Training-induced changes in population receptive field properties in visual cortex: Impact of eccentric vision training on population receptive field properties and the crowding effect.

This study aimed to investigate the impact of eccentric-vision training on population receptive field (pRF) estimates to provide insights into brain plasticity processes driven by practice. Fifteen participants underwent functional magnetic resonance imaging (fMRI) measurements before and after behavioral training on a visual crowding task, where the relative orientation of the opening (gap position: up/down, left/right) in a Landolt C optotype had to be discriminated in the presence of flanking ring stimuli. Drifting checkerboard bar stimuli were used for pRF size estimation in multiple regions of interest (ROIs): dorsal-V1 (dV1), dorsal-V2 (dV2), ventral-V1 (vV1), and ventral-V2 (vV2), including the visual cortex region corresponding to the trained retinal location. pRF estimates in V1 and V2 were obtained along eccentricities from 0.5° to 9°. Statistical analyses revealed a significant decrease of the crowding anisotropy index (p = 0.009) after training, indicating improvement on crowding task performance following training. Notably, pRF sizes at and near the trained location decreased significantly (p = 0.005). Dorsal and ventral V2 exhibited significant pRF size reductions, especially at eccentricities where the training stimuli were presented (p < 0.001). In contrast, no significant changes in pRF estimates were found in either vV1 (p = 0.181) or dV1 (p = 0.055) voxels. These findings suggest that practice on a crowding task can lead to a reduction of pRF sizes in trained visual cortex, particularly in V2, highlighting the plasticity and adaptability of the adult visual system induced by prolonged training.

Persistent MRI Findings Unique to Blast and Repetitive Mild TBI: Analysis of the CENC/LIMBIC Cohort Injury Characteristics.

INTRODUCTION: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements. MATERIAL AND METHODS: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor. RESULTS: After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non-blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus. CONCLUSIONS: In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.

Perception of brown with variation in center chromaticity and surround luminance.

Brown is a contrast color that depends on complex combinations of chromatic and achromatic signals. We measured brown perception with variations in chromaticity and luminance in center-surround configurations. In Experiment 1, the dominant wavelength and saturation in terms of S-cone stimulation were tested with five observers in a fixed surround luminance (60c d/m 2). A paired-comparison task required the observer to select the better exemplar of brown in one of two, simultaneously presented, stimuli (1.0° center diameter; annulus of 9.48° outer-diameter). In Experiment 2, the same task was tested with five observers in which surround luminance was varied (from 13.1 to 99.6c d/m 2) for two center chromaticities. The results were a set of win-loss ratios for each stimulus combination and converted to Z-scores. An ANOVA did not reveal a significant main effect of the observer factor but revealed a significant interaction with red/green (a ∗) [but not with the dominant wavelength and the S-cone stimulation (or b ∗)]. Experiment 2 revealed observer variation in interactions with surround luminance and S-cone stimulation. The averaged data plotted in 1976 L ∗ a ∗ b ∗ color space indicate that high Z-score values widely distribute in the area of a ∗ from 5 to 28 and b ∗ over 6. The balance of the strength between yellowness and blackness differs among observers owing to the amount of induced blackness required for the best brown.

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Aging of visual mechanisms.

Optical and neural changes in the aging human visual system are reviewed in terms of factors that can influence the study of light-mediated effects on circadian physiology. All aspects of early stage visual mechanisms change continuously from the first days of life, and these changes must be understood when investigating both conscious and unconscious visual responses to light throughout the life span.

Heinrich Müller (1820-1864) and the entoptic discovery of the site in the retina where vision is initiated.

Heinrich Müller was a nineteenth-century German retinal anatomist who, during his short career, was one of the discoverers of the rod photopigment rhodopsin and neuroglia in the retina, now known as Müller cells. He also described the ocular muscles and double foveae of some birds. An important, but largely neglected, insight by Müller was to combine careful psychophysical measurements and geometrical optics to find the location of the photosensitive layer of the retina in the living eye. Here, we provide translated passages from Müller's (1855) publication and compare his entoptic observations with retinal imaging using optical coherence tomography. Müller correctly deduced from his careful experiments that vision is initiated in the photoreceptors located in the back of the retina.

Pediatric Complexity Tool Best Practice Alert: Early Identification of Care Coordination for Children with Special Health Care Needs.

Care coordination programs continue to be developed for children with special health care needs (CSHCN). The goals for these programs are to improve access, increase communication, and decrease the overall length of stay for CSHCN. Care coordination optimizes resources to support children's health and well-being early in their hospitalization and facilitates a smooth discharge process and transition to home. Providing care coordination for CSHCN requires collaboration from many disciplines. To achieve high-quality care coordination, early identification of medically complex pediatric patients on admission is optimal. For more efficient and timelier enrollment into our care coordination program, we created a best practice alert within our electronic medical record to help overcome the challenges in timely identification of CSHCN. The best practice alert has helped us to provide care coordination benefits to our patients earlier in their hospital course. The purpose of this paper is to describe a quality improvement initiative to improve the early identification of CSHCN on hospital admission through the development of a best practice alert.

Imaging biomarkers of vascular and axonal injury are spatially distinct in chronic traumatic brain injury.

Traumatic Brain Injury (TBI) is associated with both diffuse axonal injury (DAI) and diffuse vascular injury (DVI), which result from inertial shearing forces. These terms are often used interchangeably, but the spatial relationships between DAI and DVI have not been carefully studied. Multimodal magnetic resonance imaging (MRI) can help distinguish these injury mechanisms: diffusion tensor imaging (DTI) provides information about axonal integrity, while arterial spin labeling (ASL) can be used to measure cerebral blood flow (CBF), and the reactivity of the Blood Oxygen Level Dependent (BOLD) signal to a hypercapnia challenge reflects cerebrovascular reactivity (CVR). Subjects with chronic TBI (n = 27) and healthy controls (n = 14) were studied with multimodal MRI. Mean values of mean diffusivity (MD), fractional anisotropy (FA), CBF, and CVR were extracted for pre-determined regions of interest (ROIs). Normalized z-score maps were generated from the pool of healthy controls. Abnormal ROIs in one modality were not predictive of abnormalities in another. Approximately 9-10% of abnormal voxels for CVR and CBF also showed an abnormal voxel value for MD, while only 1% of abnormal CVR and CBF voxels show a concomitant abnormal FA value. These data indicate that DAI and DVI represent two distinct TBI endophenotypes that are spatially independent.

Optoretinogram: optical measurement of human cone and rod photoreceptor responses to light.

Noninvasive, objective measurement of rod function is as significant as that of cone function, and for retinal diseases such as retinitis pigmentosa and age-related macular degeneration, rod function may be a more sensitive biomarker of disease progression and efficacy of treatment than cone function. Functional imaging of single human rod photoreceptors, however, has proven difficult because their small size and rapid functional response pose challenges for the resolution and speed of the imaging system. Here, we describe light-evoked, functional responses of human rods and cones, measured noninvasively using a synchronized adaptive optics optical coherence tomography (OCT) and scanning light ophthalmoscopy (SLO) system. The higher lateral resolution of the SLO images made it possible to confirm the identity of rods in the corresponding OCT volumes.

Adaptive Changes in Color Vision from Long-Term Filter Usage in Anomalous but Not Normal Trichromacy.

For over 150 years, spectrally selective filters have been proposed to improve the vision of observers with color vision deficiencies [1]. About 6% of males and <1% of females have anomalies in their gene arrays coded on the X chromosome that result in significantly decreased spectral separation between their middle- (M-) and long- (L-) wave sensitive cone photoreceptors [2]. These shifts alter individuals' color-matching and chromatic discrimination such that they are classified as anomalous trichromats [3, 4]. Broad-band spectrally selective filters proposed to improve the vision of color-deficient observers principally modify the illuminant and are largely ineffective in enhancing discrimination or perception because they do not sufficiently change the relative activity of M- and L-photoreceptors [5, 6]. Properly tailored notch filters, by contrast, might increase the difference of anomalous M- and L-cone signals. Here, we evaluated the effects of long-term usage of a commercial filter designed for this purpose on luminance and chromatic contrast response, estimated with a signal detection-based scaling method. We found that sustained use over two weeks was accompanied by increased chromatic contrast response in anomalous trichromats. Importantly, these improvements were observed when tested without the filters, thereby demonstrating an adaptive visual response. Normal observers and a placebo control showed no such changes in contrast response. These findings demonstrate a boosted chromatic response from exposure to enhanced chromatic contrasts in observers with reduced spectral discrimination. They invite the suggestion that modifications of photoreceptor signals activate a plastic post-receptoral substrate that could potentially be exploited for visual rehabilitation.

Suprathreshold contrast response in normal and anomalous trichromats.

Maximum likelihood difference scaling was used to measure suprathreshold contrast response difference scales for low-frequency Gabor patterns, modulated along luminance and L-M color directions in normal, protanomalous, and deuteranomalous observers. Based on a signal-detection model, perceptual scale values, parameterized as $ d^\prime $d', were estimated by maximum likelihood. The difference scales were well fit by a Michaelis-Menten model, permitting estimates of response and contrast gain parameters for each subject. Anomalous observers showed no significant differences in response or contrast gain from normal observers for luminance contrast. For chromatic modulation, however, anomalous observers displayed higher contrast and lower response gain compared to normal observers. These effects cannot be explained by simple pigment shift models, and they support a compensation mechanism to optimize the mapping of the input contrast range to the neural response range. A linear relation between response and contrast gain suggests a neural trade-off between them.

AimB Is a Small Protein Regulator of Cell Size and MreB Assembly.

The MreB actin-like cytoskeleton assembles into dynamic polymers that coordinate cell shape in many bacteria. In contrast to most other cytoskeleton systems, few MreB-interacting proteins have been well characterized. Here, we identify a small protein from Caulobacter crescentus, an assembly inhibitor of MreB (AimB). AimB overexpression mimics inhibition of MreB polymerization, leading to increased cell width and MreB delocalization. Furthermore, aimB appears to be essential, and its depletion results in decreased cell width and increased resistance to A22, a small-molecule inhibitor of MreB assembly. Molecular dynamics simulations suggest that AimB binds MreB at its monomer-monomer protofilament interaction cleft and that this interaction is favored for C. crescentus MreB over Escherichia coli MreB because of a closer match in the degree of opening with AimB size, suggesting coevolution of AimB with MreB conformational dynamics in C. crescentus. We support this model through functional analysis of point mutants in both AimB and MreB, photo-cross-linking studies with site-specific unnatural amino acids, and species-specific activity of AimB. Together, our findings are consistent with AimB promoting MreB dynamics by inhibiting monomer-monomer assembly interactions, representing a new mechanism for regulating actin-like polymers and the first identification of a non-toxin MreB assembly inhibitor. Because AimB has only 104 amino acids and small proteins are often poorly characterized, our work suggests the possibility of more bacterial cytoskeletal regulators to be found in this class. Thus, like FtsZ and eukaryotic actin, MreB may have a rich repertoire of regulators to tune its precise assembly and dynamics.

Age-Related Effects on Cross-Modal Duration Perception.

Reliable duration perception of external events is necessary to coordinate perception with action, precisely discriminate speech, and for other daily functions. Visual duration perception can be heavily influenced by concurrent auditory signals; however, age-related effects on this process have received minimal attention. In the present study, we examined the effect of aging on duration perception by quantifying (1) duration discrimination thresholds, (2) auditory temporal dominance, and (3) visual duration expansion/compression percepts induced by an accompanying auditory stimulus of longer/shorter duration. Duration discrimination thresholds were significantly greater for visual than auditory tasks in both age groups, however there was no effect of age. While the auditory modality retained dominance in duration perception with age, older adults still performed worse than young adults when comparing durations of two target stimuli (e.g., visual) in the presence of distractors from the other modality (e.g., auditory). Finally, both age groups perceived similar visual duration compression, whereas older adults exhibited visual duration expansion over a wider range of auditory durations compared to their younger counterparts. Results are discussed in terms of multisensory integration and possible decision strategies that change with age.

Automated quantification of choriocapillaris anatomical features in ultrahigh-speed optical coherence tomography angiograms.

In vivo visualization and quantification of choriocapillaris vascular anatomy is a fundamental step in understanding the relation between choriocapillaris degradation and atrophic retinopathies, including geographic atrophy. We describe a process utilizing ultrahigh-speed swept-source optical coherence tomography and a custom-designed "local min-max normalized masking" algorithm to extract in vivo anatomical metrics of the choriocapillaris. We used a swept-source optical coherence tomography system with a 1.6 MHz A-scan rate to image healthy retinas. With the postprocessing algorithm, we reduced noise, optimized visibility of vasculature, and skeletonized the vasculature within the images. These skeletonizations were in 89 % agreement with those made by skilled technicians and were, on average, completed in 18.6 s as compared to the 5.6 h technicians required. Anatomy within the processed images and skeletonizations was analyzed to identify average values ( mean ± SD ) of flow void radius ( 9.8 ± 0.7 µm ), flow void area ( 749 ± 110 µm 2 ), vessel radius ( 5.0 ± 0.3 µm ), branch-point to branch-point vessel length ( 26.8 ± 1.1 µm ), and branches per branch-point ( 3.1 ± 0.1 ) . To exemplify the uses of this tool a retina with geographic atrophy was imaged and processed to reveal statistically significant ( p < 0.05 ) increases in flow void radii and decreases in vessel radii under atrophic lesions as compared to atrophy-free regions on the same retina. Our results demonstrate a new avenue for quantifying choriocapillaris anatomy and studying vasculature changes in atrophic retinopathies.

Coextensive synchronized SLO-OCT with adaptive optics for human retinal imaging.

We describe the details of a multimodal retinal imaging system which combines adaptive optics (AO) with an integrated scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT) imaging system. The OCT subsystem consisted of a swept-source, Fourier-domain mode-locked (FDML) laser, with a very high A-scan rate (1.6 MHz), whose beam was raster scanned on the retina by two scanners-one resonant scanner and one galvanometer. The high sweep rate of the FDML permitted the SLO and OCT to utilize the same scanners for in vivo retinal imaging and, unlike existing multimodal systems, concurrently acquired SLO frames and OCT volumes with approximate en face correspondence at a rate of 6 Hz. The AO provided diffraction-limited cellular resolution for both imaging channels.

Megahertz-rate optical coherence tomography angiography improves the contrast of the choriocapillaris and choroid in human retinal imaging.

Angiographic imaging of the human eye with optical coherence tomography (OCT) is becoming an increasingly important tool in the scientific investigation and clinical management of several blinding diseases, including age-related macular degeneration and diabetic retinopathy. We have observed that OCT angiography (OCTA) of the human choriocapillaris and choroid with a 1.64 MHz A-scan rate swept-source laser yields higher contrast images as compared to a slower rate system operating at 100 kHz. This result is unexpected because signal sensitivity is reduced when acquisition rates are increased, and the incident illumination power is kept constant. The contrast of angiography images generated by acquiring multiple sequential frames and calculating the variation caused by blood flow, however, appears to be improved significantly when lower-contrast images are taken more rapidly. To demonstrate that the acquisition rate plays a role in the quality improvement, we have imaged five healthy subjects with a narrow field of view (1.2 mm) OCTA imaging system using two separate swept-source lasers of different A-line rates and compared the results quantitatively using the radially-averaged power spectrum. The average improvement in the contrast is 23.0% (+/-7.6%). Although the underlying cause of this enhancement is not explicitly determined here, we speculate that the higher-speed system suppresses the noise contribution from eye motion in subjects and operates with an inter-scan time that better discriminates the flow velocities present in the choroid and choriocapillaris. Our result informs OCT system developers on the merits of ultrahigh-speed acquisition in functional imaging applications.

Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration.

Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive. Currently, techniques are being developed to directly transdifferentiate cardiac fibroblasts into induced cardiomyocytes. Viral vector-driven expression of a combination of transcription factors including Gata4, Mef2c, and Tbx5 induced cardiomyocyte development in mice. Subsequent combinational modifications have extended these results to human cell lines and increased efficacy. The miRNAs including combinations of miR-1, miR-133, miR-208, and miR-499 can improve or independently drive regeneration of cardiomyocytes. Similar results could be obtained by combinations of small molecules with or without transcription factor or miRNA expression. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-ß, enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.