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A key question for the scientific study of consciousness is whether it is possible to identify specific features in brain activity that are uniquely linked to conscious experience. This question has important implications for the development of markers to detect covert consciousness in unresponsive patients. In this regard, many studies have focused on investigating the neural response to complex auditory regularities. One noteworthy example is the local global paradigm, which allows for the investigation of auditory regularity encoding at the 'global' level, based on the repetition of groups of sounds. The inference of global regularities is thought to depend on conscious access to such complex auditory stimuli as mostly shown in chronic stages of disorders of consciousness patients. However, whether global regularity encoding can identify covert consciousness along the consciousness spectrum including earlier stages of these disorders remains controversial. Here, we aim to fill this gap by investigating whether the inference of global auditory regularities can occur in acute coma, in the absence of consciousness, and how this may be modulated by the severity of the patients' clinical condition and consciousness level measured using the Full Outline of UnResponsiveness (FOUR) score. We will acquire 63-channel continuous electroencephalography to measure the neural response to global auditory regularity in comatose patients ( N = 30) during the first day after cardiac arrest, when patients are unconscious, sedated and under normothermia, and during the second day (with reduced or absent sedation and body temperature control). We hypothesize that global regularity encoding will persist in the absence of consciousness independent of patient outcome, observed as above chance decoding of the neural response to global regularities using multivariate decoding analyses. We further hypothesize that decoding performance will positively correlate with the FOUR score, which indexes consciousness level, and typically improves between the first and second day after coma onset following cardiac arrest in patients with favourable outcome. In an exploratory analysis, we will also evaluate whether global regularity encoding may be influenced by the patients' clinical management, specifically sedation, also shown to affect global deviance detection. Our results will shed light on the neurophysiological correlates of complex auditory regularity processing in unconscious patients and on the link to residual levels of consciousness during the underexplored state of coma upon the first days after cardiac arrest., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The human brain can encode auditory regularities with fixed sound-to-sound intervals and with sound onsets locked to cardiac inputs. Here, we investigated auditory and cardio-audio regularity encoding during sleep, when bodily and environmental stimulus processing may be altered. Using electroencephalography and electrocardiography in healthy volunteers (N = 26) during wakefulness and sleep, we measured the response to unexpected sound omissions within three regularity conditions: synchronous, where sound and heartbeat are temporally coupled, isochronous, with fixed sound-to-sound intervals, and a control condition without regularity. Cardio-audio regularity encoding manifested as a heartbeat deceleration upon omissions across vigilance states. The synchronous and isochronous sequences induced a modulation of the omission-evoked neural response in wakefulness and N2 sleep, the former accompanied by background oscillatory activity reorganization. The violation of cardio-audio and auditory regularity elicits cardiac and neural responses across vigilance states, laying the ground for similar investigations in altered consciousness states such as coma and anaesthesia., (© 2024. The Author(s).)

Assessing axonal morphology in vivo opens new avenues for the combined study of brain structure and function. A novel approach has recently been introduced to estimate the morphology of axonal fibers from the combination of magnetic resonance imaging (MRI) data and electroencephalography (EEG) measures of the interhemispheric transfer time (IHTT). In the original study, the IHTT measures were computed from EEG data averaged across a group, leading to bias of the axonal morphology estimates. Here, we seek to estimate axonal morphology from individual measures of IHTT, obtained from EEG data acquired in a visual evoked potential experiment. Subject-specific IHTTs are computed in a data-driven framework with minimal a priori constraints, based on the maximal peak of neural responses to visual stimuli within periods of statistically significant evoked activity in the inverse solution space. The subject-specific IHTT estimates ranged from 8 to 29 ms except for one participant and the between-session variability was comparable to between-subject variability. The mean radius of the axonal radius distribution, computed from the IHTT estimates and the MRI data, ranged from 0 to 1.09 μm across subjects. The change in axonal g-ratio with axonal radius ranged from 0.62 to 0.81 μm -α . The single-subject measurement of the IHTT yields estimates of axonal morphology that are consistent with histological values. However, improvement of the repeatability of the IHTT estimates is required to improve the specificity of the single-subject axonal morphology estimates., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Early prognostication of long-term outcome of comatose patients after cardiac arrest remains challenging. Electroencephalography-based power spectra after cardiac arrest have been shown to help with the identification of patients with favourable outcome during the first day of coma. Here, we aim at comparing the power spectra prognostic value during the first and second day after coma onset following cardiac arrest and to investigate the impact of sedation on prognostication. In this cohort observational study, we included comatose patients ( N = 91) after cardiac arrest for whom resting-state electroencephalography was collected on the first and second day after cardiac arrest in four Swiss hospitals. We evaluated whether the average power spectra values at 4.6-15.2 Hz were predictive of patients' outcome based on the best cerebral performance category score at 3 months, with scores ranging from 1 to 5 and dichotomized as favourable (1-2) and unfavourable (3-5). We assessed the effect of sedation and its interaction with the electroencephalography-based power spectra on patient outcome prediction through a generalized linear mixed model. Power spectra values provided 100% positive predictive value (95% confidence intervals: 0.81-1.00) on the first day of coma, with correctly predicted 18 out of 45 favourable outcome patients. On the second day, power spectra values were not predictive of patients' outcome (positive predictive value: 0.46, 95% confidence intervals: 0.19-0.75). On the first day, we did not find evidence of any significant contribution of sedative infusion rates to the patient outcome prediction ( P > 0.05). Comatose patients' outcome prediction based on electroencephalographic power spectra is higher on the first compared with the second day after cardiac arrest. Sedation does not appear to impact patient outcome prediction., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Assessing the integrity of neural functions in coma after cardiac arrest remains an open challenge. Prognostication of coma outcome relies mainly on visual expert scoring of physiological signals, which is prone to subjectivity and leaves a considerable number of patients in a 'grey zone', with uncertain prognosis. Quantitative analysis of EEG responses to auditory stimuli can provide a window into neural functions in coma and information about patients' chances of awakening. However, responses to standardized auditory stimulation are far from being used in a clinical routine due to heterogeneous and cumbersome protocols. Here, we hypothesize that convolutional neural networks can assist in extracting interpretable patterns of EEG responses to auditory stimuli during the first day of coma that are predictive of patients' chances of awakening and survival at 3 months. We used convolutional neural networks (CNNs) to model single-trial EEG responses to auditory stimuli in the first day of coma, under standardized sedation and targeted temperature management, in a multicentre and multiprotocol patient cohort and predict outcome at 3 months. The use of CNNs resulted in a positive predictive power for predicting awakening of 0.83 ± 0.04 and 0.81 ± 0.06 and an area under the curve in predicting outcome of 0.69 ± 0.05 and 0.70 ± 0.05, for patients undergoing therapeutic hypothermia and normothermia, respectively. These results also persisted in a subset of patients that were in a clinical 'grey zone'. The network's confidence in predicting outcome was based on interpretable features: it strongly correlated to the neural synchrony and complexity of EEG responses and was modulated by independent clinical evaluations, such as the EEG reactivity, background burst-suppression or motor responses. Our results highlight the strong potential of interpretable deep learning algorithms in combination with auditory stimulation to improve prognostication of coma outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Visuo-motor integration shapes our daily experience and underpins the sense of feeling in control over our actions. The last decade has seen a surge in robotically and virtually mediated interactions, whereby bodily actions ultimately result in an artificial movement. But despite the growing number of applications, the neurophysiological correlates of visuo-motor processing during human-machine interactions under dynamic conditions remain scarce. Here we address this issue by employing a bimanual robotic interface able to track voluntary hands movement, rendered in real-time into the motion of two virtual hands. We experimentally manipulated the visual feedback in the virtual reality with spatial and temporal conflicts and investigated their impact on (1) visuo-motor integration and (2) the subjective experience of being the author of one's action (i.e., sense of agency). Using somatosensory evoked responses measured with electroencephalography, we investigated neural differences occurring when the integration between motor commands and visual feedback is disrupted. Our results show that the right posterior parietal cortex encodes for differences between congruent and spatially-incongruent interactions. The experimental manipulations also induced a decrease in the sense of agency over the robotically-mediated actions. These findings offer solid neurophysiological grounds that can be used in the future to monitor integration mechanisms during movements and ultimately enhance subjective experience during human-machine interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marchesotti, Bernasconi, Rognini, De Lucia, Bleuler and Blanke.)

Purpose: We present a novel approach that allows the estimation of morphological features of axonal fibers from data acquired in vivo in humans. This approach allows the assessment of white matter microscopic properties non-invasively with improved specificity., Theory: The proposed approach is based on a biophysical model of Magnetic Resonance Imaging (MRI) data and of axonal conduction velocity estimates obtained with Electroencephalography (EEG). In a white matter tract of interest, these data depend on (1) the distribution of axonal radius [ P ( r )] and (2) the g-ratio of the individual axons that compose this tract [ g ( r )]. P ( r ) is assumed to follow a Gamma distribution with mode and scale parameters, M and θ, and g ( r ) is described by a power law with parameters α and β., Methods: MRI and EEG data were recorded from 14 healthy volunteers. MRI data were collected with a 3T scanner. MRI-measured g-ratio maps were computed and sampled along the visual transcallosal tract. EEG data were recorded using a 128-lead system with a visual Poffenberg paradigm. The interhemispheric transfer time and axonal conduction velocity were computed from the EEG current density at the group level. Using the MRI and EEG measures and the proposed model, we estimated morphological properties of axons in the visual transcallosal tract., Results: The estimated interhemispheric transfer time was 11.72 ± 2.87 ms, leading to an average conduction velocity across subjects of 13.22 ± 1.18 m/s. Out of the 4 free parameters of the proposed model, we estimated θ - the width of the right tail of the axonal radius distribution - and β - the scaling factor of the axonal g-ratio, a measure of fiber myelination. Across subjects, the parameter θ was 0.40 ± 0.07 μm and the parameter β was 0.67 ± 0.02 μm -α ., Conclusion: The estimates of axonal radius and myelination are consistent with histological findings, illustrating the feasibility of this approach. The proposed method allows the measurement of the distribution of axonal radius and myelination within a white matter tract, opening new avenues for the combined study of brain structure and function, and for in vivo histological studies of the human brain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oliveira, Pelentritou, Di Domenicantonio, De Lucia and Lutti.)

Objective: Early prognostication in comatose patients after cardiac arrest (CA) is difficult but essential to inform relatives and optimize treatment. Here we investigate the predictive value of heart-rate variability captured by multiscale entropy (MSE) for long-term outcomes in comatose patients during the first 24 hours after CA., Methods: In this retrospective analysis of prospective multi-centric cohort, we analyzed MSE of the heart rate in 79 comatose patients after CA while undergoing targeted temperature management and sedation during the first day of coma. From the MSE, two complexity indices were derived by summing values over short and long time scales (CI s and CI l ). We splitted the data in training and test datasets for analysing the predictive value for patient outcomes (defined as best cerebral performance category within 3 months) of CI s and CI l ., Results: Across the whole dataset, CI l provided the best sensitivity, specificity, and accuracy (88%, 75%, and 82%, respectively). Positive and negative predictive power were 81% and 84%., Conclusions: Characterizing the complexity of the ECG in patients after CA provides an accurate prediction of both favorable and unfavorable outcomes., Significance: The analysis of heartrate variability by means of MSE provides accurate outcome prediction on the first day of coma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Mechanical vibration of muscle tendons in specific frequencies - termed functional proprioceptive stimulation (FPS) - has the ability to induce the illusion of a movement which is congruent with a lengthening of the vibrated tendon and muscle. The majority of previous reports of the brain correlates of this illusion are based on functional neuroimaging. Contrary to the electroencephalogram (EEG) however, such technologies are not suitable for bedside or ambulant use. While a handful of studies have shown EEG changes during FPS, it remains underinvestigated whether these changes were due to the perceived illusion or the perceived vibration. Here, we aimed at disentangling the neural correlates of the illusory movement from those produced by the vibration sensation by comparing the neural responses to two vibration types, one that did and one that did not elicit an illusion. We recruited 40 naïve participants, 20 for the EEG experiment and 20 for a supporting behavioral study, who received functional tendon co-vibration on the biceps and triceps tendon at their left elbow, pseudo-randomly switching between the illusion and non-illusion trials. Time-frequency decomposition uncovered a strong and lasting event-related desynchronization (ERD) in the mu and beta band in both conditions, suggesting a strong somatosensory response to the vibration. Additionally, the analysis of the evoked potentials revealed a significant difference between the two experimental conditions from 310 to 990ms post stimulus onset. Training classifiers on the frequency-based and voltage-based correlates of illusion perception yielded above chance accuracies for 17 and 13 out of the 20 subjects respectively. Our findings show that FPS-induced illusions produce EEG correlates that are distinct from a vibration-based control and which can be classified reliably in a large number of participants. These results encourage pursuing EEG-based detection of kinesthetic illusions as a tool for clinical use, e.g., to uncover aspects of cognitive perception in unresponsive patients., (Copyright © 2021. Published by Elsevier Inc.)

Electrophysiological group studies in brain-damaged patients can be run to capture the EEG correlates of specific cognitive impairments. Nonetheless, this procedure is not adequate to characterize the inter-individual variability present in major neuropsychological syndromes. We tested the possibility of getting a reliable individual EEG characterization of deficits of endogenous orienting of spatial attention in right-brain damaged (RBD) patients with left spatial neglect (N+). We used a single-trial topographical analysis (STTA; [39] of individual scalp EEG topographies recorded during leftward and rightward orienting of attention with central cues in RBD patients with and without (N-) neglect and in healthy controls (HC). We found that the STTA successfully decoded EEG signals related to leftward and rightward orienting in five out of the six N+, five out of the six N- patients and in all the six HC. In agreement with findings from conventional average-group studies, successful classifications of EEG signals in N+ were observed during the 400-800 ms period post-cue-onset, which reflects preserved voluntary engagement of attention resources (ADAN component). These results suggest the possibility of acquiring reliable individual EEG profiles of neglect patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: In patients with disorders of consciousness (DOC), properties of functional brain networks at rest are informative of the degree of consciousness impairment and of long-term outcome. Here we investigate whether connectivity differences between patients with favorable and unfavorable outcome are already present within 24 h of coma onset., Methods: We prospectively recorded 63-channel electroencephalography (EEG) at rest during the first day of coma after cardiac arrest. We analyzed 98 adults, of whom 57 survived beyond unresponsive wakefulness. Functional connectivity was estimated by computing the 'debiased weighted phase lag index' over epochs of five seconds duration. We evaluated the network's topological features, including clustering coefficient, path length, modularity and participation coefficient and computed their variance over time. Finally, we estimated the predictive value of these topological features for patients' outcomes by splitting the patient sample in training and test datasets., Results: Group-level analysis revealed lower clustering coefficient, higher modularity and path length variance in patients with favorable compared to those with unfavorable outcomes (p < 0.01). Within all features, the path length variance in the network provided the best positive predictive value (PPV) for favorable outcome and specificity for unfavorable outcome in the test dataset (PPV: 0.83, p < 0.01; specificity: 0.86, p < 0.01) with above-chance negative predictive value and accuracy. Of note, the exclusion of patients with epileptiform activity (20 in total) eliminates all false positive predictions (n = 6) for path length variance., Interpretation: Topological features of functional connectivity differ as a function of long-term outcome in patients on the first day of coma. These differences are not interpretable in terms of consciousness levels as all patients were in a deep unconscious state. The time variance of path length is informative of comatose patients' outcome, as patients with favorable outcome exhibit a richer repertoire of path length than those with unfavorable outcomes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Outcome prediction in comatose patients following cardiac arrest remains challenging. Here, we assess the predictive performance of electroencephalography-based power spectra within 24 h from coma onset., Methods: We acquired electroencephalography (EEG) from comatose patients (n = 138) on the first day of coma in four hospital sites in Switzerland. Outcome was categorised as favourable or unfavourable based on the best state within three months. Data were split in training and test sets. We evaluated the predictive performance of EEG power spectra for long term outcome and its added value to standard clinical tests., Results: Out of 138 patients, 80 had a favourable outcome. Power spectra comparison between favourable and unfavourable outcome in the training set yielded significant differences at 5.2-13.2 Hz and above 21 Hz. Outcome prediction based on power at 5.2-13.2 Hz was accurate in training and test sets. Overall, power spectra predicted patients' outcome with maximum specificity and positive predictive value: 1.00 (95% with CI: 0.94-1.00 and 0.89-1.00, respectively). The combination of power spectra and reactivity yielded better accuracy and sensitivity (0.81, 95% CI: 0.71-0.89) than prediction based on power spectra alone., Conclusions: On the first day of coma following cardiac arrest, low power spectra values around 10 Hz, typically linked to impaired cortico-thalamic structural connections, are highly specific of unfavourable outcome. Peaks in this frequency range can predict long-term outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Inhibitory control deficits represent a key aspect of the cognitive declines associated with aging. Practicing inhibitory control has thus been advanced as a potential approach to compensate for age-induced neurocognitive impairments. Yet, the functional brain changes associated with practicing inhibitory control tasks in older adults and whether they differ from those observed in young populations remains unresolved. We compared electrical neuroimaging analyses of ERPs recorded during a Go/NoGo practice session with a Group (Young; Older adults) by Session (Beginning; End of the practice) design to identify whether the practice of an inhibition task in older adults reinforces already implemented compensatory activity or reduce it by enhancing the functioning of the brain networks primarily involved in the tasks. We observed an equivalent small effect of practice on performance in the two age-groups. The topographic ERP analyses and source estimations revealed qualitatively different effects of the practice over the N2 and P3 ERP components, respectively driven by a decrease in supplementary motor area activity and an increase in left ventrolateral prefrontal activity in the older but not in the young adults with practice. Our results thus indicate that inhibition task practice in older adults increases age-related divergences in the underlying functional processes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To assess whether stimulus-induced modifications of electromyographic activity observed on scalp EEG have a prognostic value in comatose patients after cardiac arrest., Methods: 184 adult patients from a multi-centric prospective register who underwent an early EEG after cardiac arrest were included. Auditory and somatosensory stimulation was performed during EEG-recording. EEG reactivity (EEG-R) and EMG reactivity (EMG-R) were retrospectively assessed visually by board-certified electroencephalographers, and compared with clinical outcome (cerebral performance category, CPC) at three months. A favorable functional outcome was defined as CPC 1-2, an unfavorable outcome as CPC 3-5., Results: Both EEG-R and EMG-R were predictors for good outcome (EEG-R accuracy 72% (95%-CI 66-79), sensitivity 86% (78-93), specificity 60% (50-69); EMG-R accuracy 65% (58-72), sensitivity 61% (51-75), specificity 69% (60-78)). When reactivity was defined as EEG-R and/or EMG-R, the accuracy was 73% (67-70), the sensitivity 94% (90-99), and the specificity 53% (43-63)., Conclusion: Taking EMG into account when assessing reactivity of EEG seems to reduce false negative predictions for identifying patients with favorable outcome after cardiac arrest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Behavioral assessments of consciousness based on overt command following cannot differentiate patients with disorders of consciousness (DOC) from those who demonstrate a dissociation between intent/awareness and motor capacity: cognitive motor dissociation (CMD). We argue that delineation of peri-personal space (PPS) - the multisensory-motor space immediately surrounding the body - may differentiate these patients due to its central role in mediating human-environment interactions, and putatively in scaffolding a minimal form of selfhood. In Experiment 1, we determined a normative physiological index of PPS by recording electrophysiological (EEG) responses to tactile, auditory, or audio-tactile stimulation at different distances (5 vs. 75 cm) in healthy volunteers (N = 19). Contrasts between paired (AT) and summed (A + T) responses demonstrated multisensory supra-additivity when AT stimuli were presented near, i.e., within the PPS, and highlighted somatosensory-motor sensors as electrodes of interest. In Experiment 2, we recorded EEG in patients behaviorally diagnosed as DOC or putative CMD (N = 17, 30 sessions). The PPS-measure developed in Experiment 1 was analyzed in relation with both standard clinical diagnosis (i.e., Coma Recovery Scale; CRS-R) and a measure of neural complexity associated with consciousness. Results demonstrated a significant correlation between the PPS measure and neural complexity, but not with the CRS-R, highlighting the added value of the physiological recordings. Further, multisensory processing in PPS was preserved in putative CMD but not in DOC patients. Together, the findings suggest that indexing PPS allows differentiating between groups of patients whom both show overt motor impairments (DOC and CMD) but putatively distinct levels of awareness or motor intent., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Prominent research in patients with disorders of consciousness investigated the electrophysiological correlates of auditory deviance detection as a marker of consciousness recovery. Here, we extend previous studies by investigating whether somatosensory deviance detection provides an added value for outcome prediction in postanoxic comatose patients., Methods: Electroencephalography responses to frequent and rare stimuli were obtained from 66 patients on the first and second day after coma onset., Results: Multivariate decoding analysis revealed an above chance-level auditory discrimination in 25 patients on the first day and in 31 patients on the second day. Tactile discrimination was significant in 16 patients on the first day and in 23 patients on the second day. Single-day sensory discrimination was unrelated to patients' outcome in both modalities. However, improvement of auditory discrimination from first to the second day was predictive of good outcome with a positive predictive power (PPV) of 0.73 (CI = 0.52-0.88). Analyses considering the improvement of tactile, auditory and tactile, or either auditory or tactile discrimination showed no significant prediction of good outcome (PPVs = 0.58-0.68)., Interpretation: Our results show that in the acute phase of coma deviance detection is largely preserved for both auditory and tactile modalities. However, we found no evidence for an added value of somatosensory to auditory deviance detection function for coma-outcome prediction.

Studies with event-related potentials have highlighted deficits in the early phases of orienting to left visual targets in right-brain-damaged patients with left spatial neglect (N+). However, brain responses associated with preparatory orienting of attention, with target novelty and with the detection of a match/mismatch between expected and actual targets (contextual updating), have not been explored in N+. Here in a study in healthy humans and brain-damaged patients of both sexes we demonstrate that frontal activity that reflects supramodal mechanisms of attentional orienting (Anterior Directing Attention Negativity, ADAN) is entirely spared in N+. In contrast, posterior responses that mark the early phases of cued orienting (Early Directing Attention Negativity, EDAN) and the setting up of sensory facilitation over the visual cortex (Late Directing Attention Positivity, LDAP) are suppressed in N+. This uncoupling is associated with damage of parietal-frontal white matter. N+ also exhibit exaggerated novelty reaction to targets in the right side of space and reduced novelty reaction for those in the left side (P3a) together with impaired contextual updating (P3b) in the left space. Finally, we highlight a drop in the amplitude and latency of the P1 that over the left hemisphere signals the early blocking of sensory processing in the right space when targets occur in the left one: this identifies a new electrophysiological marker of the rightward attentional bias in N+. The heterogeneous effects and spatial biases produced by localized brain damage on the different phases of attentional processing indicate relevant functional independence among their underlying neural mechanisms and improve the understanding of the spatial neglect syndrome. SIGNIFICANCE STATEMENT Our investigation answers important questions: are the different components of preparatory orienting (EDAN, ADAN, LDAP) functionally independent in the healthy brain? Is preparatory orienting of attention spared in left spatial neglect? Does the sparing of preparatory orienting have an impact on deficits in reflexive orienting and in the assignment of behavioral relevance to the left space? We show that supramodal preparatory orienting in frontal areas is entirely spared in neglect patients though this does not counterbalance deficits in preparatory parietal-occipital activity, reflexive orienting, and contextual updating. This points at relevant functional dissociations among different components of attention and suggests that improving voluntary attention in N+ might be behaviorally ineffective unless associated with stimulations boosting the response of posterior parietal-occipital areas., (Copyright © 2018 the authors 0270-6474/18/383792-17$15.00/0.)

Objectives: To show that subjective estimate of patient's condition is related to objective cognitive and functional outcome in cardiac arrest survivors., Design: Longitudinal cohort study., Setting: ICU and Neuropsychology Service in two hospitals in Switzerland., Patients: Fifty survivors included from a prospective cohort of 138 patients admitted at the ICU for cardiopulmonary arrest., Interventions: Comprehensive cognitive and functional evaluation at 6 months follow-up., Measurements and Main Results: Subjectively, 70% of survivors reported satisfactory recovery and 29% reported no complaints. Objectively, 76% were classified as good neurologic outcome (Cerebral Performance Category 1), 26% as having no symptoms (modified Rankin Scale 0), and 38% as upper good recovery (Glasgow Outcome Scale Extended 1). Cognitive assessment detected substantial cognitive impairment in 26%, primarily concerning processing speed, language, long-term memory, and executive functions. Subjective complaints severity correlated significantly with objective cognitive impairment (rS = 0.64; p < 0.001). Finally, patients reporting unsatisfactory recovery displayed lower functional scores than those reporting satisfactory recovery (e.g., quality of life satisfaction: 64% vs 81%; Z = 2.18; p = 0.03) and more cognitive impairment (three vs one cognitive domains impaired; Z = -3.21; p < 0.001), concerning in particular learning and long-term verbal and visual memory., Conclusions: Long-term subjective and objective outcome appears good in the majority of cardiac arrest survivors. Specific functional and cognitive impairments were found in patients reporting unsatisfactory recovery. Subjective recovery was strongly correlated with objective assessment.

Successful prediction of future events depends on the brain's capacity to extract temporal regularities from sensory inputs. Neuroimaging studies mainly investigated regularity processing for exteroceptive sensory inputs (i.e. from outside the body). Here we investigated whether interoceptive signals (i.e. from inside the body) can mediate auditory regularity processing. Human participants passively listened to sound sequences presented in synchrony or asynchrony to their heartbeat while concomitant electroencephalography was recorded. We hypothesized that the cardio-audio synchronicity would induce a brain expectation of future sounds. Electrical neuroimaging analysis revealed a surprise response at 158-270 ms upon omission of the expected sounds in the synchronous condition only. Control analyses ruled out that this effect was trivially based on expectation from the auditory temporal structure or on differences in heartbeat physiological signals. Implicit neural monitoring of temporal regularities across interoceptive and exteroceptive signals drives prediction of future events in auditory sequences.

Background: Outcome prognostication in postanoxic comatose patients is more accurate in predicting poor than good recovery. Using electroencephalography recordings in patients treated with targeted temperature management at 33°C (TTM 33), we have previously shown that improvement in auditory discrimination over the first days of coma predicted awakening. Given the increased application of a 36°C temperature target (TTM 36), here we aimed at validating the predictive value of auditory discrimination in the TTM 36 setting., Methods: In this prospective multicenter study, we analyzed the EEG responses to auditory stimuli from 60 consecutive patients from the first and second coma day. A semiautomatic decoding analysis was applied to single patient data to quantify discrimination performance between frequently repeated and deviant sounds. The decoding change from the first to second day was used for predicting patient outcome., Results: We observed an increase in auditory discrimination in 25 out of 60 patients. Among them, 17 awoke from coma (68% positive predictive value; 95% confidence interval: 0.46-0.85). By excluding patients with electroencephalographic epileptiform features, 15 of 18 exhibited improvement in auditory discrimination (83% positive predictive value; 95% confidence interval: 0.59-0.96). Specificity of good outcome prediction increased after adding auditory discrimination to EEG reactivity., Conclusion: These results suggest that tracking of auditory discrimination over time is informative of good recovery independent of the temperature target. This quantitative test provides complementary information to existing clinical tools by identifying patients with high chances of recovery and encouraging the maintenance of life support., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To date, no clinical test is able to predict cognitive and functional outcome of cardiac arrest survivors. Improvement of auditory discrimination in acute coma indicates survival with high specificity. Whether the degree of this improvement is indicative of recovery remains unknown. Here we investigated if progression of auditory discrimination can predict cognitive and functional outcome., Methods: We prospectively recorded electroencephalography responses to auditory stimuli of post-anoxic comatose patients on the first and second day after admission. For each recording, auditory discrimination was quantified and its evolution over the two recordings was used to classify survivors as "predicted" when it increased vs. "other" if not. Cognitive functions were tested on awakening and functional outcome was assessed at 3 months using the Cerebral Performance Categories (CPC) scale., Results: Thirty-two patients were included, 14 "predicted survivors" and 18 "other survivors". "Predicted survivors" were more likely to recover basic cognitive functions shortly after awakening (ability to follow a standardized neuropsychological battery: 86% vs. 44%; p=0.03 (Fisher)) and to show a very good functional outcome at 3 months (CPC 1: 86% vs. 33%; p=0.004 (Fisher)). Moreover, progression of auditory discrimination during coma was strongly correlated with cognitive performance on awakening (phonemic verbal fluency: rs=0.48; p=0.009 (Spearman))., Conclusions: Progression of auditory discrimination during coma provides early indication of future recovery of cognitive functions. The degree of improvement is informative of the degree of functional impairment. If confirmed in a larger cohort, this test would be the first to predict detailed outcome at the single-patient level., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Interactions between stimuli's acoustic features and experience-based internal models of the environment enable listeners to compensate for the disruptions in auditory streams that are regularly encountered in noisy environments. However, whether auditory gaps are filled in predictively or restored a posteriori remains unclear. The current lack of positive statistical evidence that internal models can actually shape brain activity as would real sounds precludes accepting predictive accounts of filling-in phenomenon. We investigated the neurophysiological effects of internal models by testing whether single-trial electrophysiological responses to omitted sounds in a rule-based sequence of tones with varying pitch could be decoded from the responses to real sounds and by analyzing the ERPs to the omissions with data-driven electrical neuroimaging methods. The decoding of the brain responses to different expected, but omitted, tones in both passive and active listening conditions was above chance based on the responses to the real sound in active listening conditions. Topographic ERP analyses and electrical source estimations revealed that, in the absence of any stimulation, experience-based internal models elicit an electrophysiological activity different from noise and that the temporal dynamics of this activity depend on attention. We further found that the expected change in pitch direction of omitted tones modulated the activity of left posterior temporal areas 140-200 msec after the onset of omissions. Collectively, our results indicate that, even in the absence of any stimulation, internal models modulate brain activity as do real sounds, indicating that auditory filling in can be accounted for by predictive activity.

Background: Recent neuroimaging studies suggest that value-based decision-making may rely on mechanisms of evidence accumulation. However no studies have explicitly investigated the time when single decisions are taken based on such an accumulation process., New Method: Here, we outline a novel electroencephalography (EEG) decoding technique which is based on accumulating the probability of appearance of prototypical voltage topographies and can be used for predicting subjects' decisions. We use this approach for studying the time-course of single decisions, during a task where subjects were asked to compare reward vs. loss points for accepting or rejecting offers., Results: We show that based on this new method, we can accurately decode decisions for the majority of the subjects. The typical time-period for accurate decoding was modulated by task difficulty on a trial-by-trial basis. Typical latencies of when decisions are made were detected at ∼500 ms for 'easy' vs. ∼700 ms for 'hard' decisions, well before subjects' response (∼340 ms). Importantly, this decision time correlated with the drift rates of a diffusion model, evaluated independently at the behavioral level., Comparison With Existing Method(s): We compare the performance of our algorithm with logistic regression and support vector machine and show that we obtain significant results for a higher number of subjects than with these two approaches. We also carry out analyses at the average event-related potential level, for comparison with previous studies on decision-making., Conclusions: We present a novel approach for studying the timing of value-based decision-making, by accumulating patterns of topographic EEG activity at single-trial level., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Analyses of brain responses to external stimuli are typically based on the means computed across conditions. However in many cognitive and clinical applications, taking into account their variability across trials has turned out to be statistically more sensitive than comparing their means., New Method: In this study we present a novel implementation of a single-trial topographic analysis (STTA) for discriminating auditory evoked potentials at predefined time-windows. This analysis has been previously introduced for extracting spatio-temporal features at the level of the whole neural response. Adapting the STTA on specific time windows is an essential step for comparing its performance to other time-window based algorithms., Results: We analyzed responses to standard vs. deviant sounds and showed that the new implementation of the STTA gives above-chance decoding results in all subjects (in comparison to 7 out of 11 with the original method). In comatose patients, the improvement of the decoding performance was even more pronounced than in healthy controls and doubled the number of significant results., Comparison With Existing Method(s): We compared the results obtained with the new STTA to those based on a logistic regression in healthy controls and patients. We showed that the first of these two comparisons provided a better performance of the logistic regression; however only the new STTA provided significant results in comatose patients at group level., Conclusions: Our results provide quantitative evidence that a systematic investigation of the accuracy of established methods in normal and clinical population is an essential step for optimizing decoding performance., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The neural response to a violation of sequences of identical sounds is a typical example of the brain's sensitivity to auditory regularities. Previous literature interprets this effect as a pre-attentive and unconscious processing of sensory stimuli. By contrast, a violation to auditory global regularities, i.e. based on repeating groups of sounds, is typically detectable when subjects can consciously perceive them. Here, we challenge the notion that global detection implies consciousness by testing the neural response to global violations in a group of 24 patients with post-anoxic coma (three females, age range 45-87 years), treated with mild therapeutic hypothermia and sedation. By applying a decoding analysis to electroencephalographic responses to standard versus deviant sound sequences, we found above-chance decoding performance in 10 of 24 patients (Wilcoxon signed-rank test, P < 0.001), despite five of them being mildly hypothermic, sedated and unarousable. Furthermore, consistently with previous findings based on the mismatch negativity the progression of this decoding performance was informative of patients' chances of awakening (78% predictive of awakening). Our results show for the first time that detection of global regularities at neural level exists despite a deeply unconscious state., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: EEG and somatosensory evoked potential are highly predictive of poor outcome after cardiac arrest; their accuracy for good recovery is however low. We evaluated whether addition of an automated mismatch negativity-based auditory discrimination paradigm (ADP) to EEG and somatosensory evoked potential improves prediction of awakening., Methods: EEG and ADP were prospectively recorded in 30 adults during therapeutic hypothermia and in normothermia. We studied the progression of auditory discrimination on single-trial multivariate analyses from therapeutic hypothermia to normothermia, and its correlation to outcome at 3 months, assessed with cerebral performance categories., Results: At 3 months, 18 of 30 patients (60%) survived; 5 had severe neurologic impairment (cerebral performance categories = 3) and 13 had good recovery (cerebral performance categories = 1-2). All 10 subjects showing improvements of auditory discrimination from therapeutic hypothermia to normothermia regained consciousness: ADP was 100% predictive for awakening. The addition of ADP significantly improved mortality prediction (area under the curve, 0.77 for standard model including clinical examination, EEG, somatosensory evoked potential, versus 0.86 after adding ADP, P = 0.02)., Conclusions: This automated ADP significantly improves early coma prognostic accuracy after cardiac arrest and therapeutic hypothermia. The progression of auditory discrimination is strongly predictive of favorable recovery and appears complementary to existing prognosticators of poor outcome. Before routine implementation, validation on larger cohorts is warranted.

Humans can recognize categories of environmental sounds, including vocalizations produced by humans and animals and the sounds of man-made objects. Most neuroimaging investigations of environmental sound discrimination have studied subjects while consciously perceiving and often explicitly recognizing the stimuli. Consequently, it remains unclear to what extent auditory object processing occurs independently of task demands and consciousness. Studies in animal models have shown that environmental sound discrimination at a neural level persists even in anesthetized preparations, whereas data from anesthetized humans has thus far provided null results. Here, we studied comatose patients as a model of environmental sound discrimination capacities during unconsciousness. We included 19 comatose patients treated with therapeutic hypothermia (TH) during the first 2 days of coma, while recording nineteen-channel electroencephalography (EEG). At the level of each individual patient, we applied a decoding algorithm to quantify the differential EEG responses to human vs. animal vocalizations as well as to sounds of living vocalizations vs. man-made objects. Discrimination between vocalization types was accurate in 11 patients and discrimination between sounds from living and man-made sources in 10 patients. At the group level, the results were significant only for the comparison between vocalization types. These results lay the groundwork for disentangling truly preferential activations in response to auditory categories, and the contribution of awareness to auditory category discrimination.

The study aims to investigate zinc biosorption by strains of lactobacilli and bifidobacteria with a view to exploit them as organic matrixes for zinc dietary supplementation. Sixteen human strains of Lactobacillus and Bifidobacterium were assayed for zinc uptake. The minimum inhibitory concentration of zinc salts differed among the strains, but was never below 15 mmol L(-1). When cultured in MRS broth containing 10 mmol L(-1) ZnSO4, all the strains were capable of accumulating zinc in the range between 11 and 135 μmol g(-1). The highest amount of cell-bound zinc was obtained in L. acidophilus WC 0203. pH-controlled batch cultures of this strain revealed that zinc uptake started in the growth phase, but occurred mostly during the stationary phase. Pasteurized and viable cultures accumulated similar amount of zinc, suggesting that a nonmetabolically mediated mechanism is involved in zinc uptake. These results provide new perspectives on the specific use of probiotics, since L. acidophilus WC 0203 could function as an organic matrix for zinc incorporation. The bioavailability of Lactobacillus-bound zinc deserves to be investigated to provide a future basis for optimization of zinc supplementation or fortification.

Auditory evoked potentials are informative of intact cortical functions of comatose patients. The integrity of auditory functions evaluated using mismatch negativity paradigms has been associated with their chances of survival. However, because auditory discrimination is assessed at various delays after coma onset, it is still unclear whether this impairment depends on the time of the recording. We hypothesized that impairment in auditory discrimination capabilities is indicative of coma progression, rather than of the comatose state itself and that rudimentary auditory discrimination remains intact during acute stages of coma. We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and five healthy, age-matched controls. Using a mismatch negativity paradigm, we performed two electroencephalography recordings with a standard 19-channel clinical montage: the first within 24 h after coma onset and under mild therapeutic hypothermia, and the second after 1 day and under normothermic conditions. We analysed electroencephalography responses based on a multivariate decoding algorithm that automatically quantifies neural discrimination at the single patient level. Results showed high average decoding accuracy in discriminating sounds both for control subjects and comatose patients. Importantly, accurate decoding was largely independent of patients' chance of survival. However, the progression of auditory discrimination between the first and second recordings was informative of a patient's chance of survival. A deterioration of auditory discrimination was observed in all non-survivors (equivalent to 100% positive predictive value for survivors). We show, for the first time, evidence of intact auditory processing even in comatose patients who do not survive and that progression of sound discrimination over time is informative of a patient's chance of survival. Tracking auditory discrimination in comatose patients could provide new insight to the chance of awakening in a quantitative and automatic fashion during early stages of coma.

Decision-making in an uncertain environment is driven by two major needs: exploring the environment to gather information or exploiting acquired knowledge to maximize reward. The neural processes underlying exploratory decision-making have been mainly studied by means of functional magnetic resonance imaging, overlooking any information about the time when decisions are made. Here, we carried out an electroencephalography (EEG) experiment, in order to detect the time when the brain generators responsible for these decisions have been sufficiently activated to lead to the next decision. Our analyses, based on a classification scheme, extract time-unlocked voltage topographies during reward presentation and use them to predict the type of decisions made on the subsequent trial. Classification accuracy, measured as the area under the Receiver Operator's Characteristic curve was on average 0.65 across 7 subjects. Classification accuracy was above chance levels already after 516 ms on average, across subjects. We speculate that decisions were already made before this critical period, as confirmed by a positive correlation with reaction times across subjects. On an individual subject basis, distributed source estimations were performed on the extracted topographies to statistically evaluate the neural correlates of decision-making. For trials leading to exploration, there was significantly higher activity in dorsolateral prefrontal cortex and the right supramarginal gyrus; areas responsible for modulating behavior under risk and deduction. No area was more active during exploitation. We show for the first time the temporal evolution of differential patterns of brain activation in an exploratory decision-making task on a single-trial basis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Discriminating complex sounds relies on multiple stages of differential brain activity. The specific roles of these stages and their links to perception were the focus of the present study. We presented 250 ms duration sounds of living and man-made objects while recording 160-channel electroencephalography (EEG). Subjects categorized each sound as that of a living, man-made or unknown item. We tested whether/when the brain discriminates between sound categories even when not transpiring behaviorally. We applied a single-trial classifier that identified voltage topographies and latencies at which brain responses are most discriminative. For sounds that the subjects could not categorize, we could successfully decode the semantic category based on differences in voltage topographies during the 116-174 ms post-stimulus period. Sounds that were correctly categorized as that of a living or man-made item by the same subjects exhibited two periods of differences in voltage topographies at the single-trial level. Subjects exhibited differential activity before the sound ended (starting at 112 ms) and on a separate period at ~270 ms post-stimulus onset. Because each of these periods could be used to reliably decode semantic categories, we interpreted the first as being related to an implicit tuning for sound representations and the second as being linked to perceptual decision-making processes. Collectively, our results show that the brain discriminates environmental sounds during early stages and independently of behavioral proficiency and that explicit sound categorization requires a subsequent processing stage., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This tutorial review details some of the recent advances in signal analyses applied to event-related potential (ERP) data. These "electrical neuroimaging" analyses provide reference-independent measurements of response strength and response topography that circumvent statistical and interpretational caveats of canonical ERP analysis methods while also taking advantage of the greater information provided by high-density electrode montages. Electrical neuroimaging can be applied across scales ranging from group-averaged ERPs to single-subject and single-trial datasets. We illustrate these methods with a tutorial dataset and place particular emphasis on their suitability for studies of clinical and/or developmental populations.

Behavioral and brain responses to identical stimuli can vary with experimental and task parameters, including the context of stimulus presentation or attention. More surprisingly, computational models suggest that noise-related random fluctuations in brain responses to stimuli would alone be sufficient to engender perceptual differences between physically identical stimuli. In two experiments combining psychophysics and EEG in healthy humans, we investigated brain mechanisms whereby identical stimuli are (erroneously) perceived as different (higher vs lower in pitch or longer vs shorter in duration) in the absence of any change in the experimental context. Even though, as expected, participants' percepts to identical stimuli varied randomly, a classification algorithm based on a mixture of Gaussians model (GMM) showed that there was sufficient information in single-trial EEG to reliably predict participants' judgments of the stimulus dimension. By contrasting electrical neuroimaging analyses of auditory evoked potentials (AEPs) to the identical stimuli as a function of participants' percepts, we identified the precise timing and neural correlates (strength vs topographic modulations) as well as intracranial sources of these erroneous perceptions. In both experiments, AEP differences first occurred ~100 ms after stimulus onset and were the result of topographic modulations following from changes in the configuration of active brain networks. Source estimations localized the origin of variations in perceived pitch of identical stimuli within right temporal and left frontal areas and of variations in perceived duration within right temporoparietal areas. We discuss our results in terms of providing neurophysiologic evidence for the contribution of random fluctuations in brain activity to conscious perception.

Increasing evidence suggests that working memory and perceptual processes are dynamically interrelated due to modulating activity in overlapping brain networks. However, the direct influence of working memory on the spatio-temporal brain dynamics of behaviorally relevant intervening information remains unclear. To investigate this issue, subjects performed a visual proximity grid perception task under three different visual-spatial working memory (VSWM) load conditions. VSWM load was manipulated by asking subjects to memorize the spatial locations of 6 or 3 disks. The grid was always presented between the encoding and recognition of the disk pattern. As a baseline condition, grid stimuli were presented without a VSWM context. VSWM load altered both perceptual performance and neural networks active during intervening grid encoding. Participants performed faster and more accurately on a challenging perceptual task under high VSWM load as compared to the low load and the baseline condition. Visual evoked potential (VEP) analyses identified changes in the configuration of the underlying sources in one particular period occurring 160-190 ms post-stimulus onset. Source analyses further showed an occipito-parietal down-regulation concurrent to the increased involvement of temporal and frontal resources in the high VSWM context. Together, these data suggest that cognitive control mechanisms supporting working memory may selectively enhance concurrent visual processing related to an independent goal. More broadly, our findings are in line with theoretical models implicating the engagement of frontal regions in synchronizing and optimizing mnemonic and perceptual resources towards multiple goals., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

The human auditory system is comprised of specialized but interacting anatomic and functional pathways encoding object, spatial, and temporal information. We review how learning-induced plasticity manifests along these pathways and to what extent there are common mechanisms subserving such plasticity. A first series of experiments establishes a temporal hierarchy along which sounds of objects are discriminated along basic to fine-grained categorical boundaries and learned representations. A widespread network of temporal and (pre)frontal brain regions contributes to object discrimination via recursive processing. Learning-induced plasticity typically manifested as repetition suppression within a common set of brain regions. A second series considered how the temporal sequence of sound sources is represented. We show that lateralized responsiveness during the initial encoding phase of pairs of auditory spatial stimuli is critical for their accurate ordered perception. Finally, we consider how spatial representations are formed and modified through training-induced learning. A population-based model of spatial processing is supported wherein temporal and parietal structures interact in the encoding of relative and absolute spatial information over the initial ~300 ms post-stimulus onset. Collectively, these data provide insights into the functional organization of human audition and open directions for new developments in targeted diagnostic and neurorehabilitation strategies., (© 2010 Elsevier B.V. All rights reserved.)

This study investigated the spatial, spectral, temporal and functional proprieties of functional brain connections involved in the concurrent execution of unrelated visual perception and working memory tasks. Electroencephalography data was analysed using a novel data-driven approach assessing source coherence at the whole-brain level. Three connections in the beta-band (18-24 Hz) and one in the gamma-band (30-40 Hz) were modulated by dual-task performance. Beta-coherence increased within two dorsofrontal-occipital connections in dual-task conditions compared to the single-task condition, with the highest coherence seen during low working memory load trials. In contrast, beta-coherence in a prefrontal-occipital functional connection and gamma-coherence in an inferior frontal-occipitoparietal connection was not affected by the addition of the second task and only showed elevated coherence under high working memory load. Analysis of coherence as a function of time suggested that the dorsofrontal-occipital beta-connections were relevant to working memory maintenance, while the prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal gamma-connection were involved in top-down control of concurrent visual processing. The fact that increased coherence in the gamma-connection, from low to high working memory load, was negatively correlated with faster reaction time on the perception task supports this interpretation. Together, these results demonstrate that dual-task demands trigger non-linear changes in functional interactions between frontal-executive and occipitoparietal-perceptual cortices.

Background: The production of microbial lipids has attracted considerable interest during the past decade since they can be successfully used to produce biodiesel by catalyzed transesterification with short chain alcohols. Certain yeast species, including several psychrophilic isolates, are oleaginous and accumulate lipids from 20 to 70% of biomass under appropriate cultivation conditions. Among them, Rhodotorula glacialis is a psychrophilic basidiomycetous species capable to accumulate intracellular lipids., Results: Rhodotorula glacialis DBVPG 4785 is an oleaginous psychrophilic yeast isolated from a glacial environment. Despite its origin, the strain abundantly grew and accumulated lipids between -3 to 20°C. The temperature did not influence the yield coefficients of both biomass and lipids production, but had positive effect on the growth rate and thus on volumetric productivity of lipid. In glucose-based media, cellular multiplication occurred first, while the lipogenic phase followed whenever the culture was limited by a nutrient other than glucose. The extent of the carbon excess had positive effects on triacylglycerols production, that was maximum with 120 g L-1 glucose, in terms of lipid concentration (19 g L-1), lipid/biomass (68%) and lipid/glucose yields (16%). Both glucose concentration and growth temperature influenced the composition of fatty acids, whose unsaturation degree decreased when the temperature or glucose excess increased., Conclusions: This study is the first proposed biotechnological application for Rhodotorula glacialis species, whose oleaginous biomass accumulates high amounts of lipids within a wide range of temperatures through appropriate cultivation C:N ratio. Although R. glacialis DBVPG 4785 is a cold adapted yeast, lipid production occurs over a broad range of temperatures and it can be considered an interesting microorganism for the production of single cell oils.

The ability to discriminate conspecific vocalizations is observed across species and early during development. However, its neurophysiologic mechanism remains controversial, particularly regarding whether it involves specialized processes with dedicated neural machinery. We identified spatiotemporal brain mechanisms for conspecific vocalization discrimination in humans by applying electrical neuroimaging analyses to auditory evoked potentials (AEPs) in response to acoustically and psychophysically controlled nonverbal human and animal vocalizations as well as sounds of man-made objects. AEP strength modulations in the absence of topographic modulations are suggestive of statistically indistinguishable brain networks. First, responses were significantly stronger, but topographically indistinguishable to human versus animal vocalizations starting at 169-219 ms after stimulus onset and within regions of the right superior temporal sulcus and superior temporal gyrus. This effect correlated with another AEP strength modulation occurring at 291-357 ms that was localized within the left inferior prefrontal and precentral gyri. Temporally segregated and spatially distributed stages of vocalization discrimination are thus functionally coupled and demonstrate how conventional views of functional specialization must incorporate network dynamics. Second, vocalization discrimination is not subject to facilitated processing in time, but instead lags more general categorization by approximately 100 ms, indicative of hierarchical processing during object discrimination. Third, although differences between human and animal vocalizations persisted when analyses were performed at a single-object level or extended to include additional (man-made) sound categories, at no latency were responses to human vocalizations stronger than those to all other categories. Vocalization discrimination transpires at times synchronous with that of face discrimination but is not functionally specialized.

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what" pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieved.

Single-trial analysis of human electroencephalography (EEG) has been recently proposed for better understanding the contribution of individual subjects to a group-analysis effect as well as for investigating single-subject mechanisms. Independent Component Analysis (ICA) has been repeatedly applied to concatenated single-trial responses and at a single-subject level in order to extract those components that resemble activities of interest. More recently we have proposed a single-trial method based on topographic maps that determines which voltage configurations are reliably observed at the event-related potential (ERP) level taking advantage of repetitions across trials. Here, we investigated the correspondence between the maps obtained by ICA versus the topographies that we obtained by the single-trial clustering algorithm that best explained the variance of the ERP. To do this, we used exemplar data provided from the EEGLAB website that are based on a dataset from a visual target detection task. We show there to be robust correspondence both at the level of the activation time courses and at the level of voltage configurations of a subset of relevant maps. We additionally show the estimated inverse solution (based on low-resolution electromagnetic tomography) of two corresponding maps occurring at approximately 300 ms post-stimulus onset, as estimated by the two aforementioned approaches. The spatial distribution of the estimated sources significantly correlated and had in common a right parietal activation within Brodmann's Area (BA) 40. Despite their differences in terms of theoretical bases, the consistency between the results of these two approaches shows that their underlying assumptions are indeed compatible.

Action representations can interact with object recognition processes. For example, so-called mirror neurons respond both when performing an action and when seeing or hearing such actions. Investigations of auditory object processing have largely focused on categorical discrimination, which begins within the initial 100 ms post-stimulus onset and subsequently engages distinct cortical networks. Whether action representations themselves contribute to auditory object recognition and the precise kinds of actions recruiting the auditory-visual mirror neuron system remain poorly understood. We applied electrical neuroimaging analyses to auditory evoked potentials (AEPs) in response to sounds of man-made objects that were further subdivided between sounds conveying a socio-functional context and typically cuing a responsive action by the listener (e.g. a ringing telephone) and those that are not linked to such a context and do not typically elicit responsive actions (e.g. notes on a piano). This distinction was validated psychophysically by a separate cohort of listeners. Beginning approximately 300 ms, responses to such context-related sounds significantly differed from context-free sounds both in the strength and topography of the electric field. This latency is >200 ms subsequent to general categorical discrimination. Additionally, such topographic differences indicate that sounds of different action sub-types engage distinct configurations of intracranial generators. Statistical analysis of source estimations identified differential activity within premotor and inferior (pre)frontal regions (Brodmann's areas (BA) 6, BA8, and BA45/46/47) in response to sounds of actions typically cuing a responsive action. We discuss our results in terms of a spatio-temporal model of auditory object processing and the interplay between semantic and action representations.

Twenty-two strains of Bifidobacterium, representative of eight major species of human origin, were screened for their ability to transform the isoflavones daidzin and daidzein. Most of the strains released the aglycone from daidzin and 12 gave yields higher than 90%. The kinetics of growth, daidzin consumption, and daidzein production indicated that the hydrolytic activity occurred during the growth. The supernatant of the majority of the strains did not release the aglycone from daidzin, suggesting that cell-associated beta-glucosidases (beta-Glu) are mainly responsible for the metabolism of soybean glyco-conjugates. Cell-associated beta-Glu was mainly intracellular and significantly varied among the species and the strains. The lack of beta-Glu was correlated with the inability to hydrolyze daidzin. Although S-equol production by anaerobic intestinal bacteria has been established, information on S-equol-producing bifidobacteria is contradictory. In this study, 22 bifidobacteria failed to transform daidzein into reduced metabolites under all the experimental conditions, excluding any role in the reductive pathway of daidzein toward the production of S-equol. These results suggest that selected probiotic strains of Bifidobacterium can be used to speed up the release of daidzein, improving its bioavailability for absorption by colonic mucosa and/or biotransformation to S-equol by other intestinal microorganisms.

Electrical Impedance Tomography (EIT) is an imaging method which enables a volume conductivity map of a subject to be produced from multiple impedance measurements. It has the potential to become a portable non-invasive imaging technique of particular use in imaging brain function. Accurate numerical forward models may be used to improve image reconstruction but, until now, have employed an assumption of isotropic tissue conductivity. This may be expected to introduce inaccuracy, as body tissues, especially those such as white matter and the skull in head imaging, are highly anisotropic. The purpose of this study was, for the first time, to develop a method for incorporating anisotropy in a forward numerical model for EIT of the head and assess the resulting improvement in image quality in the case of linear reconstruction of one example of the human head. A realistic Finite Element Model (FEM) of an adult human head with segments for the scalp, skull, CSF, and brain was produced from a structural MRI. Anisotropy of the brain was estimated from a diffusion tensor-MRI of the same subject and anisotropy of the skull was approximated from the structural information. A method for incorporation of anisotropy in the forward model and its use in image reconstruction was produced. The improvement in reconstructed image quality was assessed in computer simulation by producing forward data, and then linear reconstruction using a sensitivity matrix approach. The mean boundary data difference between anisotropic and isotropic forward models for a reference conductivity was 50%. Use of the correct anisotropic FEM in image reconstruction, as opposed to an isotropic one, corrected an error of 24 mm in imaging a 10% conductivity decrease located in the hippocampus, improved localisation for conductivity changes deep in the brain and due to epilepsy by 4-17 mm, and, overall, led to a substantial improvement on image quality. This suggests that incorporation of anisotropy in numerical models used for image reconstruction is likely to improve EIT image quality.

Diagnosis of several neurological disorders is based on the detection of typical pathological patterns in the electroencephalogram (EEG). This is a time-consuming task requiring significant training and experience. Automatic detection of these EEG patterns would greatly assist in quantitative analysis and interpretation. We present a method, which allows automatic detection of epileptiform events and discrimination of them from eye blinks, and is based on features derived using a novel application of independent component analysis. The algorithm was trained and cross validated using seven EEGs with epileptiform activity. For epileptiform events with compensation for eyeblinks, the sensitivity was 65 +/- 22% at a specificity of 86 +/- 7% (mean +/- SD). With feature extraction by PCA or classification of raw data, specificity reduced to 76 and 74%, respectively, for the same sensitivity. On exactly the same data, the commercially available software Reveal had a maximum sensitivity of 30% and concurrent specificity of 77%. Our algorithm performed well at detecting epileptiform events in this preliminary test and offers a flexible tool that is intended to be generalized to the simultaneous classification of many waveforms in the EEG.

The aim of this work was to study the degree of neuronal synchronization occurring within the portion of the somatosensory cortex devoted to hand control during an external sensory stimulation. In this way, we focused on the properties of the sensory cortical representation, rather than the more investigated motor one. To this aim, we collected magnetoencephalograhic data from healthy subjects during separate stimulation of their thumbs and little fingers and analyzed these data by means of a time-dependent 'synchronization index'. The properties of this index within the beta [16-32 Hz] and gamma [36-44 Hz] frequency bands suggest that the hand representation in the human primary cortex follows a frequency coding, in addition to the somatotopic one, for discriminating different districts. Our results showed that the gamma synchronization is higher following stimulation of the thumb than of the little finger and we suggest that the strength of gamma band synchronization works as a code for functional prevalence. In particular, our comparative analysis of the dynamic synchronization index and the signal amplitude suggests that a prevalent district (thumb) recruits a smaller number of higher-synchronic gamma band tuned neurons than a non-prevalent district (little finger).