Week in Review: Number 20

As Novel Sights Become Familiar, High Frequency Brain Rhythms Transition to Lower Frequency Brain Rhythms
Attending to novel stimuli in one's environment is a behavioral response that benefits survival. However, once you learn that the novel stimulus is nothing of significance, it is equally adaptive to no longer pay attention to it. Thus, determining whether a stimulus is novel or not is integral to normal brain function. Dubbed "visual cognition memory," the researchers used a mouse model to study how stimulus selective response plasticity (SRP) correlated with habituation, the behavioral loss of interest in exploring an increasingly familiar stimulus. Their research showed that long-term potentiation (LTP), a strengthening of neural connections amid frequent activity, is involved but does not fully explain visual cognition memory. Inhibitory neurons called parvalbumin (PV) expressing neurons, which produce high frequency gamma rhythms in the cortex, also seem to be involved. As novel visual stimuli become familiar, the gamma rhythms of these PV neurons give way to lower frequency beta rhythms by inhibitory somatostatin (SOM) expressing neurons. The experiments involved engineered mice whose PV or SOM neurons would flash when active, and could be detected with two-photon microscopy. These mice were shown the same grating patterns over several days (including challenge trials) as researchers measured changes in their neuronal activity. This brain rhythm shift provides an externally measurable indicator of the transition from the novel to the familiar. The senior author further explains, "It also offers a new hypothesis for how visual recognition memory is enforced: PV activity, which initially inhibits the SRP electrical response, eventually itself becomes inhibited by SOM activity." The researchers next plan to use optogenetics to manipulate SOM neurons to further test the hypothesis that SOM neurons inhibit PV neurons in the perception of stimuli as novel versus familiar. They also intend to explore whether this neural frequency transition could be used as a biomarker for autism spectrum disorders.

High Caffeine Consumption May Increase Risk of Glaucoma in Those with a Genetic Predisposition
Large amounts of caffeine consumption may increase risk of glaucoma for those with high genetic risk for the disease, according to a study that analyzed medical records of more than 120,000 participants in the U.K. Biobank database between 2006 and 2010. Three years after answering a variety of questionnaires about their caffeine intake and family history, the participants' intraocular pressure was measured. The investigators found that for individuals who consumed more than 321 milligrams of daily caffeine (roughly three cups of coffee), there was a 3.9-fold higher glaucoma prevalence when compared to those who drink no or minimal caffeine and did not have a strong family history of glaucoma. Additionally, those who consumed the highest amount of daily caffeine (more than 480 milligrams or roughly four cups of coffee) had a 0.35 mmHg higher IOP. The lead author adds, “We previously published work suggesting that high caffeine intake increased the risk of the high-tension open angle glaucoma among people with a family history of disease. In this study we show that an adverse relation between high caffeine intake and glaucoma was evident only among those with the highest genetic risk score [those in the top 25th percentile of risk] for elevated eye pressure.” These findings about dietary-genetic interaction in glaucoma could help to inform patients' lifestyle to decrease risk for those with a strong predisposition to elevated eye pressure.

International Coalition Classifies 25 Subtypes of Uveitis
The Standardization of Uveitis Nomenclature (SUN) Working Group, an international coalition of uveitis experts, developed classification criteria for 25 of the most common types of uveitis. Collectively describing over 30 eye diseases characterized by inflammation of the eye, these diseases together comprise the fifth leading cause of blindness in the United States, according to the National Eye Institute. Such inflammation can be seen in structures beyond the uvea, depending on the type of disease, and have different causes, courses, prognoses, and treatment needs. As the project lead comments, "The agreement among uveitis experts on the diagnosis of individual diseases was modest at best." Until recently, the classification of uveitis was based on the primary location of inflammation, such as anterior and posterior uveitis, or intermediate uveitis and panuveitis. To help them identify the important characteristics that distinguished each disease, the team first used informatics to standardize language used to describe the individual diseases, followed by formal consensus techniques among nine uveitis experts reviewing 5,766 cases (averaging 100-250 of each uveitis type), and finally applied machine learning to the 4,046 cases that had at least 75% agreement among the expert reviewers. The overall performance of the criteria was over 90% within uveitic class. Such a classification system would greatly enhance research efforts in "epidemiological studies, translational studies, pathogenesis research, outcomes research, and clinical trials," says the project lead, and "hopefully will yield better disease-specific approaches to diagnosis and treatment."

Echolocation Training in Blind and Sighted People
Researchers in the U.K. investigated factors that influence learning a new sensory skill, in this case click-based echolocation, in both blind and sighted individuals. Specifically, they wanted to determine whether blindness and age affected learning of the new auditory skill. The study involved 14 sighted participants and 12 blind participants, ranging from 21 to 79 years of age, over a 10-week training program. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life. "We found that both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training," the authors report, "Importantly, neither age nor blindness was a limiting factor in participants’ rate of learning (i.e. their difference in performance from the first to the final session) or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing." The results suggest that neither age nor level of vision was a limiting factor in learning click-based echolocation. Though there is the possibility of a perceived stigma surrounding making the required clicks in social environments, the findings in this group of participants indicate that both blind and sighted people were confident to use it in social situations. Currently, click-based echolocation is not taught as part of mobility training and rehabilitation for blind people, though based on surveys of improved independence and well-being in blind individuals, introducing training in this sensory modality should be considered.

Both Active & Sham Play Improve Visuo-Motor Skills
Vision guides movement. But input from the motor cortex may also guide the visual system. To explore the connection, the authors designed an experiment with three scenarios: (1) "active play" of a racing video game with traditional hand controls, (2) "sham play" in which participants were made to believe they were controlling the video game with their brain activity, (3) and "passive viewing" of a prerecorded playback of the video game. Because movement (both real and imagined) also produces increased attention that could affect changes in visual processing, the authors developed a second study in which participants were asked to count the appearance of specific images on the screen while passively viewing the game. Electroencephalography (EEG) of alpha-band (8–12 Hz) activity, which appear before performing motor tasks, showed reduced correlation during passive viewing, but no difference between active and sham play, indicating recruitment of the motor cortex despite the absence of overt movement. Counting showed weak evidence, less than statistical significance, that attention was not responsible for the observed differences. The latter finding are likely due to the very small sample size of only 24 participants, of which only one-third were assigned to the sham task. Despite this limitation, the study provides some evidence for the effect of both active and sham play in eliciting visual evoked potentials as compared to passive viewing in support of the view that visual signals are enhanced during movement. That is, motion might also guide vision. Future studies with larger population sizes would provide greater statistical significance.

In Other News
(1) Visual masking phenomenon in infants
(2) How blind people see with sound (2019)
(3) Encouraging parents to schedule eye exam for kids