Frequency-dependent dynamics of steady-state visual evoked potentials under sustained flicker stimulation.

Steady-state visual evoked potentials (SSVEP) are electroencephalographic signals elicited when the brain is exposed to a visual stimulus with a steady frequency. We analyzed the temporal dynamics of SSVEP during sustained flicker stimulation at 5, 10, 15, 20 and 40 Hz. We found that the amplitudes of the responses were not stable over time. For a 5 Hz stimulus, the responses progressively increased, while, for higher flicker frequencies, the amplitude increased during the first few seconds and often showed a continuous decline afterward. We hypothesize that these two distinct sets of frequency-dependent SSVEP signal properties reflect the contribution of parvocellular and magnocellular visual pathways generating sustained and transient responses, respectively. These results may have important applications for SSVEP signals used in research and brain-computer interface technology and may contribute to a better understanding of the frequency-dependent temporal mechanisms involved in the processing of prolonged periodic visual stimuli.

Implications of depressive mood in OSAHS patients: insights from event-related potential.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a chronic breathing disorder characterized by recurrent upper airway obstruction during sleep. Although previous studies have shown a link between OSAHS and depressive mood, the neurobiological mechanisms underlying mood disorders in OSAHS patients remain poorly understood. This study aims to investigate the emotion processing mechanism in OSAHS patients with depressive mood using event-related potentials (ERPs). METHODS: Seventy-four OSAHS patients were divided into the depressive mood and non-depressive mood groups according to their Self-rating Depression Scale (SDS) scores. Patients underwent overnight polysomnography and completed various cognitive and emotional questionnaires. The patients were shown facial images displaying positive, neutral, and negative emotions and tasked to identify the emotion category, while their visual evoked potential was simultaneously recorded. RESULTS: The two groups did not differ significantly in age, BMI, and years of education, but showed significant differences in their slow wave sleep ratio (P = 0.039), ESS (P = 0.006), MMSE (P < 0.001), and MOCA scores (P = 0.043). No significant difference was found in accuracy and response time on emotional face recognition between the two groups. N170 latency in the depressive group was significantly longer than the non-depressive group (P = 0.014 and 0.007) at the bilateral parieto-occipital lobe, while no significant difference in N170 amplitude was found. No significant difference in P300 amplitude or latency between the two groups. Furthermore, N170 amplitude at PO7 was positively correlated with the arousal index and negatively with MOCA scores (both P < 0.01). CONCLUSION: OSAHS patients with depressive mood exhibit increased N170 latency and impaired facial emotion recognition ability. Special attention towards the depressive mood among OSAHS patients is warranted for its implications for patient care.

Improving SSVEP-BCI Performance Through Repetitive Anodal tDCS-Based Neuromodulation: Insights From Fractal EEG and Brain Functional Connectivity.

This study embarks on a comprehensive investigation of the effectiveness of repetitive transcranial direct current stimulation (tDCS)-based neuromodulation in augmenting steady-state visual evoked potential (SSVEP) brain-computer interfaces (BCIs), alongside exploring pertinent electroencephalography (EEG) biomarkers for assessing brain states and evaluating tDCS efficacy. EEG data were garnered across three distinct task modes (eyes open, eyes closed, and SSVEP stimulation) and two neuromodulation patterns (sham-tDCS and anodal-tDCS). Brain arousal and brain functional connectivity were measured by extracting features of fractal EEG and information flow gain, respectively. Anodal-tDCS led to diminished offsets and enhanced information flow gains, indicating improvements in both brain arousal and brain information transmission capacity. Additionally, anodal-tDCS markedly enhanced SSVEP-BCIs performance as evidenced by increased amplitudes and accuracies, whereas sham-tDCS exhibited lesser efficacy. This study proffers invaluable insights into the application of neuromodulation methods for bolstering BCI performance, and concurrently authenticates two potent electrophysiological markers for multifaceted characterization of brain states.

Neuronal Modeling of Cross-Sensory Visual Evoked Magnetoencephalography Responses in the Auditory Cortex.

Previous studies have demonstrated that auditory cortex activity can be influenced by cross-sensory visual inputs. Intracortical laminar recordings in nonhuman primates have suggested a feedforward (FF) type profile for auditory evoked but feedback (FB) type for visual evoked activity in the auditory cortex. To test whether cross-sensory visual evoked activity in the auditory cortex is associated with FB inputs also in humans, we analyzed magnetoencephalography (MEG) responses from eight human subjects (six females) evoked by simple auditory or visual stimuli. In the estimated MEG source waveforms for auditory cortex regions of interest, auditory evoked response showed peaks at 37 and 90 ms and visual evoked response at 125 ms. The inputs to the auditory cortex were modeled through FF- and FB-type connections targeting different cortical layers using the Human Neocortical Neurosolver (HNN), which links cellular- and circuit-level mechanisms to MEG signals. HNN modeling suggested that the experimentally observed auditory response could be explained by an FF input followed by an FB input, whereas the cross-sensory visual response could be adequately explained by just an FB input. Thus, the combined MEG and HNN results support the hypothesis that cross-sensory visual input in the auditory cortex is of FB type. The results also illustrate how the dynamic patterns of the estimated MEG source activity can provide information about the characteristics of the input into a cortical area in terms of the hierarchical organization among areas.

Differences in cognitive processing between snakes and guns: Evidence from electroencephalography.

The aim of the study is to explore differences in cognitive processing of phylogenetic and ontogenetic stimulus using the electroencephalography (EEG) technology. The researcher chose snakes and guns as representatives of phylogenetic stimulus and ontogenetic stimulus, respectively, and used the Oddball paradigm to present the experimental stimuli and explore the cognitive processing differences between them through time-domain analysis and time-frequency analysis. The results of time-domain analysis showed that snakes elicited larger N1, P2, and P3 amplitudes and a shorter P3 latency than guns and neutral stimuli, and that guns elicited greater P2 and P3 amplitudes than neutral stimuli. The findings of time-frequency analysis showed that the beta-band (320-420 ms, 25-35 Hz) power elicited by snakes was significantly greater than by guns and neutral stimuli, and that the beta-band power elicited by guns was significantly greater than by neutral stimuli. The results indicated that the brain has a cognitive processing advantage for both snakes and guns, which is more obvious for snakes than for guns, and that the brain is more sensitive to snakes.

The effect of inherently threatening contexts on visuocortical engagement to conditioned threat.

Fear and anxiety are crucial for adaptive responding in life-threatening situations. Whereas fear is a phasic response to an acute threat accompanied by selective attention, anxiety is characterized by a sustained feeling of apprehension and hypervigilance during situations of potential threat. In the current literature, fear and anxiety are usually considered mutually exclusive, with partially separated neural underpinnings. However, there is accumulating evidence that challenges this distinction between fear and anxiety, and simultaneous activation of fear and anxiety networks has been reported. Therefore, the current study experimentally tested potential interactions between fear and anxiety. Fifty-two healthy participants completed a differential fear conditioning paradigm followed by a test phase in which the conditioned stimuli were presented in front of threatening or neutral contextual images. To capture defense system activation, we recorded subjective (threat, US-expectancy), physiological (skin conductance, heart rate) and visuocortical (steady-state visual evoked potentials) responses to the conditioned stimuli as a function of contextual threat. Results demonstrated successful fear conditioning in all measures. In addition, threat and US-expectancy ratings, cardiac deceleration, and visuocortical activity were enhanced for fear cues presented in threatening compared with neutral contexts. These results are in line with an additive or interactive rather than an exclusive model of fear and anxiety, indicating facilitated defensive behavior to imminent danger in situations of potential threat.

Origins of direction selectivity in the primate retina.

From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the earliest stage of the visual process. In primates, by contrast, direction selectivity is a hallmark of motion processing areas in visual cortex, but has not been found in the retina, despite significant effort. Here we combined functional recordings of light-evoked responses and connectomic reconstruction to identify diverse direction-selective cell types in the macaque monkey retina with distinctive physiological properties and synaptic motifs. This circuitry includes an ON-OFF ganglion cell type, a spiking, ON-OFF polyaxonal amacrine cell and the starburst amacrine cell, all of which show direction selectivity. Moreover, we discovered that macaque starburst cells possess a strong, non-GABAergic, antagonistic surround mediated by input from excitatory bipolar cells that is critical for the generation of radial motion sensitivity in these cells. Our findings open a door to investigation of a precortical circuitry that computes motion direction in the primate visual system.

Remyelination in humans due to a retinoid-X receptor agonist is age-dependent.

Remyelination efficiency declines with advancing age in animal models, but this has been harder to demonstrate in people with multiple sclerosis. We show that bexarotene, a putatively remyelinating retinoid-X receptor agonist, shortened the visual evoked potential latency in patients with chronic optic neuropathy aged under 42 years only (with the effect diminishing by 0.45 ms per year of age); and increased the magnetization transfer ratio of deep gray matter lesions in those under 43 years only. Addressing this age-related decline in human remyelination capacity will be an important step in the development of remyelinating therapies that work across the lifespan.

Optimizing intact skull intrinsic signal imaging for subsequent targeted electrophysiology across mouse visual cortex.

Understanding brain function requires repeatable measurements of neural activity across multiple scales and multiple brain areas. In mice, large scale cortical neural activity evokes hemodynamic changes readily observable with intrinsic signal imaging (ISI). Pairing ISI with visual stimulation allows identification of primary visual cortex (V1) and higher visual areas (HVAs), typically through cranial windows that thin or remove the skull. These procedures can diminish long-term mechanical and physiological stability required for delicate electrophysiological measurements made weeks to months after imaging (e.g., in subjects undergoing behavioral training). Here, we optimized and directly validated an intact skull ISI system in mice. We first assessed how imaging quality and duration affect reliability of retinotopic maps in V1 and HVAs. We then verified ISI map retinotopy in V1 and HVAs with targeted, multi-site electrophysiology several weeks after imaging. Reliable ISI maps of V1 and multiple HVAs emerged with ~ 60 trials of imaging (65 ± 6 min), and these showed strong correlation to local field potential (LFP) retinotopy in superficial cortical layers (r2 = 0.74-0.82). This system is thus well-suited for targeted, multi-area electrophysiology weeks to months after imaging. We provide detailed instructions and code for other researchers to implement this system.

Neuronal modulation in the mouse superior colliculus during covert visual selective attention.

Covert visual attention is accomplished by a cascade of mechanisms distributed across multiple brain regions. Visual cortex is associated with enhanced representations of relevant stimulus features, whereas the contributions of subcortical circuits are less well understood but have been associated with selection of relevant spatial locations and suppression of distracting stimuli. As a step toward understanding these subcortical circuits, here we identified how neuronal activity in the intermediate layers of the superior colliculus (SC) of head-fixed mice is modulated during covert visual attention. We found that spatial cues modulated both firing rate and spike-count correlations. Crucially, the cue-related modulation in firing rate was due to enhancement of activity at the cued spatial location rather than suppression at the uncued location, indicating that SC neurons in our task were modulated by an excitatory or disinhibitory circuit mechanism focused on the relevant location, rather than broad inhibition of irrelevant locations. This modulation improved the neuronal discriminability of visual-change-evoked activity, but only when assessed for neuronal activity between the contralateral and ipsilateral SC. Together, our findings indicate that neurons in the mouse SC can contribute to covert visual selective attention by biasing processing in favor of locations expected to contain task-relevant information.

Conditioned up and down modulations of short latency gamma band oscillations in visual cortex during fear learning in humans.

Over the course of evolution, the human brain has been shaped to prioritize cues that signal potential danger. Thereby, the brain does not only favor species-specific prepared stimulus sets such as snakes or spiders but can learn associations between new cues and aversive outcomes. One important mechanism to achieve this is associated with learning induced plasticity changes in sensory cortex that optimizes the representation of motivationally relevant sensory stimuli. Animal studies have shown that the modulation of gamma band oscillations predicts plasticity changes in sensory cortices by shifting neurons' responses to fear relevant features as acquired by Pavlovian fear conditioning. Here, we report conditioned gamma band modulations in humans during fear conditioning of orthogonally oriented sine gratings representing fear relevant and irrelevant conditioned cues. Thereby, pairing of a sine grating with an aversive loud noise not only increased short latency (during the first 180 ms) evoked visual gamma band responses, but was also accompanied by strong gamma power reductions for the fear irrelevant control grating. The current findings will be discussed in the light of recent neurobiological models of plasticity changes in sensory cortices and classic learning models such as the Rescorla-Wagner framework.

Riemannian classification of single-trial surface EEG and sources during checkerboard and navigational images in humans.

OBJECTIVE: Different visual stimuli are classically used for triggering visual evoked potentials comprising well-defined components linked to the content of the displayed image. These evoked components result from the average of ongoing EEG signals in which additive and oscillatory mechanisms contribute to the component morphology. The evoked related potentials often resulted from a mixed situation (power variation and phase-locking) making basic and clinical interpretations difficult. Besides, the grand average methodology produced artificial constructs that do not reflect individual peculiarities. This motivated new approaches based on single-trial analysis as recently used in the brain-computer interface field. APPROACH: We hypothesize that EEG signals may include specific information about the visual features of the displayed image and that such distinctive traits can be identified by state-of-the-art classification algorithms based on Riemannian geometry. The same classification algorithms are also applied to the dipole sources estimated by sLORETA. MAIN RESULTS AND SIGNIFICANCE: We show that our classification pipeline can effectively discriminate between the display of different visual items (Checkerboard versus 3D navigational image) in single EEG trials throughout multiple subjects. The present methodology reaches a single-trial classification accuracy of about 84% and 93% for inter-subject and intra-subject classification respectively using surface EEG. Interestingly, we note that the classification algorithms trained on sLORETA sources estimation fail to generalize among multiple subjects (63%), which may be due to either the average head model used by sLORETA or the subsequent spatial filtering failing to extract discriminative information, but reach an intra-subject classification accuracy of 82%.

A new perspective on individual reliability beyond group effect for event-related potentials: A multisensory investigation and computational modeling.

The dominant approach in investigating the individual reliability for event-related potentials (ERPs) is to extract peak-related features at electrodes showing the strongest group effects. Such a peak-based approach implicitly assumes ERP components showing a stronger group effect are also more reliable, but this assumption has not been substantially validated and few studies have investigated the reliability of ERPs beyond peaks. In this study, we performed a rigorous evaluation of the test-retest reliability of ERPs collected in a multisensory and cognitive experiment from 82 healthy adolescents, each having two sessions. By comparing group effects and individual reliability, we found that a stronger group-level response in ERPs did not guarantee higher reliability. A perspective of neural oscillation should be adopted for the analysis of reliability. Further, by simulating ERPs with an oscillation-based computational model, we found that the consistency between group-level ERP responses and individual reliability was modulated by inter-subject latency jitter and inter-trial variability. The current findings suggest that the conventional peak-based approach may underestimate the individual reliability in ERPs and a neural oscillation perspective on ERP reliability should be considered. Hence, a comprehensive evaluation of the reliability of ERP measurements should be considered in individual-level neurophysiological trait evaluation and psychiatric disorder diagnosis.

A high-density 256-channel cap for dry electroencephalography.

High-density electroencephalography (HD-EEG) is currently limited to laboratory environments since state-of-the-art electrode caps require skilled staff and extensive preparation. We propose and evaluate a 256-channel cap with dry multipin electrodes for HD-EEG. We describe the designs of the dry electrodes made from polyurethane and coated with Ag/AgCl. We compare in a study with 30 volunteers the novel dry HD-EEG cap to a conventional gel-based cap for electrode-skin impedances, resting state EEG, and visual evoked potentials (VEP). We perform wearing tests with eight electrodes mimicking cap applications on real human and artificial skin. Average impedances below 900 kΩ for 252 out of 256 dry electrodes enables recording with state-of-the-art EEG amplifiers. For the dry EEG cap, we obtained a channel reliability of 84% and a reduction of the preparation time of 69%. After exclusion of an average of 16% (dry) and 3% (gel-based) bad channels, resting state EEG, alpha activity, and pattern reversal VEP can be recorded with less than 5% significant differences in all compared signal characteristics metrics. Volunteers reported wearing comfort of 3.6 ± 1.5 and 4.0 ± 1.8 for the dry and 2.5 ± 1.0 and 3.0 ± 1.1 for the gel-based cap prior and after the EEG recordings, respectively (scale 1-10). Wearing tests indicated that up to 3,200 applications are possible for the dry electrodes. The 256-channel HD-EEG dry electrode cap overcomes the principal limitations of HD-EEG regarding preparation complexity and allows rapid application by not medically trained persons, enabling new use cases for HD-EEG.

An optimized facial stimuli paradigm for hybrid SSVEP+P300 brain computer interface.

BACKGROUND: In this paper, hybrid brain-computer interface (BCI) that merges event related potentials (P300) and steady state visual evoked potentials (SSVEP) simultaneously is proposed to enhance the performance of four-choice command system. Here we integrate human facial structure in external visual stimulus to evoke stronger cortical responses in hybrid SSVEP+P300 BCI and compare it with non-face stimuli. We also addressed question of feasibility of eliciting one potential by face and other by non-face stimuli. To evoke SSVEP and P300 responses, paradigms with non-face stimuli, neutral face stimuli, and facial expression changes stimuli are proposed. We also projected additional paradigm where SSVEP is elicited by non-face and P300 by flashing different facial expressions. Results proved the last paradigm evoke stronger cortical potentials and thereby improve system accuracy and ITR than other paradigms. We discuss external stimulus parameters that might affect simultaneous evocation of multiple brain potentials and their deterioration effect on individual potentials. METHODS: Ten healthy volunteers (seven male, aged 22-28 years, mean 25.6 years) contribute in our experiment. LCD screen with refresh rate of 60 Hz is used for external stimulus and all trials are performed in darkened room. RESULTS: The ideal BCI system should have maximum ITR and comfortable rating. We have proven among our paradigms, face emotional and flickering paradigm has maximum comfortableness with highest ITR. CONCLUSIONS: In this paper, we have proposed four paradigms as non-face paradigm, face neutral paradigm, face emotional paradigm, and face-emotional and flicker paradigm. We have tested all paradigms and compared them with each other about potential response strength, accuracy, ITR and comfortableness. Result show that face-emotional and flicker paradigm performed better in all aspects than all four paradigms.

Motion Processing Deficits in Children With Cerebral Visual Impairment and Good Visual Acuity.

Purpose: We sought to characterize neural motion processing deficits in children with cerebral visual impairment (CVI) who have good visual acuity using an objective, quantifiable method (steady-state visual evoked potentials [SSVEPs]). Methods: We recorded SSVEPs in response to three types of visual motion - absolute motion and more complex relative and rotary motion, comparing them to form-related vernier and contour responses. We studied a group of 31 children with CVI diagnosed via detailed clinical examinations and 28 age-matched healthy controls. Results: Using measurements made at the appropriate response harmonics of the stimulation frequency, we found significant deficits in cerebral processing of relative and rotary motion but not of absolute motion in children with CVI compared with healthy controls. Vernier acuity, in keeping with good recognition acuity in both groups, was not different, nor were contour-related form responses. Conclusions: Deficits for complex motion but relative sparing of elementary motion and form-related signals suggests preferential damage to extra-striate visual motion areas in children with CVI. The fact that these preferential losses occur in the absence of significant acuity loss indicates that they are not secondary to reduced visual acuity, but rather are an independent vulnerability in CVI. These results corroborate parental and caregivers' reports of difficulties with tasks that involve motion perception in children with CVI.

Electrophysiological Biomarkers in Genetic Epilepsies.

Precision treatments for epilepsy targeting the underlying genetic diagnoses are becoming a reality. Historically, the goal of epilepsy treatments was to reduce seizure frequency. In the era of precision medicine, however, outcomes such as prevention of epilepsy progression or even improvements in cognitive functions are both aspirational targets for any intervention. Developing methods, both in clinical trial design and in novel endpoints, will be necessary for measuring, not only seizures, but also the other neurodevelopmental outcomes that are predicted to be targeted by precision treatments. Biomarkers that quantitatively measure disease progression or network level changes are needed to allow for unbiased measurements of the effects of any gene-level treatments. Here, we discuss some of the promising electrophysiological biomarkers that may be of use in clinical trials of precision therapies, as well as the difficulties in implementing them.

Visual exposure enhances stimulus encoding and persistence in primary cortex.

The brain adapts to the sensory environment. For example, simple sensory exposure can modify the response properties of early sensory neurons. How these changes affect the overall encoding and maintenance of stimulus information across neuronal populations remains unclear. We perform parallel recordings in the primary visual cortex of anesthetized cats and find that brief, repetitive exposure to structured visual stimuli enhances stimulus encoding by decreasing the selectivity and increasing the range of the neuronal responses that persist after stimulus presentation. Low-dimensional projection methods and simple classifiers demonstrate that visual exposure increases the segregation of persistent neuronal population responses into stimulus-specific clusters. These observed refinements preserve the representational details required for stimulus reconstruction and are detectable in postexposure spontaneous activity. Assuming response facilitation and recurrent network interactions as the core mechanisms underlying stimulus persistence, we show that the exposure-driven segregation of stimulus responses can arise through strictly local plasticity mechanisms, also in the absence of firing rate changes. Our findings provide evidence for the existence of an automatic, unguided optimization process that enhances the encoding power of neuronal populations in early visual cortex, thus potentially benefiting simple readouts at higher stages of visual processing.

Excitatory Contribution to Binocular Interactions in Human Visual Cortex Is Reduced in Strabismic Amblyopia.

Binocular summation in strabismic amblyopia is typically reported as being absent or greatly reduced in behavioral studies and is thought to be because of a preferential loss of excitatory interactions between the eyes. Here, we studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with strabismic and anisometropic amblyopia in both sexes, using source-imaged steady-state visual evoked potentials (SSVEP) over a wide range of relative contrast between the two eyes. Dichoptic parallel grating stimuli modulated at unique temporal frequencies in each eye allowed us to quantify spectral response components associated with monocular inputs (self-terms) and the response components because of interaction of the inputs of the two eyes [intermodulation (IM) terms]. Although anisometropic amblyopes revealed a similar pattern of responses to normal-vision observers, strabismic amblyopes exhibited substantially reduced IM responses across cortical regions of interest (V1, V3a, hV4, hMT+ and lateral occipital cortex), indicating reduced interocular interactions in visual cortex. A contrast gain control model that simultaneously fits self- and IM-term responses within each cortical area revealed different patterns of binocular interactions between individuals with normal and disrupted binocularity. Our model fits show that in strabismic amblyopia, the excitatory contribution to binocular interactions is significantly reduced in both V1 and extra-striate cortex, whereas suppressive contributions remain intact. Our results provide robust electrophysiological evidence supporting the view that disruption of binocular interactions in strabismus or amblyopia is because of preferential loss of excitatory interactions between the eyes.SIGNIFICANCE STATEMENT We studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with normal and amblyopic vision, using source-imaged SSVEP and frequency-domain analysis of dichoptic stimuli over a wide range of relative contrast between the two eyes. A dichoptic contrast gain control model was used to characterize these interactions in amblyopia and provided a quantitative comparison to normal vision. Our model fits revealed different patterns of binocular interactions between normal and amblyopic vision. Strabismic amblyopia significantly reduced excitatory contributions to binocular interactions, whereas suppressive contributions remained intact. Our results provide robust evidence supporting the view that the preferential loss of excitatory interactions disrupts binocular interactions in strabismic amblyopia.

A visual brain-computer interface as communication aid for patients with amyotrophic lateral sclerosis.

OBJECTIVE: Brain-Computer Interface (BCI) spellers that make use of code-modulated Visual Evoked Potentials (cVEP) may provide a fast and more accurate alternative to existing visual BCI spellers for patients with Amyotrophic Lateral Sclerosis (ALS). However, so far the cVEP speller has only been tested on healthy participants. METHODS: We assess the brain responses, BCI performance and user experience of the cVEP speller in 20 healthy participants and 10 ALS patients. All participants performed a cued and free spelling task, and a free selection of Yes/No answers. RESULTS: 27 out of 30 participants could perform the cued spelling task with an average accuracy of 79% for ALS patients, 88% for healthy older participants and 94% for healthy young participants. All 30 participants could answer Yes/No questions freely, with an average accuracy of around 90%. CONCLUSIONS: With ALS patients typing on average 10 characters per minute, the cVEP speller presented in this paper outperforms other visual BCI spellers. SIGNIFICANCE: These results support a general usability of cVEP signals for ALS patients, which may extend far beyond the tested speller to control e.g. an alarm, automatic door, or TV within a smart home.