PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Insulin action and lipotoxicity in the development of polycystic ovary syndrome: A review.

Polycystic ovary syndrome (PCOS) is a common condition affecting women of reproductive age. This disorder is characterized by hyperandrogenism and anovulation and is frequently associated with comorbidities such as infertility, metabolic syndrome, type 2 diabetes, and cardiovascular risk factors. Although the causes of PCOS are unknown, this review focuses on the most accepted theory involving insulin action but will also elaborate on a novel concept: the role of lipotoxicity in the development of androgen overproduction, in addition to its known role in insulin resistance. This review will also shed a spotlight on 2 drugs that target lipotoxicity and are, therefore, known or promising for the treatment of PCOS manifestations: peroxisome proliferator-activated receptor γ and angiotensin II type 2 receptor agonists. This paper, therefore, emphasizes the need to further explore the pathophysiology of PCOS and particularly the role of lipotoxicity. Indeed, this new mechanism deserves attention to develop therapeutic approaches that will directly target the root of this condition and not only bandage its associated consequences.

The bifoil photodyne: a photonic crystal oscillator.

Optical tweezers is an example how to use light to generate a physical force. They have been used to levitate viruses, bacteria, cells, and sub cellular organisms. Nonetheless it would be beneficial to use such force to develop a new kind of applications. However the radiation pressure usually is small to think in moving larger objects. Currently, there is some research investigating novel photonic working principles to generate a higher force. Here, we studied theoretically and experimentally the induction of electromagnetic forces in one-dimensional photonic crystals when light impinges on the off-axis direction. The photonic structure consists of a micro-cavity like structure formed of two one-dimensional photonic crystals made of free-standing porous silicon, separated by a variable air gap and the working wavelength is 633 nm. We show experimental evidence of this force when the photonic structure is capable of making auto-oscillations and forced-oscillations. We measured peak displacements and velocities ranging from 2 up to 35 microns and 0.4 up to 2.1 mm/s with a power of 13 mW. Recent evidence showed that giant resonant light forces could induce average velocity values of 0.45 mm/s in microspheres embedded in water with 43 mW light power.

Visually induced postural reactivity is velocity-dependent at low temporal frequencies and frequency-dependent at high temporal frequencies.

Visual stimulation alone is sufficient to produce visually induced postural reactivity (VIPR). While some studies have shown that VIPR increases with the velocity of a moving visual stimulus, others have shown that it decreases with the temporal frequency of an oscillating visual stimulus. These results seem contradictory given that these two variables co-vary in the same direction. The purpose of this study is to determine whether the VIPR can be different depending on the frequency range being considered. Twelve subjects were placed standing up in a virtual reality environment that simulated a black and white checkerboard at floor level. This checkerboard oscillated at seven frequencies (0.03-2.0 Hz) and three amplitudes (2, 4, and 8°), corresponding to nine velocities (0.125-32°/s). The virtual floor oscillated from left to right (mediolateral) or from front to back (anteroposterior). We calculated the subjects' mean velocity (Ω) based on data from electromagnetic sensors positioned on the head and lower back. Our experiment shows that for temporal frequencies below 0.12 Hz, VIPR is visually dependent and increases with stimulus velocity. When stimulus velocity becomes too high, the body becomes incapable of following, and the VIPR saturates between 0.12 and 0.25 Hz. In this frequency range, maximal postural oscillation seems to depend on biomechanical constraints imposed by the positioning of the feet. For frequencies above 0.5 Hz, the body can no longer maintain the same oscillation state. This saturation may be linked to proprioceptive feedback mechanisms in the postural system.

Effective tactile noise facilitates visual perception.

The fulcrum principle establishes that a subthreshold excitatory signal (entering in one sense) that is synchronous with a facilitation signal (entering in a different sense) can be increased (up to a resonant-like level) and then decreased by the energy and frequency content of the facilitating signal. As a result, the sensation of the signal changes according to the excitatory signal strength. In this context, the sensitivity transitions represent the change from subthreshold activity to a firing activity in multisensory neurons. Initially the energy of their activity (supplied by the weak signals) is not enough to be detected but when the facilitating signal enters the brain, it generates a general activation among multisensory neurons, modifying their original activity. In our opinion, the result is an integrated activation that promotes sensitivity transitions and the signals are then perceived. In other words, the activity created by the interaction of the excitatory signal (e.g., visual) and the facilitating signal (tactile noise) at some specific energy, produces the capability for a central detection of an otherwise weak signal. In this work we investigate the effect of an effective tactile noise on visual perception. Specifically we show that tactile noise is capable of decreasing luminance modulated thresholds.

Anomalous patterned scattering spectra of one-dimensional porous silicon photonic crystals.

Far-field secondary emission spectra of one-dimensional periodic photonic structures based on porous silicon show characteristic co-focal rings centered close to the structure plane normal. The rings appear when the frequency of picosecond excitation laser pulses is tuned to the edges of the fourth photonic band gap. They can be clearly distinguished from the typical reflected and transmitted light in the oblique incidence geometry. The rings number is dependent on the excitation frequency and the incidence angle. We explain these anomalous spectral features of porous silicon structures by the spectral filtering of light elastically scattered inside the photonic structure by the narrow photonic bands. The elastic scattering of light due to the photonic disorder in the structure causes the appearance of secondary waves propagating in any direction. But only those waves which fall into the allowed photonic bands penetrate through the whole structure and move through its front or back surfaces. The observed patterned secondary emission is an example of efficient photonic engineering by simple means of multilayer porous silicon structures.

Multiband negative refraction in one-dimensional photonic crystals.

We simulate a lossless one-dimensional photonic crystals (1DPC) structure and show that negative refraction could be present near the low frequency edge of at least the second, fourth and sixth bandgaps. We experimentally demonstrate for the first time negative refraction in strongly modulated porous silicon 1D-PC in the visible and near infrared regions. This 1D-PC structure may allow the realization of short-focus Veselago lenses in different optical bands. An advantage of our structure is its simplicity allowing for cheap and rapid fabrication of samples.

Integrative cortical dysfunction and pervasive motion perception deficit in fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS) is associated with neurologic deficits recently attributed to the magnocellular pathway of the lateral geniculate nucleus. OBJECTIVE: To test the hypotheses that FXS individuals 1) have a pervasive visual motion perception impairment affecting neocortical circuits in the parietal lobe and 2) have deficits in integrative neocortical mechanisms necessary for perception of complex stimuli. METHODS: Psychophysical tests of visual motion and form perception defined by either first-order (luminance) or second-order (texture) attributes were used to probe early and later occipito-temporal and occipito-parietal functioning. RESULTS: When compared to developmental- and age-matched controls, FXS individuals displayed severe impairments in first- and second-order motion perception. This deficit was accompanied by near normal perception for first-order form stimuli but not second-order form stimuli. CONCLUSIONS: Impaired visual motion processing for first- and second-order stimuli suggests that both early- and later-level neurologic function of the parietal lobe are affected in Fragile X syndrome (FXS). Furthermore, this deficit likely stems from abnormal input from the magnocellular compartment of the lateral geniculate nucleus. Impaired visual form and motion processing for complex visual stimuli with normal processing for simple (i.e., first-order) form stimuli suggests that FXS individuals have normal early form processing accompanied by a generalized impairment in neurologic mechanisms necessary for integrating all early visual input.

Simple and complex visual motion response properties in the anterior medial bank of the lateral suprasylvian cortex.

The cortical regions surrounding the suprasylvian sulcus have previously been associated with motion processing. Of the six areas originally described by Palmer et al. [J Comp Neurol 177 (1978) 237], the posteromedial lateral suprasylvian (PMLS) cortex has attracted the greatest attention. Very little physiological information is available concerning other suprasylvian visual areas, and in particular, the anteromedial lateral suprasylvian cortex (AMLS). Based on its cortical and sub-cortical connectivity patterns, the AMLS cortex is a likely candidate for higher-order motion processing in cat visual cortex. We have investigated this possibility by studying the receptive field sensitivity of AMLS neurons to complex motion stimuli. Neurons in AMLS cortex exhibited large (mean of 354 degrees (2)) and complex-like receptive fields, and most of them (74%) were classified as direction selective on the basis of their responses to sinusoidal drifting gratings. Most importantly, direction selectivity was present for complex motion stimuli. A subset of the neurons sampled (eight of 38 cells; 21%) exhibited pattern-motion selectivity in response to moving plaid patterns. The capacity of AMLS neurons to signal higher-order stimuli was further supported by their selectivity to moving complex random-dot kinematograms. Finally, 45% of 20 neurons were direction selective to a radial optic flow stimulus. Overall, these results suggest that AMLS cortex is involved in higher-order analyses of visual motion. It is possible that the AMLS cortex represents a region between PMLS and the anterior ectosylvian visual area in a functional hierarchy of areas involved in motion integration.

Stereoscopic processing in the human brain as a function of binocular luminance rivalry.

We investigated the neural substrates of a recent model of human stereodepth perception by obtaining measurements of regional cerebral blood flow (rCBF) using PET. Subjects experienced the perceptual properties of stereopsis by viewing rival-luminance stereograms displaying an identical random-dot pattern in their central portion while the backgrounds exhibited correspondent dots contrasting in black/white luminance. The stereoscopic vision induced by retinal luminance rivalry coincided with a significant elevation of rCBF in the dorsal visual pathway. Area V5 (MT) was activated bilaterally by the experimental condition while the remaining active loci were restricted to the right hemisphere. The neural sites that responded to this novel stereoscopic stimulus are similar to those activated by traditional stereograms containing horizontal disparities.

A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.

From visual consciousness to spectral absorption in the human retina.

In this paper, we present work that started as an interest in visual consciousness with the study of the blindsight phenomena and color processing. This led us to develop an intraocular reflection and absorption model of the human eye that is sufficient to account for luminance and color detection in blindsight subjects. Luminance and color thresholds were obtained in the good and blind field of hemidecorticated patients under controlled conditions. To determine the role of internal scatter and absorption properties of the human eye we tested the model predictions in three ways. By psychophysical means, by measuring absorption and scatter properties of the human eye, and by building an electromechanical sensor apparatus mimicking Lambertian reflection in the eye. The results of the simulations and measurements support the notion that the sensitivity functions obtained with the hemidecorticated patients can be explained by reflection and absorption properties of the human eye that have not been fully accounted for in the blindsight literature. In the light of such findings, future blindsight experiments must necessarily account for intraocular absorption and reflective properties of the human eye of the type described.

Cortical representation of inward and outward radial motion in man.

We have used positron emission tomography to investigate the cortical areas of the normal human brain involved in processing inward (Expansion) and outward (Contraction) radial motion simulated with an optic flow stimulus. The optical flow display was made out of dots moving radially away from or toward the center of the display monitor. In the Control condition, the dots' motion was randomized in order to remove any sensation of radial motion. In the Expansion condition, several loci of activation were observed: visual areas V2-V3 and the superior parietal lobule (BA 7), predominantly in the right hemisphere. In the Contraction condition activation sites were found in the same visual areas (V2 and V3) in the right hemisphere but the increase in rCBF in these regions was much lower than in the Expansion condition. BA 7 was activated in both hemispheres. When the motion component of the stimulus was isolated by subtracting the static condition from the incoherent motion condition, we obtained activations of areas V2, V3, and MT (putative V5). These results indicate that the detection of radial motion derived from an optic flow stimulus is mediated by structures forming the dorsal part of the visual cortical system and confirm that area MT is not specifically involved in flow analysis.

The moving Dynamic Random Dot Stereosize test: development, age norms, and comparison with the Frisby, Randot, and Stereo Smile tests.

PURPOSE: To determine the response of infants and children to the Moving Dynamic Random Dot Stereosize (MDRS) test and to collect cross-sectional age-related data. METHODS: Sixty visually normal individuals were divided into four age groups: 0.5-<2, 2-<5, 5-<8, and 8-<20 years. Stereopsis was measured with the MDRS test on two occasions, plus the Frisby, Randot, or Stereo Smile tests, as was age appropriate. RESULTS: All children aged >2 years and 80% of the children between ages 6 months and 2 years were able to perform the MDRS test on at least one occasion. Sixty percent of the 6-month to 2-year-old children were able to perform the Stereo Smile test on both occasions. Performance on the MDRS test improved with age up to 9 years. Improvement on the Frisby and Randot tests was seen in children aged up to 7 years. Mean and 95% confidence interval ranges for each test are given. CONCLUSION: This study gives evidence that aspects of the visual system are not fully mature until age 7-9 years. The MDRS test is a visually demanding but cognitively simple test that shows potential for detecting visual anomalies in young children.

Functional sub-regions for optic flow processing in the posteromedial lateral suprasylvian cortex of the cat.

During locomotion, an observer sees a large and complex pattern of visual motion called optic flow. This phenomenon is characterized by elements in the environment accelerating and expanding as they move peripherally. In cats, previous studies have indicated that the posteromedial part of the lateral suprasylvian (PMLS) cortex may be involved in the processing of optic flow fields. We further addressed this issue by studying the importance of specific parameters of the optic flow patterns and investigating whether cell responses to these stimuli depend on receptive field (RF) location in the visual field. Results can be summarized as follows: approximately two-thirds of PMLS cells responded to optic flow fields and a subset of these (84/153) showed a clear direction selectivity for motion along the frontal axis. Of these units, the majority responded preferentially to expansion rather than contraction of the pattern. Cells' responses depend on RF location in the visual field. For centrally located RFs, tested both when the origin of motion was within the RF or at the area centralis, responses were generally comparable whether or not size or speed gradients were removed from the optic flow pattern. A different tendency was observed for peripherally located RFs. In general, these cells exhibited a preferred direction almost exclusively when the origin of motion was placed at the area centralis, and neuronal discharges and direction selectivity for many of them were reduced when the optic flow cues were removed from the pattern. The results of this study suggest that there may be functional differences in response properties between PMLS cells located in the central and peripheral parts of the visual field that may reflect a specialization of the PMLS cortex in optic flow processing.

Global motion integration in the cat's lateral posterior-pulvinar complex.

Our laboratory previously showed that thalamic neurons in an extrageniculate nucleus, the lateral posterior-pulvinar complex (LP-pulvinar) could perform higher-order neuronal operations that had until then only been attributed to higher-level cortical areas. To further assess the role of the thalamus in the analysis of complex percepts, we have investigated whether neurons in the LP-pulvinar complex can signal the direction of motion of random-dot kinematograms wherein the individual elements of the pattern do not provide coherent motion cues. Our results indicate that a subset of LP-pulvinar cells can integrate the displacement of individual elements into a global motion percept and that their large receptive fields permit the integration of motion for elements separated by large spatial intervals. We also found that almost all of the global motion-sensitive neurons were not systematically pattern-motion-selective when tested with plaid patterns. The results indicate that LP-pulvinar cells can perform the higher-level spatio-temporal integration required to detect the global displacement of objects in a complex visual scene, further supporting the notion that extrageniculate thalamic cells are involved in higher-order motion processing. Furthermore, these results provide some evidence that there may be specialized mechanisms for processing different types of complex motion within the LP-pulvinar complex.

Perceived length in the central visual field: evidence for visual field asymmetries.

Visual performance for judging the length of a simultaneously presented pair of radial lines, reciprocally opposed by 180 degrees at a central fixation point, was assessed for 24 radial positions of test lines, for three viewing conditions (binocular, left and right monocular) and five different standard line sizes (1.43-7.13 degrees ). Generally, the results showed underestimation of the test line. Furthermore, clear visual field asymmetries were observed between the upper versus lower visual fields and the left versus right visual fields with greater underestimation for test lines presented in the lower and right visual fields. Also, asymmetries tended to be strongest along the 30 and 150 degrees radial orientations. Fourier analysis indicated that these asymmetries are mainly described by summing up the f0, f1, f2 and f5 components.

Transverse chromatic aberration and colour-defined motion.

A number of recent studies have explored the role of the chromatic system in motion processes using the isoluminance paradigm. A major concern when using such methodological procedures is potential artefacts produced by chromatic aberrations. In the present study we address the problem of optically induced luminance artefacts produced by transverse chromatic aberrations (TCA), which may contaminate the results obtained in chromatic motion-nulling experiments. Results show that different TCA levels artificially increase chromatic motion sensitivity values to varying degrees above 0.5 cpd for red/green gratings. The data also suggest the notion that naturally occurring TCA can decrease motion-nulling thresholds for chromatic gratings at high spatial frequencies. Furthermore, our data show that the motion-nulling paradigm for chromatic gratings may in fact be an efficient functional method for assessing the amount of TCA produced by optical factors.

Aging, perception, and visual short-term memory for luminance-defined form.

The sensory, perceptual, and visual short-term memory (VSTM) capacity of young and older observers for processing luminance-defined shape information was assessed in a series of experiments. The following were assessed: each individual's threshold necessary to detect a square from its background as measured by luminance thresholds; the capacity for making simultaneous size discriminations when compensating for individual differences in sensory input; the capacity for making sequential size discriminations; and the capacity for remembering size differences over time. The results show a selective deficit for simultaneous perceptual processing for older subjects, which cannot be attributed to differences in sensory input, task difficulty, interhemispheric transfer, or VSTM.

Binocular vision in older people with adventitious visual impairment: sometimes one eye is better than two.

PURPOSE: To determine the effect of adventitious visual impairment (low vision) on monocular and binocular spatial contrast sensitivity of older people. DESIGN: A between-within repeated measures design. PARTICIPANTS: Fifty-nine older adults between the ages of 50 and 96; 49 of the observers had age-related macular degeneration (AMD). MEASURES: Visual acuity screening and spatial contrast sensitivity. RESULTS: In almost half of the population with AMD, the sensitivity to spatial information, as measured by spatial contrast sensitivity, is worse when both eyes are used than when the stimuli are viewed with only one eye. This "binocular inhibition" is not related to the contrast sensitivity of the better eye or to acuities. Furthermore, this inhibition process is reflected primarily in images with medium to low spatial frequency components (medium to large size bars). CONCLUSIONS: These results have important implications for understanding the functional impact of low vision in older people. They suggest that almost one-half of older people with AMD view the world best using only one of their eyes, whereas for the other half, there is an advantage to using binocular vision for certain visual tasks.

Larger effect of aging on the perception of higher-order stimuli.

Widespread deficits are known to accompany normal aging. Contrast thresholds of older and younger observers were measured for static and drifting gratings defined by luminance (first-order) or by contrast (second-order), and for a temporally segmented second-order motion stimulus. Results showed that older individuals had a larger threshold elevation for the perception of second-order stimuli than for the perception of first-order stimuli. This suggests a dissociation between the mechanisms underlying the perception of first and second-order stimuli, and demonstrates that aging may affect the more numerous processing steps required for the analysis of higher level stimuli.