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Background: One in 3 patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of major depressive disorder. However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by functional magnetic resonance imaging has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor., Methods: Patients (n = 56) who had remitted from a depressive episode while taking antidepressants underwent electroencephalography (EEG) recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a 6-month follow-up period. Thirty five healthy control participants were also tested. Current source density of the EEG power in the alpha band (8-13 Hz) was extracted and alpha asymmetry was computed by comparing the power across 2 hemispheres at frontal electrodes (F5 and F6)., Results: Sad mood induction was robust across all groups. Reactivity of alpha asymmetry to sad mood did not distinguish healthy control participants from patients with remitted major depressive disorder on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in alpha asymmetry compared with patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy and a positive predictive value of 0.75)., Conclusions: A simple EEG-based measure of emotional reactivity may have potential to contribute to clinical prediction models of antidepressant discontinuation. Given the very small sample size, this finding must be interpreted with caution and requires replication in a larger study., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Mismatch negativity (MMN) is an event-related potential (ERP) component generated when an unexpected deviant stimulus occurs in a pattern of standard stimuli. Several studies showed that the MMN response to both auditory and visual stimuli is attenuated in schizophrenia. While previous studies investigated auditory and visual MMN in different cohorts, here we examined the potential clinical utility of MMN responses to auditory and visual stimuli within the same group of patients. Altogether 39 patients with schizophrenia and 39 healthy controls matched in age, gender, and education were enrolled. We recorded EEG using 64 channels in eight experimental blocks where we presented auditory and visual stimulus sequences. Mismatch responses were obtained by subtracting responses to standard from the physically identical deviant stimuli. We found a significant MMN response to the acoustic stimuli in the control group, whereas no significant mismatch response was observed in the patient group. The group difference was significant for the acoustic stimuli. The 12 vane windmill pattern evoked a significant MMN response in the early time window in the control group but not in the patient group. The 6 vane windmill pattern evoked MMN only in the patient group. However, we found no significant difference between the groups. Furthermore, we found no correlation between the clinical variables and the MMN amplitudes. Our results suggest that predictive processes underlying mismatch generation in patients with schizophrenia may be more affected in the acoustic compared to the visual domain. Acoustic MMN tends to be a more promising biomarker in schizophrenia., (© 2024. The Author(s).)

The human brain efficiently extracts the temporal statistics of sensory environments and automatically generates expectations about future events. An influential Hypothesis holds that these expectations can find their implementation in neural oscillations, notably in the delta band (.5-3 Hz). Rhythmic fluctuations of cortical excitement are thought to align and match up in phase to the temporal structure of the sensory environment. This alignment is thought to result in the more excitable phase range of neural oscillations to overlap with the predicted onset of sensory events which in turn results in more efficient processing of sensory input, especially so in audition. An unresolved issue concerns whether such phase-aligned rhythmic brain activity is driven exclusively by the exogenous temporal structure of the input, or whether it also reflects phase re-alignment due to endogenous expectations based on stimulus probability and task relevance. In a seminal study, Stefanics et al. (2010) presented stimuli in a rhythmic stream and observed that delta phase consistency across trials was modulated by endogenous target onset expectations: delta phase consistency was higher prior to more probable (strongly expected) compared to less probable (weakly expected) target onsets. The present study replicates Experiment II of the original study, most importantly the modulation of delta phase consistency by endogenous expectations, and underlines a direct relationship between phase locking and behaviour. Our additional analyses locate the sources of the delta phase-alignment to motor, pre-motor, parietal, and temporal areas, and provide evidence for an ongoing delta oscillation, in line with the interpretation of oscillatory phase alignment rather than a transient evoked response. Importantly, this work shows that the phase of delta oscillations can be modulated by top-down control, and hence qualifies as a potential mechanism for the neural implementation of (rhythmic) temporal predictions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network., Methods: We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA)., Results: We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers., Conclusions: We found altered effective and structural connectivity within the ACC-thalamus network in SZ. Our results indicate that ACC-thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

Current theories of object perception emphasize the automatic nature of perceptual inference. Repetition suppression (RS), the successive decrease of brain responses to repeated stimuli, is thought to reflect the optimization of perceptual inference through neural plasticity. While functional imaging studies revealed brain regions that show suppressed responses to the repeated presentation of an object, little is known about the intra-trial time course of repetition effects to everyday objects. Here, we used event-related potentials (ERPs) to task-irrelevant line-drawn objects, while participants engaged in a distractor task. We quantified changes in ERPs over repetitions using three general linear models that modeled RS by an exponential, linear, or categorical "change detection" function in each subject. Our aim was to select the model with highest evidence and determine the within-trial time-course and scalp distribution of repetition effects using that model. Model comparison revealed the superiority of the exponential model indicating that repetition effects are observable for trials beyond the first repetition. Model parameter estimates revealed a sequence of RS effects in three time windows (86-140, 322-360, and 400-446 ms) and with occipital, temporoparietal, and frontotemporal distribution, respectively. An interval of repetition enhancement (RE) was also observed (320-340 ms) over occipitotemporal sensors. Our results show that automatic processing of task-irrelevant objects involves multiple intervals of RS with distinct scalp topographies. These sequential intervals of RS and RE might reflect the short-term plasticity required for optimization of perceptual inference and the associated changes in prediction errors and predictions, respectively, over stimulus repetitions during automatic object processing., (© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Recently developed methods for functional MRI at the resolution of cortical layers (laminar fMRI) offer a novel window into neurophysiological mechanisms of cortical activity. Beyond physiology, laminar fMRI also offers an unprecedented opportunity to test influential theories of brain function. Specifically, hierarchical Bayesian theories of brain function, such as predictive coding, assign specific computational roles to different cortical layers. Combined with computational models, laminar fMRI offers a unique opportunity to test these proposals noninvasively in humans. This review provides a brief overview of predictive coding and related hierarchical Bayesian theories, summarises their predictions with regard to layered cortical computations, examines how these predictions could be tested by laminar fMRI, and considers methodological challenges. We conclude by discussing the potential of laminar fMRI for clinically useful computational assays of layer-specific information processing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Predictive coding (PC) theory posits that our brain employs a predictive model of the environment to infer the causes of its sensory inputs. A fundamental but untested prediction of this theory is that the same stimulus should elicit distinct precision weighted prediction errors (pwPEs) when different (feature-specific) predictions are violated, even in the absence of attention. Here, we tested this hypothesis using functional magnetic resonance imaging (fMRI) and a multi-feature roving visual mismatch paradigm where rare changes in either color (red, green), or emotional expression (happy, fearful) of faces elicited pwPE responses in human participants. Using a computational model of learning and inference, we simulated pwPE and prediction trajectories of a Bayes-optimal observer and used these to analyze changes in blood oxygen level dependent (BOLD) responses to changes in color and emotional expression of faces while participants engaged in a distractor task. Controlling for visual attention by eye-tracking, we found pwPE responses to unexpected color changes in the fusiform gyrus. Conversely, unexpected changes of facial emotions elicited pwPE responses in cortico-thalamo-cerebellar structures associated with emotion and theory of mind processing. Predictions pertaining to emotions activated fusiform, occipital and temporal areas. Our results are consistent with a general role of PC across perception, from low-level to complex and socially relevant object features, and suggest that monitoring of the social environment occurs continuously and automatically, even in the absence of attention., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fatigue is one of the most common symptoms in multiple sclerosis (MS), with a major impact on patients' quality of life. Currently, treatment proceeds by trial and error with limited success, probably due to the presence of multiple different underlying mechanisms. Recent neuroscientific advances offer the potential to develop tools for differentiating these mechanisms in individual patients and ultimately provide a principled basis for treatment selection. However, development of these tools for differential diagnosis will require guidance by pathophysiological and cognitive theories that propose mechanisms which can be assessed in individual patients. This article provides an overview of contemporary pathophysiological theories of fatigue in MS and discusses how the mechanisms they propose may become measurable with emerging technologies and thus lay a foundation for future personalised treatments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

It is not known to what extent the automatic encoding and change detection of peripherally presented facial emotion is altered in dysphoria. The negative bias in automatic face processing in particular has rarely been studied. We used magnetoencephalography (MEG) to record automatic brain responses to happy and sad faces in dysphoric (Beck's Depression Inventory ≥ 13) and control participants. Stimuli were presented in a passive oddball condition, which allowed potential negative bias in dysphoria at different stages of face processing (M100, M170, and M300) and alterations of change detection (visual mismatch negativity, vMMN) to be investigated. The magnetic counterpart of the vMMN was elicited at all stages of face processing, indexing automatic deviance detection in facial emotions. The M170 amplitude was modulated by emotion, response amplitudes being larger for sad faces than happy faces. Group differences were found for the M300, and they were indexed by two different interaction effects. At the left occipital region of interest, the dysphoric group had larger amplitudes for sad than happy deviant faces, reflecting negative bias in deviance detection, which was not found in the control group. On the other hand, the dysphoric group showed no vMMN to changes in facial emotions, while the vMMN was observed in the control group at the right occipital region of interest. Our results indicate that there is a negative bias in automatic visual deviance detection, but also a general change detection deficit in dysphoria.

Predictive coding (PC) posits that the brain uses a generative model to infer the environmental causes of its sensory data and uses precision-weighted prediction errors (pwPEs) to continuously update this model. While supported by much circumstantial evidence, experimental tests grounded in formal trial-by-trial predictions are rare. One partial exception is event-related potential (ERP) studies of the auditory mismatch negativity (MMN), where computational models have found signatures of pwPEs and related model-updating processes. Here, we tested this hypothesis in the visual domain, examining possible links between visual mismatch responses and pwPEs. We used a novel visual "roving standard" paradigm to elicit mismatch responses in humans (of both sexes) by unexpected changes in either color or emotional expression of faces. Using a hierarchical Bayesian model, we simulated pwPE trajectories of a Bayes-optimal observer and used these to conduct a comprehensive trial-by-trial analysis across the time × sensor space. We found significant modulation of brain activity by both color and emotion pwPEs. The scalp distribution and timing of these single-trial pwPE responses were in agreement with visual mismatch responses obtained by traditional averaging and subtraction (deviant-minus-standard) approaches. Finally, we compared the Bayesian model to a more classical change model of MMN. Model comparison revealed that trial-wise pwPEs explained the observed mismatch responses better than categorical change detection. Our results suggest that visual mismatch responses reflect trial-wise pwPEs, as postulated by PC. These findings go beyond classical ERP analyses of visual mismatch and illustrate the utility of computational analyses for studying automatic perceptual processes. SIGNIFICANCE STATEMENT Human perception is thought to rely on a predictive model of the environment that is updated via precision-weighted prediction errors (pwPEs) when events violate expectations. This "predictive coding" view is supported by studies of the auditory mismatch negativity brain potential. However, it is less well known whether visual perception of mismatch relies on similar processes. Here we combined computational modeling and electroencephalography to test whether visual mismatch responses reflected trial-by-trial pwPEs. Applying a Bayesian model to series of face stimuli that violated expectations about color or emotional expression, we found significant modulation of brain activity by both color and emotion pwPEs. A categorical change detection model performed less convincingly. Our findings support the predictive coding interpretation of visual mismatch responses., (Copyright © 2018 the authors 0270-6474/18/384020-11$15.00/0.)

Here we critically review studies that used electroencephalography (EEG) or event-related potential (ERP) indices as a biomarker of Alzheimer's disease. In the first part we overview studies that relied on visual inspection of EEG traces and spectral characteristics of EEG. Second, we survey analysis methods motivated by dynamical systems theory (DST) as well as more recent network connectivity approaches. In the third part we review studies of sleep.  Next, we compare the utility of early and late ERP components in dementia research. In the section on mismatch negativity (MMN) studies we summarize their results and limitations and outline the emerging field of computational neurology. In the following we overview the use of EEG in the differential diagnosis of the most common neurocognitive disorders. Finally, we provide a summary of the state of the field and conclude that several promising EEG/ERP indices of synaptic neurotransmission are worth considering as potential biomarkers. Furthermore, we highlight some practical issues and discuss future challenges as well.

The visual mismatch negativity (vMMN) response is an event-related potential (ERP) component, which is automatically elicited by events that violate predictions based on prior events. VMMN experiments use visual stimulus repetition to induce predictions, and vMMN is obtained by subtracting the response to rare unpredicted stimuli from those to frequent stimuli. One increasingly popular interpretation of the mismatch response postulates that vMMN, similar to its auditory counterpart (aMMN), represents a prediction error response generated by cortical mechanisms forming probabilistic representations of sensory signals. Here we discuss the physiological and theoretical basis of vMMN and review thirty-three studies from the emerging field of its clinical applications, presenting a meta-analysis of findings in schizophrenia, mood disorders, substance abuse, neurodegenerative disorders, developmental disorders, deafness, panic disorder and hypertension. Furthermore, we include reports on aging and maturation as they bear upon many clinically relevant conditions. Surveying the literature we found that vMMN is altered in several clinical populations which is in line with aMMN findings. An important potential advantage of vMMN however is that it allows the investigation of deficits in predictive processing in cognitive domains which rely primarily on visual information; a principal sensory modality and thus of vital importance in environmental information processing and response, and a modality which arguably may be more sensitive to some pathological changes. However, due to the relative infancy of research in vMMN compared to aMMN in clinical populations its potential for clinical application is not yet fully appreciated. The aim of this review and meta-analysis therefore is to present, in a detailed systematic manner, the findings from clinically-based vMMN studies, to discuss their potential impact and application, to raise awareness of this measure and to improve our understanding of disease upon fundamental aspects of visual information processing., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Millions of people use mobile phones (MP) while drinking coffee or other caffeine containing beverages. Little is known about the potential combined effects of MP irradiation and caffeine on cognitive functions. Here we investigated whether caffeine intake and concurrent exposure to Universal Mobile Telecommunications System (UMTS) MP-like irradiation may interactively influence neuro-cognitive function in an active visual oddball paradigm. In a full factorial experimental design, 25 participants performed a simple visual target detection task while reaction time (RT) and electroencephalogram (EEG) was recorded. Target trials were divided into Low and High probability sets based on target-to-target distance. We analyzed single trial RT and alpha-band power (amplitude) in the pre-target interval. We found that RT was shorter in High vs. Low local probability trials, and caffeine further shortened RT in High probability trials relative to the baseline condition suggesting that caffeine improves the efficiency of implicit short-term memory. Caffeine also decreased pre-target alpha amplitude resulting in higher arousal level. Furthermore, pre-target gamma power positively correlated with RT, which may have facilitated target detection. However, in the present pharmacologically validated study UMTS exposure either alone or in combination with caffeine did not alter RT or pre-stimulus oscillatory brain activity.

Introduction: Mismatch negativity (MMN) is an automatic brain response to unexpected events. It represents a prediction error (PE) response, reflecting the difference between the sensory input and predictions. While deficits in auditory MMN are well known in schizophrenia, only few studies investigated impairments in predictive visual processing in schizophrenia. These studies used complex stimuli such as motion direction and emotional facial expressions. Here we studied whether automatic predictive processing of elementary features such as orientation is also impaired in schizophrenia., Methods: Altogether 28 patients with schizophrenia and 27 healthy controls matched in age, gender, and education participated in the study. EEG was recorded using 128 channels in the two experimental blocks. Using an oddball paradigm, horizontal stripes of Gabor patches were presented as frequent standards and vertical stripes as rare deviants in one block. Stimulus probabilities were swapped in the other block. Mismatch responses were obtained by subtracting responses to standard from those to deviant stimuli., Results: We found significant mismatch responses in healthy controls but not in patients in the prefrontal and occipital-parietal regions in the 90-200ms interval. Furthermore patients showed significantly decreased deviant minus standard difference waveforms relative to controls in the same regions with moderate to large effect sizes., Conclusions: Our findings demonstrate that predictive processing of unattended low-level visual features such as orientation is impaired in schizophrenia. Our results complement reports of sensory deficits found in tasks requiring attentive processing and suggest that deficits are present in automatic visual sensory processes putatively mediated by glutamatergic functioning., (Copyright © 2015. Published by Elsevier B.V.)

An increasing number of studies investigate the visual mismatch negativity (vMMN) or use the vMMN as a tool to probe various aspects of human cognition. This paper reviews the theoretical underpinnings of vMMN in the light of methodological considerations and provides recommendations for measuring and interpreting the vMMN. The following key issues are discussed from the experimentalist's point of view in a predictive coding framework: (1) experimental protocols and procedures to control "refractoriness" effects; (2) methods to control attention; (3) vMMN and veridical perception.

Background: Caffeine affects information processing by acting predominantly on cortical activation, arousal and attention. Millions consume caffeine and simultaneously use their mobile phone (MP) during everyday activities. However, it is not known whether and how MP-emitted electromagnetic fields (EMFs) can modulate known psychoactive effects of caffeine. Here we investigated behavioral and neural correlates of caffeine and simultaneous MP exposure in a third generation (3G) Universal Mobile Telecommunication System (UMTS) signal modulation scheme., Methods: We recorded electroencephalography (EEG) and event related potentials (ERP) in an oddball paradigm to frequent standard (p=0.8) and rare target (p=0.2) stimuli in a placebo controlled, double blind, within-subject protocol in four experimental sessions: 1) no caffeine and no MP, 2) caffeine only, 3) MP only, and 4) caffeine and MP. The subjects' task was to discriminate between standard and target stimuli and respond to the latter by pressing a button while reaction time (RT) and EEG were recorded. To provide a complete analysis of any possible caffeine and/or MP treatment effects that may have occurred, we analyzed the P300 ERP wave using four different ERP measures: 1) peak latency, 2) peak amplitude, 3) 50% fractional area latency (FAL) and 4) area under the curve (AUC)., Results: Caffeine significantly shortened RT and decreased AUC of the P300 component compared to the control or the UMTS MP alone conditions. However, no effects were observed on RT or P300 in the UMTS MP exposure sessions, neither alone nor in combination with caffeine., Conclusion: Overall, the present results did not demonstrate any interactive or synergistic effects of caffeine and UMTS MP like EMF exposure on basic neural or cognitive measures. However, we found that caffeine consistently enhanced behavioral and ERP measures of visual target detection, showing that present results were obtained using a pharmacologically validated, consistent and replicable methodology., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Recognizing intentions of strangers from facial cues is crucial in everyday social interactions. Recent studies demonstrated enhanced event-related potential (ERP) responses to untrustworthy compared to trustworthy faces. The aim of the present study was to investigate the electrophysiological correlates of automatic processing of trustworthiness cues in a visual oddball paradigm in two consecutive experimental blocks. In one block, frequent trustworthy (p = 0.9) and rare untrustworthy face stimuli (p = 0.1) were briefly presented on a computer screen with each stimulus consisting of four peripherally positioned faces. In the other block stimuli were presented with reversed probabilities enabling the comparison of ERPs evoked by physically identical deviant and standard stimuli. To avoid attentional effects participants engaged in a central detection task. Analyses of deviant minus standard difference waveforms revealed that deviant untrustworthy but not trustworthy faces elicited the visual mismatch negativity (vMMN) component. The present results indicate that adaptation occurred to repeated unattended trustworthy (but not untrustworthy) faces, i.e., an automatic expectation was elicited towards trustworthiness signals, which was violated by deviant untrustworthy faces. As an evolutionary adaptive mechanism, the observed fast detection of trustworthiness-related social facial cues may serve as the basis of conscious recognition of reliable partners.

Growing evidence suggests that abnormalities in the synchronized oscillatory activity of neurons in schizophrenia may lead to impaired neural activation and temporal coding and thus lead to neurocognitive dysfunctions, such as deficits in facial affect recognition. To gain an insight into the neurobiological processes linked to facial affect recognition, we investigated both induced and evoked oscillatory activity by calculating the Event Related Spectral Perturbation (ERSP) and the Inter Trial Coherence (ITC) during facial affect recognition. Fearful and neutral faces as well as nonface patches were presented to 24 patients with schizophrenia and 24 matched healthy controls while EEG was recorded. The participants' task was to recognize facial expressions. Because previous findings with healthy controls showed that facial feature decoding was associated primarily with oscillatory activity in the theta band, we analyzed ERSP and ITC in this frequency band in the time interval of 140-200 ms, which corresponds to the N170 component. Event-related theta activity and phase-locking to facial expressions, but not to nonface patches, predicted emotion recognition performance in both controls and patients. Event-related changes in theta amplitude and phase-locking were found to be significantly weaker in patients compared with healthy controls, which is in line with previous investigations showing decreased neural synchronization in the low frequency bands in patients with schizophrenia. Neural synchrony is thought to underlie distributed information processing. Our results indicate a less effective functioning in the recognition process of facial features, which may contribute to a less effective social cognition in schizophrenia., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Plastic interactions between face and hand cortical tactile circuits occur after severe injuries that affect the hand such as in amputation or spinal cord injury. However, whether loss of facial movements alters the cortical circuits involved in processing tactile inputs from the hand remains unknown. In this prospective observational study we used electroencephalography (EEG) to measure cortical activity evoked by tactile stimulation of the hands before and after botulinum toxin-A-induced facial paralysis. We found a reduction in the tactile event-related potentials (ERPs) 6 weeks after the treatment. This suggests that the limited paralysis of facial muscles induced during cosmetic interventions designed to smooth lines and wrinkles on the face is sufficient to alter the cortical processing of tactile inputs from the hand.

Background and Objectives: Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals., Experimental Design: The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated., Principal Observations: Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250-360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity., Conclusions: Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition.

Boundary extension (BE) is a rapidly occurring memory error in which participants incorrectly remember having seen beyond the boundaries of a view. However, behavioral data has provided no insight into how quickly after the onset of a test picture the effect is detected. To determine the time course of BE from neural responses we conducted a BE experiment while recording EEG. We exploited a diagnostic response asymmetry to mismatched views (a closer and wider view of the same scene) in which the same pair of views is rated as more similar when the closer item is shown first than vice versa. On each trial, a closer or wider view was presented for 250 ms followed by a 250-ms mask and either the identical view or a mismatched view. Boundary ratings replicated the typical asymmetry. We found a similar asymmetry in ERP responses in the 265-285 ms interval where the second member of the close-then-wide pairs evoked less negative responses at left parieto-temporal sites compared to the wide-then-close condition. We also found diagnostic ERP effects in the 500-560 ms range, where ERPs to wide-then-close pairs were more positive at centro-parietal sites than in the other three conditions, which is thought to be related to participants' confidence in their perceptual decision. The ERP effect in the 265-285 ms range suggests the falsely remembered region beyond the view-boundaries of S1 is rapidly available and impacts assessment of the test picture within the first 265 ms of viewing, suggesting that extrapolated scene structure may be computed rapidly enough to play a role in the integration of successive views during visual scanning.

Background: Emotional expressions are important acts of communication, and impairment in facial emotion recognition has been shown to be related to impairments in social cognition in schizophrenia. We used an event-related potential (ERP) paradigm to identify and delineate the temporal characteristics in the electrophysiological cascade related to fearful facial affect processing in patients with schizophrenia as compared to healthy controls., Methods: Twenty-four subjects with schizophrenia and 24 individually matched healthy controls participated in an emotion recognition task. Ekman faces displaying neutral and fearful facial expressions were used as stimuli. ERPs were recorded using a 128-channel EEG system., Results: Based on the analysis of Global Field Power (GFP) in the 150-190 ms time window both groups differentiated between fearful and neutral faces. Schizophrenia patients showed an additional differential processing of fearful vs. neutral faces in the 330-450 ms time window, and this ERP effect correlated with psychopathology., Conclusions: Both patients and healthy controls differentiate fearful and neutral faces in early phases of emotion processing. Our results also indicate that schizophrenia patients show increased responsivity to fearful faces at a later processing stage. This could be related to the overrating of negative emotions, and the symptomatology associated with fear processing in patients with schizophrenia., (© 2013.)

Potential effects of a 30 min exposure to third generation (3G) Universal Mobile Telecommunications System (UMTS) mobile phone-like electromagnetic fields (EMFs) were investigated on human brain electrical activity in two experiments. In the first experiment, spontaneous electroencephalography (sEEG) was analyzed (n = 17); in the second experiment, auditory event-related potentials (ERPs) and automatic deviance detection processes reflected by mismatch negativity (MMN) were investigated in a passive oddball paradigm (n = 26). Both sEEG and ERP experiments followed a double-blind protocol where subjects were exposed to either genuine or sham irradiation in two separate sessions. In both experiments, electroencephalograms (EEG) were recorded at midline electrode sites before and after exposure while subjects were watching a silent documentary. Spectral power of sEEG data was analyzed in the delta, theta, alpha, and beta frequency bands. In the ERP experiment, subjects were presented with a random series of standard (90%) and frequency-deviant (10%) tones in a passive binaural oddball paradigm. The amplitude and latency of the P50, N100, P200, MMN, and P3a components were analyzed. We found no measurable effects of a 30 min 3G mobile phone irradiation on the EEG spectral power in any frequency band studied. Also, we found no significant effects of EMF irradiation on the amplitude and latency of any of the ERP components. In summary, the present results do not support the notion that a 30 min unilateral 3G EMF exposure interferes with human sEEG activity, auditory evoked potentials or automatic deviance detection indexed by MMN., (Copyright © 2012 Wiley Periodicals, Inc.)

Little is known about how the human brain keeps track of body parts in the visual field. Here we show that unattended images of right/left hands elicit a mismatch response when they violate a regularity established by repeated visual presentations of the other hand. In a visual oddball experiment we found mismatch responses to hands with unexpected laterality (e.g. left versus predicted right hand) in the periphery of the visual field. Unexpected left hands were processed predominantly in the contralateral superior parietal cortex, whereas unexpected right hands evoked differential activity in the contralateral superior parietal, ventral premotor, prefrontal and temporal areas, indicating a more elaborate automatic processing of the dominant hand. The amplitude of the differential activity to the right hand correlated with handedness test scores. Our results reveal the continuous monitoring of the left or right identity of hands, which is prerequisite to the ability to automatically transform observed actions into the observer's ego-centric spatial reference frame., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Facial emotions express our internal states and are fundamental in social interactions. Here we explore whether the repetition of unattended facial emotions builds up a predictive representation of frequently encountered emotions in the visual system. Participants (n=24) were presented peripherally with facial stimuli expressing emotions while they performed a visual detection task presented in the center of the visual field. Facial stimuli consisted of four faces of different identity, but expressed the same emotion (happy or fearful). Facial stimuli were presented in blocks of oddball sequence (standard emotion: p=0.9, deviant emotion: p=0.1). Event-related potentials (ERPs) to the same emotions were compared when the emotions were deviant and standard, respectively. We found visual mismatch negativity (vMMN) responses to unattended deviant emotions in the 170-360 ms post-stimulus range over bilateral occipito-temporal sites. Our results demonstrate that information about the emotional content of unattended faces presented at the periphery of the visual field is rapidly processed and stored in a predictive memory representation by the visual system. We also found evidence that differential processing of deviant fearful faces starts already at 70-120 ms after stimulus onset. This finding shows a 'negativity bias' under unattended conditions. Differential processing of fearful deviants were more pronounced in the right hemisphere in the 195-275 ms and 360-390 ms intervals, whereas processing of happy deviants evoked larger differential response in the left hemisphere in the 360-390 ms range, indicating differential hemispheric specialization for automatic processing of positive and negative affect., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The core difficulty in developmental dyslexia across languages is a "phonological deficit", a specific difficulty with the neural representation of the sound structure of words. Recent data across languages suggest that this phonological deficit arises in part from inefficient auditory processing of the rate of change of the amplitude envelope at syllable onset (inefficient sensory processing of rise time). Rise time is a complex percept that also involves changes in duration and perceived intensity. Understanding the neural mechanisms that give rise to the phonological deficit in dyslexia is important for optimising educational interventions. In a three-deviant passive 'oddball' paradigm and a corresponding blocked 'deviant-alone' control condition we recorded ERPs to tones varying in rise time, duration and intensity in children with dyslexia and typically developing children longitudinally. We report here results from test Phases 1 and 2, when participants were aged 8-10 years. We found an MMN to duration, but not to rise time nor intensity deviants, at both time points for both groups. For rise time, duration and intensity we found group effects in both the Oddball and Blocked conditions. There was a slower fronto-central P1 response in the dyslexic group compared to controls. The amplitude of the P1 fronto-centrally to tones with slower rise times and lower intensity was smaller compared to tones with sharper rise times and higher intensity in the Oddball condition, for children with dyslexia only. The latency of this ERP component for all three stimuli was shorter on the right compared to the left hemisphere, only for the dyslexic group in the Blocked condition. Furthermore, we found decreased N1c amplitude to tones with slower rise times compared to tones with sharper rise times for children with dyslexia, only in the Oddball condition. Several other effects of stimulus type, age and laterality were also observed. Our data suggest that neuronal responses underlying some aspects of auditory sensory processing may be impaired in dyslexia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Sequential regularities are abstract rules based on repeating sequences of environmental events, which are useful to make predictions about future events. Here, we tested whether the visual system is capable to detect sequential regularity in unattended stimulus sequences. The visual mismatch negativity (vMMN) component of the event-related potentials is sensitive to the violation of complex regularities (e.g., object-related characteristics, temporal patterns). We used the vMMN component as an index of violation of conditional (if, then) regularities. In the first experiment, to investigate emergence of vMMN and other change-related activity to the violation of conditional rules, red and green disk patterns were delivered in pairs. The majority of pairs comprised of disk patterns with identical colors, whereas in deviant pairs the colors were different. The probabilities of the two colors were equal. The second member of the deviant pairs elicited a vMMN with longer latency and more extended spatial distribution to deviants with lower probability (10 vs. 30%). In the second (control) experiment the emergence of vMMN to violation of a simple, feature-related rule was studied using oddball sequences of stimulus pairs where deviant colors were presented with 20% probabilities. Deviant colored patterns elicited a vMMN, and this component was larger for the second member of the pair, i.e., after a shorter inter-stimulus interval. This result corresponds to the SOA/(v)MMN relationship, expected on the basis of a memory-mismatch process. Our results show that the system underlying vMMN is sensitive to abstract, conditional rules. Representation of such rules implicates expectation of a subsequent event, therefore vMMN can be considered as a correlate of violated predictions about the characteristics of environmental events.

Any occasional changes in the acoustic environment are of potential importance for survival. In humans, the preattentive detection of such changes generates the mismatch negativity (MMN) component of event-related brain potentials. MMN is elicited to rare changes ('deviants') in a series of otherwise regularly repeating stimuli ('standards'). Deviant stimuli are detected on the basis of a neural comparison process between the input from the current stimulus and the sensory memory trace of the standard stimuli. It is, however, unclear to what extent animals show a similar comparison process in response to auditory changes. To resolve this issue, epidural potentials were recorded above the primary auditory cortex of urethane-anesthetized rats. In an oddball condition, tone frequency was used to differentiate deviants interspersed randomly among a standard tone. Mismatch responses were observed at 60-100 ms after stimulus onset for frequency increases of 5% and 12.5% but not for similarly descending deviants. The response diminished when the silent inter-stimulus interval was increased from 375 ms to 600 ms for +5% deviants and from 600 ms to 1000 ms for +12.5% deviants. In comparison to the oddball condition the response also diminished in a control condition in which no repetitive standards were presented (equiprobable condition). These findings suggest that the rat mismatch response is similar to the human MMN and indicate that anesthetized rats provide a valuable model for studies of central auditory processing.

The more we anticipate a response to a predictable stimulus, the faster we react. This empirical observation has been confirmed and quantified by many investigators suggesting that the processing of behaviorally relevant stimuli is facilitated by probability-based confidence of anticipation. However, the exact neural mechanisms underlying this phenomenon are largely unknown. Here we show that performance changes related to different levels of expectancy originate in dynamic modulation of delta oscillation phase. Our results obtained in rhythmic auditory target detection tasks indicated significant entrainment of the EEG delta rhythm to the onset of the target tones with increasing phase synchronization at higher levels of predictability. Reaction times correlated with the phase of the delta band oscillation at target onset. The fastest reactions occurred during the delta phase that most commonly coincided with the target event in the high expectancy conditions. These results suggest that low-frequency oscillations play a functional role in human anticipatory mechanisms, presumably by modulating synchronized rhythmic fluctuations in the excitability of large neuronal populations and by facilitating efficient task-related neuronal communication among brain areas responsible for sensory processing and response execution.

The aim of this study, which was performed in the framework of the European project EMFnEAR, was to investigate the potential effects of Universal Mobile Telecommunications System (UMTS, also known as 3G) exposure at a high specific absorption rate (SAR) on the human auditory system. Participants were healthy young adults with no hearing or ear disorders. Auditory function was assessed immediately before and after exposure to radiofrequency (RF) radiation, and only the exposed ear was tested. Tests for the assessment of auditory function were hearing threshold level (HTL), distortion product otoacoustic emissions (DPOAE), contralateral suppression of transiently evoked otoacoustic emission (CAS effect on TEOAE), and auditory evoked potentials (AEP). The exposure consisted of speech at a typical conversational level delivered via an earphone to one ear, plus genuine or sham RF-radiation exposure obtained by an exposure system based on a patch antenna and controlled by software. Results from 73 participants did not show any consistent pattern of effects on the auditory system after a 20-min UMTS exposure at 1947 MHz at a maximum SAR over 1 g of 1.75 W/kg at a position equivalent to the cochlea. Analysis entailed a double-blind comparison of genuine and sham exposure. It is concluded that short-term UMTS exposure at this relatively high SAR does not cause measurable immediate effects on the human auditory system.

Objective: We investigated whether the auditory system of newborn babies extracts the constancy of a pitch interval from exemplars varying in absolute pitch., Methods: Event-related brain potentials (ERP) were recorded from healthy newborn infants in an oddball paradigm consisting of frequent standard and infrequent deviant tone pairs. Tone pairs varied in absolute frequency. Standard and deviant pairs differed in the amount of pitch difference within the pairs, but not in the direction of pitch change., Results: Deviant tone pairs elicited a discriminative ERP response., Conclusions: This result suggests that the neonate auditory system represents pitch intervals similarly to adults., Significance: Adult-like processing of pitch intervals allows newborn infants to learn music, speech prosody, and to process various important auditory cues based on spectral acoustic features.

The ability to separate pitch from other spectral sound features, such as timbre, is an important prerequisite of veridical auditory perception underlying speech acquisition and music cognition. The current study investigated whether or not newborn infants generalize pitch across different timbres. Perceived resonator size is an aspect of timbre that informs the listener about the size of the sound source, a cue that may be important already at birth. Therefore, detection of infrequent pitch changes was tested by recording event-related brain potentials in healthy newborn infants to frequent standard and infrequent pitch-deviant sounds while the perceived resonator size of all sounds was randomly varied. The elicitation of an early negative and a later positive discriminative response by deviant sounds demonstrated that the neonate auditory system represents pitch separately from timbre, thus showing advanced pitch processing capabilities.

We investigated the potential effects of 20 min irradiation from a new generation Universal Mobile Telecommunication System (UMTS) 3G mobile phone on human event related potentials (ERPs) in an auditory oddball paradigm. In a double-blind task design, subjects were exposed to either genuine or sham irradiation in two separate sessions. Before and after irradiation subjects were presented with a random series of 50 ms tone burst (frequent standards: 1 kHz, P=0.8, rare deviants: 1.5 kHz, P=0.2) at a mean repetition rate of 1500 ms while electroencephalogram (EEG) was recorded. The subjects' task was to silently count the appearance of targets. The amplitude and latency of the N100, N200, P200 and P300 components for targets and standards were analyzed in 29 subjects. We found no significant effects of electromagnetic field (EMF) irradiation on the amplitude and latency of the above ERP components. In order to study possible effects of EMF on attentional processes, we applied a wavelet-based time-frequency method to analyze the early gamma component of brain responses to auditory stimuli. We found that the early evoked gamma activity was insensitive to UMTS RF exposition. Our results support the notion, that a single 20 min irradiation from new generation 3G mobile phones does not induce measurable changes in latency or amplitude of ERP components or in oscillatory gamma-band activity in an auditory oddball paradigm.

Background: There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system., Methods: Auditory Brainstem Response (ABR) was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18-26 years) with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF) emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure., Results: Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure., Conclusion: The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

Adults normally perceive auditory scenes in terms of sound patterns emitted by concurrently active sources. Thus pattern formation is an important process of auditory object perception. The aim of the present study was to determine whether neonates group sounds by repeating pitch patterns. Standard ("S"; p=80%) and deviant tones ("D", p=20%) differing only in pitch were delivered either in a randomized order (random condition) or in a repeating SSSSD pattern (grouped condition). Both event-related brain potentials and gamma-band activity differed between the S and D tones in the random condition but not in the grouped condition. These results suggest that in the grouped condition, the S and D tones were processed as part of the same higher order regularity by the neonate auditory system. Also, for the first time, we observed oscillatory gamma-band activity in neonates, which was sensitive to infrequent pitch changes.

The study of large-scale interactions from magnetoencephalographic data based on the magnitude of the complex coherence computed at channel level is a widely used method to track the coupling between neural signals. Traditionally, a measure based on the magnitude of the complex coherence estimated by Fourier analysis, has been used under the assumption that the neural signals are stationary. Here, we split the complex coherence in its real and imaginary parts and focus on the latter with the advantage that the imaginary part is insensitive to spurious connectivity resulting from volume conducted "self interaction". Furthermore, interacting sources alone contribute to a non-vanishing imaginary part of the complex coherence whereas the contribute of non-interacting sources is also mapped from the magnitude of the complex coherence. Since it has been extensively shown that non-stationary stochastic processes contribute to the generation of neural signals, it is fundamental to be able to define interaction measures that are able to follow the temporal variations in the coupling between neural signals. To this purpose time-frequency domain techniques to estimate the magnitude of the complex coherence have been developed in the past decades. Similarly, we extend the analysis of the imaginary part of complex coherence to the time-frequency domain, by using the short-time Fourier transform to analyze the complex coherence as a function of time. In this way, it is possible to get an indication about the dynamic of the underlying source interaction pattern by looking at channel level interactions without the bias introduced by artifactual self-interaction by volume conduction or by the contribute of non-interacting sources. Furthermore, the corresponding imaginary part of the cross-spectrogram can be used to estimate interactions on a source level by localizing pools of sources interacting at a given frequency and by characterizing their dynamics. The method has been applied to magnetoencephalographic data from a cross-modal visual auditory stimulation and provided evidence for the involvement of temporal and occipital areas in the integrated information processing for simultaneous audio-visual stimulation. Furthermore, the source interaction pattern shows a variation in time that reflects a dynamical synchronization of the involved brain sources in the frequency bands of interest.

EEG was recorded in 3 visual oddball experiments during presentation of natural photos of butterflies and plants in order to study the early gamma activity evoked by familiar and novel stimuli. In all three experiments a picture of one specific butterfly served as the target and the subjects' task was to silently count them. In Experiment 1 neutral stimuli were individual pictures of butterflies from other species, in Experiment 2 neutral stimuli were individual pictures of plants and in Experiment 3 both types of neutral stimuli were applied. Phase-locking factor was computed by complex sinusoid wavelet method. Consistent with other studies, significant phase-locked gamma-synchronization was found at 80-140 ms post stimulus interval in the 20-50 Hz range at parietal and occipital sites in response to the repeating target. Non-target stimuli did not evoke similar activity in the gamma-frequency range. The observed difference can be explained if we assume that the repeated experience of an object may lead to the rapid formation of a neural assembly representing the object causing the repetition priming effect. In our study the single target stimulus was introduced to the subjects before the experiment, whereas individual non-target stimuli were unfamiliar images. Thus, subjects could form a neural representation of the target only. We suggest, that the early phase-locked gamma-activity in the 20-50 Hz range might reflect the activation of the neural representation of the familiar target stimulus.