detectable to undetectable at different times. This highlights the fact that regular and repeated assessments are extremely important when using MMN as a neurophysiological predictor of coma emergence.
... In patients with disorders of consciousness, the integrity of neural responses to external stimuli has been shown to track depth and severity of coma ( Boly et al., 2011;Daltrozzo et al., 2009;Fischer et al., 2004;Pfeiffer et al., 2017;Tzovara, 2016;Tzovara et al., 2013 ). Auditory evoked potentials (AEPs) are particularly important in the acute coma phase, during the first days after coma onset, as they are informative of chances of regaining consciousness ( Comanducci et al., 2020;Tzovara, 2016;Tzovara et al., 2013 ), and of long-term cognitive outcome ( Juan et al., 2016 ). ...
An open challenge in consciousness research is understanding how neural functions are altered by pathological loss of consciousness. To maintain consciousness, the brain needs synchronized communication of information across brain regions, and sufficient complexity in neural activity. Coordination of brain activity, typically indexed through measures of neural synchrony, has been shown to decrease when consciousness is lost and to reflect the clinical state of patients with disorders of consciousness. Moreover, when consciousness is lost, neural activity loses complexity, while the levels of neural noise, indexed by the slope of the electroencephalography (EEG) spectral exponent decreases. Although these properties have been well investigated in resting state activity, it remains unknown whether the sensory processing network, which has been shown to be preserved in coma, suffers from a loss of synchronization or information content. Here, we focused on acute coma and hypothesized that neural synchrony in response to auditory stimuli would reflect coma severity, while complexity, or neural noise, would reflect the presence or loss of consciousness. Results showed that neural synchrony of EEG signals was stronger for survivors than non-survivors and predictive of patients’ outcome, but indistinguishable between survivors and healthy controls. Measures of neural complexity and neural ’noise’ were not informative of patients outcome and had high or low values for patients compared to controls. Our results suggest different roles for neural synchrony and complexity in acute coma. Synchrony represents a precondition for consciousness, while complexity needs an equilibrium between high or low values to support conscious cognition.
... EPs and ERPs are a practical neurophysiological tool for the assessment of sensory information processing and covert basic cognitive functions in comatose (Kane et al. 1993;Fischer et al. 1999Fischer et al. , 2004Daltrozzo et al. 2009) and DoC patients (Neumann and Kotchoubey 2004;Kotchoubey et al. 2005;Boly et al. 2011). Recorded at the bedside, they can be used to probe the integrity of different stages of information processing, ranging from basic sensory elaboration to conscious detection of specific complex sequences (see Figure 2 for a schematic overview of the EP/ERP components). ...
The analysis of spontaneous EEG activity and evoked potentials is a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). The past few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury, opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of both consolidated and investigational electrophysiological techniques for the prognostic and diagnostic assessment of DoC. We describe conventional EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats. The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in ICU and rehabilitation.
... Impairment in auditory discrimination has been repeatedly reported in patients with DOCs. MMN, as an electrophysiological index, reflects the auditory discrimination, which is considered to be a predictor of awakening (Kane et al., 1993;Fischer et al., 1999;Wijnen et al., 2007;Daltrozzo et al., 2009). At present, the MMN amplitudes increased across time when compared to baseline. ...
Objective
To evaluate the effects of long-term High-definition transcranial direct current stimulation (HD-tDCS) over precuneus on the level of consciousness (LOC) and the relationship between Mismatch negativity (MMN) and the LOC over the therapy period in patients with Disorders of consciousness (DOCs).
Methods
We employed a with-in group repeated measures design with an anode HD-tDCS protocol (2 mA, 20 min, the precuneus) on 11 (2 vegetative state and nine minimally conscious state) patients with DOCs. MMN and Coma Recovery Scale-Revised (CRS-R) scores were measured at four time points: before the treatment of HD-tDCS (T0), after a single session of HD-tDCS (T1), after the treatment of 7 days (T2) and 14 days (T3). A frequency-deviant oddball paradigm with two deviation magnitudes (standard stimulus: 1000 Hz, small deviant stimuli: 1050 Hz, large deviant stimuli: 1200 Hz) was adopted to elicit MMN.
Results
Significant improvements of CRS-R score were found after 7-day (T2) and 14-day (T3) treatment compared with baseline (T0). Regarding the MMN, significant improvements of MMN amplitudes were observed after a single session of stimulation (T1), 7-day (T2) and 14-day treatment (T3) compared with baseline (T0). Additionally, there were significant negative correlations between CRS-R scores and MMN amplitudes elicited by both large and small deviant stimuli.
Conclusion
Long-term HD-tDCS over precuneus might improve signs of consciousness in patients with DOCs as measured by CRS-R total scores, and MMN could be an assistant assessment in the course of tDCS treatment.
... This may reflect a disinterest in the kind of BCI paradigms that could be designed around a N400 effect, or, a (perceived) difficulty to make such paradigms work. To obtain more insight, we searched for the keywords "Brain Computer Interface" and "N400" and identified three research lines that do make use of an N400 effect: (1) the use of the N400 in response to familiar face stimuli for boosting performance of the matrix speller [10][11][12], (2) to detect the absence or presence of language processing in patients with impaired levels of consciousness (Disorders of Consciousness) [13][14][15], and (3) to probe for information about the active mental state of the user, e.g., a category or word on the user's mind, by presenting stimuli that elicit responses of relatedness with regard to this mental context [16][17][18]. ...
The N400 is an Event Related Potential that is evoked in response to conceptually meaningful stimuli. It is for instance more negative in response to incongruent than congruent words in a sentence, and more negative for unrelated than related words following a prime word. This sensitivity to semantic content of a stimulus in relation to the mental context of an individual makes it a signal of interest for Brain Computer Interfaces. Given this potential it is notable that the BCI literature exploiting the N400 is limited. We identify three existing application areas: (1) exploiting the semantic processing of faces to enhance matrix speller performance, (2) detecting language processing in patients with Disorders of Consciousness, and (3) using semantic stimuli to probe what is on a user's mind. Drawing on studies from these application areas, we illustrate that the N400 can successfully be exploited for BCI purposes, but that the signal-to-noise ratio is a limiting factor, with signal strength also varying strongly across subjects. Furthermore, we put findings in context of the general N400 literature, noting open questions and identifying opportunities for further research.
... The continuous wavelet transformation combined with Student's ttests (t-CWT) is yet another method for single-subject ERP analysis (Bostanov, 2004;Bostanov, 2015), variants of which have previously been shown to be relatively sensitive and noise-resistant (Bostanov and Kotchoubey, 2006;Daltrozzo et al., 2009;Gabriel et al., 2016;Real et al., 2014;Steppacher et al., 2013). The t-CWT method is designed to extract a set of features from ERP signals and preserve the maximum amount of useful information. ...
... Despite the promising results obtained with the t-CWT method, the optimal approach among those described above and in the literature has not yet been fully established. In addition, not all previous studies have specified the parameter values used in the analyses (Daltrozzo et al., 2009;Steppacher et al., 2013). Due to the lack of a standard approach for t-CWT analysis, we have chosen to include in the present study several approaches which are available in the published software package. ...
... The difference between N400 components for congruous and incongruous stimuli is called the N400 effect. N400 effect has been widely used in the clinical setting at singlesubject level to test whether semantic processing is present in patients with disorders of consciousness (Balconi and Arangio, 2015;Beukema et al., 2016;Daltrozzo et al., 2009;Erlbeck et al., 2017;Hinterberger et al., 2005;Kotchoubey et al., 2005;Kotchoubey, 2005;Schoenle and Witzke, 2004). Further, its occurrence is associated with good neurological outcome Steppacher et al., 2013). ...
There are several different approaches to analyze event-related potentials (ERPs) at single-subject level, and the aim of the current study is to provide information for choosing a method based on its ability to detect ERP effects and factors influencing the results. We used data from 79 healthy participants with EEG referenced to mastoid average and investigated the detection rate of auditory N400 effect in single-subject analysis using five methods: visual inspection of participant-wise averaged ERPs, analysis of variance (ANOVA) for amplitude averages in a time window, cluster-based non-parametric testing, a novel Bayesian approach and Studentized continuous wavelet transform (t-CWT). Visual inspection by three independent raters yielded N400 effect detection in 85% of the participants in at least one paradigm (active responding or passive listening), whereas ANOVA identified the effect in 68%, the cluster-method in 59%, the Bayesian method in 89%, and different versions of t-CWT in 22-59% of the participants. Thus, the Bayesian method was the most liberal and also showed the greatest concordance between the experimental paradigms (active/passive). ANOVA detected significant effect only in cases with converging evidence from other methods. The t-CWT and cluster-based method were the most conservative methods. As we show in the current study, different analysis methods provide results that do not completely overlap. The method of choice for determining the presence of an ERP component at single-subject level thus remains unresolved. Relying on a single statistical method may not be sufficient for drawing conclusions on single-subject ERPs.
... The continuous wavelet transformation combined with Student's ttests (t-CWT) is yet another method for single-subject ERP analysis (Bostanov, 2004;Bostanov, 2015), variants of which have previously been shown to be relatively sensitive and noise-resistant ( Bostanov and Kotchoubey, 2006;Daltrozzo et al., 2009;Gabriel et al., 2016;Real et al., 2014;Steppacher et al., 2013). The t-CWT method is designed to extract a set of features from ERP signals and preserve the maximum amount of useful information. ...
... Despite the promising results obtained with the t-CWT method, the optimal approach among those described above and in the literature has not yet been fully established. In addition, not all previous studies have specified the parameter values used in the analyses ( Daltrozzo et al., 2009;Steppacher et al., 2013). Due to the lack of a standard approach for t-CWT analysis, we have chosen to include in the present study several approaches which are available in the published software package. ...
... The difference between N400 components for congruous and incongruous stimuli is called the N400 effect. N400 effect has been widely used in the clinical setting at singlesubject level to test whether semantic processing is present in patients with disorders of consciousness ( Balconi and Arangio, 2015;Beukema et al., 2016;Daltrozzo et al., 2009;Erlbeck et al., 2017;Hinterberger et al., 2005;Kotchoubey et al., 2005;Kotchoubey, 2005;Schoenle and Witzke, 2004). Further, its occurrence is associated with good neurological outcome Steppacher et al., 2013). ...
... The lack of N100 is a negative prognostic factor [24], whereas the illicitness of N100 could reflect the integrity of the auditory cortex and it is considered as a positive but not sufficient [25] prognostic factor. A P300 response in unconscious patients is suggested to be a positive prognostic factor. ...
... Instead of focusing on group changes in particular, well-known ERP components, we assessed complex individual changes in the whole ERPs. This approach is standard in brain-computer interface (BCI) applications (Blankertz et al., 2004;Bostanov, 2004) and has also been used in neurological diagnostics (Bostanov and Kotchoubey, 2006;Daltrozzo et al., 2009;Steppacher et al., 2013;Kotchoubey, 2015). But is it justified in the measurement of mindfulness? ...
Mindfulness-based interventions have proved effective in reducing various clinical symptoms and in improving general mental health and well-being. The investigation of the mechanisms of therapeutic change needs methods for assessment of mindfulness. Existing self-report measures have, however, been strongly criticized on various grounds, including distortion of the original concept, response bias, and other. We propose a psychophysiological method for the assessment of the mindfulness learned through time-limited mindfulness-based therapy by people who undergo meditation training for the first time. We use the individual pre-post-therapy changes (dERPi) in the event-related brain potentials (ERPs) recorded in a passive meditation task as a measure of increased mindfulness. dERPi is computed through multivariate assessment of individual participant's ERPs. We tested the proposed method in a group of about 70 recurrently depressed participants, randomly assigned in 1.7:1 ratio to mindfulness-based cognitive therapy (MBCT) or cognitive therapy (CT). The therapy outcome was measured by the long-term change (dDS) relative to baseline in the depression symptoms (DS) assessed weekly, for 60 weeks, by an online self-report questionnaire. We found a strong, highly significant, negative correlation (r = −0.55) between dERPi (mean = 0.4) and dDS (mean = −0.7) in the MBCT group. Compared to this result, the relationship between dDS and the other (self-report) measures of mindfulness we used was substantially weaker and not significant. So was also the relationship between dERPi and dDS in the CT group. The interpretation of dERPi as a measure of increased mindfulness was further supported by positive correlations between dERPi and the other measures of mindfulness. In this study, we also replicated a previous result, namely, the increase (dLCNV) of the late contingent negative variation (LCNV) of the ERP in the MBCT group, but not in the control group (in this case, CT). We interpreted dLCNV as a measure of increased meditative concentration. The relationship between dLCNV and dDS was, however, very week, which suggests that concentration might be relatively unimportant for the therapeutic effect of mindfulness. The proposed psychophysiological method could become an important component of a “mindfulness test battery” together with self-report questionnaires and other newly developed instruments.
... This includes states of being awake or arousal which is a key factor for the occurrence of conscious experience. On the other hand being in a state of dreamless sleep or coma makes it impossible to have ongoing conscious experience (Searle, 1990) even though this state is accompanied by cortical information processing (Daltrozzo et al., 2009). ...
Consciousness still stands as one of the most interesting and the most elusive problems of neuroscience. Finding its correlates is the first step toward its satisfactory explanation. Several theories have proposed its correlates but none of them seem to be generally accepted even though most of them share some very similar elements. These elements are the activity of the thalamus, which is considered by some as the central region for consciousness, and gamma synchronization, which should be the general principal for the emergence of conscious experience. However, all of these proposed theories share one characteristic and that is that they do not take into consideration the recently discovered endogenous activity of the brain, which is generally associated with the default mode network. Although the activity of this large scale brain network is in correlation with various levels of consciousness it is still missing in discussions of consciousness. This review recognizes the importance of endogenous activity and points out the important discoveries of endogenous activity that could be an important step toward a satisfactory explanation of consciousness.
