Cortical Networks Relating to Arousal Are Differentially Coupled to Neural Activity and Hemodynamics.

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25, respectively, at a time lag of 0 s. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in the prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies >1 Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity.

Amygdala and Cortex Relationships during Learning of a Sensory Discrimination Task.

During learning of a sensory discrimination task, the cortical and subcortical regions display complex spatiotemporal dynamics. During learning, both the amygdala and cortex link stimulus information to its appropriate association, for example, a reward. In addition, both structures are also related to nonsensory parameters such as body movements and licking during the reward period. However, the emergence of the cortico-amygdala relationships during learning is largely unknown. To study this, we combined wide-field cortical imaging with fiber photometry to simultaneously record cortico-amygdala population dynamics as male mice learn a whisker-dependent go/no-go task. We were able to simultaneously record neuronal populations from the posterior cortex and either the basolateral amygdala (BLA) or central/medial amygdala (CEM). Prior to learning, the somatosensory and associative cortex responded during sensation, while amygdala areas did not show significant responses. As mice became experts, amygdala responses emerged early during the sensation period, increasing in the CEM, while decreasing in the BLA. Interestingly, amygdala and cortical responses were associated with task-related body movement, displaying significant responses ∼200 ms before movement initiation which led to licking for the reward. A correlation analysis between the cortex and amygdala revealed negative and positive correlation with the BLA and CEM, respectively, only in the expert case. These results imply that learning induces an involvement of the cortex and amygdala which may aid to link sensory stimuli with appropriate associations.

Refining hemodynamic correction in in vivo wide-field fluorescent imaging through linear regression analysis.

Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach.

DNA choreography: correlating mobility and organization of DNA across different resolutions from loops to chromosomes.

The dynamics of DNA in the cell nucleus plays a role in cellular processes and fates but the interplay of DNA mobility with the hierarchical levels of DNA organization is still underexplored. Here, we made use of DNA replication to directly label genomic DNA in an unbiased genome-wide manner. This was followed by live-cell time-lapse microscopy of the labeled DNA combining imaging at different resolutions levels simultaneously and allowing one to trace DNA motion across organization levels within the same cells. Quantification of the labeled DNA segments at different microscopic resolution levels revealed sizes comparable to the ones reported for DNA loops using 3D super-resolution microscopy, topologically associated domains (TAD) using 3D widefield microscopy, and also entire chromosomes. By employing advanced chromatin tracking and image registration, we discovered that DNA exhibited higher mobility at the individual loop level compared to the TAD level and even less at the chromosome level. Additionally, our findings indicate that chromatin movement, regardless of the resolution, slowed down during the S phase of the cell cycle compared to the G1/G2 phases. Furthermore, we found that a fraction of DNA loops and TADs exhibited directed movement with the majority depicting constrained movement. Our data also indicated spatial mobility differences with DNA loops and TADs at the nuclear periphery and the nuclear interior exhibiting lower velocity and radius of gyration than the intermediate locations. On the basis of these insights, we propose that there is a link between DNA mobility and its organizational structure including spatial distribution, which impacts cellular processes.

Ultra-Widefield-Guided Swept-Source OCT Findings of Peripheral Vitreoretinal Abnormality in Young Myopes.

PURPOSE: To evaluate the ultra-widefield fundus photography (UWF-FP)-guided swept-source OCT (SS-OCT) images of peripheral vitreoretinal abnormality (PVRA) in young asymptomatic myopes. DESIGN: Cross-sectional, single-center study. PARTICIPANTS: A total of 1966 eyes of 983 consecutive patients aged 18 to 42 years with refractive error in the spherical equivalent of < 0 diopters (D) who visited KEYE Eye Center, Seoul, Republic of Korea, for refractive surgery. METHODS: The prevalence of PVRA and their characteristics, including shape, location, presence of pigmentation, membrane, retinal breaks, and detachment, were evaluated. A logistic regression analysis was done to evaluate the risk factors of PVRA and the risk of retinal breaks or detachment among eyes with PVRA. RESULTS: Among 1966 eyes, 317 (16.1%) had PVRA, and 182 (57.4%) and 135 (42.6%) had focal and linear lesions, respectively. The risk of PVRA was increased with axial length of the eyes (odds ratio [OR], 1.238, 95% confidence interval [CI], 1.112-1.379, P < 0.001), corneal astigmatism (OR, 1.320, 95% CI, 1.148-1.519, P < 0.001), presence of discrete margins of different retinal reflectivity (DMDRR; indicating outer retinal disruption from abnormal vitreoretinal traction) (OR, 1.751, 95% CI, 1.334-2.300, P < 0.001), and posterior vitreous detachment (PVD) at the posterior pole of the retina (OR, 1.833, 95% CI, 1.352-2.485, P < 0.001). Among eyes with PVRA, patient age (OR, 1.063, 95% CI, 1.008-1.121, P = 0.025), linear lesions (OR, 15.234, 95% CI, 7.891-29.407, P < 0.001), and multiple lesions (OR, 3.432, 95% CI, 1.780-6.620, P < 0.001) were independently associated with the presence of retinal breaks or detachment. CONCLUSIONS: The follow-up for PVRA among young myopes should be personalized on the basis of their ocular characteristics, including asymmetric ocular expansion (axial length and astigmatism) and vitreoretinal interface status. The treatment plan for PVRA eyes should emphasize the greater risk of retinal breaks and detachment with increasing age and the presence of linear and multiple lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluation of peripheral retinal degenerations using ultra-widefield swept source optical coherence tomography.

PURPOSE: To describe the features of peripheral retinal degenerations using an Ultra-Widefield (UWF) Swept Source Optical Coherence Tomography (SS-OCT). METHOD: In this cross-sectional study done at a tertiary eye care centre in Northern India, peripheral retinal degenerations such as lattices, snail track lesion, paving stone, White With-Out Pressure(WWOP), micro-cystoid lesions, retinoschisis and other suspicious lesions were identified with clinical examination. Following clinical examination, these eyes with peripheral retinal degenerations underwent UWF OCT. RESULTS: 100 eyes with 14 peripheral lesions like lattices (31%), snail track lesions (10.4%), peripheral retinoschisis (7.5%), non-specific pigmented doubtful lesions (13.2%), WWOP (7.5%), paving stone (6.6%), peripheral retinal detachment (3.8%) along with CHRPE, micro-cystoid lesions and dark without pressure areas were identified. All the lesions could be imaged with the help of UWF-OCT. It significantly helped in improving diagnostic capability with early identification of specific structural features such as vitreoretinal attachment and traction, full-thickness hole or tear, and sub-retinal fluid which were not so evident on indirect ophthalmoscopy. CONCLUSION: UWF-OCT deepens our understanding of the structure of the retina and its associated peripheral pathologies, allowing early recognition of vision-threatening lesions that may influence clinical management.

Relationship between ischemic index, leakage index, and macular edema in branch retinal vein occlusion.

PURPOSE: To investigate the combined association of the ischemic index and leakage index with macular edema on ultra-widefield fluorescein angiography (UWFFA) in patients with branch retinal vein occlusion (BRVO). METHODS: Retrospective image analysis study. The leakage index and ischemic index were calculated using Fiji after aligning early and late UWFFA images. Differences in the ischemic index, leakage index, and central macular thickness (CMT) between ischemic and non-ischemic BRVO were compared. Moreover, the association between the ischemic index, leakage index, and macular edema was analyzed. RESULTS: Eighty-three patients with BRVO were enrolled, including 53 non-ischemic BRVO and 30 ischemic BRVO patients. No significant differences were observed in leakage index and CMT between ischemic BRVO and non-ischemic BRVO (all P > 0.05). In all included patients, CMT correlated with the panretina and all subregion leakage indexes (all P < 0.01), but not with the ischemic index (all P > 0.05). In the ischemic BRVO group, CMT showed a correlation with the leakage index in several regions, but not with the ischemic index. After adjusting for the ischemic index and other clinical features, CMT remained significantly correlated with the leakage index in all regions. CONCLUSION: The leakage index may be a more effective biomarker for monitoring BRVO-associated macular edema compared to the ischemic index. Further follow-up studies are warranted to validate these findings.

One-year choroidal thickness changes after photodynamic therapy for central serous chorioretinopathy evaluated by widefield optical coherence tomography.

PURPOSE: To evaluate the changes in choroidal thickness 1 year after half-dose photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) using widefield swept-source optical coherence tomography. METHODS: We retrospectively reviewed 21 patients with CSC who unilaterally underwent half-dose PDT and completed a 12-month follow-up. Choroidal thickness was evaluated before and after PDT within an 18-mm circular grid centered on the fovea subdivided into nine areas in the treated and untreated fellow eyes. RESULTS: All 21 treated eyes showed complete resolution of subretinal fluid at 3 months after PDT, without any recurrence at 12 months. The mean choroidal thickness in all nine areas significantly decreased after PDT at 3 months (P < 0.05) and remained unchanged at 12 months (P < 0.05) compared with that at baseline. However, the subtracted choroidal thickness maps between 3 and 12 months detected significant variations among the cases, classified into an enhanced pattern in 10 eyes (47.6%), an attenuated pattern in six eyes (28.6%), and a stable pattern in five eyes (23.8%). The 21 untreated fellow eyes also showed a decrease in mean choroidal thickness in three of the nine subdivided areas at 12 months (P < 0.05), but this decrease was limited posteriorly. CONCLUSION: The reduction in mean choroidal thickness after half-dose PDT for CSC was extensively maintained for 1 year. However, subclinical hemodynamic changes in the entire choroid occurred longitudinally even in the absence of disease recurrence.

Comparisons of choroidal thickness and volume in eyes with central serous chorioretinopathy to that of control eyes determined by ultra-widefield optical coherence tomography.

PURPOSE: To compare choroidal thickness and volume in eyes with central serous chorioretinopathy (CSC) and healthy control eyes over a wide area of the fundus using ultra-widefield optical coherence tomography (UWF-OCT). METHODS: Thirty-three eyes of 29 patients with CSC and 36 eyes of 21 healthy controls were examined retrospectively. Choroidal images were obtained with a prototype UWF-OCT device with a field of view of 105° or approximately 31.5-mm wide by 10.9-mm deep. Choroidal thickness and volume were measured in the images of 12 radial scans (every 15°) from the horizontal scan. The "new index" of the extent of focal choroidal protrusion was defined as the maximum steepness of choroidal thickness (MSCT). RESULTS: Choroidal volume in CSC eyes was significantly larger than in control eyes within the central 50° (P < 0.001). However, there was no significant difference in choroidal volume in the peripheral 50 to 105° (P = 0.071). The MSCTs were significantly steeper in CSC eyes than in control eyes at scan lines 1, 6, 7, 8, and 10 (P < 0.01, P < 0.001, P < 0.05, P < 0.01, P < 0.05). CONCLUSIONS: The choroid in CSC eyes was thickened only at the posterior pole, and its protrusion was significant mainly in the vertical direction. Focal choroidal thickening at the posterior pole, which we speculate includes congenital scleral changes, may affect the pathophysiology of CSC.

ETDRS grading with CLARUS ultra-widefield images shows agreement with 7-fields colour fundus photography.

BACKGROUND: To analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system. METHODS: A cross-sectional analysis of retinal images of patients with type 2 diabetes (n = 160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC-50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques. RESULTS: Images of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10-20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k > 0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions. CONCLUSIONS: UWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images. TRIAL REGISTRATION: Approved by the AIBILI - Association for Innovation and Biomedical Research on Light and Image Ethics Committee for Health with number CEC/009/17- EYEMARKER.

Clinical features of primary and compound forms of wide macular posterior staphyloma in high myopia.

BACKGROUND: To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity. METHODS: In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS. RESULTS: A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P < 0.001) than those with primary WMPS. Compared to primary WMPS, compound WMPS had a higher grade of myopic macular degeneration (P < 0.001) and a higher frequency of lamellar or full-thickness macular hole associated with myopic traction (21.5% vs. 10.4%; P = 0.028) and active or scarred myopic choroidal neovascularization (33.8% vs. 20.1%; P = 0.030). On swept-source optical coherence tomography, eyes with compound WMPS had significantly thinner choroid and sclera. CONCLUSIONS: The compound form of WMPS had more severe myopic macular changes and worse visual prognosis compared to the primary form of WMPS, and these were associated with more structural deformation in the posterior eyeball. Compound WMPS should be considered as an advanced form of staphyloma.

Clinical and genetic features in autosomal recessive bestrophinopathy in Chinese cohort.

PURPOSE: To provide a genotype and phenotype characterization of the BEST1 mutation in Chinese patients with autosomal recessive bestrophinopathy (ARB) through multimodal imaging and next-generation sequencing (NGS). METHODS: Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants. RESULTS: Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9-68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5. CONCLUSIONS: This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research.

Excellent accuracy of trained neonatal nurses in the detection of referral-warranted retinopathy of prematurity within an established telemedicine screening programme.

AIM: To evaluate level of agreement of specialist trained retinopathy of prematurity (ROP) nurses compared with an experienced paediatric ophthalmologist in detection of referral-warranted ROP (RWROP) using wide-field digital retinal imaging. METHODS: This is a prospective, observational, blinded study of neonates in a level III neonatal intensive care unit, from July 2020 to November 2022. Image capture using wide-field digital retinal imaging followed by ROP grading and staging was completed by trained ROP nurses. This was then compared with findings by an experienced paediatric ophthalmologist. The primary outcome was presence of RWROP in either eye. RESULTS: One hundred and ninety-five neonates (55% male) with a total of 768 screening visits were included. At the initial screen, nurse and ophthalmologist agreed about presence of RWROP for 191 of 195 neonates (98%, kappa = 0.79, P < 0.0001), with 100% sensitivity for RWROP detection. Including all 768 screening episodes, agreement was 98% for RWROP. There was disagreement in 16 screenings (2%) for 11 (6%) neonates. Of the five screenings (0.7%) that the ophthalmologist thought were RWROP and the nurse did not, three were disagreements about whether the zone was posterior zone 2 or zone 1. CONCLUSIONS: We found excellent levels of agreement and add evidence that interpretations by specialist trained nurses could be safely integrated into a 'hybrid ROP screening system'.

Real-Time 3D Tracking of Multi-Particle in the Wide-Field Illumination Based on Deep Learning.

In diverse realms of research, such as holographic optical tweezer mechanical measurements, colloidal particle motion state examinations, cell tracking, and drug delivery, the localization and analysis of particle motion command paramount significance. Algorithms ranging from conventional numerical methods to advanced deep-learning networks mark substantial strides in the sphere of particle orientation analysis. However, the need for datasets has hindered the application of deep learning in particle tracking. In this work, we elucidated an efficacious methodology pivoted toward generating synthetic datasets conducive to this domain that resonates with robustness and precision when applied to real-world data of tracking 3D particles. We developed a 3D real-time particle positioning network based on the CenterNet network. After conducting experiments, our network has achieved a horizontal positioning error of 0.0478 µm and a z-axis positioning error of 0.1990 µm. It shows the capability to handle real-time tracking of particles, diverse in dimensions, near the focal plane with high precision. In addition, we have rendered all datasets cultivated during this investigation accessible.

Tailoring Two-Dimensional Matter Using Strong Light-Matter Interactions.

The shaping of matter into desired nanometric structures with on-demand functionalities can enhance the miniaturization of devices in nanotechnology. Herein, strong light-matter interaction was used as an optical lithographic tool to tailor two-dimensional (2D) matter into nanoscale architectures. We transformed 2D black phosphorus (BP) into ultrafine, well-defined, beyond-diffraction-limit nanostructures of ten times smaller size and a hundred times smaller spacing than the incident, femtosecond-pulsed light wavelength. Consequently, nanoribbons and nanocubes/cuboids scaling tens of nanometers were formed by the structured ablation along the extremely confined periodic light fields originating from modulation instability, the tailoring process of which was visualized in real time via light-coupled in situ transmission electron microscopy. The current findings on the controllable nanoscale shaping of BP will enable exotic physical phenomena and further advance the optical lithographic techniques for 2D materials.

Exploring the Magnetic Properties of Individual Barcode Nanowires using Wide-Field Diamond Microscopy.

A barcode magnetic nanowire typically comprises a multilayer magnetic structure in a single body with more than one segment type. Interestingly, due to selective functionalization and novel interactions between the layers, it has attracted significant attention, particularly in bioengineering. However, analyzing the magnetic properties at the individual nanowire level remains challenging. Herein, the characterization of a single magnetic nanowire is investigated at room temperature under ambient conditions based on magnetic images obtained via wide-field quantum microscopy with nitrogen-vacancy centers in diamond. Consequently, critical magnetic properties of a single nanowire can be extracted, such as saturation magnetization and coercivity, by comparing the experimental result with that of micromagnetic simulation. This study opens up the possibility for a versatile in situ characterization method suited to individual magnetic nanowires.

Taking molecular pathology to the next level: Whole slide multicolor confocal imaging with the Pannoramic Confocal digital pathology scanner.

The emergence and fast advance of digital pathology allows the acquisition, digital storage, interactive recall and analysis of morphology at the tissue level. When applying immunohistochemistry, it also affords the correlation of morphology with the expression of one or two specific molecule of interest. The rise of fluorescence pathology scanners expands the number of detected molecules based on multiplex labeling. The Pannoramic Confocal (created by 3DHistech, Hungary) is a first-of-the-kind digital pathology scanner that affords not only multiplexed fluorescent detection on top of conventional transmission imaging, but also confocality. We have benchmarked this scanner in terms of stability, precision, light efficiency, linearity and sensitivity. X-Y stability and relocalisation precision were well below resolution limit (≤50 nm). Light throughput in confocal mode was 4-5 times higher than that of a point scanning confocal microscope, yielding similar calculated confocal intensities but with the potential for improving signal to noise ratio or scan speed. Response was linear with R2 ≥ 0.9996. Calibrated measurements showed that using indirect labeling ≥2000 molecules per cell could be well detected and imaged on the cell surface. Both standard-based and statistical post-acquisition flatfield corrections are implemented. We have also measured the point spread function (PSF) of the instrument. The dimensions of the PSF are somewhat larger and less symmetric than of the theoretical PSF of a conventional CLSM, however, the spatial homogeneity of these parameters allows for obtaining a specific system PSF for each optical path and using it for optional on-the-fly deconvolution. In conclusion, the Pannoramic Confocal provides sensitive, quantitative widefield and confocal detection of multiplexed fluorescence signals, with optical sectioning and 3D reconstruction, in addition to brightfield transmission imaging. High speed scanning of large samples, analysis of tissue heterogeneity, and detection of rare events open up new ways for quantitatively analyzing tissue sections, organoid cultures or large numbers of adherent cells.

Global, Low-Amplitude Cortical State Predicts Response Outcomes in a Selective Detection Task in Mice.

Spontaneous neuronal activity strongly impacts stimulus encoding and behavioral responses. We sought to determine the effects of neocortical prestimulus activity on stimulus detection. We trained mice in a selective whisker detection task, in which they learned to respond (lick) to target stimuli in one whisker field and ignore distractor stimuli in the contralateral whisker field. During expert task performance, we used widefield Ca2+ imaging to assess prestimulus and post-stimulus neuronal activity broadly across frontal and parietal cortices. We found that lower prestimulus activity correlated with enhanced stimulus detection: lower prestimulus activity predicted response versus no response outcomes and faster reaction times. The activity predictive of trial outcome was distributed through dorsal neocortex, rather than being restricted to whisker or licking regions. Using principal component analysis, we demonstrate that response trials are associated with a distinct and less variable prestimulus neuronal subspace. For single units, prestimulus choice probability was weak yet distributed broadly, with lower than chance choice probability correlating with stronger sensory and motor encoding. These findings support low amplitude and low variability as an optimal prestimulus cortical state for stimulus detection that presents globally and predicts response outcomes for both target and distractor stimuli.

Retinopathy of prematurity detection: a retrospective quality improvement project before-after implementation of retinal digital imaging for screening.

Screening of retinopathy of prematurity (ROP) was modified in a level-3 neonatal intensive care unit by the introduction of a wide-field retinal imaging. The aim of this study was to evaluate whether retinopathy of prematurity (ROP) diagnosis was improved or not compared to previously used binocular indirect ophthalmoscopy (BIO). This was a retrospective, uncontrolled, quality improvement project. Records of consecutive premature newborns screened for ROP over two 1-year periods were reviewed. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. ROP screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (Panocam™ pro) in 2019. Records of N = 297 patients were analyzed (N = 159 in 2014 and N = 138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n = 46/138, 33.1%) compared to 2014 (n = 11/159, 6.9%) (p < 0.0001). Most neonates presented with mild forms of ROP during both 1-year periods analyzed. After adjustment for all parameters influencing ROP occurrence, the variables contributing independently to the diagnosis of any stage of ROP were birth weight (p = 0.002), duration of mechanical ventilation (p = 0.028) and wide-field fundus camera-assisted screening (p < 0.001). CONCLUSION: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated with higher ROP detection. WHAT IS KNOWN: • No consensus has been reached to replace binocular indirect ophthalmoscopy by retinal imaging for ROP screening. • Diagnostic accuracy and high sensitivity and specificity has been reported for wide-field digital imaging. WHAT IS NEW: • The introduction of wide-field imaging for ROP screening in at level-3 reference center was independently associated to higher ROP detection.

Widefield oct-angiography-based classification of sickle cell retinopathy.

PURPOSE: To assess the capillary non-perfusion in different concentric sectors on widefield optical coherence tomography angiography (WF-OCTA) and to correlate the ratio of non-perfusion (RNP) to the severity of sickle cell retinopathy (SCR). METHODS: This retrospective, cross-sectional study included eyes of patients with various sickle cell disease (SCD) genotypes having undergone WF-OCTA and ultra-widefield color fundus photography (UWF-CFP). Eyes were grouped as no SCR, non-proliferative SCR or proliferative SCR. RNP was assessed on WF-OCTA montage in different field-of-view (FOV) sectors centered on the fovea: 0-10-degrees circle excluding the foveal avascular zone, the 10-30-degrees circle excluding the optic nerve, the 30-60-degrees circle, and the full 60-degrees circle. RESULTS: Forty-two eyes of twenty-eight patients were included. Within each SCR group, mean RNP of the FOV 30-60 sector was higher than all other sectors (p < 0.05). Mean RNP of all sectors were significatively different between no SCR group and proliferative SCR group (p < 0.05). To distinguish no SCR versus non-proliferative SCR FOV 30-60 had a good sensitivity and specificity of 41.67% and 93.33%, respectively (cutoff RNP > 22.72%, AUC = 0.75, 95% CI 0.56-0.94, p = 0.028). To differentiate non-proliferative versus proliferative SCR, FOV 0-10 had good sensitivity and specificity of 33.33% and 91.67%, respectively (cutoff RNP > 18.09, AUC = 0.73, 95% CI 0.53 to 0.93, p = 0.041). To discern no SCR versus proliferative SCR, all sectors had optimal sensitivity and specificity (p < 0.05). CONCLUSION: WF OCTA-based RNP provides non-invasive diagnostic information regarding the presence and severity of SCR, and correlates with disease stage in certain FOV sectors.