Compensation comparison method for assessment of retinal straylight,”

PURPOSE. Presently, no instrument or method exists that is generally accepted for routine clinical assessment of (functional) retinal straylight. Yet retinal straylight is the cause of major patient complaints, such as hindrance from glare and loss of contrast. It results from disturbances in the optical media that increase light-scattering over angles of 1°to 90°. Its assessment would help to decide whether to perform surgery for (early) cataract and would help in the evaluation of corneal or vitreal turbidity. METHODS. The psychophysical technique of the "direct compensation" method was adapted to make it suitable for routine clinical assessment. In the new approach, called "compensation comparison, " the central test field is subdivided into two half fields: one with and one without counterphase compensation light. The subject's task is a forced-choice comparison between the two half fields, to decide which half flickers more strongly. A theoretical form for the respective psychometric function was defined and experimentally verified in a laboratory experiment involving seven subjects, with and without artificially increased light scattering. The method was applied in a separate multicenter study. Its reliability was additionally tested with a commercial implement (C-Quant; Oculus Optikgeräte, Wetzlar-Dutenhofen, Germany). RESULTS. A repeated-measures SD of 0.07 log units was achieved, to be compared with differences in the young normal population of 0.4 log units and an increase with healthy aging by 0.5 log units at 80 years and by 1.0 or more log units with (early) cataract or corneal disturbances. Reliability was further found to be high when using the commercial version of the method. CONCLUSIONS. The compensation comparison method for measuring retinal straylight is suited for clinical use to diagnose patients with complaints caused by large angle light scattering in the eye such as early cataract. (Invest Ophthalmol Vis Sci

Sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children

Background and Aim: The role of sleep in the enhancement of motor skills has been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children. Hypothesis: We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics. Methods:: 30 children (19 females, 10.7 ± 0.8 years of age; mean ± SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography (PSG) night. Initial and delayed performance were assessed over 12 h of wake; 12 h with sleep; and 24 h with wake and sleep. For the 12 h with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions. Analyses: Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy. Results and Conclusions: Children enhance their accuracy only over an interval with sleep. Unlike previously reported in adults, children enhance their speed independent of sleep, a capacity that may to be lost in adulthood. Individual differences in the dominant frequency of spindles and slow waves were predictive for performance: children performed better if they had less slow spindles, more fast spindles and faster slow waves. On the other hand, overnight enhancement of accuracy was most pronounced in children with more slow spindles and slower slow waves, i.e., the ones with an initial lower performance. Associations of spindle and slow wave characteristics with initial performance may confound interpretation of their involvement in overnight enhancement. Slower frequencies of characteristic sleep events may mark slower learning and immaturity of networks involved in motor skills

NINscope, a versatile miniscope for multi-region circuit investigations

Miniaturized fluorescence microscopes (miniscopes) have been instrumental to monitor neural signals during unrestrained behavior and their open-source versions have made them affordable. Often, the footprint and weight of open-source miniscopes is sacrificed for added functionality. Here, we present NINscope: a light-weight miniscope with a small footprint that integrates a high-sensitivity image sensor, an inertial measurement unit and an LED driver for an external optogenetic probe. We use it to perform the first concurrent cellular resolution recordings from cerebellum and cerebral cortex in unrestrained mice, demonstrate its optogenetic stimulation capabilities to examine cerebello-cerebral or cortico-striatal connectivity, and replicate findings of action encoding in dorsal striatum. In combination with cross-platform acquisition and control software, our miniscope is a versatile addition to the expanding tool chest of open-source miniscopes that will increase access to multi-region circuit investigations during unrestrained behavior

Derivation of Lenticular Transmittance from Fluorophotometry

PURPOSE. To derive transmittance spectra for the human lens using the ratio between posterior and anterior autofluorescence of the lens as measured by fluorophotometry. METHODS. Transmittance spectra of the lens can be described with a one-parameter model to a high degree of accuracy. The parameter m of this model defines the differences between lens transmittance spectra of individuals. In fluorophotometry literature another parameter related to lens transmittance, T, has been defined as the square root of the ratio between posterior and anterior lenticular autofluorescence. T can be predicted from parameter m, given the spectra of the excitation light, of the fluorescence emitted by the lens and of the detecting device are known, and assuming that the anterior and posterior fluorescence efficiencies of the lens are equal. When this relation is inverted, parameter m can be derived from T, giving the complete transmittance spectrum on the basis of T. RESULTS. A transformation curve was calculated to determine T from m and vice versa. The light transmittance spectrum of the lens was calculated as a function of T. The validity of this approach was evaluated using an independent method for assessment of lenticular transmittance. This method consisted of making color slitlamp slides, grading the observed color of these slides with the LOCS III NC grading system, and transforming these grades into the model parameter m using published transformation curves. CONCLUSIONS. The total transmittance spectrum can be calculated reliably from a fluorophotometric scan of the human lens. (Invest Ophthalmol Vis Sci. 2002;43:3003-3007

Lightweight, wireless LED implant for chronic manipulation in vivo of spontaneous activity in neonatal mice

Background: Long-term manipulation of activity in the neonatal rodent brain can help us understand healthy development, but also involves a set of challenges unique to the neonatal animal. As pups are small, cannot be separated from their mother for long periods of time, and must be housed in a nest, many traditional techniques are unusable during the first two postnatal weeks. New method: Here, we describe the use of magnetic resonance induction to allow wireless and chronic optogenetic manipulation of spontaneous activity in mouse pups during the second postnatal week. Results: Pups were implanted with a lightweight receiver coupled to an LED and successfully returned to the homecage. A transmitter coil surrounding the homecage drove the implanted LED and was regulated by a microcontroller to allow flexible, precisely-timed and wireless control over neuronal manipulation. In vivo patch-clamp recordings verified that activation of the LED triggered bursts of action potentials in layer 2/3 neurons that expressed channelrhodopsin-2 in the visual cortex without directly affecting neighboring, non-expressing neurons. The implants are stable and functional for at least 10 days and do not have an impact on the weight gain of pups. Implanted pups’ behavior is mildly affected only briefly after surgery, while maternal behavior of dams remains unaffected. Comparison with existing method(s): In contrast to most other methods for wireless optogenetic stimulation, the small size and low weight of the receiver allow complete implantation in animals that are as small as a newborn mouse. Conclusions: This method is ideal for investigating the function and development of cortical circuits in small and developing animals. Furthermore, our method is economical and easy to adapt to diverse experimental designs

Morphometry of Dermal Collagen Orientation by Fourier Analysis Is Superior to Multi-Observer Assessment

In human dermis, collagen bundle architecture appears randomly organized, whereas in pathological conditions, such as scar tissue and connective tissue disorders, collagen bundle architecture is arranged in a more parallel fashion. Histological examination by one or two observers using polarized light is the most common method to determine collagen orientation. The hypothesis on which this study is based is that an objective image analysis technique, Fourier analysis, would improve the reliability (are the measurements reproducible?) and the accuracy (does the method measure what it is supposed to measure?) of collagen orientation assessment, compared with observer ratings. Fourier analysis was applied to 271 images of scar tissue and normal skin that were acquired by confocal laser-scanning microscopy. Observers rated the same areas using polarized light as well as the confocal microscopy images. Computer images consisting of different types of ellipses were generated with a fixed orientation. Observers and Fourier analysis evaluated the images to evaluate accuracy. The inter-observer reliability was acceptable when at least three observers rated polarized light images (r > 0.69), whereas two observers were sufficient for rating confocal microscopy images (r > 0.71). Fourier analysis correlated better with observer ratings of confocal microscopy images (r = 0.69) than with polarized light microscopy images (r = 0.42). Fourier analysis was more accurate than four observers for the evaluation of the 'true' orientation for almost all types of computer-generated images. For the first time it is shown that Fourier image analysis is suitable for the morphometry of dermal collagen orientation and leads to a superior measurement of collagen orientation compared with subjective histological evaluation by several experts. If an evaluation is performed by conventional light microscopy, at least three observers are required to attain an acceptable inter-observer reliability

In-vitro recording of forward light-scatter by human lens capsules and different types of posterior capsule opacification

The purpose of the present study was to elucidate the effect of posterior capsule opacification (PCO) on the straylight domain of visual function. PCO is heterogeneous with regard to morphology and severity; both aspects contribute to its functional effect. The isolated impact of capsule areas with specific morphology and severity on straylight was studied in-vitro by recording forward light-scatter. Forward light-scatter by four different capsule types, i.c. anterior capsule (AC), clear posterior capsule (PC), fibrotic and regeneratory PCO, was recorded at several visual angles with a goniometer, using different wavelengths. Angular (theta(a)) and wavelength dependencies (lambda(b)) were studied by determining exponents a and b. Recorded straylight values of isolated capsule areas varied between 10 x below to 10 x above the value normal for the human eye, depending on the capsule's condition (clear to opacified). The angular dependence of light scattered by clear PCs was weaker, whereas in the other capsule types it was stronger than in the normal eye. On average, the wavelength dependence of light scattered by different capsule types was similar, but the variation was considerable. At the smallest visual angles, increased angular and decreased wavelength dependence was found, especially in fibrotic and regeneratory PCO. It was concluded that the range of straylight values found in-vitro in lens capsules properly corresponded to that found previously in in-vivo pseudophakics. Surprisingly, the wavelength dependence of PCO indicated that small-particle light-scattering is important in PCO. Refractile effects were more important at small visual angles, as indicated by the combined stronger angular and weaker wavelength dependence. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserve

Individual Differences in the Post-Illumination Pupil Response to Blue Light: Assessment without Mydriatics

Melanopsin-containing retinal ganglion cells play an important role in the non-image forming effects of light, through their direct projections on brain circuits involved in circadian rhythms, mood and alertness. Individual differences in the functionality of the melanopsin-signaling circuitry can be reliably quantified using the maximum post-illumination pupil response (PIPR) after blue light. Previous protocols for acquiring PIPR relied on the use of mydriatics to dilate the light-exposed eye. However, pharmacological pupil dilation is uncomfortable for the participants and requires ophthalmological expertise. Hence, we here investigated whether an individual's maximum PIPR can be validly obtained in a protocol that does not use mydriatics but rather increases the intensity of the light stimulus. In 18 participants (5 males, mean age ± SD: 34.6 ± 13.6 years) we evaluated the PIPR after exposure to intensified blue light (550 µW/cm²) provided to an undilated dynamic pupil. The test-retest reliability of the primary PIPR outcome parameter was very high, both between day-to-day assessments (Intraclass Correlation Coefficient (ICC) = 0.85), as well as between winter and summer assessments (ICC = 0.83). Compared to the PIPR obtained with the use of mydriatics and 160 µW/cm² blue light exposure, the method with intensified light without mydriatics showed almost zero bias according to Bland-Altman plots and had moderate to strong reliability (ICC = 0.67). In conclusion, for PIPR assessments, increasing the light intensity is a feasible and reliable alternative to pupil dilation to relieve the participant's burden and to allow for performance outside the ophthalmological clinic