Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14âeuro"20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a âeuro~kinestheticâeuro? mechanism for UM and a âeuro~visual imageryâeuro? mechanism for BM tapping movement.

Increased eeg synchronization in schizophrenia patients by the glutathione precursor, n-acetyl-cysteine

Background: Glutathione (GSH) dysregulation at the gene, protein and functional levels observed in schizophrenia patients, and schizophrenia-like anomalies in GSH deficit experimental models, suggest that genetic glutathione synthesis impairments represent one major risk factor for the disease (Do et al., 2009). In a randomized, double blind, placebo controlled, add-on clinical trial of 140 patients, the GSH precursor N-Acetyl-Cysteine (NAC, 2 g/day, 6 months) significantly improved the negative symptoms and reduced side-effects due to antipsychotics (Berk et al., 2008). In a subset of patients (n=7), NAC (2 g/day, 2 months, cross-over design) also improved auditory evoked potentials, the NMDAdependent mismatch negativity (Lavoie et al, 2008). Methods: To determine whether increased GSH levels would modulate the topography of functional brain connectivity, we applied a multivariate phase synchronization (MPS) estimator (Knyazeva et al, 2008) to dense-array EEGs recorded during rest with eyes closed at the protocol onset, the point of crossover, and at its end. Phase synchronization phenomena are appealing because they can be associated to synchronized phases while the amplitudes stay uncorrelated. MPS measures the degree of interactions among the recorded neuronal oscillators by quantifiying to what extent they behave like a macro-oscillator (i.e. the oscillators are phase synchronous). To assess the whole-head synchronization topography, we computed the MPS sensor-wise over the cluster of locations defined by the sensor itself and he surrounding ones belonging to its second-order neighborhood (Carmeli et al, 2005). Such a cluster spans about 12 cm on average. Abstracts 245 Results: The whole-head imaging revealed a specific synchronization landscape in NAC compared to placebo condition. In particular, NAC increased MPS over frontal and left temporal regions in a frequency-specific manner. Importantly, the topography and direction of MPS changes were similar and robust in all 7 patients. Moreover, these changes correlated with the changes in the Liddle's score of disorganization (Liddle, 1987) thus linking EEG synchronization to the improvement of clinical picture. Discussion: The data suggest an important pathway towards new therapeutic strategies that target GSH dysregulation in schizophrenia. They also show the utility of MPS mapping as a marker of treatment efficacy.

EEG-based functional networks in schizophrenia.

Schizophrenia is often considered as a dysconnection syndrome in which, abnormal interactions between large-scale functional brain networks result in cognitive and perceptual deficits. In this article we apply the graph theoretic measures to brain functional networks based on the resting EEGs of fourteen schizophrenic patients in comparison with those of fourteen matched control subjects. The networks were extracted from common-average-referenced EEG time-series through partial and unpartial cross-correlation methods. Unpartial correlation detects functional connectivity based on direct and/or indirect links, while partial correlation allows one to ignore indirect links. We quantified the network properties with the graph metrics, including mall-worldness, vulnerability, modularity, assortativity, and synchronizability. The schizophrenic patients showed method-specific and frequency-specific changes especially pronounced for modularity, assortativity, and synchronizability measures. However, the differences between schizophrenia patients and normal controls in terms of graph theory metrics were stronger for the unpartial correlation method.

Early EEG correlates of neuronal injury after brain anoxia.

OBJECTIVES: EEG and serum neuron-specific enolase (NSE) are used for outcome prognostication in patients with postanoxic coma; however, it is unclear if EEG abnormalities reflect transient neuronal dysfunction or neuronal death. To assess this question, EEG abnormalities were correlated with NSE. Moreover, NSE cutoff values and hypothermic EEG features related with poor outcome were explored.¦METHODS: In a prospective cohort of 61 adults treated with therapeutic hypothermia (TH) after cardiac arrest (CA), multichannel EEG recorded during TH was assessed for background reactivity and continuity, presence of epileptiform transients, and correlated with serum NSE collected at 24-48 hours after CA. Demographic, clinical, and functional outcome data (at 3 months) were collected and integrated in the analyses.¦RESULTS: In-hospital mortality was 41%, and 82% of survivors had good neurologic outcome at 3 months. Serum NSE and EEG findings were strongly correlated (Spearman rho = 0.45; p < 0.001). Median NSE peak values were higher in patients with unreactive EEG background (p < 0.001) and discontinuous patterns (p = 0.001). While all subjects with nonreactive EEG died, 5 survivors (3 with good outcome) had NSE levels >33 μg/L.¦CONCLUSION: The correlation between EEG during TH and serum NSE levels supports the hypothesis that early EEG alterations reflect permanent neuronal damage. Furthermore, this study confirms that absent EEG background reactivity and presence of epileptiform transients are robust predictors of poor outcome after CA, and that survival with good neurologic recovery is possible despite serum NSE levels> 33 μg/L. This underscores the importance of multimodal assessments in this setting.

Correlations between negative-induced cerebral dynamics and idiopathic intellectual disability: an EEG study

Intellectual disability has long been associated with deficits in socio-emotional processing. However, studies investigating brain dynamics of maladaptive socio-emotional skills associated with intellectual disability are scarce. Here, we compared differences in brain activity between low intelligence quotient (I.Q.<75, N=13) and normal controls (N=15) while evaluating their subjective emotions. Positive (P) and negative (N) valenced pictures were presented one at a time to participants of both groups, at a rate of ¾. The task required that each participant evaluate their subjective emotion and press a predefined push-button when done, alternatively P and N. Electroencephalographic (EEG) signals were continuously recorded, and the 1000ms time window following each picture was analyzed offline for power in frequency domain. Alpha low (8-10Hz) and upper (10-13Hz) frequency bands were then compared for both groups and for both P and N emotions in 12 distributed scalp electrodes. The qualitative evaluation of emotions was similar between both groups, with constant longer reaction times for the low IQ participants. The EEG signal comparison shows marked power decrease in upper alpha frequency range for N emotions in low intelligence group. Otherwise no significant difference was noticed between low and normal IQ. Main findings of the present study are (1) results do not support the hypothesis that impairment in developmental intelligence roots in maladaptive emotional processing; (2) the strong alpha power suppression during negative-induced emotions suggests the involvement of an extended neural network and more effortful inhibition processes than positive ones. We call for further studies with a larger sample.

Cross-frequency coupling in EEG revealed by adaptive oscillation tracking.

Introduction: Neuronal oscillations have been the focus of increasing interest in the neuroscientific community, in part because they have been considered as a possible integrating mechanism through which internal states can influence stimulus processing in a top-down way (Engel et al., 2001). Moreover, increasing evidence indicates that oscillations in different frequency bands interact with one other through coupling mechanisms (Jensen and Colgin, 2007). The existence and the importance of these cross-frequency couplings during various tasks have been verified by recent studies (Canolty et al., 2006; Lakatos et al., 2007). In this study, we measure the strength and directionality of two types of couplings - phase-amplitude couplings and phase-phase couplings - between various bands in EEG data recorded during an illusory contour experiment that were identified using a recently-proposed adaptive frequency tracking algorithm (Van Zaen et al., 2010). Methods: The data used in this study have been taken from a previously published study examining the spatiotemporal mechanisms of illusory contour processing (Murray et al., 2002). The EEG in the present study were from a subset of nine subjects. Each stimulus was composed of 'pac-man' inducers presented in two orientations: IC, when an illusory contour was present, and NC, when no contour could be detected. The signals recorded by the electrodes P2, P4, P6, PO4 and PO6 were averaged, and filtered into the following bands: 4-8Hz, 8-12Hz, 15-25Hz, 35-45Hz, 45-55Hz, 55-65Hz and 65-75Hz. An adaptive frequency tracking algorithm (Van Zaen et al., 2010) was then applied in each band in order to extract the main oscillation and estimate its frequency. This additional step ensures that clean phase information is obtained when taking the Hilbert transform. The frequency estimated by the tracker was averaged over sliding windows and then used to compare the two conditions. Two types of cross-frequency couplings were considered: phase-amplitude couplings and phase-phase couplings. Both types were measured with the phase locking value (PLV, Lachaux et al., 1999) over sliding windows. The phase-amplitude couplings were computed with the phase of the low frequency oscillation and the phase of the amplitude of the high frequency one. Different coupling coefficients were used when measuring phase-phase couplings in order to estimate different m:n synchronizations (4:3, 3:2, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 and 9:1) and to take into account the frequency differences across bands. Moreover, the direction of coupling was estimated with a directionality index (Bahraminasab et al., 2008). Finally, the two conditions IC and NC were compared with ANOVAs with 'subject' as a random effect and 'condition' as a fixed effect. Before computing the statistical tests, the PLV values were transformed into approximately normal variables (Penny et al., 2008). Results: When comparing the mean estimated frequency across conditions, a significant difference was found only in the 4-8Hz band, such that the frequency within this band was significantly higher for IC than NC stimuli starting at ~250ms post-stimulus onset (Fig. 1; solid line shows IC and dashed line NC). Significant differences in phase-amplitude couplings were obtained only when the 4-8 Hz band was taken as the low frequency band. Moreover, in all significant situations, the coupling strength is higher for the NC than IC condition. An example of significant difference between conditions is shown in Fig. 2 for the phase-amplitude coupling between the 4-8Hz and 55-65Hz bands (p-value in top panel and mean PLV values in the bottom panel). A decrease in coupling strength was observed shortly after stimulus onset for both conditions and was greater for the condition IC. This phenomenon was observed with all other frequency bands. The results obtained for the phase-phase couplings were more complex. As for the phase-amplitude couplings, all significant differences were obtained when the 4-8Hz band was considered as the low frequency band. The stimulus condition exhibiting the higher coupling strength depended on the ratio of the coupling coefficients. When this ratio was small, the IC condition exhibited the higher phase-phase coupling strength. When this ratio was large, the NC condition exhibited the higher coupling strength. Fig. 3 shows the phase-phase couplings between the 4-8Hz and 35-45Hz bands for the coupling coefficient 6:1, and the coupling strength was significantly higher for the IC than NC condition. By contrast, for the coupling coefficient 9:1 the NC condition gave the higher coupling strength (Fig. 4). Control analyses verified that it is not a consequence of the frequency difference between the two conditions in the 4-8Hz band. The directionality measures indicated a transfer of information from the low frequency components towards the high frequency ones. Conclusions: Adaptive tracking is a feasible method for EEG analyses, revealing information both about stimulus-related differences and coupling patterns across frequencies. Theta oscillations play a central role in illusory shape processing and more generally in visual processing. The presence vs. absence of illusory shapes was paralleled by faster theta oscillations. Phase-amplitude couplings were decreased more for IC than NC and might be due to a resetting mechanism. The complex patterns in phase-phase coupling between theta and beta/gamma suggest that the contribution of these oscillations to visual binding and stimulus processing are not as straightforward as conventionally held. Causality analyses further suggest that theta oscillations drive beta/gamma oscillations (see also Schroeder and Lakatos, 2009). The present findings highlight the need for applying more sophisticated signal analyses in order to establish a fuller understanding of the functional role of neural oscillations.

A characteristic EEG pattern in 4p-syndrome: case report and review of the literature.

Deletions on the short arm of chromosome 4 cause Wolf-Hirschhorn syndrome (WHS) and Pitt-Rogers-Danks syndrome (PRDS). WHS is associated with severe growth and mental retardation, microcephaly, a characteristic facies and congenital malformations. The PRDS phenotype is similar to WHS but generally less severe. Seizures occur in the majority of WHS and PRDS patients. Sgrò et al. [17] described a stereotypic electroclinical pattern in four unrelated WHS patients, consisting of intermittent bursts of 2-3 Hz high voltage slow waves with spike wave activity in the parietal areas during drowsiness and sleep associated with myoclonic jerks. We report a patient with PRDS and the typical EEG pattern and review 14 WHS patients with similar EEG findings reported in the literature. CONCLUSION: Awareness and recognition of the characteristic electroclinical findings in Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome might help in the early diagnosis of such patients.

Decoding auditory EEG responses in healthy and clinical populations: A comparative study.

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.

Clinical evolution after a non-reactive hypothermic EEG following cardiac arrest.

BACKGROUND: Lack of electroencephalography (EEG) background reactivity during therapeutic hypothermia (TH) has been associated with poor outcome in post-anoxic comatose patients. However, decision on intensive care withdrawal is based on normothermic (NT) evaluations. This study aims at exploring whether patients showing recovery of EEG reactivity in NT after a non-reactive EEG in TH differ from those remaining non-reactive. METHODS: Patients with non-reactive EEG during TH were identified from our prospective registry of consecutive comatose adults admitted after successful resuscitation from CA between April 2009 and June 2014. Variables including neurological examination, serum neuron-specific enolase (NSE), procalcitonin, and EEG features were compared regarding impact on functional outcome at 3 months. RESULTS: Seventy-two of 197 patients (37 %) had a non-reactive EEG background during TH with thirteen (18 %) evolving towards reactivity in NT. Compared to those remaining non-reactive (n = 59), they showed significantly better recovery of brainstem reflexes (p < 0.001), better motor responses (p < 0.001), transitory consciousness improvement (p = 0.008), and a tendency toward lower NSE (p = 0.067). One patient recovering EEG reactivity survived with good functional outcome at 3 months. CONCLUSIONS: Recovery of EEG reactivity from TH to NT seems to distinguish two patients' subgroups regarding early neurological assessment and transitory consciousness improvement, corroborating the role of EEG in providing information about cerebral functions. Understanding these dynamic changes encourages maintenance of intensive support in selected patients even after a non-reactive EEG background in TH, as a small subgroup may indeed recover with good functional outcome.

Quantifying the time for accurate EEG decoding of single value-based decisions.

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 ∼500ms for 'easy' vs. ∼700ms for 'hard' decisions, well before subjects' response (∼340ms). 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.

Predicting the outcome of post-anoxic comatose patients based on single-trial EEG analysis

Les maladies cardio-vasculaires représentent la première cause de mortalité en Suisse. Après un arrêt cardio-respiratoire, une minorité des patients survit sans ou avec peu de séquelles fonctionnelles. L'évaluation du pronostic se fait classiquement selon des critères établis par l'Académie Américaine de Neurologie (AAN) en 2006, soit précédant l'introduction de l'hypothermie thérapeutique. Depuis, ces critères semblent insuffisants, et de nouveaux examens para-cliniques sont nécessaires afin d'identifier les patients ayant un pronostic favorable. La détection d'irrégularités auditives, et plus particulièrement l'évolution de cette détection sur plusieurs jours, pourrait être un indicateur du pronostic de patients comateux suite à une anoxie cérébrale. En effet, lors d'une violation de la régularité établie par des séries de sons identiques, deux signaux sont détectables à l'électro- encéphalographie (EEG). Le premier, dénommé «Mismatch negativity» (MMN), peut être enregistré après une violation locale d'une régularité établie au niveau de chaque son. Il reflète un processus inconscient et ne demandant pas de ressources attentionnelles. Le deuxième, dénommé « complexe P300 » survient par contre après une violation globale d'une régularité établie au niveau de groupes de sons. La littérature actuelle indique que ce deuxième phénomène requerrait la présence de capacités attentionnelles. Dans notre étude, nous avons testé l'existence de cette détection d'irrégularités auditives globales chez des patients dans une phase précoce de coma post-anoxique, sous hypothermie thérapeutique. Nous avons enregistré la réponse électro-encéphalographique lors de violations de régularités auditives globales, à l'aide d'un protocole expérimental qui intégrait en plus un paradigme de MMN classique, afin de tester la détection d'irrégularités auditives locales également. Notre analyse finale inclut 24 patients comateux ayant subi un arrêt cardio-respiratoire, et bénéficié du protocole hypothermie du Centre Hospitalier Universitaire Vaudois (CHUV) à Lausanne. Après une analyse multivariée des réponses électro-encéphalographiques de chaque tracé individuellement (« single-trial »), nous avons trouvé que 8 patients sur 24 pouvaient discriminer une irrégularité globale, alors qu'étant définis comateux selon l'échelle de Glasgow (GCS). De plus, l'amélioration de la détection d' irrégularités auditives entre deux EEG consécutifs (en hypo- puis normothermie), était un facteur de bon pronostic. Notre test pourrait ainsi être un complément para-clinique dans l'évaluation du pronostic de patients en coma post- anoxique.