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OBJECTIVE: Glutamic acid decarboxylase, an enzyme in GABA biosynthesis, is encoded by the GAD1 gene, the transcriptional activity of which is affected by the rs3749034 polymorphism. The aim was to investigate the effects of rs3749034 on cognitive event-related potentials (P300) in healthy subjects and schizophrenic patients. METHODS: Determination of rs3749034 polymorphism was performed in 89 healthy volunteers and 109 schizophrenic patients (males). Two-stimulus oddball task performance and P300 auditory evoked potentials were analyzed and patient symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: An increased frequency of C allele carriers was disclosed in patients. In controls, superior task performance was observed in cytosine-thymine carriers, while a greater P300 amplitude and shorter latency were found in C/C carriers. Analogous effects were found in patients with a disease onset before 25 years of age. Higher N5 and lower P3 and G5 PANSS scales were revealed in C/C homozygotes. CONCLUSIONS: The findings substantiate an involvement of GABA-ergic mechanisms in maintaining an optimal excitatory-inhibitory balance and an association of rs3749034 with early-onset disorder and negative symptoms of schizophrenia. SIGNIFICANCE: These results are important for understanding underlying mechanisms and the development of evidence-based methods for assessing the risk of schizophrenia.

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Aircraft pilots face a high mental workload (MW) under environmental constraints induced by high altitude and sometimes sleep restriction (SR). Our aim was to assess the combined effects of hypoxia and sleep restriction on cognitive and physiological responses to different MW levels using the Multi-Attribute Test Battery (MATB)-II with an additional auditory Oddball-like task. Seventeen healthy subjects were subjected in random order to three 12-min periods of increased MW level (low, medium, and high): sleep restriction (SR, <3 h of total sleep time (TST)) vs. habitual sleep (HS, >6 h TST), hypoxia (HY, 2 h, FIO2 = 13.6%, ~3500 m vs. normoxia, NO, FIO2 = 21%). Following each MW level, participants completed the NASA-TLX subjective MW scale. Increasing MW decreases performance on the MATB-II Tracking task (p = 0.001, MW difficulty main effect) and increases NASA-TLX (p = 0.001). In the combined HY/SR condition, MATB-II performance was lower, and the NASA-TLX score was higher compared with the NO/HS condition, while no effect of hypoxia alone was observed. In the accuracy of the auditory task, there is a significant interaction between hypoxia and MW difficulty (F(2-176) = 3.14, p = 0.04), with lower values at high MW under hypoxic conditions. Breathing rate, pupil size, and amplitude of pupil dilation response (PDR) to auditory stimuli are associated with increased MW. These parameters are the best predictors of increased MW, independently of physiological constraints. Adding ECG, SpO2, or electrodermal conductance does not improve model performance. In conclusion, hypoxia and sleep restriction have an additive effect on MW. Physiological and electrophysiological responses must be taken into account when designing a MW predictive model and cross-validation.

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Electroencephalography (EEG) is a non-invasive method used to track human brain activity over time. The time-locked EEG to an external event is known as event-related potential (ERP). ERP can be a biomarker of human perception and other cognitive processes. The success of ERP research depends on the laboratory conditions and attentiveness of the test subjects. Specifically, the inability to control experimental variables has reduced ERP research in the real world. This study collected EEG data under various experimental circumstances within an auditory oddball paradigm experiment to enable the use of ERP as an active biomarker in normal laboratory conditions. Then, ERP epochs were analyzed to identify unfocused epochs, affected by typical artifacts and external distortion. For the initial comparison, the ability of four unsupervised machine learning algorithms (MLAs) was evaluated to identify unfocused epochs. Then, their accuracy was compared with the human inspection and a current EEG analysis tool (EEGLab). All four MLAs were typically 95-100% accurate. In summary, our analysis finds that humans might miss subtle differences in the regular ERP patterns, but MLAs could efficiently identify those. Thus, our analysis suggests that unsupervised MLAs perform better for detecting unfocused ERP epochs compared with the other two standard methods.

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The orienting reaction (OR) towards a new stimulus is subject to habituation, i.e., progressively attenuates with stimulus repetition. The skin conductance responses (SCRs) are known to represent a reliable measure of OR at the peripheral level. Yet, it is still a matter of debate which of the P3 subcomponents is the most likely to represent the central counterpart of the OR. The aim of the present work was to study habituation, recovery, and dishabituation phenomena intrinsic to a two-stimulus auditory oddball paradigm, one of the most-used paradigms both in research and clinic, by simultaneously recording SCRs and P3 in twenty healthy volunteers. Our findings show that the target stimulus was capable of triggering a more marked OR, as indexed by both SCRs and P3, compared to the standard stimulus, that could be due to its affective saliency and relevance for task completion; the application of temporal principal components analysis (PCA) to the P3 complex allowed us to identify several subcomponents including both early and late P3a (eP3a; lP3a), P3b, novelty P3 (nP3), and both a positive and a negative Slow Wave (+SW; -SW). Particularly, lP3a and P3b subcomponents showed a similar behavior to that observed for SCRs , suggesting them as central counterparts of OR. Finally, the P3 evoked by the first standard stimulus after the target showed a significant dishabituation phenomenon which could represent a sign of the local stimulus change. However, it did not reach a sufficient level to trigger an SCR/OR since it did not represent a salient event in the context of the task.

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Sensory memory traces are assessed via oddball paradigms in which deviant (infrequent) stimuli are interspersed into a string of standard (frequent) stimuli. Once a memory trace for the standard is established, the deviant spurs a change detection response measured via the resulting event related potential (ERP). Response magnitude is sensitive to the differences in stimuli properties or categories and influenced by individual experience. The goal of the present study was to use ERPs to test the relation between individual digits in the somatosensory cortex and the extent to which digit representations are influenced by individual differences in experience such as independent mobility and playing video games. The present study of 60 undergraduates utilized a passive tactile oddball paradigm, stimulating the thumb, middle, and little fingers. The oddball paradigm was fully matched with each digit serving as the standard and deviant. A temporal principal component analysis (tPCA) identified factors that matched three a priori ERP components: N80, somatosensory mismatch negativity (sMMN), and P300. Analyses confirmed the anticipated differences between standards and deviants and provided some support for prior ERP work suggesting the thumb is in a different functional category than the other digits. Independent control of individual digits (such as the little finger) was positively related to only one aspect of the ERP (P3a) while video game experience was not associated with ERP differences. Cumulatively, these results provide a more nuanced examination of tactile oddball paradigms and how ERP methods can shed light on the relations between different digits.

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INTRODUCTION: The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. MATERIALS AND METHODS: This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. RESULTS: Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. CONCLUSIONS: These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

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Tinnitus denotes the perception of a non-environmental sound and might result from aberrant auditory prediction. Successful prediction of formal (e.g., type) and temporal sound characteristics facilitates the filtering of irrelevant information, also labelled as 'sensory gating' (SG). Here, we explored if and how parallel manipulations of formal prediction violations and temporal predictability affect SG in persons with and without tinnitus. Age-, education- and sex-matched persons with and without tinnitus (N = 52) participated and listened to paired-tone oddball sequences, varying in formal (standard vs. deviant pitch) and temporal predictability (isochronous vs. random timing). EEG was recorded from 128 channels and data were analyzed by means of temporal spatial principal component analysis (tsPCA). SG was assessed by amplitude suppression for the 2nd tone in a pair and was observed in P50-like activity in both timing conditions and groups. Correspondingly, deviants elicited overall larger amplitudes than standards. However, only persons without tinnitus displayed a larger N100-like deviance response in the isochronous compared to the random timing condition. This result might imply that persons with tinnitus do not benefit similarly as persons without tinnitus from temporal predictability in deviance processing. Thus, persons with tinnitus might display less temporal sensitivity in auditory processing than persons without tinnitus.

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A wealth of behavioral evidence indicate that sounds with increasing intensity (i.e. appear to be looming towards the listener) are processed with increased attentional and physiological resources compared to receding sounds. However, the neurophysiological mechanism responsible for such cognitive amplification remains elusive. Here, we show that the large differences seen between cortical responses to looming and receding sounds are in fact almost entirely explained away by nonlinear encoding at the level of the auditory periphery. We collected electroencephalography (EEG) data during an oddball paradigm to elicit mismatch negativity (MMN) and others Event Related Potentials (EPRs), in response to deviant stimuli with both dynamic (looming and receding) and constant level (flat) differences to the standard in the same participants. We then combined a computational model of the auditory periphery with generative EEG methods (temporal response functions, TRFs) to model the single-participant ERPs responses to flat deviants, and used them to predict the effect of the same mechanism on looming and receding stimuli. The flat model explained 45% variance of the looming response, and 33% of the receding response. This provide striking evidence that difference wave responses to looming and receding sounds result from the same cortical mechanism that generate responses to constant-level deviants: all such differences are the sole consequence of their particular physical morphology getting amplified and integrated by peripheral auditory mechanisms. Thus, not all effects seen cortically proceed from top-down modulations by high-level decision variables, but can rather be performed early and efficiently by feed-forward peripheral mechanisms that evolved precisely to sparing subsequent networks with the necessity to implement such mechanisms.

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Objective.Presence is an important aspect of user experience in virtual reality (VR). It corresponds to the illusion of being physically located in a virtual environment (VE). This feeling is usually measured through questionnaires that disrupt presence, are subjective and do not allow for real-time measurement. Electroencephalography (EEG), which measures brain activity, is increasingly used to monitor the state of users, especially while immersed in VR.Approach.In this paper, we present a way of evaluating presence, through the measure of the attention dedicated to the real environment via an EEG oddball paradigm. Using breaks in presence, this experimental protocol constitutes an ecological method for the study of presence, as different levels of presence are experienced in an identical VE.Main results.Through analysing the EEG data of 18 participants, a significant increase in the neurophysiological reaction to the oddball, i.e. the P300 amplitude, was found in low presence condition compared to high presence condition. This amplitude was significantly correlated with the self-reported measure of presence. Using Riemannian geometry to perform single-trial classification, we present a classification algorithm with 79% accuracy in detecting between two presence conditions.Significance.Taken together our results promote the use of EEG and oddball stimuli to monitor presence offline or in real-time without interrupting the user in the VE.

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Creativity has previously been linked with various attentional phenomena, including unfocused or broad attention. Although this has typically been interpreted through an executive functioning framework, such phenomena may also arise from atypical incentive salience processing. Across two studies, we examine this hypothesis both neurally and psychologically. First we examine the relationship between figural creativity and event-related potentials during an audio-visual oddball task, finding that rater creativity of drawings is associated with a diminished P300 response at midline electrodes, while abstractness and elaborateness of the drawings is associated with an altered distribution of the P300 over posterior electrodes. These findings support the notion that creativity may involve an atypical attribution of salience to prominent information. We further explore the incentive salience hypothesis by examining relationships between creativity and a psychological indicator of incentive salience captured by participants' ratings of enjoyment (liking) and their motivation to pursue (wanting) diverse real world rewards, as well as their positive spontaneous thoughts about those rewards. Here we find enhanced motivation to pursue activities as well as a reduced relationship between the overall tendency to enjoy rewards and the tendency to pursue them. Collectively, these findings indicate that creativity may be associated with atypical allocation of attentional and motivational resources to novel and rewarding information, potentially allowing more types of information access to attentional resources and motivating more diverse behaviors. We discuss the possibility that salience attribution in creatives may be less dependent on task-relevance or hedonic pleasure, and suggest that atypical salience attribution may represent a trait-like feature of creativity.

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Introduction: Inhibition control, as the core component of executive function, might play a crucial role in the understanding of attention deficit/hyperactivity disorder (ADHD) and specific learning disorders (SLD). Inhibition control deficits have been observed in children with ADHD or SLD. This study sought to test in a multi-modal fashion (i.e., behavior and plus brain imaging) whether inhibition control abilities would be further deteriorated in the ADHD children due to the comorbidity of SLD. Method: A total number of 90 children (aged 6-12 years) were recruited, including 30 ADHD, 30 ADHD+SLD (children with the comorbidity of ADHD and SLD), and 30 typically developing (TD) children. For each participant, a 44-channel functional near infrared spectroscopy (fNIRS) equipment was first adopted to capture behavioral and cortical hemodynamic responses during a two-choice Oddball task (a relatively new inhibition control paradigm). Then, 50 metrics were extracted, including 6 behavioral metrics (i.e., OddballACC, baselineACC, totalACC, OddballRT, baselineRT, and totalRT) and 44 beta values in 44 channels based on general linear model. Finally, differences in those 50 metrics among the TD, ADHD, and ADHD+SLD children were analyzed. Results: Findings showed that: (1) OddballACC (i.e., the response accuracy in deviant stimuli) is the most sensitive metric in identifying the differences between the ADHD and ADHD+SLD children; and (2) The ADHD+SLD children exhibited decreased behavioral response accuracy and brain activation level in some channels (e.g., channel CH35) than both the ADHD and TD children. Discussion: Findings seem to support that inhibition control abilities would be further decreased in the ADHD children due to the comorbidity of SLD.

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Developmental changes in functional neural networks are sensitive to environmental influences. This EEG study investigated how infant brain responses relate to the social context that their families live in. Event-related potentials of 255 healthy, awake infants between six and fourteen months were measured during a passive auditory oddball paradigm. Infants were presented with 200 standard tones and 48 randomly distributed deviants. All infants are part of a longitudinal study focusing on families with socioeconomic and/or cultural challenges (Bremen Initiative to Foster Early Childhood Development; BRISE; Germany). As part of their familial socioeconomic status (SES), parental level of education and infant's migration background were assessed with questionnaires. For 30.6% of the infants both parents had a low level of education (≤10 years of schooling) and for 43.1% of the infants at least one parent was born abroad. The N2-P3a complex is associated with unintentional directing of attention to deviant stimuli and was analysed in frontocentral brain regions. Age was utilised as a control variable. Our results show that tone deviations in infants trigger an immature N2-P3a complex. Contrary to studies with older children or adults, the N2 amplitude was more positive for deviants than for standards. This may be related to an immature superposition of the N2 with the P3a. For infants whose parents had no high-school degree and were born abroad, this tendency was increased, indicating that facing multiple challenges as a young family impacts on the infant's early neural development. As such, attending to unexpected stimulus changes may be important for early learning processes. Variations of the infant N2-P3a complex may, thus, relate to early changes in attentional capacity and learning experiences due to familial challenges. This points towards the importance of early prevention programs.

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Earlier research has suggested gender differences in event-related potentials/oscillations (ERPs/EROs). Yet, the alteration in event-related oscillations (EROs) in the delta and theta frequency bands have not been explored between genders across the three age groups of adulthood, i.e., 18-50, 51-65, and >65 years. Data from 155 healthy elderly participants who underwent a neurological examination, comprehensive neuropsychological assessment (including attention, memory, executive function, language, and visuospatial skills), and magnetic resonance imaging (MRI) from past studies were used. The delta and theta ERO powers across the age groups and between genders were compared and correlational analyses among the ERO power, age, and neuropsychological tests were performed. The results indicated that females displayed higher theta ERO responses than males in the frontal, central, and parietal regions but not in the occipital location between 18 and 50 years of adulthood. The declining theta power of EROs in women reached that of men after the age of 50 while the theta ERO power was more stable across the age groups in men. Our results imply that the cohorts must be recruited at specified age ranges across genders, and clinical trials using neurophysiological biomarkers as an intervention endpoint should take gender into account in the future.

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Research findings indicate that when a task-irrelevant stimulus feature deviates from an otherwise predictable pattern, participants performing a categorization task exhibit slower responses (deviance distraction). This deviance distraction effect reflects the violation of the sensory predictions generated by the cognitive system. In this study, we sought to examine for the first time whether these predictions can be incidentally modulated by the auditory environment. Participants categorized the duration (short vs long) of a colored shape (red square or blue circle) while instructed to disregard the stimulus' visual features and the sound played in the background (two distinct chords played by different instruments). While the two visual stimuli shapes were equiprobable across the task, one was highly likely (p=.882) and the other rare (p=.118) in one auditory context and vice versa in the other context. Our results showed that participants were significantly slower in the duration judgement task whenever the stimulus was unexpected within a given auditory context (context-dependent distraction), and that the reset of their sensory predictions was completed upon the trial following a change of context. We conclude that object features and environmental context are processed in relation to each other and that sensory predictions are produced in relation to the environmental context, evidencing the first demonstration of auditory context-dependent modulation of attention.

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Mild cognitive impairment (MCI) may progress to severe forms of dementia, so therapy is needed to maintain cognitive abilities. The neural circuitry for oculomotor control is closely linked to that which controls cognitive behavior. In this study, we tested whether training the oculomotor system with gaze-controlled video games could improve cognitive behavior in MCI patients. Patients played a simple game for 2-3 weeks while a control group played the same game using a mouse. Cognitive improvement was assessed using the MoCA screening test and CANTAB. We also measured eye pupil and vergence responses in an oddball paradigm. The results showed an increased score on the MoCA test specifically for the visuospatial domain and on the Rapid Visual Information Processing test of the CANTAB battery. Pupil responses also increased to target stimuli. Patients in the control group did not show significant improvements. This pilot study provides evidence for the potential cognitive benefits of gaze-controlled gaming in MCI patients.

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Past research has demonstrated that it is possible to detect implicit responses to face trustworthiness using fast periodic visual stimulation (FPVS). Because people readily retrieve affective associations with faces, the current study investigated whether learned trustworthiness would yield similar responses to face trustworthiness as measured via FPVS. After learning to associate faces with untrustworthy or trustworthy behaviors, participants completed three separate tasks while electroencephalography (EEG) was recorded. In each of these tasks, participants viewed oddball sequences of faces where a single base face was presented repeatedly at a rate of 6 Hz and oddball faces with different identities were presented every fifth face (6 Hz/5 = 1.2 Hz). Providing evidence of learning, the oddball response at 1.2 Hz and its harmonics was stronger for the learned faces compared to novel faces over bilateral occipitotemporal cortex and beyond. In addition, reproducing previous findings with face trustworthiness, we observed a stronger response at 1.2 Hz and its harmonics for sequences with less trustworthy-looking versus trustworthy-looking oddball faces over bilateral occipitotemporal cortex and other sites. However, contrary to our predictions, we did not observe a significant influence of learned trustworthiness on the oddball response. These data indicate that impressions based on learning are treated differently than impressions based on appearance, and they raise questions about the types of design and stimuli that yield responses that are measurable via FPVS.

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The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

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When a novel stimulus (oddball) appears after repeated presentation of an identical stimulus, the oddball is perceived to last longer than the repeated stimuli, a phenomenon known as the oddball effect. We investigated whether the perceptual or physical differences between the repeated and oddball stimuli are more important for the oddball effect. To manipulate the perceptual difference while keeping their physical visual features constant, we used the Thatcher illusion, in which an inversion of a face hinders recognition of distortion in its facial features. We found that the Thatcherized face presented after repeated presentation of an intact face induced a stronger oddball effect when the faces were upright than when they were inverted (Experiment 1). However, the difference in the oddball effect between face orientations was not observed when the intact face was presented as the oddball after repeated presentation of a Thatcherized face (Experiment 2). These results were replicated when participants performed both the intact-repeated and Thatcherized-repeated conditions in a single experiment (Experiment 3). Two control experiments confirmed that the repeated presentation of the preceding stimuli is necessary for the difference in duration distortion to occur (Experiments 4 and 5). The results suggest the considerable role of perceptual processing in the oddball effect. We discuss the discrepancy in the results between the intact-repeated and Thatcherized-repeated conditions in terms of predictive coding.

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Background: Schizophrenia often occurs in youth, and psychosis risk syndrome (PRS) occurs before the onset of psychosis. Assessing the neuropsychological abnormalities of PRS individuals can help in early identification and active intervention of mental illness. Auditory P300 amplitude defect is an important manifestation of attention processing abnormality in PRS, but it is still unclear whether there are abnormalities in the attention processing of rhythmic compound tone stimuli in PRS individuals, and whether the P300 amplitude induced by these stimuli is specific to PRS individuals and related to their clinical outcomes. Methods: In total, 226 participants, including 122 patients with PRS, 51 patients with emotional disorders (ED), and 53 healthy controls (HC) were assessed. Baseline electroencephalography was recorded during the compound tone oddball task. The event-related potentials (ERPs) induced by rhythmic compound tone stimuli of two frequencies (20-Hz, 40-Hz) were measured. Almost all patients with PRS were followed up for 12 months and reclassified into four groups: PRS-conversion, PRS-symptomatic, PRS-emotional disorder, and PRS-complete remission. The differences in baseline ERPs were compared among the clinical outcome groups. Results: Regardless of the stimulation frequency, the average P300 amplitude were significantly higher in patients with PRS than in those with ED (p = 0.003, d = 0.48) and in HC (p = 0.002, d = 0.44) group. The average P300 amplitude of PRS-conversion group was significantly higher than that of the PRS-complete remission (p = 0.016, d = 0.72) and HC group (p = 0.001, d = 0.76), and the average P300 amplitude of PRS-symptomatic group was significantly higher than that of the HC group (p = 0.006, d = 0.48)...(AU)

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The birth and following growth of social media platforms has influenced a lot. In addition to beneficial features, it has long-been noticed that heavy consumption of social media can have negative effects beyond a simple lack of time for other things. Of particular interest is the idea that consuming short videos lasting only fractions of a minute and watched one after another can lead to deficits in concentration and attention. Completing the existing literature that already reports evidence for attention deficits related to heavy social media use, the present study aims to contribute to this acute topic by adding neurophysiological data to it. In particular, this study made use of a well-known experimental paradigm, which is able to detect attention-related changes on a neurophysiological level. The so-called oddball paradigm was applied and the hypothesis that heavy social media users mainly consuming short videos show a reduced P300 event-related potential (ERP) component was tested, which has been found to reflect attention-related brain functions. For this, we invited twenty-nine participants and designed a visual oddball experiment including a white circle on black background as the low-frequency target stimulus and a white triangle on black background as the high-frequency non-target stimulus. On the basis of their self-reported short-video-based social media usage habits, all participants were grouped into heavy (more than 4 h daily usage) and regular (below 3 h daily usage) users, and finally data from 14 heavy and 15 regular users were further analyzed. It was found that only regular users show a clear P300 ERP component, while this particular brain potential amplitude reflecting attentional processes was significantly reduced in heavy users. This result provides empirical brain imaging evidence that heavy short-video-based social media use indeed affects attentional brain processes in a negative way.