Week in Review: Number 42

Optical Illusion Combines Phi Phenomenon and Oscillating High Contrast Patterns
A new optical illusion is making its rounds for the enjoyment of netizens. The original version, which first appeared in 2020 and attributed to Japanese digital artist Jagarikin, displays a pair of rotating blue-and-yellow circles each encompassing one or four arrows that change directions, with the direction that the arrows point to influencing the perception of the forward motion of the circles. Other variations of the illusion have been created since then, including a black and white version and a version in rainbow colors. (A variation using Necker cubes also seems to be related.) The latest version in rainbow colors has been dissected by viewers to demonstrate, for example, that the illusion persists even when the arrows are removed and that the circles are indeed stationary. For cognitive—in addition to visual—entertainment, curious observers have also investigated the underlying properties that give the illusion its effect. The first is the phi phenomenon, which most of us are familiar with in the form of animated films. In its simplest instantiation, spots moving in succession in the form of a circle create the illusion of forward motion. (In a related phenomenon, called the reverse phi phenomenon, if the second point becomes light rather than dark, then we perceive the motion as moving in the opposite or reverse direction.) Other elements of the optical illusion perhaps include the Müller-Lyer illusion (as seen in a star formation here), wherein varying the direction of arrowheads influences the perception of length. (Additionally, the version in black and white seems to make use of the barberpole illusion.) And finally, it has been noted (in still frame) that each circle is flanked by inner and outer edges with colors that contrast with the body of the circle. The high contrast suggests that the subtleties of the illusion also rely on oscillating positive-negative patterns, for example as seen in two-stroke or four-stroke apparent motion. For both visual and cognitive reasons, optical illusions provide a perplexing but fun reminder of the complex, and sometimes inaccurate, ways in which our visual systems represent the world we see.

Eye-Tracking Software Developed for fMRI
Viewing behavior can provide meaningful information about neurological health. As such, eye-tracking technology can be clinically relevant in the diagnosis and management of neurological injury. Typically, this eye-tracking comes in the form of sensor technology, in which infrared light is projected onto the retina, reflected, and then measured by the sensor. Although functional magnetic resonance imaging (fMRI) is the gold standard of functional brain imaging, MRIs use strong magnets and integrating MRI-compatible camera systems often comes at a high cost. This has thus far prevented the widespread use of eye-tracking in MRI exams. Researchers at the Max Planck Institute in Germany sought to improve upon eye-tracking availability by directly applying software to fMRI. These researchers developed a software called DeepMReye, a convolutional neural network (CNN) that decodes gaze position from the magnetic resonance signal of the eyeballs. Notable features of this technology include the fact that it performs cameraless eye-tracking during an fMRI scan, and works even in existing datasets and when the eyes are closed. First author of the study explains, "The neural network we use detects specific patterns in the MRI signal from the eyes. This allows us to predict where the person is looking." The software is trained on both publicly available data and study participants to now be able to perform eye-tracking on data that it was not trained on, such as existing MRI imaging that was previously acquired without eye-tracking. Because the software can predict eye movements even when the eyes are closed, it can facilitate studies of individuals in a sleeping state or of individuals who are blind. In the latter case, the researchers remark that whereas traditional eye-tracking has suffered from calibration difficulties in blind patients, "Here too, studies can be carried out more easily with DeepMReye, as the artificial intelligence can be calibrated with the help of healthy subjects and then be applied in examinations of blind patients." They have made the DeepMReye software an open source application for other researchers to use in the hopes of making eye-tracking more widespread in MRI examinations.

Drusen Formation Linked to Extracellular Vesicle Release by RPE Cells
Drusen are deposits that accumulate under the retina, between the retinal pigmented epithelium (RPE) and Bruch's membrane of the underlying choriocapillaris (of the choroid). The accumulation of drusen signals the, often age-related, decline in RPE function in recycling and maintaining photoreceptor health, leading to retinal diseases such as age-related macular degeneration (AMD). Researchers have for the first time observed evidence of RPE cells releasing exosomes that contain both normal proteins and proteins that are associated with drusen. This occurs in normal physiological conditions, and is increased 20 times under conditions of cellular stress. Moreover, the secretion of extracellular vesicles (EVs) by the RPE cells exhibited polarity or directionality. The authors write, "Notably, drusen-associated proteins exhibited distinctive directional secretion modes in homeostatic conditions and, differential modulation of this directional secretion in response to AMD stressors." For example, when treated with cigarette smoke extract (CSE) as a stressor and known risk factor for AMD, the RPE cells exhibited notably increased release of EVs from their apical surface compared to their basal surface. The RPE and Bruch's membrane share an apex-to-apex attachment, due to involution of the optic cup during development. The researchers suggest that these drusen-associated proteins could provide an early biomarker of AMD. First author of the study remarks, "Knowing that extracellular vesicles are releasing drusen-associated proteins presents an opportunity for novel diagnostic and therapeutical approaches. If we can define assays to measure these proteins released in these exosomes, we could potentially diagnose the disease early." Senior researcher of the project adds, "If we understand how drusen form and what cells or mechanisms contribute to their formation, we may be able to control the formation of drusen and slow down or even, perhaps prevent, some of the pathological events leading to AMD." They conclude, "Collectively, our results strongly support an active role of RPE-derived EVs as a key source of drusen proteins and important contributors to drusen development and growth."

Retinoids Explored as Treatment for Usher Syndrome
Usher syndrome type 1F (USH1F) is characterized by deafness, progressive retinal degeneration, and vestibular areflexia. Its prevalance is highest among Ashkenazi Jews, with carrier genes accounting for roughly 60% of their Usher syndrome type 1 cases. Thus far, there is no treatment for the disease. In the 2000s, a few scientists began collecting data about the natural history of USH1F disease progression, enrolling 13 participants with USH1F to follow the natural progression of their accompanying blindness over 20 or more years. This longitudinal phenotyping revealed progressive retinal degeneration leading to severe vision loss with macular atrophy by the sixth decade, with half of the individuals being legally blind by their mid-50s. Simultaneously, other scientists were working on a mouse model of an Usher syndrome variant found in 13 of the patients in the natural history project. The most recent work combined the research findings that had been independently collected in the human subjects and the mouse models. The collaboration led to new discoveries, such as identifying the function of a previously identified gene, PCDH15, that leads to a shortened version of the protein protocadherin-15 (mutation Pcdh15^R250X). They found that protocadherin-15 helps light-dark cycle proteins move back and forth between the different compartments of the eye's photoreceptors, and is required in recycling of retinoids by the retinal pigmented epithelium (RPE). Reduced levels of retinoid cycle proteins (RPE65 and CRALBP) were found in mice with USH1F mutation. Next, the researchers explored whether supplementing retinoids would improve vision in these mice. They report that "[e]xogenous 9-cis retinal improved ERG amplitudes in Pcdh15^R250X mice." One of the researchers remarks, "There are currently FDA-approved relatives of these retinoid drugs that are available and have passed clinical trials for safety, along with others that are in Phase II clinical trials to treat other types of vision loss disorders." They hope to test these drugs in clinical trials. Although the drugs will not recover lost vision, they might help Usher syndrome patients with function of the retinal tissue that they still have.

A Shared Neural Code for Recognizing Familiar Faces
The ability to recognize familiar faces is important in shaping social interaction. Scientists wondered whether there is a shared neural code for recognition of visually and personally familiar faces across the brains of individuals who know each other. The study recruited 14 graduate students from the same PhD program (who had known each other for at least two years) and obtained fMRI data of their brain activity in three sessions. The researchers used two methods to study face and identity perception: hyperalignment and between-subject classifiers. Hyperalignment aligns participants' brain activity to a common representational space to allow for comparing of similarities between participants. Between-subject multivariate decoding uses machine learning to predict what stimuli a participant is looking at based on the brain activity of other participants, here serving as a direct test for the presence of shared information across the brains of different participants. In two of the fMRI tasks, participants were presented images of four other personally familiar graduate students and four visually familiar people unknown to them. In a third task, participants watched parts of a movie. Hyperalignment and between-subject classifiers were applied to this data.

The results showed that the identity of visually familiar faces was decoded with accuracy in brain areas involved in visual processing of faces (e.g., the occipital face area and the fusiform face area). However, the identity of personally familiar faces was decoded with accuracy in brain areas involved in both visual processing and social cognition; these additional brain areas include the dorsal medial prefrontal cortex (processes other people's intentions), the precuneus (personally familiar faces), the insula (emotions), and the temporal parietal junction (social cognition, theory of mind). Stated differently, the identity of both visually and personally familiar faces could be decoded across participants from brain activity in visual areas, but only the identity of personally familiar faces could be decoded in areas involved in social cognition. One of the authors of the study remarks, “It would have been quite possible that everybody has their own private code for what people are like, but this is not the case. Our research shows that processing familiar faces really has to do with general knowledge about people.” In other words, individually distinct information about faces is encoded in brain activity that is shared across brains. The researchers next plan to investigate how shared person knowledge maps onto psychological dimensions and the role of individual differences in mapping shared representational space. First author of the study states, “Our findings and methodological approach might help elucidate impairments in social interactions for some classes of disorders.”

In the News
(1) Distinctive Voices Lecture: Seeing what isn't there (optical illusions)
(2) Optical illusions: colors and context
(3) Jays found to be sensitive to cognitive illusions