Timo Stein

Neural correlates of Alzheimer's disease and mild cognitive impairment: A systematic and quantitative meta-analysis involving 1351 patients

Alzheimers disease is the most common form of dementia. Its prodromal stage amnestic mild cognitive impairment is characterized by deficits of anterograde episodic memory. The development of standardized imaging inclusion criteria has to be regarded as a prerequisite for future diagnostic systems. Moreover, successful treatment requires isolating imaging markers predicting the disease. Accordingly, we conducted a systematic and quantitative meta-analysis to reveal the prototypical neural correlates of Alzheimers disease and its prodromal stage. To prevent any a priori assumptions and enable a data-driven approach only studies applying quantitative automated whole brain analysis were included. Finally, 40 studies were identified involving 1351 patients and 1097 healthy control subjects reporting either atrophy or decreases in glucose utilization and perfusion. The currently most sophisticated and best-validated of coordinate-based voxel-wise meta-analyses was applied (anatomical likelihood estimates). The meta-analysis reveals that early Alzheimers disease affects structurally the (trans-)entorhinal and hippocampal regions, functionally the inferior parietal lobules and precuneus. Results further may suggest that atrophy in the (trans-)entorhinal area/hippocampus and hypometabolism/hypoperfusion in the inferior parietal lobules predicts most reliably the progression from amnestic mild cognitive impairment to Alzheimers disease, whereas changes in the posterior cingulate cortex and precuneus are unspecific. Fully developed Alzheimers disease involved additionally a frontomedian-thalamic network. In conclusion, the meta-analysis characterizes the prototypical neural substrates of Alzheimers disease and its prodromal stage amnestic mild cognitive impairment. By isolating predictive markers it enables successful treatment strategies in the future and contributes to standardized imaging inclusion criteria for Alzheimers disease as suggested for future diagnostic systems.

Breaking Continuous Flash Suppression: A New Measure of Unconscious Processing during Interocular Suppression?

Until recently, it has been thought that under interocular suppression high-level visual processing is strongly inhibited if not abolished. With the development of continuous flash suppression (CFS), a variant of binocular rivalry, this notion has now been challenged by a number of reports showing that even high-level aspects of visual stimuli, such as familiarity, affect the time stimuli need to overcome CFS and emerge into awareness. In this “breaking continuous flash suppression” (b-CFS) paradigm, differential unconscious processing during suppression is inferred when (a) speeded detection responses to initially invisible stimuli differ, and (b) no comparable differences are found in non-rivalrous control conditions supposed to measure non-specific threshold differences between stimuli. The aim of the present study was to critically evaluate these assumptions. In six experiments we compared the detection of upright and inverted faces. We found that not only under CFS, but also in control conditions upright faces were detected faster and more accurately than inverted faces, although the effect was larger during CFS. However, reaction time (RT) distributions indicated critical differences between the CFS and the control condition. When RT distributions were matched, similar effect sizes were obtained in both conditions. Moreover, subjective ratings revealed that CFS and control conditions are not perceptually comparable. These findings cast doubt on the usefulness of non-rivalrous control conditions to rule out non-specific threshold differences as a cause of shorter detection latencies during CFS. Thus, at least in its present form, the b-CFS paradigm cannot provide unequivocal evidence for unconscious processing under interocular suppression. Nevertheless, our findings also demonstrate that the b-CFS paradigm can be fruitfully applied as a highly sensitive device to probe differences between stimuli in their potency to gain access to awareness.

Eye contact facilitates awareness of faces during interocular suppression

Eye contact captures attention and receives prioritized visual processing. Here we asked whether eye contact might be processed outside conscious awareness. Faces with direct and averted gaze were rendered invisible using interocular suppression. In two experiments we found that faces with direct gaze overcame such suppression more rapidly than faces with averted gaze. Control experiments ruled out the influence of low-level stimulus differences and differential response criteria. These results indicate an enhanced unconscious representation of direct gaze, enabling the automatic and rapid detection of other individuals making eye contact with the observer.

Privileged Detection of Conspecifics: Evidence from Inversion Effects during Continuous Flash Suppression.

The rapid visual detection of other people in our environment is an important first step in social cognition. Here we provide evidence for selective sensitivity of the human visual system to upright depictions of conspecifics. In a series of seven experiments, we assessed the impact of stimulus inversion on the detection of person silhouettes, headless bodies, faces and other objects from a wide range of animate and inanimate control categories. We used continuous flash suppression (CFS), a variant of binocular rivalry, to render stimuli invisible at the beginning of each trial and measured the time upright and inverted stimuli needed to overcome such interocular suppression. Inversion strongly interfered with access to awareness for human faces, headless human bodies, person silhouettes, and even highly variable body postures, while suppression durations for control objects were not (inanimate objects) or only mildly (animal faces and bodies) affected by inversion. Furthermore, inversion effects were eliminated when the normal body configuration was distorted. The absence of strong inversion effects in a binocular control condition not involving interocular suppression suggests that non-conscious mechanisms mediated the effect of inversion on body and face detection during CFS. These results indicate that perceptual mechanisms that govern access to visual awareness are highly sensitive to the presence of conspecifics.

Neural processing of visual information under interocular suppression: a critical review

When dissimilar stimuli are presented to the two eyes, only one stimulus dominates at a time while the other stimulus is invisible due to interocular suppression. When both stimuli are equally potent in competing for awareness, perception alternates spontaneously between the two stimuli, a phenomenon called binocular rivalry. However, when one stimulus is much stronger, e.g., due to higher contrast, the weaker stimulus can be suppressed for prolonged periods of time. A technique that has recently become very popular for the investigation of unconscious visual processing is continuous flash suppression (CFS): High-contrast dynamic patterns shown to one eye can render a low-contrast stimulus shown to the other eye invisible for up to minutes. Studies using CFS have produced new insights but also controversies regarding the types of visual information that can be processed unconsciously as well as the neural sites and the relevance of such unconscious processing. Here, we review the current state of knowledge in regard to neural processing of interocularly suppressed information. Focusing on recent neuroimaging findings, we discuss whether and to what degree such suppressed visual information is processed at early and more advanced levels of the visual processing hierarchy. We review controversial findings related to the influence of attention on early visual processing under interocular suppression, the putative differential roles of dorsal and ventral areas in unconscious object processing, and evidence suggesting privileged unconscious processing of emotional and other socially relevant information. On a more general note, we discuss methodological and conceptual issues, from practical issues of how unawareness of a stimulus is assessed to the overarching question of what constitutes an adequate operational definition of unawareness. Finally, we propose approaches for future research to resolve current controversies in this exciting research area.

Rapid Fear Detection Relies on High Spatial Frequencies

Signals of threat—such as fearful faces—are processed with priority and have privileged access to awareness. This fear advantage is commonly believed to engage a specialized subcortical pathway to the amygdala that bypasses visual cortex and processes predominantly low-spatial-frequency information but is largely insensitive to high spatial frequencies. We tested visual detection of low- and high-pass-filtered fearful and neutral faces under continuous flash suppression and sandwich masking, and we found consistently that the fear advantage was specific to high spatial frequencies. This demonstrates that rapid fear detection relies not on low- but on high-spatial-frequency information—indicative of an involvement of cortical visual areas. These findings challenge the traditional notion that a subcortical pathway to the amygdala is essential for the initial processing of fear signals and support the emerging view that the cerebral cortex is crucial for the processing of ecologically relevant signals.

Unconscious processing under interocular suppression: getting the right measure.

In order to demonstrate unconscious visual processing, researchers need to select a technique for rendering stimuli invisible and a measure reflecting the processing of these stimuli. The most popular techniques are backward masking, in which the visibility of a very brief stimulus is degraded by the presentation of a succeeding visual pattern (Breitmeyer and Ogmen, 2006), and interocular suppression, where a stimulus shown to one eye degrades the visibility of a stimulus presented to the other eye (Lin and He, 2009). Recently, much work has been carried out using continuous flash suppression (CFS; Tsuchiya and Koch, 2005), a particularly potent interocular suppression technique. In CFS, a train of high-contrast patterns flashed into one eye can suppress the visibility of a stationary stimulus shown to the other eye for up to several seconds (Figure ​(Figure1).1). Because CFS allows for extended periods of reliable invisibility of complex stimuli, this technique has sparked a surge of interest in unconscious visual processing. Figure 1 Competing models of the processes mediating detection performance in the b-CFS paradigm. (A) The single-process model posits that both the CFS and the control condition measure differences between stimuli in accessing awareness that exist independent ... Ideally, research aimed at delineating the scope and limits of visual processing without awareness should adopt the technique that is most sensitive to unconscious processing. This is because a failure to find evidence for a certain unconscious effect could always be due to constraints imposed by the specific technique rather than to the genuine absence of unconscious processing (Faivre et al., 2012). However, since the extent to which a technique allows for unconscious processing is difficult to determine, and due to a lack of general consensus on valid measures of unconscious processing, no definite criteria exist for choosing the most sensitive technique.

High-level face shape adaptation depends on visual awareness: Evidence from continuous flash suppression

When incompatible images are presented to the two eyes, one image dominates awareness while the other is rendered invisible by interocular suppression. It has remained unclear whether complex visual information can reach high-level processing stages in the ventral visual pathway during such interocular suppression. Here, we asked whether basic face shape, which is thought to be encoded in areas of the ventral stream, can be processed without visual awareness. We measured aftereffects induced by prolonged exposure to distorted faces during continuous flash suppression. Despite constant physical stimulation, in some trials the adaptor face was fully suppressed from awareness, while in other trials it overcame suppression and became partially visible. Aftereffects were induced even by entirely invisible adaptors, albeit reduced compared to partially visible adaptors, and only when adaptor and test stimuli were presented in the same size to the same eye. However, when adaptor and test stimuli were presented to different eyes or to the same eye but in different sizes, aftereffects were restricted to partially visible adaptors. These results suggest that a monocular, low-level component of face shape adaptation escapes interocular suppression and can proceed without visual awareness. By contrast, high-level components of basic face shape encoding involving ventral stream processing are eliminated by interocular suppression and require visual awareness.

The effect of fearful faces on the attentional blink is task dependent.

In a set of three rapid serial visual presentation experiments, we investigated the effect of fearful and neutral face stimuli on the report of trailing scene targets. When the emotional expression of the face stimuli had to be indicated, fearful faces induced a stronger attentional blink (AB) than did neutral faces. However, with identical physical stimulation, the enhancement of the AB by fearful faces disappeared when participants had to judge the faces’ gender. If faces did not have to be reported, no AB was observed. Thus, fearful faces exhibited an effect on the AB that crucially depended on the observer’s attentional set. Hence, the AB can be influenced by an emotional T1 when T1 has to be reported, but this influence is modulated by task context. This result indicates a close connection between temporal attention and emotional processing that is modulated by task context.

Not Just Another Face in The Crowd: Detecting Emotional Schematic Faces During Continuous Flash Suppression

To test whether threatening visual information receives prioritized processing, many studies have examined visual search for emotional schematic faces. Still, it has remained unclear whether negative or positive schematic faces are processed more efficiently. We used continuous flash suppression, a variant of binocular rivalry, to render single emotional schematic faces invisible and measured whether negative or positive faces have an advantage in accessing awareness. Across three experiments, positive faces were detected more quickly than negative faces. A fourth experiment indicated that this positive face advantage was unrelated to the valence of the face stimuli but due to the relative orientation of the mouth curvature and the face contour. These findings demonstrate the impact of configural stimulus properties on perceptual suppression during binocular rivalry and point to a perceptual confound present in emotional schematic faces that might account for some ambiguous results obtained with schematic face stimuli in previous studies.