Week in Review: Number 43

Regions in the Infant Brain are Selective for Visual Targets as Early as Two Months of Age
The prevailing train of thought among neuroscientists is that it takes several years of visual experience for regions in the developing brain to gradually become selective for their specific targets, whether they be faces, body parts, scenes, etc. This hypothesis had been in part due to difficulties in scanning the brains of younger subjects, such as infants, with the same high-resolution imaging that is conducted for adult subjects. Researchers at MIT built a specialized fMRI scanner and protocols that were both more comfortable for babies (such as custom headphones) as well as provided greater power with an adjustable 32-channel coil, at similar imaging resolution as that found in fMRI used to study adult brains. They then recruited nearly 90 babies for the study, ranging in age from two to nine months. Usable data was collected for 52 of the infants, a higher number than any research lab had been able to scan previously. Half of these infants also contributed higher-resolution data. The findings revealed that specific regions of the infant visual cortex show highly selective responses to faces, body parts, and natural scenes, in the same locations where those responses are seen in the adult brain. The cortical areas studied for processing faces included the fusiform face area (FFA), the occipital face area (OFA), and the anterior temporal lobe (ATL); however, only the FFA showed statistically significant selective responses in the infant brain. First author of the study comments, "A lot of theories have grown up in the field of visual neuroscience to accommodate the view that you need years of development for these specialized regions to emerge. And what we're saying is actually, no, you only really need a couple of months." In terms of the fusiform face area in particular, the researchers plan to further investigate how development progresses from the youngest babies they studied to the oldest. These results also help to inform our understanding of brain development in general, for example, how the brain "builds" sets of functionally distinct regions in more or less the same location in each individual person.

Retinal Imaging to Detect Alzheimer's Disease Risk
The vasculature of the retina and its exposure as an extension of the brain allow the eyes to be an excellent organ for monitoring of neurological and systemic diseases. The ability to visibly access the retina via noninvasive imaging techniques opens a valuable window for evaluation of neurological pathologies by retinal fundus imaging, especially as an early biomarker to assess disease risk. Researchers at UC San Diego conducted a cross-sectional pilot study investigating the feasibility of detecting amyloid plaques, a hallmark of Alzheimer's disease, in the retina in the context of clinical trials. Specifically, they analyzed the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial, a nationwide clinical trial exploring ways to reduce or prevent the formation of beta-amyloid deposits in neural tissue. The researchers compared retinal and cerebral amyloid in clinically normal individuals who screened positive for high amyloid levels through positron emission tomography (PET). Additionally, the researchers looked at the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study, which comprises a cohort of individuals who exhibited low levels of amyloid on PET. The authors report, "The four participants from the A4 trial showed a greater number of retinal spots compared to the four participants from the LEARN study. We observed a positive correlation between retinal spots and brain amyloid, as measured by the standardized uptake value ratio (SUVr)." The researchers acknowledge the limitations of the small pilot dataset of only eights patients, adding that "these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD—a preclinical diagnosis—using retinal imaging, rather than more difficult and costly brain scans." They look forward to larger studies, both cross-sectionally and longitudinally.

Once Weekly AM Exposure to Long Wavelength Light Could Improve Declining Color Vision
Mitochondria are the energy organelles of eukaryotic cells, including the eye's photoreceptors, where they exist in high concentration to support the transduction of light that leads to vision. The function of mitochondria naturally decline with age, with an estimated 70% ATP reduction over a lifetime. Some researchers in the U.K. are looking into ways to boost their activity through deep wavelength light stimulation. Specifically, these researchers are translating results they had earlier compiled in animal models such as mice, bumblebees and fruit flies, all showing that exposure to 670 nm (long wavelength) deep red light produced significant improvements in the function of the retina’s photoreceptors. An earlier study from 2020 saw positive results in color vision after 3 minutes of daily exposure to 670 nm light in human subjects. In the present study, the researchers wanted to hone in on the effect of a single 3-minute exposure of deep red light and also reduce the LED wattage from 40mW/cm2 to 8mW/cm2, noting that both are safe. They recruited 20 participants between 34 and 70 years of age and asked them to use a provided LED device emitting 670 nm deep red light for 3 minutes in the morning between 8am and 9am. The participants' color vision was tested 3 hours later, and 10 of the participants were tested again one week later. On average, at 3 hours post-exposure, the participants saw improvement in color contrast sensitivity threshold of 17% for the tritan (blue-yellow) axis and 12% for the protan (red-green) axis. At one week post-exposure, the improvements were maintained at 10% for the tritan axis and 8% for the protan axis. Separate research in flies revealed that mitochondria have "shifting workloads" depending on the time of day. The researchers confirmed this finding in humans when they tested 6 of the 20 participants again several months later for an afternoon protocol from 12pm to 1pm; the subsequent color vision tests showed no improvement in that case. The authors acknowledge a lot of "noise" and variability in their data; nonetheless, these early results are encouraging for improvement of mitochondria-related decline in color contrast sensitivity in older age.

Suppression of Microsaccades in the Foveola
Although each of our two eyes possesses a field of vision of 160 degrees, only the most central region of vision, at the foveola where the cones are most densely packed, contains sharp acuity. In order to direct this tiny area of high resolution at a wide range of objects in the visual field, the eyes dart about, often without conscious awareness, in fixational eye movements called saccades. However, these abrupt "sweeps" across the retina also cause a transient blur in vision, which the brain compensates for in the form of saccadic suppression to create a stabilized percept, or a stable view of the world. That is, the brain briefly, so briefly it does not reach conscious awareness, turns off vision as the eyes shift gaze between objects of fixation. Researchers were interested in whether this transient suppression also happens during microsaccades and whether it affects central vision. Senior author of the study explains, "In our lab we have the high-resolution tools to study vision at this small scale, whereas other research has historically focused on the peripheral regions of the eye, where such precision and accuracy are not required." The researchers designed a computer game of dots jumping on a "naturalistic noise-field background" to represent fleas jumping on animal fur, in turn simulating primate grooming behavior. They then recruited eight participants for two sets of experiments and monitored their gaze with eye-tracking. The results showed that suppression occurred immediately before and immediately after the participants shifted gaze. Surprisingly, however, the researchers also found that central vision contrast sensitivity increased after a saccade, so that overall the effect was transiently enhanced. Although the sample size is small, the authors conclude, "These results shed light on the modulations experienced by foveal vision during the saccade-fixation cycle and explain some of the benefits of microsaccades." They will further look into the balance between saccadic suppression and visual enhancement in future work.

High-Throughput Screening Identifies a Rhodopsin Dimer Enhancer Candidate, GPCRs Studied
The transduction of light in the eye's rod photoreceptors relies on G protein-coupled receptors (GPCR) called rhodopsins (Rh), which are the visual pigments in rod photoreceptors. Researchers at UC Irvine sought to study rhodopsin oligomerization, or self-aggregation, and its effect on the rhodopsin G protein-coupled signaling cascade. They performed high-throughput screening on a diverse library of 50,000 small molecules, including a novel assay to detect rhodopsin dimerization. This screening method identified nine small molecules that either disrupted or enhanced rhodopsin dimer contacts in vitro. One of the compounds (hit compound #7) "significantly slowed down the light response kinetics of intact rods," while another compound (hit compound #1) "cause a significant reduction in light sensitivity." Subsequent free-cell binding analysis showed spectra profiles that are consistent with all nine compounds being allosteric modulators. The authors report "the discovery of new allosteric modulators of rhodopsin dimerization that can also alter rod photoreceptor physiology" and new tools for studying the rhodopsin signaling cascade. Because G protein-coupled receptors (including opioid and adrenergic receptors) mediate a variety of physiological functions, studying these receptors can add to knowledge about how they serve as therapeutic targets for a wide range of diseases. They state that next steps include applying medicinal chemistry to improve the pharmacological properties of the identified compounds.

A Look at COVID-19 Ocular Symptoms
Although loss of taste and smell are by now well-known symptoms of SARS-CoV-2 infection, ocular symptoms have been more perplexing. However, even from the onset of the COVID-19 pandemic, a connection between eyes and the SARS-CoV-2 virus had been noted, for example, in Chinese ophthalmologist Li Wenliang's observations among glaucoma patients. Scientific American  reported on a few recent studies. Almost two years into the pandemic, isolated reports of SARS-CoV-2 ocular signs and symptoms are still far from conclusive. However, systematic review data as of early 2021 estimated that 11% of people who contract COVID-19 develop ocular manifestations, including dry eye or foreign body sensation, redness, tearing, itching, eye pain, and discharge. Conjunctivitis was the most common diagnosis, affecting nearly 90% (79 of 89) of COVID-19 patients with ocular manifestations, suggesting broader consideration of symptoms in the detection of COVID-19. A study from April 2021 found a similar statistic: 9.5% (38 of 400) patients who were hospitalized for COVID-19 in Michigan had ocular manifestations; symptoms in these patients included "conjunctival injection, followed by vision changes and ocular irritation." In Italy, a study from March 2021 found SARS-CoV-2 on the ocular surface of 57% (52 of 91) of patients who were hospitalized for COVID-19. Although SARS-CoV-2 infection via ocular tissue was strongly implicated, but not proven, in some studies of hospital workers with and without mask-wearing, an intervention study in rhesus macaques found direct evidence that inoculating ocular conjunctiva with SARS-CoV-2 caused mild COVID-19 in these monkeys. Although most ocular symptoms resolve on their own, a minority of cases can result in permanent damage, for example, to corneal nerves, rendering susceptible to subsequent injury. Ultimately, the trigeminal nerve, and other facial nerves, provide a connection between the nasal passages, where a respiratory virus such as SAR-CoV-2 is most active, and the eyes. As such, the eyes can display early warning signs of infection, while at the same time being an organ that is susceptible to secondary damage.

In Other News
(1) COVID-19 direct infection in cells of the eye (Related) (Related)
(2) COVID linked to a long list of eye abnormalities
(3) Systematic review: The effect of eye protection on SARS-CoV-2 transmission
(4) Traits that make dogs more likely to catch our eye