Empathy in schizophrenia: neural alterations during emotion recognition and affective sharing.

Introduction: Deficits in emotion recognition and processing are characteristic for patients with schizophrenia [SCZ]. Methods: We targeted both emotion recognition and affective sharing, one in static and one in dynamic facial stimuli, during functional magnetic resonance imaging [fMRI] in 22 SCZ patients and 22 matched healthy controls [HC]. Current symptomatology and cognitive deficits were assessed as potential influencing factors. Results: Behaviorally, patients only showed a prolonged response time in age-discrimination trials. For emotion-processing trials, patients showed a difference in neural response, without an observable behavioral correlate. During emotion and age recognition in static stimuli, a reduced activation of the bilateral anterior cingulate cortex [ACC] and the right anterior insula [AI] emerged. In the affective sharing task, patients showed a reduced activation in the left and right caudate nucleus, right AI and inferior frontal gyrus [IFG], right cerebellum, and left thalamus, key areas of empathy. Discussion: We conclude that patients have deficits in complex visual information processing regardless of emotional content on a behavioral level and that these deficits coincide with aberrant neural activation patterns in emotion processing networks. The right AI as an integrator of these networks plays a key role in these aberrant neural activation patterns and, thus, is a promising candidate area for neurofeedback approaches.

Reduced Gray Matter Volume and Cortical Thickness in Patients With Small-Fiber Neuropathy.

Small-fiber neuropathy (SFN) is defined by degeneration or dysfunction of peripheral sensory nerve endings. Central correlates have been identified on the level of gray matter volume (GMV) and cortical thickness (CT) changes. However, across SFN etiologies knowledge about a common structural brain signature is still lacking. Therefore, we recruited 26 SFN patients and 25 age- and sex-matched healthy controls to conduct voxel-based- and surface-based morphometry. Across all patients, we found reduced GMV in widespread frontal regions, left caudate, insula and superior parietal lobule. Surface-based morphometry analysis revealed reduced CT in the right precentral gyrus of SFN patients. In a region-based approach, patients had reduced GMV in the left caudate. Since pathogenic gain-of-function variants in voltage-gated sodium channels (Nav) have been associated with SFN pathophysiology, we explored brain morphological patterns in a homogenous subsample of patients carrying rare heterozygous missense variants. Whole brain- and region-based approaches revealed GMV reductions in the bilateral caudate for Nav variant carriers. Further research is needed to analyze the specific role of Nav variants for structural brain alterations. Together, we conclude that SFN patients have specific GMV and CT alterations, potentially forming potential new central biomarkers for this condition. Our results might help to better understand underlying or compensatory mechanisms of chronic pain perception in the future. PERSPECTIVE: This study reveals structural brain changes in small-fiber neuropathy (SFN) patients, particularly in frontal regions, caudate, insula, and parietal lobule. Notably, individuals with SFN and specific Nav variants exhibit bilateral caudate abnormalities. These findings may serve as potential central biomarkers for SFN and provide insights into chronic pain perception mechanisms.

Neural correlates of multisensory integration in the human brain: an ALE meta-analysis.

Previous fMRI research identified superior temporal sulcus as central integration area for audiovisual stimuli. However, less is known about a general multisensory integration network across senses. Therefore, we conducted activation likelihood estimation meta-analysis with multiple sensory modalities to identify a common brain network. We included 49 studies covering all Aristotelian senses i.e., auditory, visual, tactile, gustatory, and olfactory stimuli. Analysis revealed significant activation in bilateral superior temporal gyrus, middle temporal gyrus, thalamus, right insula, and left inferior frontal gyrus. We assume these regions to be part of a general multisensory integration network comprising different functional roles. Here, thalamus operate as first subcortical relay projecting sensory information to higher cortical integration centers in superior temporal gyrus/sulcus while conflict-processing brain regions as insula and inferior frontal gyrus facilitate integration of incongruent information. We additionally performed meta-analytic connectivity modelling and found each brain region showed co-activations within the identified multisensory integration network. Therefore, by including multiple sensory modalities in our meta-analysis the results may provide evidence for a common brain network that supports different functional roles for multisensory integration.

A neural mechanism underlying predictive visual motion processing in patients with schizophrenia.

Psychotic symptoms may be traced back to sensory sensitivity. Thereby, visual motion (VM) processing particularly has been suggested to be impaired in schizophrenia (SCZ). In healthy brains, VM underlies predictive processing within hierarchically structured systems. However, less is known about predictive VM processing in SCZ. Therefore, we performed fMRI during a VM paradigm with three conditions of varying predictability, i.e., Predictable-, Random-, and Arbitrary motion. The study sample comprised 17 SCZ patients and 23 healthy controls. We calculated general linear model (GLM) analysis to assess group differences in VM processing across motion conditions. Here, we identified significantly lower activity in right temporoparietal junction (TPJ) for SCZ patients. Therefore, right TPJ was set as seed for connectivity analyses. For patients, across conditions we identified increased connections to higher regions, namely medial prefrontal cortex, or paracingulate gyrus. Healthy subjects activated sensory regions as area V5, or superior parietal lobule. Reduced TPJ activity may reflect both a failure in the bottom-up flow of visual information and a decrease of signal processing as consequence of increased top-down input from frontal areas. In sum, these altered neural patterns provide a framework for future studies focusing on predictive VM processing to identify potential biomarkers of psychosis.

Effects of exogenous testosterone application on network connectivity within emotion regulation systems.

Studies with steroid hormones underlined the vital role of testosterone on social-emotional processing. However, there is still a lack of studies investigating whether testosterone modulates network connectivity during resting-state. Here, we tested how the exogenous application of testosterone would affect functional connectivity between regions implicated in emotion regulation. In total, 96 male participants underwent resting-state fMRI scanning. Before the measurement, half of the subjects received 5 g TestimTM gel (containing 50 mg testosterone) and the other half a corresponding amount of placebo gel. Seeds for the connectivity analysis were meta-analytically defined. First, all regions associated with emotion regulation were chosen via Neurosynth (data driven). Among those, specific seeds were selected and categorized based on the neural model of emotion regulation by Etkin and colleagues (Etkin et al., 2015) (theory-guided). Resting-state connectivity analysis revealed decreased connectivity between the right DLPFC and the right amygdala as well as between the VMPFC and the left IPL for the testosterone group compared to the placebo group. A complementary dynamic causal modeling (DCM) analysis on findings from the resting-state connectivity analysis underlined a bidirectional coupling which was decreased close to zero by testosterone administration. Our results demonstrate that testosterone administration disrupts resting-state connectivity within fronto-subcortical and fronto-parietal circuits. The findings suggest that even without a specific task (e.g. challenge, reward processing) testosterone modulates brain networks important for social-emotional processing.

Externalization Errors of Olfactory Source Monitoring in Healthy Controls-An fMRI Study.

Using a combined approach of functional magnetic resonance imaging (fMRI) and noninvasive brain stimulation (transcranial direct current stimulation [tDCS]), the present study investigated source memory and its link to mental imagery in the olfactory domain, as well as in the auditory domain. Source memory refers to the knowledge of the origin of mental experiences, differentiating events that have occurred and memories of imagined events. Because of a confusion between internally generated and externally perceived information, patients that are prone to hallucinations show decreased source memory accuracy; also, vivid mental imagery can lead to similar results in healthy controls. We tested source memory following cathodal tDCS stimulation using a mental imagery task, which required participants to perceive or imagine a set of the same olfactory and auditory stimuli during fMRI. The supplementary motor area (SMA) is involved in mental imagery across different modalities and potentially linked to source memory. Therefore, we attempted to modulate participants' SMA activation before entering the scanner using tDCS to influence source memory accuracy in healthy participants. Our results showed the same source memory accuracy between the olfactory and auditory modalities with no effects of stimulation. Finally, we found SMA's subregions differentially involved in olfactory and auditory imagery, with activation of dorsal SMA correlated with auditory source memory.

Audio-visual and olfactory-visual integration in healthy participants and subjects with autism spectrum disorder.

The human capacity to integrate sensory signals has been investigated with respect to different sensory modalities. A common denominator of the neural network underlying the integration of sensory clues has yet to be identified. Additionally, brain imaging data from patients with autism spectrum disorder (ASD) do not cover disparities in neuronal sensory processing. In this fMRI study, we compared the underlying neural networks of both olfactory-visual and auditory-visual integration in patients with ASD and a group of matched healthy participants. The aim was to disentangle sensory-specific networks so as to derive a potential (amodal) common source of multisensory integration (MSI) and to investigate differences in brain networks with sensory processing in individuals with ASD. In both groups, similar neural networks were found to be involved in the olfactory-visual and auditory-visual integration processes, including the primary visual cortex, the inferior parietal sulcus (IPS), and the medial and inferior frontal cortices. Amygdala activation was observed specifically during olfactory-visual integration, with superior temporal activation having been seen during auditory-visual integration. A dynamic causal modeling analysis revealed a nonlinear top-down IPS modulation of the connection between the respective primary sensory regions in both experimental conditions and in both groups. Thus, we demonstrate that MSI has shared neural sources across olfactory-visual and audio-visual stimulation in patients and controls. The enhanced recruitment of the IPS to modulate changes between areas is relevant to sensory perception. Our results also indicate that, with respect to MSI processing, adults with ASD do not significantly differ from their healthy counterparts.

Task-dependent functional organizations of the visual ventral stream.

The visual hierarchy of the ventral stream has been widely studied. However, it remains unclear how the hierarchical system organizes its functional coupling during top-down cognitive process. The present fMRI study investigated task-dependent functional connectivity along the ventral stream, while twenty-eight participants performed object recognition tasks that required different types of visual processing: i) searching or ii) memorizing visual objects embedded in natural scene images or iii) free viewing of the same images. Utilizing a seed-based approach that explicitly compared task-specific BOLD time-series, we identified task-dependent functional connectivity of the visual ventral stream, demonstrating different correlation structures. Searching for a target object manifested both correlated and anti-correlated structures, separating the visual areas V1 and V4 from the posterior part of the inferior temporal cortex (PIT). In contrast, the ventral stream structure remained correlated during memorizing objects, but increased the correlation between the right V4 and PIT. On the other hand, V1 and V4 showed task-dependent activation, whereas PIT was deactivated. These results highlight the context-dependent nature of the visual ventral stream and shed light on how the visual hierarchy is selectively organized to bias object recognition toward features of interest.

Distinct modes of top-down cognitive processing in the ventral visual cortex.

Top-down cognitive control leads to changes in the sensory processing of the brain. In visual perception such changes can take place in the ventral visual cortex altering the functional asymmetry in forward and backward connections. Here we used fixation-related evoked responses of EEG measurement and dynamic causal modeling to examine hierarchical forward-backward asymmetry, while twenty-six healthy adults performed cognitive tasks that require different types of top-down cognitive control (memorizing or searching visual objects embedded in a natural scene image). The generative model revealed an enhanced asymmetry toward forward connections during memorizing, whereas enhanced backward connections were found during searching. This task-dependent modulation of forward and backward connections suggests two distinct modes of top-down cognitive processing in cortical networks. The alteration in forward-backward asymmetry might underlie the functional role in the cognitive control of visual information processing.

Exogenous testosterone and the monoamine-oxidase A polymorphism influence anger, aggression and neural responses to provocation in males.

Testosterone and the monoamine oxidase-A (MAOA) polymorphism are potential neuromodulators for aggression. By acting on similar brain circuits, they might interactively influence human behavior. The current study investigates the causal role of testosterone on aggression-related brain activity and the potential interaction with the MAOA polymorphism. In a double-blind process, 93 healthy males received a testosterone or placebo gel. In an fMRI session, participants performed a Taylor aggression paradigm in which they received provoking feedback and could afterwards decide how aggressively they would react. Testosterone and cortisol levels as well as subjective anger were assessed prior and after the task. Circulating testosterone levels were higher in carriers of the long compared to the short MAOA allele. An interaction of the MAOA polymorphism and testosterone administration was identified in the cuneus, where short allele carriers in the placebo group showed diminished activity in the decision period. Task-related anger was significantly higher in this group. Overall, a mesocorticolimbic network was implicated in processing of high versus low provoking feedback, and core hubs of the default mode network were implicated in the subsequent decision after high versus low provocation. Testosterone administration increased activation in this network. The data provides evidence for an interaction of the MAOA polymorphism and exogenous testosterone on anger and suggests that interactive effects on the brain signal could underlie differential emotional reactivity. The increased default mode activation in the testosterone group suggests an enhanced engagement of social cognition related regions possibly supporting responsivity towards social provocation. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Cerebral and behavioural response to human voices is mediated by sex and sexual orientation.

Several studies report sex differences in sensitivity to gendered stimuli. We assume many of these to reflect differences as to the sex to which one feels attracted rather than to biological sex per se. Investigating voice perception, a function of high social relevance, we show that the behavioural and neural (BOLD) responses to male and female voices are mediated by sex and sexual orientation. In heterosexual men and women, we found an opposite-sex effect, reflected in higher classification accuracy for and a response bias towards voices of the other sex, while the effect became apparent as same-sex effect in homosexual men and women. Overall, sexual orientation had a greater impact in women than in men and homosexual women were closer to men in their behavioural responses to female voices. The activation patterns were similar for hetero- and homosexual men, both groups showing increased activation in response to male compared to female voices in regions distributed across the temporo-parietal and insular cortex. In contrast, women had increased activation in response to voices of the desired sex. It appears that both sex and sexual orientation impact on a function as basal as voice perception. Our results underline the need to assess sexual orientation in study participants if conclusions on sex differences shall be drawn. Many of the reported sex differences in behaviour and brain function might be mediated by sexual orientation and we encourage further research into the interplay between sex and sexual orientation.

Gender incongruence and the brain - Behavioral and neural correlates of voice gender perception in transgender people.

The phenomenon of gender incongruence is hypothesized to arise from a discrepant sexual development of the brain and the genitals, contingent on genetic and hormonal mechanisms. We aimed at visualizing transgender identity on a neurobiological level, assuming a higher functional similarity to individuals of the aspired rather than assigned sex. Implementing a gender perception paradigm featuring male and female voice stimuli, behavioral and functional imaging data of transmen were compared to men and women, and to transwomen, respectively. Men had decreased activation in response to voices of the other sex in regions across the frontoparietal and insular cortex, while the activation patterns of women and transmen were characterized by little or no differentiation between male and female voices. Further, transmen had a comparatively high discrimination performance for ambiguous male voices, possibly reflecting a high sensitivity for voices of the aspired sex. Comparing transmen and transwomen yielded only few differences in the processing of male compared to female voices. In the insula, we observed a pattern similar to that of men and women, the neural responses of the transgender group being in accordance with their gender identity rather than assigned sex. Notwithstanding the similarities found dependent on biological sex, the findings support the hypothesis of gender incongruence being a condition in which neural processing modes are partly incongruent with one's assigned sex.

Progressively analogous evidence of covert face recognition from functional magnetic resonance imaging and skin conductance responses studies involving a patient with dissociative amnesia.

This is a case study involving a female patient (NN) with complete loss of autobiographical memory and identity despite normal neurological assessment. To test the hypothesis that patients with dissociative amnesia (DA) possess the ability to covertly process facial identities they are unaware of, we conducted functional magnetic resonance imaging (fMRI) and assessed skin conductance responses (SCR) to (a) strangers, (b) celebrities, and (c) familiar faces not seen since the onset of DA. We also performed associative face-name memory tasks to test the patient's ability to learn and recall newly learned face-name pairs. Although NN did not recognize any of the faces of her friends and relatives, their images triggered a stronger involvement of the left fusiform gyrus, the bilateral hippocampus/amygdala region, the orbitofrontal cortex, the middle temporal regions, and the precuneus, along with higher SCR. During recollection of previously learned face-name pairs, NN (compared to healthy controls) demonstrated a weaker involvement of the hippocampus. Our findings suggest that, in DA, specific arousal systems remain capable of being activated by familiar faces outside of conscious awareness. The decreased activation observed in the hippocampus demonstrates that the functioning of memory-sensitive regions may be impaired by trauma.

Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males.

Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status-seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants' choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se. In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone.

Decreasing predictability of visual motion enhances feed-forward processing in visual cortex when stimuli are behaviorally relevant.

Recent views of information processing in the (human) brain emphasize the hierarchical structure of the central nervous system, which is assumed to form the basis of a functional hierarchy. Hierarchical predictive processing refers to the notion that higher levels try to predict activity in lower areas, while lower levels transmit a prediction error up the hierarchy whenever the predictions fail. The present study aims at testing hypothetical modulatory effects of unpredictable visual motion on forward connectivities within the visual cortex. Functional magnetic resonance imaging was acquired from 35 healthy volunteers while viewing a moving ball under three different levels of predictability. In two different runs subjects were asked to attend to direction changes in the ball's motion, where a button-press was required in one of these runs only. Dynamic causal modeling was applied to a network comprising V1, V5 and posterior parietal cortex in the right hemisphere. The winning model of a Bayesian model selection indicated an enhanced strength in the forward connection from V1 to V5 with decreasing predictability for the run requiring motor response. These results support the notion of hierarchical predictive processing in the sense of an augmented bottom-up transmission of prediction error with increasing uncertainty about motion direction. This finding may be of importance for promoting our understanding of trait characteristics in psychiatric disorders, as an increased forward propagation of prediction error is assumed to underlie schizophrenia and may be observable at early stages of the disease.

Disorder-specific characteristics of borderline personality disorder with co-occurring depression and its comparison with major depression: An fMRI study with emotional interference task.

Borderline personality disorder (BPD) and major depressive disorder (MDD) are both associated with abnormalities in the regulation of emotion, with BPD being highly comorbid with MDD. Disorder-specific dysfunctions in BPD, however, have hardly been addressed, hence the lack of knowledge pertaining to the specificity of emotion processing deficits and their commonality with MDD. 24 healthy comparison subjects, 21 patients with MDD, and 13 patients with comorbid BPD and MDD (BPD + MDD group) were studied using functional MRI. The subjects were required to perform an emotional interference task that entailed categorizing facial affect while ignoring words that labeled the emotional contents of the external stimuli. Collapsing across emotional face types, we observed that participants with BPD + MDD uniquely displayed a greater involvement of the visual areas and the cerebellum. During emotional conflict processing, on the other hand, the lateral prefrontal cortex (LPFC) appeared to be affected in both patient groups. In comparison to the HC, the MDD group showed differences also in the posterior medial frontal cortex (pMFC) and the inferior parietal lobule (IPL). Thus, our data indicate dysfunctionality in the neural circuitry responsible for emotional conflict control in both disorders. The enhanced visual cortex activation in BPD + MDD suggests the visual system's hyperresponsiveness to faces at an early perceptual level. Not being associated with co-occurring depression, this effect in BPD + MDD appears to represent specific personality traits such as disturbed reactivity toward emotionally expressive facial stimuli.

Follow your nose: Implicit spatial processing within the chemosensory systems.

Although most studies agree that humans cannot smell in stereo, it was recently suggested that olfactory localization is possible when assessed implicitly. In a spatial cueing paradigm, lateralized olfactory cues impaired the detection of congruently presented visual targets, an effect contrary to the typical facilitation observed in other sensory domains. Here, we examined the specificity and the robustness of this finding by studying implicit localization abilities in another chemosensory system and by accounting for possible confounds in a modified paradigm. Sixty participants completed a spatial cueing task along with an explicit localization task, using trigeminal (Experiment 1) and olfactory (Experiment 2) stimuli. A control task was implemented to control for residual somatosensory stimulation (Experiment 3). In the trigeminal experiment, stimuli were localized with high accuracy on the explicit level, while the cueing effect in form of facilitation was limited to response accuracy. In the olfactory experiment, responses were slowed by congruent cues on the implicit level, while no explicit localization was observed. Our results point to the robustness of the olfactory interference effect, corroborating the implicit-explicit dissociation of olfactory localization, and challenging the view that humans lost the ability to extract spatial information from smell. The absence of a similar interference for trigeminal cues suggests distinct implicit spatial processing mechanisms within the chemosensory systems. Moreover, the lack of a typical facilitation effect in the trigeminal domain points to important differences from spatial information processing in other, nonchemosensory domains. The possible mechanisms driving the effects are discussed. (PsycINFO Database Record

Task-irrelevant fear enhances amygdala-FFG inhibition and decreases subsequent face processing.

Facial threat is associated with changes in limbic activity as well as modifications in the cortical face-related N170. It remains unclear if task-irrelevant threat modulates the response to a subsequent facial stimulus, and whether the amygdala's role in early threat perception is independent and direct, or modulatory. In 19 participants, crowds of emotional faces were followed by target faces and a rating task while simultaneous EEG-fMRI were recorded. In addition to conventional analyses, fMRI-informed EEG analyses and fMRI dynamic causal modeling (DCM) were performed. Fearful crowds reduced EEG N170 target face amplitudes and increased responses in a fMRI network comprising insula, amygdala and inferior frontal cortex. Multimodal analyses showed that amygdala response was present ∼60 ms before the right fusiform gyrus-derived N170. DCM indicated inhibitory connections from amygdala to fusiform gyrus, strengthened when fearful crowds preceded a target face. Results demonstrated the suppressing influence of task-irrelevant fearful crowds on subsequent face processing. The amygdala may be sensitive to task-irrelevant fearful crowds and subsequently strengthen its inhibitory influence on face-responsive fusiform N170 generators. This provides spatiotemporal evidence for a feedback mechanism of the amygdala by narrowing attention in order to focus on potential threats.

Incidental Memory Encoding Assessed with Signal Detection Theory and Functional Magnetic Resonance Imaging (fMRI).

In functional magnetic resonance imaging (fMRI) studies that apply a "subsequent memory" approach, successful encoding is indicated by increased fMRI activity during the encoding phase for hits vs. misses, in areas underlying memory encoding such as the hippocampal formation. Signal-detection theory (SDT) can be used to analyze memory-related fMRI activity as a function of the participant's memory trace strength (d(')). The goal of the present study was to use SDT to examine the relationship between fMRI activity during incidental encoding and participants' recognition performance. To implement a new approach, post-experimental group assignment into High- or Low Performers (HP or LP) was based on 29 healthy participants' recognition performance, assessed with SDT. The analyses focused on the interaction between the factors group (HP vs. LP) and recognition performance (hits vs. misses). A whole-brain analysis revealed increased activation for HP vs. LP during incidental encoding for remembered vs. forgotten items (hits > misses) in the insula/temporo-parietal junction (TPJ) and the fusiform gyrus (FFG). Parameter estimates in these regions exhibited a significant positive correlation with d('). As these brain regions are highly relevant for salience detection (insula), stimulus-driven attention (TPJ), and content-specific processing of mnemonic stimuli (FFG), we suggest that HPs' elevated memory performance was associated with enhanced attentional and content-specific sensory processing during the encoding phase. We provide first correlative evidence that encoding-related activity in content-specific sensory areas and content-independent attention and salience detection areas influences memory performance in a task with incidental encoding of facial stimuli. Based on our findings, we discuss whether the aforementioned group differences in brain activity during incidental encoding might constitute the basis of general differences in memory performance between HP and LP.

On utilizing uncertainty information in template-based EEG-fMRI ballistocardiogram artifact removal.

The correction of ballistocardiogram artifacts in simultaneous EEG-fMRI often yields unsatisfactory results. To improve the signal-to-noise ratio (SNR) of results, we inferred EEG signal uncertainty from postcorrection artifact residuals and computed the uncertainty-weighted mean of ERPs. Using an uncertainty-weighted mean significantly and consistently reduced both inter- and intrasubject SEM in the analysis of auditory evoked responses (AER, indicated by the N1-P2 complex) and in the effects of an auditory oddball paradigm (N1-P3 complex, standard-deviant difference). SNR increased by 3% on average for the AER amplitude (intrasubject) and 17% on average for the auditory oddball ERP (intersubject). This demonstrates that weighting by uncertainty complements existing artifact correction algorithms to increase SNR in ERPs. More specifically, it is an efficient method to utilize seemingly corrupt (difficult-to-correct) EEG data that might otherwise be discarded.