Cortical Event-related Potentials Research Articles

Machine learning and EEG can classify passive viewing of discrete categories of visual stimuli but not the observation of pain

Previous studies have demonstrated the potential of machine learning (ML) in classifying physical pain from non-pain states using electroencephalographic (EEG) data. However, the application of ML to EEG data to categorise the observation of pain versus non-pain images of human facial expressions or scenes depicting pain being inflicted has not been explored. The present study aimed to address this by training Random Forest (RF) models on cortical event-related potentials (ERPs) recorded while participants passively viewed faces displaying either pain or neutral expressions, as well as action scenes depicting pain or matched non-pain (neutral) scenarios. Ninety-one participants were recruited across three samples, which included a model development group (n = 40) and a cross-subject validation group (n = 51). Additionally, 25 participants from the model development group completed a second experimental session, providing a within-subject temporal validation sample. The analysis of ERPs revealed an enhanced N170 component in response to faces compared to action scenes. Moreover, an increased late positive potential (LPP) was observed during the viewing of pain scenes compared to neutral scenes. Additionally, an enhanced P3 response was found when participants viewed faces displaying pain expressions compared to neutral expressions. Subsequently, three RF models were developed to classify images into faces and scenes, neutral and pain scenes, and neutral and pain expressions. The RF model achieved classification accuracies of 75%, 64%, and 69% for cross-validation, cross-subject, and within-subject classifications, respectively, along with reasonably calibrated predictions for the classification of face versus scene images. However, the RF model was unable to classify pain versus neutral stimuli above chance levels when presented with subsequent tasks involving images from either category. These results expand upon previous findings by externally validating the use of ML in classifying ERPs related to different categories of visual images, namely faces and scenes. The results also indicate the limitations of ML in distinguishing pain and non-pain connotations using ERP responses to the passive viewing of visually similar images.

Attention reinforces human corticofugal system to aid speech perception in noise

Perceiving speech-in-noise (SIN) demands precise neural coding between brainstem and cortical levels of the hearing system. Attentional processes can then select and prioritize task-relevant cues over competing background noise for successful speech perception. In animal models, brainstem-cortical interplay is achieved via descending corticofugal projections from cortex that shape midbrain responses to behaviorally-relevant sounds. Attentional engagement of corticofugal feedback may assist SIN understanding but has never been confirmed and remains highly controversial in humans. To resolve these issues, we recorded source-level, anatomically constrained brainstem frequency-following responses (FFRs) and cortical event-related potentials (ERPs) to speech via high-density EEG while listeners performed rapid SIN identification tasks. We varied attention with active vs. passive listening scenarios whereas task difficulty was manipulated with additive noise interference. Active listening (but not arousal-control tasks) exaggerated both ERPs and FFRs, confirming attentional gain extends to lower subcortical levels of speech processing. We used functional connectivity to measure the directed strength of coupling between levels and characterize “bottom-up” vs. “top-down” (corticofugal) signaling within the auditory brainstem-cortical pathway. While attention strengthened connectivity bidirectionally, corticofugal transmission disengaged under passive (but not active) SIN listening. Our findings (i) show attention enhances the brain's transcription of speech even prior to cortex and (ii) establish a direct role of the human corticofugal feedback system as an aid to cocktail party speech perception.

Low frequency subthalamic stimulation and event-related potentials in Parkinson disease

BackgroundHigh frequency (130 Hz) subthalamic Deep-Brain-Stimulation (STN-DBS) optimally improves cardinal motor symptoms in Parkinson disease (PD). Low stimulation frequencies (60–80 Hz) improve axial symptoms in some patients and, according to preliminary evidences, may also have a beneficial effect on the cognitive component of motor planning. ObjectiveTo analyze the configuration of the P300 component of cortical event-related auditory potentials (ERPs), a reliable index of attentive cognitive functions, at different stimulation frequencies in STN-DBS in PD patients. Methods12 PD patients underwent ERPs recordings using a standard oddball auditory paradigm with STN-DBS at 60 Hz, 80 Hz, 130 Hz, and OFF-stimulation, applied in a randomized double-blind sequence. ERPs analysis considered the peak amplitude and latency of the P300 components at midline electrode positions (Fz, Cz, Pz). ResultsP300 latency over Cz and Pz electrodes significantly increased with STN-DBS at 130 Hz compared to OFF-stimulation. P300 latency was also significantly increased, though to a lesser degree, over Pz electrode with stimulation at 80 Hz. No significant P300 latency modifications were detected at 60 Hz stimulation compared to OFF-stimulation condition. P300 amplitude did not change significantly for any of the stimulation conditions tested. ConclusionsLow frequency STN-DBS is associated with minor modifications of P300 latency compared to conventional stimulation at 130 Hz, possibly suggesting that 60 and 80 Hz may have less interference with attentive and cognitive processes in PD patients.

Test-retest reliability of prepulse inhibition paradigm using auditory evoked potentials

Prepulse inhibition (PPI) is a neurological phenomenon in which a weak initial stimulus reduces the level of responses to a subsequent stronger stimulus. Although acoustic startle reflexes are usually used for PPI examinations, recent studies have observed similar phenomena with event-related cortical potentials. In the present study, test-retest reliability of PPI measured using auditory change-related cortical responses was assessed in 35 healthy adults. Four sound stimuli were randomly presented at an even probability; Standard, Test alone, Prepulse alone, and Test + Prepulse. The Standard stimulus was a train of 25-ms tone pulses at 70 dB for 650 ms, while for Test alone and Prepulse alone, the sound pressure was increased to 80 dB at 350 ms and 73 dB at 300 ms, respectively. Measurements were performed twice with at least 7 days separation, and validity was evaluated using intra-class correlation (ICC) for latency, amplitude, and suppression rate of the P50, N100, and P200 components. The results showed high ICC values for the latency and amplitude of nearly all components, except for response to Prepulse alone (0.3–0.6). Furthermore, ICC for suppression rate was greater than 0.5 for the peak-to-peak amplitude. Good reproducibility for N100 and P200 components was obtained with this method. The present results support the PPI paradigm as a reliable tool for clinical measurements of inhibitory functions.

Investigating Influences of Medial Olivocochlear Efferent System on Central Auditory Processing and Listening in Noise: A Behavioral and Event-Related Potential Study.

This electrophysiological study investigated the role of the medial olivocochlear (MOC) efferents in listening in noise. Both ears of eleven normal-hearing adult participants were tested. The physiological tests consisted of transient-evoked otoacoustic emission (TEOAE) inhibition and the measurement of cortical event-related potentials (ERPs). The mismatch negativity (MMN) and P300 responses were obtained in passive and active listening tasks, respectively. Behavioral responses for the word recognition in noise test were also analyzed. Consistent with previous findings, the TEOAE data showed significant inhibition in the presence of contralateral acoustic stimulation. However, performance in the word recognition in noise test was comparable for the two conditions (i.e., without contralateral stimulation and with contralateral stimulation). Peak latencies and peak amplitudes of MMN and P300 did not show changes with contralateral stimulation. Behavioral performance was also maintained in the P300 task. Together, the results show that the peripheral auditory efferent effects captured via otoacoustic emission (OAE) inhibition might not necessarily be reflected in measures of central cortical processing and behavioral performance. As the MOC effects may not play a role in all listening situations in adults, the functional significance of the cochlear effects of the medial olivocochlear efferents and the optimal conditions conducive to corresponding effects in behavioral and cortical responses remain to be elucidated.

Event-related cortical potentials occurring prior to speech initiation

Event-related cortical potentials occurring prior to speech initiation

Sleep restriction does not potentiate nocebo‐induced changes in pain and cortical potentials

The increased pain sensitivity following reduced sleep may be related to changes in cortical processing of nociceptive stimuli. Expectations shape pain perception and can inhibit (placebo) or enhance (nocebo) pain. Sleep restriction appears to enhance placebo responses; however, whether sleep restriction also affects nocebo responses remains unknown. The aim of the present study was to determine whether sleep restriction facilitates nocebo-induced changes in pain and pain-evoked cortical potentials. In an experimental study with a crossover design, the sensitivity to electrically induced pain was determined in 53 nurses under two sleep conditions, after habitual sleep and after two consecutive nights at work. Nocebo was induced by conditioning one-third of the pain stimuli. Pain-elicited cortical event-related potentials were recorded by electroencephalography (EEG). Data were analysed both in the time domain (N2P2 amplitude) and in the time-frequency domain (ERP magnitude). Sleepiness and vigilance were also assessed. Both nocebo alone and sleep restriction alone increased the sensitivity to electrically induced pain. However, no interaction effect was found. Moreover, the magnitude of the pain-elicited responses increased after sleep restriction and decreased after nocebo expectation, suggesting that nocebo is probably not an underlying mechanism for the commonly observed hyperalgesia induced by sleep restriction. The present work addresses whether sleep restriction, known to increase the sensitivity of the pain system, facilitates nocebo-induced hyperalgesia. Our findings suggest that this is not the case, indicating that the increased sensitivity of the pain system following nocebo and sleep restriction are mediated by different cortical mechanisms.

Somatosensory Plasticity in Pediatric Cerebral Palsy following Constraint-Induced Movement Therapy.

Cerebral palsy (CP) is predominantly a disorder of movement, with evidence of sensory-motor dysfunction. CIMT1 is a widely used treatment for hemiplegic CP. However, effects of CIMT on somatosensory processing remain unclear. To examine potential CIMT-induced changes in cortical tactile processing, we designed a prospective study, during which 10 children with hemiplegic CP (5 to 8 years old) underwent an intensive one-week-long nonremovable hard-constraint CIMT. Before and directly after the treatment, we recorded their cortical event-related potential (ERP) responses to calibrated light touch (versus a control stimulus) at the more and less affected hand. To provide insights into the core neurophysiological deficits in light touch processing in CP as well as into the plasticity of this function following CIMT, we analyzed the ERPs within an electrical neuroimaging framework. After CIMT, brain areas governing the more affected hand responded to touch in configurations similar to those activated by the hemisphere controlling the less affected hand before CIMT. This was in contrast to the affected hand where configurations resembled those of the more affected hand before CIMT. Furthermore, dysfunctional patterns of brain activity, identified using hierarchical ERP cluster analyses, appeared reduced after CIMT in proportion with changes in sensory-motor measures (grip or pinch movements). These novel results suggest recovery of functional sensory activation as one possible mechanism underlying the effectiveness of intensive constraint-based therapy on motor functions in the more affected upper extremity in CP. However, maladaptive effects on the less affected constrained extremity may also have occurred. Our findings also highlight the use of electrical neuroimaging as feasible methodology to measure changes in tactile function after treatment even in young children, as it does not require active participation.

A Comparison of Classifiers in a Task Consisting of Classifying Single Visual Event-Related Cortical Potentials in Humans

The development of neurocomputer interfaces (NCI) using the EEG requires use of effective algorithms for signal analysis. One approach to creating NCI is based on use of the characteristics of individual visual event-related potentials (VEP) for control purposes. However, this is a difficult task requiring a combination of different approaches related to signal processing, particularly blind decomposition of sources (blind source separation), machine learning, and various others. We present here results from a comparative analysis of several classifiers in a task consisting of recognition of individual VEP. Open-access EEG traces were used for this study.

Global optimal constrained ICA and its application in extraction of movement related cortical potentials from single-trial EEG signals

Background and objectiveThe constrained ICA (cICA) is a recent approach which can extract the desired source signal by using prior information. cICA employs gradient-based algorithms to optimize non convex objective functions and therefore global optimum solution is not guaranteed. In this study, we propose the Global optimal constrained ICA (GocICA) algorithm for solving the conventional cICA problems. Due to the importance of movement related cortical potentials (MRCPs) for neurorehabilitation and developing a suitable mechanism for detection of movement intention, single-trial MRCP extraction is presented as an application of GocICA. MethodsIn order to evaluate the performance of the proposed technique, two kinds of datasets including simulated and real EEG data have been utilized in this paper. The GocICA method has been implemented based on the most popular meta-heuristic optimization algorithms such as Genetic Algorithm (GA), Particle Swarm Optimization (PSO) and Charged System Search (CSS) where the results have been compared with those of conventional cICA and two ICA-based methods (JADE and Infomax). ResultsIt was found that GocICA enhanced the extracted MRCP from multi-channel EEG better than both conventional cICA and ICA-based methods and also outperformed them in single-trial MRCP detection with higher true positive rates (TPRs) and lower false positive rates (FPRs). Moreover, CSS-cICA resulted in the greatest TPR (91.2232 ± 3.4708) and the lowest FPR (8.7465 ± 3.7705) for single-trial MRCP detection from real EEG data and the greatest signal-to-noise ratio (SNR) (39.2818) and the lowest mean square error (MSE) and individual performance index (IPI) (41.8230 and 0.0012, respectively) for single-trial MRCP extraction from simulated EEG data. ConclusionsThese results confirm the superiority of GocICA with respect to conventional cICA that is due to the ability of meta-heuristic optimization algorithms to escape from local optimal point. As such, GocICA is a promising new algorithm for single-trial MRCP detection which can be used for detecting other types of event related cortical potentials (ERPs) such as P300 and also for EEG artifact removal.

Background Odors Modulate N170 ERP Component and Perception of Emotional Facial Stimuli.

Successful social interaction relies on the accurate decoding of other peoples’ emotional signals, and their contextual integration. However, little is known about how contextual odors may lead to modulation of cortical processing in response to facial expressions. We investigated how unpleasant and pleasant contextual background odors affected emotion perception and cortical event-related potential (ERP) responses to pictures of faces expressing happy, neutral and disgusted facial expressions. Faces were, regardless of expression, rated more positively in the pleasant odor condition and more negatively in the unpleasant odor condition. Faces were overall rated as more emotionally arousing in the presence of an odor, irrespective of its valence. Contextual odors also interacted with facial expressions, such that happy faces were rated as especially non-arousing in the unpleasant odor condition. The early, face-sensitive N170 ERP component also displayed an interaction effect. Here, disgusted faces were affected by the odor context such that the N170 revealed a relatively larger negativity in the context of a pleasant odor compared with an unpleasant odor. There were no odor effects on the responses to faces in other measured ERP components (P1, VPP, P2, and LPP). These results suggest that odors bias socioemotional perception early stages of the visual processing stream. However, effects may vary across emotional expressions and measurements.

Brainstem-cortical functional connectivity for speech is differentially challenged by noise and reverberation

Everyday speech perception is challenged by external acoustic interferences that hinder verbal communication. Here, we directly compared how different levels of the auditory system (brainstem vs. cortex) code speech and how their neural representations are affected by two acoustic stressors: noise and reverberation. We recorded multichannel (64 ch) brainstem frequency-following responses (FFRs) and cortical event-related potentials (ERPs) simultaneously in normal hearing individuals to speech sounds presented in mild and moderate levels of noise and reverb. We matched signal-to-noise and direct-to-reverberant ratios to equate the severity between classes of interference. Electrode recordings were parsed into source waveforms to assess the relative contribution of region-specific brain areas [i.e., brainstem (BS), primary auditory cortex (A1), inferior frontal gyrus (IFG)]. Results showed that reverberation was less detrimental to (and in some cases facilitated) the neural encoding of speech compared to additive noise. Inter-regional correlations revealed associations between BS and A1 responses, suggesting subcortical speech representations influence higher auditory-cortical areas. Functional connectivity analyses further showed that directed signaling toward A1 in both feedforward cortico-collicular (BS→A1) and feedback cortico-cortical (IFG→A1) pathways were strong predictors of degraded speech perception and differentiated “good” vs. “poor” perceivers. Our findings demonstrate a functional interplay within the brain's speech network that depends on the form and severity of acoustic interference. We infer that in addition to the quality of neural representations within individual brain regions, listeners' success at the “cocktail party” is modulated based on how information is transferred among subcortical and cortical hubs of the auditory-linguistic network.

Aberrant Cortical Event-Related Potentials During Associative Learning in Rat Models for Presymptomatic Stages of Alzheimer's Disease.

Trace eyeblink conditioning is a hippocampus-dependent associative learning paradigm which is impaired in patients with Alzheimer's disease (AD) and animal AD models. Learning in this paradigm accompanies changes in oscillatory activity in forebrain regions, some of which are loci of pathogenic changes in prodromal AD stages. These observations motivated us to examine how cortical event-related potentials (ERPs) during this paradigm are affected by two features of the asymptomatic, AD-related brain abnormality, entorhinal tau accumulation and mild cholinergic deficit. Adult rats received viral overexpression of P301L mutant human tau in the entorhinal cortex, low-dose scopolamine treatment, or both. Electroencephalograms were recorded with epidural electrodes on the surface of the frontal, parietal, and temporal cortices during differential and reversal trace eyeblink conditioning. All rats developed conditioned responses to one of two stimuli (auditory or visual) paired with mild eyelid shock (CS+), but not to the other stimulus presented alone(CS-). They were also able to adjust the response when the stimulus contingency was reversed. With learning, the amplitude of several ERP components in the frontal and temporal cortices came to differentiate the CS+ from CS-. Scopolamine affected the learning-related change in temporal P2 and other learning-unrelated components in three regions. Entorhinal tau overexpression primary affected the amplitude of temporal visual ERPs and learning-unrelated frontal and temporal auditory ERP components. The double manipulation only affected two components of temporal auditory ERPs. Thus, cortical ERPs during differential associative learning are sensitive to asymptomatic brain abnormality associated with AD.

Differential effects of hearing loss on neural and behavioral measures of speech perception in noise

Understanding speech in background noise is difficult for many listeners, and those with hearing impairment tend to show considerable variability in performance. Event-related potentials (ERPs) and associated cortical oscillations are useful for examining neural responses to speech in various listening conditions and may represent neurophysiological markers of auditory perception. The present study examined the effects of hearing impairment on the neural coding and perception of speech in noise in a group of adult listeners with varying degrees of sensorineural hearing loss. This work was also designed to determine whether cortical ERPs and oscillatory rhythms in various frequency bands can predict the effects of hearing impairment on sentence recognition in noise. Passive N1-P2 and MMN responses were elicited with a double-oddball paradigm containing a consonant and vowel change in background noise. Speech perception was evaluated using phoneme discrimination and sentence recognition in noise tasks. Anal...

Auditory-Motor Control of Vocal Production during Divided Attention: Behavioral and ERP Correlates.

When people hear unexpected perturbations in auditory feedback, they produce rapid compensatory adjustments of their vocal behavior. Recent evidence has shown enhanced vocal compensations and cortical event-related potentials (ERPs) in response to attended pitch feedback perturbations, suggesting that this reflex-like behavior is influenced by selective attention. Less is known, however, about auditory-motor integration for voice control during divided attention. The present cross-modal study investigated the behavioral and ERP correlates of auditory feedback control of vocal pitch production during divided attention. During the production of sustained vowels, 32 young adults were instructed to simultaneously attend to both pitch feedback perturbations they heard and flashing red lights they saw. The presentation rate of the visual stimuli was varied to produce a low, intermediate, and high attentional load. The behavioral results showed that the low-load condition elicited significantly smaller vocal compensations for pitch perturbations than the intermediate-load and high-load conditions. As well, the cortical processing of vocal pitch feedback was also modulated as a function of divided attention. When compared to the low-load and intermediate-load conditions, the high-load condition elicited significantly larger N1 responses and smaller P2 responses to pitch perturbations. These findings provide the first neurobehavioral evidence that divided attention can modulate auditory feedback control of vocal pitch production.

Oxytocin promotes face-sensitive neural responses to infant and adult faces in mothers

Research utilizing intranasal oxytocin (OT) administration has shown that OT may increase attention and sensitivity to social cues, such as faces. Given the pivotal role of OT in parental behaviors across mammals, the paucity of intranasal OT research investigating responses to social cues in parents and particularly mothers of young children is a critical limitation. In the current study, we recorded cortical event-related potentials (ERPs) to investigate whether intranasal OT affects the early neural responses to emotional faces in mothers of 1-year-old infants. Using a double-blind, within-subjects design, mothers (n = 38) were administered intranasal OT and placebo on separate sessions and presented with happy and sad infant and adult faces while ERP components reflecting face-sensitive brain activation and attention allocation were measured. We hypothesized that ERP responses to faces would be larger in the OT condition and that the effects of OT on ERP responses would be more pronounced for infant faces. The amplitudes of the face-sensitive N170 ERP component were larger in the OT condition to infant and adult faces, but no clear support was found for the hypothesis that the responses to infant faces would be more susceptible to OT effects than the responses to adult faces. The attention-sensitive late positive potential (LPP) component was not modulated by intranasal substance condition. The results are in line with the view that OT acts to enhance the perceptual salience of social and emotional stimuli. Demonstrating such effects in mothers of young children encourages further investigation of the potential of intranasal OT to affect the perception of social cues relevant for parent-child interaction.

Predicting auditory feedback control of speech production from subregional shape of subcortical structures.

Although a growing body of research has focused on the cortical sensorimotor mechanisms that support auditory feedback control of speech production, much less is known about the subcortical contributions to this control process. This study examined whether subregional anatomy of subcortical structures assessed by statistical shape analysis is associated with vocal compensations and cortical event-related potentials in response to pitch feedback errors. The results revealed significant negative correlations between the magnitudes of vocal compensations and subregional shape of the right thalamus, between the latencies of vocal compensations and subregional shape of the left caudate and pallidum, and between the latencies of cortical N1 responses and subregional shape of the left putamen. These associations indicate that smaller local volumes of the basal ganglia and thalamus are predictive of slower and larger neurobehavioral responses to vocal pitch errors. Furthermore, increased local volumes of the left hippocampus and right amygdala were predictive of larger vocal compensations, suggesting that there is an interplay between the memory-related subcortical structures and auditory-vocal integration. These results, for the first time, provide evidence for differential associations of subregional morphology of the basal ganglia, thalamus, hippocampus, and amygdala with neurobehavioral processing of vocal pitch errors, suggesting that subregional shape measures of subcortical structures can predict behavioral outcome of auditory-vocal integration and associated neural features. Hum Brain Mapp 39:459-471, 2018. © 2017 Wiley Periodicals, Inc.

Higher-order motor cortices actively engage in motor inhibition: Cortical stimulation and event-related potentials as an evidence from subdural grid electrodes

Higher-order motor cortices actively engage in motor inhibition: Cortical stimulation and event-related potentials as an evidence from subdural grid electrodes

Thalamic and basal ganglia regions are involved in attentional processing of behaviorally significant events: evidence from simultaneous depth and scalp EEG

Extensive descriptions exist on cortical responses to change in the acoustic environment. However, the involvement of subcortical regions is not well understood. Here we present simultaneous recordings of cortical and subcortical event-related potentials (ERPs) to different pure tones in patients undergoing surgery for deep brain stimulation (DBS). These patients had externalized electrodes in the subthalamic nucleus (STN), the ventrolateral posterior thalamus (VLp) or the globus pallidus internus (GPi). Subcortical and cortical ERPs were analyzed upon presentation of one frequent non-target stimulus and two infrequent stimuli, either being a target or a distractor stimulus. The results revealed that amplitudes of scalp-recorded P3 and subcortical late attention-modulated responses (AMR) were largest upon presentation of target stimuli compared with distractor stimuli. This suggests that thalamic and basal ganglia regions are sensitive to behaviorally relevant auditory events. Comparison of the subcortical structures showed that responses in VLp have shorter latency than in GPi and STN. Further, the subcortical responses in VLp and STN emerged significantly prior to the cortical P3 response. Our findings point to higher-order cognitive functions already at a subcortical level. Auditory events are categorized as behaviorally relevant in subcortical loops involving basal ganglia and thalamic regions. This label is then distributed to cortical regions by ascending projections.

Visual processing in patients with age-related macular degeneration performing a face detection test.

PurposePeople with age-related macular degeneration (AMD) have difficulties in familiar face recognition and facial expression discrimination. Our aim was to evaluate the visual processing of faces in AMD patients and whether this would be improved by anti-vascular endothelial growth factor therapy. This was a prospective interventional cohort study.PatientsTwelve patients with monocular wet AMD and 6 control subjects were recruited. Face detection processes were studied using cortical event-related potentials (ERPs). Patients received 3 bevacizumab intravitreal injections to the single affected eye. At baseline and 4–6 weeks after the last injection, clinical presentation and ERPs of the face task were evaluated. Face pictures were shown as targets (16.7%) among standard pictures of pixelated faces in an oddball-type paradigm.ResultsFace pictures elicited well-defined electrical components in occipital and parieto-occipital cortical areas at baseline and after treatment. The face-specific N170 component was evident in all subjects with longer peak latency in patients than in controls (170±13 vs 155±14, P=0.032). Unexpectedly, an early component reflecting unintentional prediction of perceiving a face, that is, deviance-related negativity, was present in patients and controls. Visual acuity of the affected eye seemed improved in patients from logarithm of the minimum angle of resolution 0.71 (±0.33) to 0.52 (±0.39) by 119 (±23) days without accompanying significant change in face-specific ERPs.ConclusionsMonocular wet AMD distinctly influenced face-specific brain electrophysiological components. However, the anti-vascular endothelial growth factor treatment did not improve the binocular face detection ability. The EudraCT number of this study is 2012-000765-20.