Investigating sensitivity to multi-domain prediction errors in chronic auditory phantom perception.

The perception of a continuous phantom in a sensory domain in the absence of an external stimulus is explained as a maladaptive compensation of aberrant predictive coding, a proposed unified theory of brain functioning. If this were true, these changes would occur not only in the domain of the phantom percept but in other sensory domains as well. We confirm this hypothesis by using tinnitus (continuous phantom sound) as a model and probe the predictive coding mechanism using the established local-global oddball paradigm in both the auditory and visual domains. We observe that tinnitus patients are sensitive to changes in predictive coding not only in the auditory but also in the visual domain. We report changes in well-established components of event-related EEG such as the mismatch negativity. Furthermore, deviations in stimulus characteristics were correlated with the subjective tinnitus distress. These results provide an empirical confirmation that aberrant perceptions are a symptom of a higher-order systemic disorder transcending the domain of the percept.

The P300 wave is decomposed into components reflecting response selection and automatic reactivation of stimulus-response links.

The parietal P300 wave of event-related potentials (ERPs) has been associated with various psychological operations in numerous laboratory tasks. This study aims to decompose the P3 wave of ERPs into subcomponents and link them with behavioral parameters, such as the strength of stimulus-response (S-R) links and GO/NOGO responses. EEGs (31 channels), referenced to linked ears, were recorded from 172 healthy adults (107 women) who participated in two cued GO/NOGO tasks, where the strength of S-R links was manipulated through instructions. P300 waves were observed in active conditions in response to cues, GO/NOGO stimuli, and in passive conditions when no manual response was required. Utilizing a combination of current source density transformation and blind source separation methods, we decomposed the P300 wave into two distinct components, purportedly originating from different parts of the parietal lobules. The amplitude of the parietal midline component (with current sources around Pz) closely mirrored the strength of the S-R link across proactive, reactive, and passive conditions. The amplitude of the lateral parietal component (with current sources around P3 and P4) resembled the push-pull activity of the output nuclei of the basal ganglia in action selection-inhibition operations. These findings provide insights into the neural mechanisms underlying action selection processes and the reactivation of S-R links.

Is Visual Prediction Impaired in Adolescents with Autism spectrum Disorder? Event-Related Potentials in a Cued Visual GO/NOGO Task.

Aim: Deviant visual processing has been observed in autism spectrum disorder (ASD), manifesting as decreased P1 and P2 components of visual event-related potentials (ERPs). Alterations have been attributed to a failure of Bayesian inference, characterized by hypo-activation of top-down predictive abilities. To test this hypothesis, we measured the visual negativity (vN) as an ERP index of visual preparation hypothesized to mirror predictive brain activity. Method: ERPs in a cued visual GO/NOGO task in 63 adolescents with ASD (IQ > 70, attention-deficit hyperactivity disorder excluded) were compared with ERPs in a sex- and age-matched group of 60 typically developing (TD) controls. Results: The behavioral variables (omissions, commissions, reaction time, and reaction time variability), as well as ERP components reflecting, among other processes, cognitive control (contingent negative variation, P3 GO, P3 NOGO, N2 NOGO) did not differ between the groups. There were group differences in visually based ERPs. Besides P1 and P2 differences, the vN component differentiated the 2 groups with the highest effect size (d = 0.74).Conclusion: This ERP study lends support to the hypothesis suggesting that a Bayesian hypo-prediction could underlie unique perceptual experiences in individuals with ASD. This could lead to a predisposition to perceive the world with reduced influence and modulation from contextual cues, prior experiences, and pre-existing expectations.

Application of Machine Learning to Diagnostics of Schizophrenia Patients Based on Event-Related Potentials.

Schizophrenia is a major psychiatric disorder that significantly reduces the quality of life. Early treatment is extremely important in order to mitigate the long-term negative effects. In this paper, a machine learning based diagnostics of schizophrenia was designed. Classification models were applied to the event-related potentials (ERPs) of patients and healthy subjects performing the visual cued Go/NoGo task. The sample consisted of 200 adult individuals ranging in age from 18 to 50 years. In order to apply the machine learning models, various features were extracted from the ERPs. The process of feature extraction was parametrized through a special procedure and the parameters of this procedure were selected through a grid-search technique along with the model hyperparameters. Feature extraction was followed by sequential feature selection transformation in order to prevent overfitting and reduce the computational complexity. Various models were trained on the resulting feature set. The best model was support vector machines with a sensitivity and specificity of 91% and 90.8%, respectively.

The enigma of infra-slow fluctuations in the human EEG.

Spontaneous Infra-Slow Fluctuations (ISFs) of the human EEG (EEG-ISFs) were discovered 60 years ago when appropriate amplifiers for their recordings were designed. To avoid skin-related artifacts the recording of EEG-ISFs required puncturing the skin under the electrode. In the beginning of the 21st century the interest in EEG-ISFs was renewed with the appearance of commercially available DC-coupled amplified and by observation of ISFs of the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging signal at a similar frequency. The independent components of irregular EEG-ISFs were shown to correlate with BOLD signals which in turn were driven by changes in arousal level measured by galvanic skin response (GSR), pupil size and HRV. There is no consensus regarding the temporal organization of EEG-ISFs: some studies emphasize the absence of peaks on EEG-ISFs spectra, some studies report prominent oscillations with frequency around 0.1 or 0.02 Hz, while some emphasize multiple discrete infraslow oscillations. No studies used parameters of EEG-ISFs as neuromarkers to discriminate psychiatric patients from healthy controls. Finally, a set of working hypotheses is suggested that must be tested in future research to solve the enigma of EEG-ISFs.

Low-Intensity Physical Exercise Improves Pain Catastrophizing and Other Psychological and Physical Aspects in Women with Fibromyalgia: A Randomized Controlled Trial.

Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain and other physical and psychological features. In this study, we aimed to analyze the effect of a low-intensity physical exercise (PE) program, combining endurance training and coordination, on psychological aspects (i.e., pain catastrophizing, anxiety, depression, stress), pain perception (i.e., pain acceptance, pressure pain threshold (PPT), and quality of life and physical conditioning (i.e., self-perceived functional capacity, endurance and functional capacity, power and velocity) in women with FM. For this purpose, a randomized controlled trial was carried out. Thirty-two women with FM were randomly allocated to a PE group (PEG, n = 16), performing an eight-week low-intensity PE program and a control group (CG, n = 16). Pain catastrophizing, anxiety, depression, stress, pain acceptance, PPT, quality of life, self-perceived functional capacity, endurance and functional capacity, power, and velocity were assessed before and after the intervention. We observed a significant improvement in all studied variables in the PEG after the intervention (p < 0.05). In contrast, the CG showed no improvements in any variable, which further displayed poorer values for PPT (p < 0.05). In conclusion, a low-intensity combined PE program, including endurance training and coordination, improves psychological variables, pain perception, quality of life, and physical conditioning in women with FM.

Event Related Potentials (ERPs) and other EEG Based Methods for Extracting Biomarkers of Brain Dysfunction: Examples from Pediatric Attention Deficit/Hyperactivity Disorder (ADHD).

Neuropsychiatric diagnoses like ADHD are based on subjective methods like interviews, rating scales and observations. There is a need for more brain-based supplements. Stimulant medication is the most common treatment for ADHD. Clinically useful predictors of response have so far not been reported. The aim of this paper is to describe the EEG based methods we apply to extract potential biomarkers for brain dysfunction. Examples relate to biomarkers for pediatric ADHD, and prediction of medication response. The main emphasis is on Event Related Potentials (ERPs). A nineteen channel EEG is recorded during a 3 min eyes-opened task, a 3 min eyes-closed task, and a 20 min cued visual GO/NOGO task (VCPT). ERPs are recorded during this task. The goal of the ERP protocol is to extract biomarkers of assumed brain dysfunctions that significantly differentiate between a patient group and healthy controls. The protocol includes recording during standard conditions and artifact correction. ERP waves can be used or transformed into latent components. The components of the patient group are compared with controls, empathizing components that, when compared, show relatively high effect sizes. Sub-groups of the patients are selected on the basis of the cluster analysis in the space of the components. Treatment procedure (such as medication, tDCS or neurofeedback protocol) can be applied and the changes in components related to treatment in the subgroups are observed, forming the basis for clinical recommendations. The methods described were applied in a study of 87 pediatric ADHD patients. The index of medication response discriminated significantly between responders and non-responders with a large, and clinically meaningful effect size (d = 1.84). In an ongoing study comparing ADHD children with matched controls, several variables discriminate significantly between patients and controls. The global index will exceed d = .8. The EEG based methods described here could be clinically meaningful.

EEG/ERP-based biomarker/neuroalgorithms in adults with ADHD: Development, reliability, and application in clinical practice.

Objectives: The electrophysiological characteristics of attention-deficit/hyperactivity disorder (ADHD) and recent machine-learning methods promise easy-to-use approaches that can complement existing diagnostic tools when sufficiently large samples are used. Neuroalgorithms are models of multidimensional brain networks by means of which ADHD patient data can be separated from healthy control data.Methods: Spontaneous electroencephalographic and event-related potential (ERP) data were collected three times over the course of 2 years from a multicentre sample of adults comprising 181 patients with ADHD and 147 healthy controls. Spectral power and ERP amplitude and latency measures were used as input data for a semi-automatic machine-learning framework.Results: ADHD patients and healthy controls could be classified with a sensitivity ranging from 75% to 83% and specificity values of 71% to 77%. In the analysis of the repeated measurements, sensitivity values of the selected logistic regression model remained high (72% and 76%), while specificity values slightly decreased over time (64% and 67%).Conclusions: Implementation of the system in clinical practice requires facilities to track affected networks, as well as expertise in neuropathophysiology. Therefore, the use of neuroalgorithms can enhance the diagnostic process by making it less subjective and more reliable and linking it to the underlying pathology.

Latent ERP components of cognitive dysfunctions in ADHD and schizophrenia.

OBJECTIVE: The main goal was to assess common and specific deficits of cognitive control in (Attention Deficit Hyperactivity Disorder) ADHD and schizophrenia (SZ) using event-related potentials (ERPs). METHOD: Behavioral and EEG data in cued GO/NOGO task were recorded in 132 healthy controls (HC) and age, gender and education matched 63 ADHD adults, and 68 SZ patients. RESULTS: N2d wave in NOGO-GO contrast of ERPs did not differ between the groups while the P3d wave discriminated SZ group from two other groups. Latent components of ERPs were extracted by blind source separation method based on second-order statistics Kropotov et al. (2017) and compared between the groups. A counterpart of N2d wave of a frontally distributed latent component was smaller in SZ indicating a specific frontal dysfunction of conflict detection in SZ. Two centrally distributed P3 sub-components were reduced in both groups indicating a non-specific dysfunction of action inhibition operations in ADHD and SZ. CONCLUSION: A pattern of specific and common dysfunctions in terms of latent ERP components shows a more complex picture of functional impairment in schizophrenia and ADHD in comparison to conventional N2/P3 ERP description. SIGNIFICANCE: The latent component approach shows a functionally different pattern of cognitive control impairment in comparison to the conventional ERP analysis.

Predicting Clinical Gains and Side Effects of Stimulant Medication in Pediatric Attention-Deficit/Hyperactivity Disorder by Combining Measures From qEEG and ERPs in a Cued GO/NOGO Task.

OBJECTIVES: The study aim was to develop 2 scales: predicting clinical gains and risk of acute side effects of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), combining measures from EEG spectra, event-related potentials (ERPs), and a cued visual GO/NOGO task. METHODS: Based on 4-week systematic medication trials, 87 ADHD patients aged 8 to 17 years were classified as responders (REs, n = 62) or non-REs (n = 25), and belonging to the side effects (SEs, n = 42) or no-SEs (n = 45) groups. Before starting the trial, a 19-channel EEG was registered twice: Test 1 (T1) without medication and T2 on a single dose of stimulant medication a few days before the trial. EEG was registered T1 and T2: 3 minutes eyes-closed, 3 minutes eyes-open, and 20 minutes cued GO/NOGO. EEG spectra, ERPs, omissions, commissions, reaction time (RT), and RT variability were computed. Groups were compared at T1 and T2 on quantitative EEG (qEEG), ERPs and behavioral parameters; effect sizes ( d) were estimated. Variables with d > 0.5 were converted to quartiles, multiplied by corresponding d, and summed to obtain 2 global scales. RESULTS: Six variables differed significantly between REs and non-REs (T1: theta/alpha ratio, P3NOGO amplitude. Differences T2-T1: Omissions, RT variability, P3NOGO, contingent negative variation [CNV]). The global scale d was 1.86. Accuracy (receiver operating characteristic) was 0.92. SEs and no-SEs differed significantly on 4 variables. (T1: RT, T2: novelty component and alpha peak frequency, and RT changes. Global scale d = 1.08 and accuracy = 0.78. CONCLUSION: Gains and side effects of stimulants in pediatric ADHD can be predicted with high accuracy by combining EEG spectra, ERPs, and behavior from baseline and single-dose tests. ClinicalTrials.gov identifier: NCT02695355.

Methylphenidate selectively modulates one sub-component of the no-go P3 in pediatric ADHD medication responders.

Methylphenidate (MPH) has been shown to modulate the amplitude of the no-go P3 component of the event-related potential (ERP; Øgrim, Aasen, & Brunner, 2016). Using group independent component analysis, the no-go P3 from a cued go/no-go task has been separated into two sub-components (Brunner et al., 2013). This study investigated whether sub-components of the no-go P3 could be identified in children with ADHD, and how MPH modulates their amplitudes. ERPs were registered twice (on/off MPH) in 57 children with ADHD classified as medication responders in a four-week medication trial. Two no-go P3 sub-components were identified. In the MPH session, the amplitude of one sub-component, the IC P3no-goearly (mean latency 378 ms, with a central distribution), was significantly larger than at baseline, whereas the other sub-component, the IC P3no-golate (mean latency 428 ms, with a centro-frontal distribution), was not significantly affected. These results add to the literature documenting that the no-go P3 consists of two overlapping phenomena with different functional correlates.

Functional indexes of reactive cognitive control: ERPs in cued go/no-go tasks.

We aimed to determine the functional meaning of latent (hidden) components decomposed from ERPs, in the context of a go/no-go paradigm. To accomplish this, we used a new group blind source separation method, based on joint diagonalization of covariance matrices of ERPs. Four variants of a frequently used go/no-go paradigm were designed, in which operations of reactive cognitive control, such as conflict detection and action inhibition, were independently manipulated. The results showed that a latent component, generated in the anterior cingulate cortex, induced N2/P3 fluctuation only in conditions in which the prepotent model was violated, and thus can be associated with conflict detection operations. In contrast, the two latent components generated in the vicinity of the central sulcus induced P3-like fluctuations in conditions in which the prepared action was suppressed, and thus can be associated with action inhibition operations. The advantages and limitations of the new blind source separation method in relation to ERP research are also discussed.

Neuromarkers of Post-Traumatic Stress Disorder (PTSD) in a patient after bilateral hand amputation - ERP case study.

Introduction. There is a lack in the worldwide literature of reports on the Neuromarkers of Post-Traumatic Stress Disorder (PTSD) in patients after bilateral hand amputation The aim of this study was to test a hypothesis regarding developing Post-Traumatic Stress Disorder (PTSD) in a patient after bilateral hand amputation with the use of Event Related Potentials (ERPs). On the basis of previous research, the amplitudes of P3 ERP components elicited in the cued GO/NOGO tasks have been chosen as candidates for neuromarkers of PTSD. Case study. A 24-year-old patient had undergone bilateral hand amputation 12 months previously. The patient was repeatedly operated on (he had undergone successful bilateral hand replantation) and despite the severity of the injuries, he recovered. However, the patient complained of flashbacks, anxiety and sleep difficulties. Specialist tests showed the presence of PTSD. The patient participated in the cued GO/NOGO task (Kropotov, 2009) with recording 19-channel EEG. P3 GO and NOGO waves in this task were found to be significantly smaller, in comparison to a group of healthy control subjects of the same age (N=23) taken from the HBI normative database (https://www.hbimed.com/). This observed pattern of ERP waves in the patient corresponds to the pattern found in PTSD patients. Conclusions. ERPs in a GO/NOGO task can be used in the assessment of the functional brain changes induced by chronic PTSD.

Application of ERPs neuromarkers for assessment and treatment of a patient with chronic crossed aphasia after severe TBI and long-term coma - Case Report.

 Objective. The study aimed to evaluate the application of ERPs neuromarkers for the assessment and treatment of a patient with chronic crossed aphasia after severe TBI and a long-term coma. CASE REPORT: An ambidextrous female patient, aged 29, suffered from posttraumatic chronic crossed aphasia, severe TBI and a prolonged coma after a car accident. The patient took part in two differentiated rehabilitation programmes of neurotherapy included 20 sessions of relative beta training and 20 sessions of rTMS; both programmes were combined with behavioural training. The patient was tested 3 times: before the experiment, after completion of programme A, and after completion of programme B. RESULTS: In the 1st recording, the neuromarker of aphasia was found - an excess of the P2 wave over the left temporal area. There was a cognitive control deficit - an excess of omission errors and an increase of RT variability - all indexes of sporadic ADHD. In the 2nd recording, slight improvements in cognitive control, and language functions were found. In the 3rd recording, after the rTMS sessions most of her cognitive dysfunctions had been resolved, including language functions. It should be stressed that the activation (especially the increase in the ERP potential of the right side over the frontal lobe) was found. The neuromarker of aphasia did not change, only the location had slightly moved frontally. CONCLUSIONS: The application of ERP neuromarkers assists in the diagnosis, treatment, and academic success of an ambidextrous patient with chronic posttraumatic aphasia and sporadic ADHD. ERPs can be used to assess the functional brain changes induced by neurotherapeutical programmes.

Local and Widely Distributed EEG Activity in Schizophrenia With Prevalence of Negative Symptoms.

We evaluated EEG frequency abnormalities in resting state (eyes closed and eyes open) EEG in a group of chronic schizophrenia patients as compared with healthy subjects. The study included 3 methods of analysis of deviation of EEG characteristics: genuine EEG, current source density (CSD), and group independent component (gIC). All 3 methods have shown that the EEG in schizophrenia patients is characterized by enhanced low-frequency (delta and theta) and high-frequency (beta) activity in comparison with the control group. However, the spatial pattern of differences was dependent on the type of method used. Comparative analysis has shown that increased EEG power in schizophrenia patients apparently concerns both widely spatially distributed components and local components of signal. Furthermore, the observed differences in the delta and theta range can be described mainly by the local components, and those in the beta range mostly by spatially widely distributed ones. The possible nature of the widely distributed activity is discussed.

Usage of perioperative anxiety neuromarker for improving the quality of life of a patient operated on for critical stenosis of the internal carotid artery.

OBJECTIVE: The aim of the study was to find a neuromarker of perioperative anxiety in a patient with critical carotid stenosis through the use of neuromarkers in Quantitative EEG (QEEG) and Event Related Potentials (ERPs). The indirect purpose of the research was evaluation of improvement in the patient's quality of life. CASE STUDY: A 45-year-old woman was admitted to the Department of Vascular Surgery and Endovascular Interventions at the John Paul II Hospital in Krakow, with the diagnosis of critical internal carotid stenosis (over 80%), confirmed by Doppler Ultrasound and Angio-CT examinations. Before hospitalization, the patient had not presented any symptoms of brain ischemia. It was found that severe anxiety on the Hospital Anxiety and Depression Scale (HAD) was worse before the surgery. After the operation, a reduction anxiety in occurred as well as an improvement in the majority of the dimensions of health. Therefore, her quality of life improved. CONCLUSIONS: Significant changes were observed on the Hospital Anxiety and Depression Scale (HAD). Modern neurotechnologies measures are necessary to capture all the changes in the symptoms of anxiety before and after the operation for a carotid stenosis. ERPs might be used to select patients with neuromarker of perioperative anxiety, and subsequently to serve in proper psychological care and minimalize the perioperative risk of complications.

Correction: ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Naïve Adult ADHD.

[This corrects the article DOI: 10.1371/journal.pone.0159833.].

ERP Correlates of Proactive and Reactive Cognitive Control in Treatment-Naïve Adult ADHD.

This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female) differed from healthy controls (n = 31; 17 female) in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control (Go P3, NoGo N2, and NoGo P3) derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses.

Hyper-frontality in an OCD patient - evidence from event-related potentials in a cued GO/NOGO task.

OBJECTIVE: The study aimed to evaluate the hyperactivity of the frontal lobes in a patient with obsessive-compulsive disorders. CASE DESCRIPTION: A 21-year-old female met the diagnostic criteria of DSM-5 since her behaviour was characterized by a preoccupations with negative thoughts and by repetitive attempts to decrease or stop those behaviours. Two working hypotheses were tested to find neuromarkers of OCD and anxiety in the patient described. In agreement with the 'OCD hypothesis' an increase of the frontal beta activity and an increase of the parietalalpha activity pattern was found. The 'anxiety' hypothesis found confirmation in an increased left temporal P1 wave in response to the visual stimuli observed in ERPs. In all three conditions (EO, EC, GO/NOGO task), two characteristics were deviant from the normative average data in EEG spectra. First, an increase of frontal beta activity and the increase of parietal alpha activity was noted. The independent component analysis applied for 700 ms EEG fragments in GO and NOGO conditions revealed a strong activation over the central areas. CONCLUSIONS: Specific patterns of QEEG and ERPs, the increase of beta activity frontally, and the increase of parietal alpha activity pattern which produce hyper-frontality, might be useful in the diagnosis of an OCD patient. ERPs in a GO/NOGO task can be used in the assessment of functional brain changes in OCD patients.

Effect of Aging on ERP Components of Cognitive Control.

As people age, their performance on tasks requiring cognitive control often declines. Such a decline is frequently explained as either a general or specific decline in cognitive functioning with age. In the context of hypotheses suggesting a general decline, it is often proposed that processing speed generally declines with age. A further hypothesis is that an age-related compensation mechanism is associated with a specific cognitive decline. One prominent theory is the compensation hypothesis, which proposes that deteriorated functions are compensated for by higher performing functions. In this study, we used event-related potentials (ERPs) in the context of a GO/NOGO task to examine the age-related changes observed during cognitive control in a large group of healthy subjects aged between 18 and 84 years. The main question we attempted to answer was whether we could find neurophysiological support for either a general decline in processing speed or a compensation strategy. The subjects performed a relatively demanding cued GO/NOGO task with similar omissions and reaction times across the five age groups. The ERP waves of cognitive control, such as N2, P3cue and CNV, were decomposed into latent components by means of a blind source separation method. Based on this decomposition, it was possible to more precisely delineate the different neurophysiological and psychological processes involved in cognitive control. These data support the processing speed hypothesis because the latencies of all cognitive control ERP components increased with age, by 8 ms per decade for the early components (<200 ms) and by 20 ms per decade for the late components. At the same time, the compensatory hypothesis of aging was also supported, as the amplitudes of the components localized in posterior brain areas decreased with age, while those localized in the prefrontal cortical areas increased with age in order to maintain performance on this simple task at a relatively stable level.