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Magneto- and electroencephalography (M/EEG) are widespread techniques to measure neural activity in-vivo at a high temporal resolution but low spatial resolution. Locating the neural sources underlying the M/EEG poses an inverse problem, which is ill-posed. We developed a new method based on Recursive Application of Multiple Signal Classification (MUSIC). Our proposed method is able to recover not only the locations but, in contrast to other inverse solutions, also the extent of active brain regions flexibly (FLEX-MUSIC). This is achieved by allowing it to search not only for single dipoles but also dipole clusters of increasing extent to find the best fit during each recursion. FLEX-MUSIC achieved the highest accuracy for both single dipole and extended sources compared to all other methods tested. Remarkably, FLEX-MUSIC was capable to accurately estimate the level of sparsity in the source space (r = 0.82), whereas all other approaches tested failed to do so (r ≤ 0.18). The average computation time of FLEX-MUSIC was considerably lower compared to a popular Bayesian approach and comparable to that of another recursive MUSIC approach and eLORETA. FLEX-MUSIC produces only few errors and was capable to reliably estimate the extent of sources. The accuracy and low computation time of FLEX-MUSIC renders it an improved technique to solve M/EEG inverse problems both in neuroscience research and potentially in pre-surgery diagnostic in epilepsy.

BACKGROUND: During observation of the Necker cube perception becomes unstable and alternates repeatedly between a from-above-perspective ("fap") and a from-below-perspective ("fbp") interpretation. Both interpretations are physically equally plausible, however, observers usually show an a priori top-down bias in favor of the fap interpretation. Patients with Autism spectrum disorder are known to show an altered pattern of perception with a focus on sensory details. In the present study we tested whether this altered perceptual processing affects their reversal dynamics and reduces the perceptual bias during Necker cube observation. METHODS: 19 participants with Asperger syndrome and 16 healthy controls observed a Necker cube stimulus continuously for 5 minutes and indicated perceptual reversals by key press. We compared reversal rates (number of reversals per minute) and the distributions of dwell times for the two interpretations between observer groups. RESULTS: Asperger participants showed less perceptual reversal than controls. Six Asperger participants did not perceive any reversal at all, whereas all observers from the control group perceived at least five reversals within the five minutes observation time. Further, control participants showed the typical perceptual bias with significant longer median dwell times for the fap compared to the fbp interpretation. No such perceptual bias was found in the Asperger group. DISCUSSION: The perceptual system weights the incomplete and ambiguous sensory input with memorized concepts in order to construct stable and reliable percepts. In the case of the Necker cube stimulus, two perceptual interpretations are equally compatible with the sensory information and internal fluctuations may cause perceptual alternations between them-with a slightly larger probability value for the fap interpretation (perceptual bias). Smaller reversal rates in Asperger observers may result from the dominance of bottom-up sensory input over endogenous top-down factors. The latter may also explain the absence of a fap bias.

One of the great challenges in psychiatry is finding reliable biomarkers that may allow for more accurate diagnosis and treatment of patients. Neural variability received increasing attention in recent years as a potential biomarker. In the present explorative study we investigated temporal variability in visually evoked EEG activity in a cohort of 16 adult participants with Asperger Syndrome (AS) and 19 neurotypical (NT) controls. Participants performed a visual oddball task using fine and coarse checkerboard stimuli. We investigated various measures of neural variability and found effects on multiple time scales. (1) As opposed to the previous studies, we found reduced inter-trial variability in the AS group compared to NT. (2) This effect builds up over the entire course of a 5-min experiment and (3) seems to be based on smaller variability of neural background activity in AS compared to NTs. The here reported variability effects come with considerably large effect sizes, making them promising candidates for potentially reliable biomarkers in psychiatric diagnostics. The observed pattern of universality across different time scales and stimulation conditions indicates trait-like effects. Further research with a new and larger set of participants are thus needed to verify or falsify our findings.

The electroencephalography (EEG) is a well-established non-invasive method in neuroscientific research and clinical diagnostics. It provides a high temporal but low spatial resolution of brain activity. To gain insight about the spatial dynamics of the EEG, one has to solve the inverse problem, i.e., finding the neural sources that give rise to the recorded EEG activity. The inverse problem is ill-posed, which means that more than one configuration of neural sources can evoke one and the same distribution of EEG activity on the scalp. Artificial neural networks have been previously used successfully to find either one or two dipole sources. These approaches, however, have never solved the inverse problem in a distributed dipole model with more than two dipole sources. We present ConvDip, a novel convolutional neural network (CNN) architecture, that solves the EEG inverse problem in a distributed dipole model based on simulated EEG data. We show that (1) ConvDip learned to produce inverse solutions from a single time point of EEG data and (2) outperforms state-of-the-art methods on all focused performance measures. (3) It is more flexible when dealing with varying number of sources, produces less ghost sources and misses less real sources than the comparison methods. It produces plausible inverse solutions for real EEG recordings from human participants. (4) The trained network needs <40 ms for a single prediction. Our results qualify ConvDip as an efficient and easy-to-apply novel method for source localization in EEG data, with high relevance for clinical applications, e.g., in epileptology and real-time applications.

BACKGROUND: Asperger Autism is a lifelong psychiatric condition with highly circumscribed interests and routines, problems in social cognition, verbal and nonverbal communication, and also perceptual abnormalities with sensory hypersensitivity. To objectify both lower-level visual and cognitive alterations we looked for differences in visual event-related potentials (EEG) between Asperger observers and matched controls while they observed simple checkerboard stimuli. METHODS: In a balanced oddball paradigm checkerboards of two checksizes (0.6° and 1.2°) were presented with different frequencies. Participants counted the occurrence times of the rare fine or rare coarse checkerboards in different experimental conditions. We focused on early visual ERP differences as a function of checkerboard size and the classical P3b ERP component as an indicator of cognitive processing. RESULTS: We found an early (100-200 ms after stimulus onset) occipital ERP effect of checkerboard size (dominant spatial frequency). This effect was weaker in the Asperger than in the control observers. Further a typical parietal/central oddball-P3b occurred at 500 ms with the rare checkerboards. The P3b showed a right-hemispheric lateralization, which was more prominent in Asperger than in control observers. DISCUSSION: The difference in the early occipital ERP effect between the two groups may be a physiological marker of differences in the processing of small visual details in Asperger observers compared to normal controls. The stronger lateralization of the P3b in Asperger observers may indicate a stronger involvement of the right-hemispheric network of bottom-up attention. The lateralization of the P3b signal might be a compensatory consequence of the compromised early checksize effect. Higher-level analytical information processing units may need to compensate for difficulties in low-level signal analysis.

BACKGROUND: In von Schiller's Stroboscopic Alternative Motion (SAM) stimulus two visually presented diagonal dot pairs, located on the corners of an imaginary rectangle, alternate with each other and induce either horizontal, vertical or, rarely, rotational motion percepts. SAM motion perception can be described by a psychometric function of the dot aspect ratio ("AR", i.e. the relation between vertical and horizontal dot distances). Further, with equal horizontal and vertical dot distances (AR = 1) perception is biased towards vertical motion. In a series of five experiments, we presented tactile SAM versions and studied the role of AR and of different reference frames for the perception of tactile apparent motion. METHODS: We presented tactile SAM stimuli and varied the ARs, while participants reported the perceived motion directions. Pairs of vibration stimulators were attached to the participants' forearms and stimulator distances were varied within and between forearms. We compared straight and rotated forearm conditions with each other in order to disentangle the roles of exogenous and endogenous reference frames. RESULTS: Increasing the tactile SAM's AR biased perception towards vertical motion, but the effect was weak compared to the visual modality. We found no horizontal disambiguation, even for very small tactile ARs. A forearm rotation by 90° kept the vertical bias, even though it was now coupled with small ARs. A 45° rotation condition with crossed forearms, however, evoked a strong horizontal motion bias. DISCUSSION: Existing approaches to explain the visual SAM bias fail to explain the current tactile results. Particularly puzzling is the strong horizontal bias in the crossed-forearm conditions. In the case of tactile apparent motion, there seem to be no fixed priority rule for perceptual disambiguation. Rather the weighting of available evidence seems to depend on the degree of stimulus ambiguity, the current situation and on the perceptual strategy of the individual observer.

AIM: The present study utilizes perceptual hysteresis effects to compare the ambiguity of Mona Lisa's emotional face expression (high-level ambiguity) and of geometric cube stimuli (low-level ambiguity). METHODS: In two experiments we presented series of nine Mona Lisa variants and nine cube variants. Stimulus ambiguity was manipulated by changing Mona Lisa's mouth curvature (Exp. 1) and the cubes' back-layer luminance (Exp. 2). Each experiment consisted of three conditions, two with opposite stimulus presentation sequences with increasing and decreasing degrees of ambiguity, respectively, and a third condition with a random presentation sequence. Participants indicated happy or sad face percepts (Exp. 1) and alternative 3D cube percepts (Exp. 2) by key presses. We studied the influences of a priori perceptual biases (long-term memory) and presentation order (short-term memory) on perception. RESULTS: Perception followed sigmoidal functions of the stimulus ambiguity morphing parameters. The morphing parameter for the functions' inflection points depended strongly on stimulus presentation order with similar effect sizes but different signs for the two stimulus types (positive hysteresis / priming for the cubes; negative hysteresis / adaptation for Mona Lisa). In the random conditions, the inflection points were located in the middle between those from the two directional conditions for the Mona Lisa stimuli. For the cube stimuli, they were superimposed on one sigmoidal function for the ordered condition. DISCUSSION: The hysteresis effects reflect the influence of short-term memory during the perceptual disambiguation of ambiguous sensory information. The effects for the two stimulus types are of similar size, explaining up to 34% of the perceptual variance introduced by the paradigm. We explain the qualitative difference between positive and negative hysteresis with adaptation for Mona Lisa and with priming for the cubes. In addition, the hysteresis paradigm allows a quantitative determination of the impact of adaptation and priming during the resolution of perceptual ambiguities. The asymmetric shifts of inflection points in the case of the cube stimuli is likely due to an a priori perceptual bias, reflecting an influence of long-term memory. Whether corresponding influences also exist for the Mona Lisa variants is so far unclear.

INTRODUCTION: During observation of the ambiguous Necker cube, our perception suddenly reverses between two about equally possible 3D interpretations. During passive observation, perceptual reversals seem to be sudden and spontaneous. A number of theoretical approaches postulate destabilization of neural representations as a pre-condition for reversals of ambiguous figures. In the current study, we focused on possible Electroencephalogram (EEG) correlates of perceptual destabilization, that may allow prediction of an upcoming perceptual reversal. METHODS: We presented ambiguous Necker cube stimuli in an onset-paradigm and investigated the neural processes underlying endogenous reversals as compared to perceptual stability across two consecutive stimulus presentations. In a separate experimental condition, disambiguated cube variants were alternated randomly, to exogenously induce perceptual reversals. We compared the EEG immediately before and during endogenous Necker cube reversals with corresponding time windows during exogenously induced perceptual reversals of disambiguated cube variants. RESULTS: For the ambiguous Necker cube stimuli, we found the earliest differences in the EEG between reversal trials and stability trials already 1 s before a reversal occurred, at bilateral parietal electrodes. The traces remained similar until approximately 1100 ms before a perceived reversal, became maximally different at around 890 ms (p = 7.59 × 10(-6), Cohen's d = 1.35) and remained different until shortly before offset of the stimulus preceding the reversal. No such patterns were found in the case of disambiguated cube variants. DISCUSSION: The identified EEG effects may reflect destabilized states of neural representations, related to destabilized perceptual states preceding a perceptual reversal. They further indicate that spontaneous Necker cube reversals are most probably not as spontaneous as generally thought. Rather, the destabilization may occur over a longer time scale, at least 1 s before a reversal event, despite the reversal event as such being perceived as spontaneous by the viewer.

The information available through our senses is noisy, incomplete, and to varying degrees ambiguous. The perceptual system must create stable and reliable percepts out of this restricted information. It solves this perceptual inference problem by integrating memories of previous percepts and making predictions about the perceptual future. Using ambiguous figures and a new experimental approach, we studied whether generating predictions based on regularities in the past affects processing of the present and how this is done. Event-related potentials (ERPs) were measured to investigate whether a highly regular temporal context of either ambiguous or unambiguous stimulus variants differently affects processing of a current stimulus and/or task execution. Further, we tested whether symbolic announcements about the immediate perceptual future can replace the past experience of regularities as a source for making predictions. Both ERP and reaction time varied as a function of stimulus ambiguity in the temporal context of a present stimulus. No such effects were found with symbolic announcements. Our results indicate that predictions about the future automatically alter processing of the present, even if the predictions are irrelevant for the present percept and task. However, direct experiences of past regularities are necessary for predicting the future whereas symbolic information about the future is not sufficient.

The P3b is a prominent event-related potential (ERP) with maximal amplitude between 250 ms and 500 ms after the onset of a rare target stimulus within a sequence of standard non-target stimuli (oddball paradigm). Several studies found reduced P3b amplitudes in patients with schizophrenia compared to neurotypicals. Our work and the literature suggest that temporal imprecision may play a large pathophysiological role in schizophrenia. Here, we investigated whether reduced P3b amplitudes result from reduced neural activity (power) or temporal imprecision (inter-trial phase coherence; ITC) in delta and theta bands, using two EEG datasets from different studies with different oddball paradigms (Study 1: 19 patients with schizophrenia and 17 matched controls, Study 2: 26 patients and 26 controls). Both studies revealed typical P3b ERP components with smaller amplitudes in patients. Reduced ITC in patients was found in the delta band, which correlated with P3b peak amplitudes for all participant groups (ρ = 0.58-0.89). In Study 1, we also found significant differences between patients and controls in ITC in the theta band, which also correlated with P3b peak amplitudes (patients' ρ = 0.64, controls' ρ = 0.54). This was not found in Study 2. The results indicate that P3b amplitude reduction in patients with schizophrenia is linked to a reduction in temporal precision of neural activity. These results expand the notion of imprecision in temporal processing at phenomenological, psychological, and neurological levels that have been related to disturbances of the sense of self. They confirm that temporal imprecision may be more important than the reduction of neural activity itself.

The information available through our senses is noisy, incomplete, and ambiguous. Our perceptual systems have to resolve this ambiguity to construct stable and reliable percepts. Previous EEG studies found large amplitude differences in two event-related potential (ERP) components 200 and 400 ms after stimulus onset when comparing ambiguous with disambiguated visual information ("ERP Ambiguity Effects"). These effects so far generalized across classical ambiguous figures from different visual categories at lower (geometry, motion) and intermediate (Gestalt perception) levels. The present study aimed to examine whether these ERP Effects are restricted to ambiguous figures or whether they also occur for different degrees of visibility. Smiley faces with low and high visibility of emotional expressions, as well as abstract figures with low and high visibility of a target curvature were presented. We thus compared ambiguity effects in geometric cube stimuli with visibility in emotional faces, and with visibility in abstract figures. ERP Effects were replicated for the geometric stimuli and very similar ERP Effects were found for stimuli with emotional face expressions but also for abstract figures. Conclusively, the ERP amplitude effects generalize across fundamentally different stimulus categories and show highly similar effects for different degrees of stimulus ambiguity and stimulus visibility. We postulate the existence of a high-level/meta-perceptual evaluation instance, beyond sensory details, that estimates the certainty of a perceptual decision. The ERP Effects may reflect differences in evaluation results.

The electroretinogram (ERG), a non-invasive electrophysiological tool used in ophthalmology, is increasingly applied to investigate neural correlates of depression. The present study aimed to reconsider previous findings in major depressive disorder (MDD) reporting (1) a diminished contrast sensitivity and (2) a reduced patten ERG (PERG) amplitude ratio, and additionally, to assess (3) the photopic negative response (PhNR) from the flash ERG (fERG), with the RETeval® device, a more practical option for clinical routine use. We examined 30 patients with a MDD and 42 healthy controls (HC), assessing individual contrast sensitivity thresholds with an optotype-based contrast test. Moreover, we compared the PERG ratio, an established method for early glaucoma detection, between both groups. The handheld ERG device was used to measure amplitudes and peak times of the fERG components including a-wave, b-wave and PhNR in both MDD patients and HCs. MDD patients exhibited diminished contrast sensitivity together with a reduced PERG ratio, compared to HC. With the handheld ERG device, we found reduced a-wave amplitudes in MDD, whereas no significant differences were observed in the fERG b-wave or PhNR between patients and controls. The reduced contrast sensitivity and PERG ratio in MDD patients supports the hypothesis that depression is associated with altered visual processing. The findings underscore the PERG's potential as a possible objective marker for depression. The reduced a-wave amplitude recorded with the RETeval® system in MDD patients might open new avenues for using handheld ERG devices as simplified approaches for advancing depression research compared to the PERG.

Background: The retina has gained increasing attention in non-ophthalmological research in recent years. The pattern electroretinogram (PERG), a method to evaluate retinal ganglion cell function, has been used to identify objective correlates of the essentially subjective state of depression. A reduction in the PERG contrast gain was demonstrated in patients with depression compared to healthy controls with normalization after remission. PERG responses are not only modulated by stimulus contrast, but also by check size and stimulation frequency. Therefore, the rationale was to evaluate potentially more feasible procedures for PERG recordings in daily diagnostics in psychiatry. Methods: Twenty-four participants (12 patients with major depression (MDD) and 12 age- and sex-matched healthy controls) were examined in this pilot study. We investigated PERG amplitudes for two steady-state pattern reversal frequencies (12.5/18.75 rps) and four sizes of a checkerboard stimulus (0.8°, 1.6°, 3.2°, and 16°) to optimize the PERG recordings in MDD patients. Results: Smaller PERG amplitudes in MDD patients were observed for all parameters, whereby the extent of the reduction appeared to be stimulus-specific. The most pronounced decline in the PERG of MDD patients was observed at the higher stimulation frequency and the finest pattern, whilst responses for the largest check size were less affected. Following the PERG ratio protocol for early glaucoma, where similar stimulus dependent modulations have been reported, we calculated PERG ratios (0.8°/16°) for all participants. At the higher frequency (18.75 rps), significantly reduced ratios were observed in MDD patients. Conclusion: The "normalization" of the PERG responses-via building a ratio-appears to be a very promising approach with regard to the development of an objective biomarker of the depressive state, facilitating inter-individual assessments of PERG recordings in patients with psychiatric disorders.

Since the retina shares its embryological origin with the central nervous system, optical coherence tomography (OCT), an imaging technique frequently employed in ophthalmology to analyze the macula and intraretinal layer thicknesses and volumes, has recently become increasingly important in psychiatric research. We examined 34 autistic and 31 neurotypical adults (NT) using OCT. Autistic adults had reduced overall macular and outer nuclear layer (ONL) thickness and volume compared to NT. Both macular and ONL thickness showed significant inverse associations with the severity of autistic symptoms measured with the Social Responsiveness Scale 2 (SRS-2). Longitudinal studies across different age groups are required to clarify whether retinal changes may represent a possible trait marker.

Ophthalmological methods have increasingly raised the interest of neuropsychiatric specialists. While the integrity of the retinal cell functions can be evaluated with the electroretinogram (ERG), optical coherence tomography (OCT) allows a structural investigation of retinal layer thicknesses. Previous studies indicate possible functional and structural retinal alterations in patients with schizophrenia. Twenty-five patients with paranoid schizophrenia and 25 healthy controls (HC) matched for age, sex, and smoking status participated in this study. Both, ERG and OCT were applied to obtain further insights into functional and structural retinal alterations. A significantly reduced a-wave amplitude and thickness of the corresponding para- and perifoveal outer nuclear layer (ONL) was detected in patients with paranoid schizophrenia with a positive correlation between both measurement parameters. Amplitude and peak time of the photopic negative response (PhNR) and thickness of the parafoveal ganglion cell layer (GCL) were decreased in patients with schizophrenia compared to HC. Our results show both structural and functional retinal differences between patients with paranoid schizophrenia and HC. We therefore recommend the comprehensive assessment of the visual system of patients with schizophrenia, especially to further investigate the effect of antipsychotic medication, the duration of illness, or other factors such as inflammatory or neurodegenerative processes. Moreover, longitudinal studies are required to investigate whether the functional alterations precede the structural changes.