Immunocytochemical characterization of the pregeniculate nucleus and distribution of retinal and neuropeptide Y terminals in the suprachiasmatic nucleus of the Cebus monkey

Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are modulated by photic and non-photic stimuli. In rodents, direct photic stimuli reach the SCN mainly through the retinohypothalamic tract (RHT), whereas indirect photic stimuli are mainly conveyed by the geniculohypothalamic tract (GHT). In rodents, retinal cells form a pathway that reaches the intergeniculate leaflet (IGL) where they establish synapses with neurons that express neuropeptide Y (NPY), hence forming the GHT projecting to the SCN. In contrast to the RHT, which has been well described in primates, data regarding the presence or absence of the IGL and GHT in primates are contradictory. Some studies have suggested that an area of the pregeniculate nucleus (PGN) of primates might be homologous to the IGL of rodents, but additional anatomical and functional studies on primate species are necessary to confirm this hypothesis. Therefore, this study investigated the main histochemical characteristics of the PGN and the possible existence of the GHT in the SCN of the primate Cebus, comparing the distribution of NPY immunoreactivity, serotonin (5-HT) immunoreactivity and retinal terminal fibers in these two structures. The results show that a collection of cell bodies containing NPY and serotonergic immunoreactivity and retinal innervations are present within a zone that might be homologous to the IGL of rodents. The SCN also receives dense retinal innervations and we observed an atypical distribution of NPY- and 5-HT-immunoreactive fibers without regionalization in the ventral part of the nucleus as described for other species. These data may reflect morphological differences in the structures involved in the regulation of circadian rhythms among species and support the hypothesis that the GHT is present in some higher primates (diurnal animals). (C) 2009 Elsevier B.V. All rights reserved.

Visual rehabilitation in low-moderate keratoconus : intracorneal ring segment implantation followed by same-day topography-guided photorefractive keratectomy and collagen cross linking

AIM: To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK) and corneal collagen crosslinking (CXL) after previous intrastromal corneal ring segment (ISCR) implantation for keratoconus. METHODS: An experimental clinical study on twenty-one eyes of 19 patients aged, 27.1±6.6 years (range: 19 – 43 years), with low to moderate keratoconus who were selected to undergo customized TG-PRK immediately followed by same-day CXL, 9 months after ISCR implantation in a university ophthalmology clinic. Refraction, uncorrected (UDVA) and corrected distance visual acuities (CDVA), keratometry (K) values, central corneal thickness (CCT) and coma were assessed 3 months after TG/PRK and CXL. RESULTS: After TG-PRK/CXL: the mean UDVA (logMAR) improved significantly from 0.66±0.41 to 0.20±0.25 (P<0.05); K flat value decreased from: 48.44±3.66 D to 43.71±1.95 D; K steep value decreased from 45.61±2.40 D to 41.56±2.05D; K average also decreased from 42.42±2.07 D to 47.00±2.66 D (P<0.05 for all). The mean sphere and cylinder decreased significantly post-surgery from, -3.10±2.99 D to -0.11±0.93 D and from, -3.68±1.53 to -1.11±0.75D respectively, while the CDVA, CCT and coma showed no significant changes. Compared to post-ISCR, significant reductions (P ˂ 0.05 or all) in all K-values, sphere and cylinder were observed after TG-PRK/CXL. CONCLUSION: Same-day combined topography-guided PRK and corneal crosslinking following placement of ICRS is a safe and potentially effective option in treating low-moderate keratoconus. It significantly improved all visual acuity, reduced keratometry, sphere and astigmatism, but caused no change in central corneal thickness and coma.

A neuronal topography of visual and acoustic fear conditioning within the amygdala

The lateral amygdala (LA) receives information from auditory and visual sensory modalities, and uses this information to encode lasting memories that predict threat. One unresolved question about the amygdala is how multiple memories, derived from different sensory modalities, are organized at the level of neuronal ensembles. We previously showed that fear conditioning using an auditory conditioned stimulus (CS) was spatially allocated to a stable topography of neurons within the dorsolateral amygdala (LAd) (Bergstrom et al, 2011). Here, we asked how fear conditioning using a visual CS is topographically organized within the amygdala. To induce a lasting fear memory trace we paired either an auditory (2 khz, 55 dB, 20 s) or visual (1 Hz, 0.5 s on/0.5 s off, 35 lux, 20 s) CS with a mild foot shock unconditioned stimulus (0.6 mA, 0.5 s). To detect learning-induced plasticity in amygdala neurons, we used immunohistochemistry with an antibody for phosphorylated mitogen-activated protein kinase (pMAPK). Using a principal components analysis-based approach to extract and visualize spatial patterns, we uncovered two unique spatial patterns of activated neurons in the LA that were associated with auditory and visual fear conditioning. The first spatial pattern was specific to auditory cued fear conditioning and consisted of activated neurons topographically organized throughout the LAd and ventrolateral nuclei (LAvl) of the LA. The second spatial pattern overlapped for auditory and visual fear conditioning and was comprised of activated neurons located mainly within the LAvl. Overall, the density of pMAPK labeled cells throughout the LA was greatest in the auditory CS group, even though freezing in response to the visual and auditory CS was equivalent. There were no differences detected in the number of pMAPK activated neurons within the basal amygdala nuclei. Together, these results provide the first basic knowledge about the organizational structure of two different fear engrams within the amygdala and suggest they are dissociable at the level of neuronal ensembles within the LA

Quantitative estimation of retinal nerve fiber layer height in glaucoma and the relationship with optic nerve head topography and visual field

Purpose: The authors estimated the retinal nerve fiber layer height (RNFLH) measurements in patients with glaucoma compared with those in age-matched healthy subjects as obtained by the laser scanning tomography and assessed the relationship between RNFLH measurements and optic and visual field status. Methods: Parameters of optic nerve head topography and RNFLH were evaluated in 125 eyes of 21 healthy subjects and 104 patients with glaucoma using the Heidelberg Retina Tomograph ([HRT] Heidelberg Engineering GmbH, Heidelberg, Germany) for the entire disc area and for the superior 70°(50°temporal and 20°nasal to the vertical midline) and inferior 70°sectors of the optic disc. The mean deviation of the visual field, as determined by the Humphrey program 24-2 (Humphrey Instruments, Inc., San Leonardo, CA, U.S.A) was calculated in the entire field and in the superior and inferior Bjerrum area. Result: Retinal nerve fiber layer height parameters (mean RNFLH and RNFL cross-sectional area) were decreased significantly in patients with glaucoma compared with healthy individuals. Retinal nerve fiber layer height parameters was correlated strongly with rim volume, rim area, and cup/disc area ratio. Of the various topography measures, retinal nerve fiber layer (RNFL) parameters and cup/disc area ratio showed the strongest correlation with visual field mean deviation in patients with glaucoma. Conclusion: Retinal nerve fiber layer height measures were reduced substantially in patients with glaucoma compared with age-matched healthy subjects. Retinal nerve fiber layer height was correlated strongly with topographic optic disc parameters and visual field changes in patients with glaucoma.

Event-related potential P300 microstate topography during visual one- and two-dimensional tasks in chronic schizophrenics

Reports on left-lateralized abnormalities of component P300 of event-related brain potentials (ERP) in schizophrenics typically did not vary task difficulties. We collected 16-channel ERP in 13 chronic, medicated schizophrenics (25±4.9 years) and 13 matched controls in a visual P300 paradigm with targets defined by one or two stimulus dimensions (C1: color; C2: color and tilt); subjects key-pressed to targets. The mean target-ERP map landscapes were assessed numerically by the locations of the positive and negative map-area centroids. The centroids' time-space trajectories were searched for the P300 microstate landscape defined by the positive centroid posterior of the negative centroid. At P300 microstate centre latencies in C1, patients' maps tended to a right shift of the positive centroid (p<0.10); in C2 the anterior centroid was more posterior (p<0.07) and the posterior (positive) centroid more anterior (p<0.03), but without leftright difference. Duration of P300 microstate in C2 was shorter in patients (232 vs 347 ms;p<0.03) and the latency of maximal strength of P300 microstate increased significantly in patients (C1: 459 vs 376 ms; C2: 585 vs 525 ms). In summary only the one-dimensional task C1 supported left-sided abnormalities; the two-dimensional task C2 produced abnormal P300 microstate map landscapes in schizophrenics, but no abnormal lateralization. Thus, information processing involved clearly aberrant neural populations in schizophrenics, different when processing one and two stimulus dimensions. The lack of lateralization in the two-dimensional task supported the view that left-temporal abnormality in schizophrenics is only one of several task-dependent aberrations.

Topography of visual evoked magnetic responses to pattern shift, pattern onset and flash stimuli

Different visual stimuli may activate separate channels in the visual system and produce magnetic responses from the human bran which originate from distinct regions of the visual cortex. To test this hypothesis, we have investigated the distribution of visual evoked magnetic responses to three distinct visual stimuli over the occipital region of the scalp with a DC-SQUID second-order gradiometer in an ubshielded environment. Patterned stimuli were presented full field and to the right half field, while a flash stimulus was presented full field only, in five normal subjects. Magnetic responses were recorded from 20 to 42 positions over the occipital scalp. Topographic maps were prepared of the major positive component within the first 150ms to the three stimuli, i.e., the P100m (pattern shift), C11m (pattern onset) and P2m (flash). For the pattern shift stimulus the data suggested the source of the P100m was close to the midline with the current directed towards the medial surface. The data for the pattern onset C11m suggested a source at a similar depth but with the current directed away from the midline towards the lateral surface. The flash P2m appeared to originate closer to the surface of the occipital pole than both the patterned stimuli. Hence the pattern shift (which may represent movement), and the pattern onset C11m (representing contrast and contour) appear to originate in similar areas of brain but to represent different asepcts of cortical processing. By contrast, the flash P2m (representing luminance change) appears to originate in a distinct area of visual cortex closer to the occipital pole.

Topography of the visual evoked magnetic response and hemispherical specialization

The visual evoked magnetic response CIIm component to a pattern onset stimulus presented half field produced a consistent scalp topography in 15 normal subjects. The major response was seen over the contralateral hemisphere, suggesting a dipole with current flowing away from the medial surface of the brain. Full field responses were more unpredictable. The reponses of five subjects were studied to the onset of a full, left half and right half checkerboard stimuli of 38 x 27 min arc checks appearing for 200 ms. In two subjects the full field CIIm topography was consistent with that of the mathematical summation of their relevant half field distribution. The remaining subjects had unpredictable full field topographies, showing little or no relationship to their half or summated half fields. In each of these subjects, a distribution matching that of the summated half field CIIm distribution appears at an earlier latency than that of the predominant full field waveform peak. By examining the topography of the full and half field responses at 5 ms intervals along the waveform for one such subject, the CIIm topography of the right hemisphere develops 10 ms before that of the left hemisphere, and is replaced by the following CIIIm component 20 ms earlier. Hence, the large peak seen in full field results from a combination of the CIIm component of the left hemisphere plus that of the CIIIm from the right. The earlier peak results from the CIIm generated in both hemispheres, at a latency where both show similar amplitudes. As the relative amplitudes of these two peaks alter with check and field size, topographic studies would be required for accurate CIIm identification. In addition. the CIIm-CIIIm complex lasts for 80 ms in the right hemisphere and 135 ms in the left, suggesting hemispherical apecialization in the visual processing of the pattern onset response.

A penny for your thoughts! Patterns of fMRI activity reveal the content and the spatial topography of visual mental images

Visual mental imagery is a complex process that may be influenced by the content of mental images. Neuropsychological evidence from patients with hemineglect suggests that in the imagery domain environments and objects may be represented separately and may be selectively affected by brain lesions. In the present study, we used functional magnetic resonance imaging (fMRI) to assess the possibility of neural segregation among mental images depicting parts of an object, of an environment (imagined from a first-person perspective), and of a geographical map, using both a mass univariate and a multivariate approach. Data show that different brain areas are involved in different types of mental images. Imagining an environment relies mainly on regions known to be involved in navigational skills, such as the retrosplenial complex and parahippocampal gyrus, whereas imagining a geographical map mainly requires activation of the left angular gyrus, known to be involved in the representation of categorical relations. Imagining a familiar object mainly requires activation of parietal areas involved in visual space analysis in both the imagery and the perceptual domain. We also found that the pattern of activity in most of these areas specifically codes for the spatial arrangement of the parts of the mental image. Our results clearly demonstrate a functional neural segregation for different contents of mental images and suggest that visuospatial information is coded by different patterns of activity in brain areas involved in visual mental imagery. Hum Brain Mapp 36:945-958, 2015.

Aberrations and pupil location under corneal topography and Hartmann-Shack illumination conditions

PURPOSE. This study was conducted to determine the magnitude of pupil center shift between the illumination conditions provided by corneal topography measurement (photopic illuminance) and by Hartmann-Shack aberrometry (mesopic illuminance) and to investigate the importance of this shift when calculating corneal aberrations and for the success of wavefront-guided surgical procedures. METHODS. Sixty-two subjects with emmetropia underwent corneal topography and Hartmann-Shack aberrometry. Corneal limbus and pupil edges were detected, and the differences between their respective centers were determined for both procedures. Corneal aberrations were calculated using the pupil centers for corneal topography and for Hartmann-Shack aberrometry. Bland-Altmann plots and paired t-tests were used to analyze the differences between corneal aberrations referenced to the two pupil centers. RESULTS. The mean magnitude (modulus) of the displacement of the pupil with the change of the illumination conditions was 0.21 ± 0.11 mm. The effect of this pupillary shift was manifest for coma corneal aberrations for 5-mm pupils, but the two sets of aberrations calculated with the two pupil positions were not significantly different. Sixty-eight percent of the population had differences in coma smaller than 0.05 µm, and only 4% had differences larger than 0.1 µm. Pupil displacement was not large enough to significantly affect other higher-order Zernike modes. CONCLUSIONS. Estimated corneal aberrations changed slightly between photopic and mesopic illumination conditions given by corneal topography and Hartmann-Shack aberrometry. However, this systematic pupil shift, according to the published tolerances ranges, is enough to deteriorate the optical quality below the theoretically predicted diffraction limit of wavefront-guided corneal surgery.

Corneal topography with Scheimpflug imaging and videokeratography : comparative study of normal eyes

PURPOSE: To compare the repeatability within anterior corneal topography measurements and agreement between measurements with the Pentacam HR rotating Scheimpflug camera and with a previously validated Placido disk–based videokeratoscope (Medmont E300). ------ SETTING: Contact Lens and Visual Optics Laboratory, School of Optometry, Queensland University of Technology, Brisbane, Queensland, Australia. ----- METHODS: Normal eyes in 101 young adult subjects had corneal topography measured using the Scheimpflug camera (6 repeated measurements) and videokeratoscope (4 repeated measurements). The best-fitting axial power corneal spherocylinder was calculated and converted into power vectors. Corneal higher-order aberrations (HOAs) (up to the 8th Zernike order) were calculated using the corneal elevation data from each instrument. ----- RESULTS: Both instruments showed excellent repeatability for axial power spherocylinder measurements (repeatability coefficients <0.25 diopter; intraclass correlation coefficients >0.9) and good agreement for all power vectors. Agreement between the 2 instruments was closest when the mean of multiple measurements was used in analysis. For corneal HOAs, both instruments showed reasonable repeatability for most aberration terms and good correlation and agreement for many aberrations (eg, spherical aberration, coma, higher-order root mean square). For other aberrations (eg, trefoil and tetrafoil), the 2 instruments showed relatively poor agreement. ----- CONCLUSIONS: For normal corneas, the Scheimpflug system showed excellent repeatability and reasonable agreement with a previously validated videokeratoscope for the anterior corneal axial curvature best-fitting spherocylinder and several corneal HOAs. However, for certain aberrations with higher azimuthal frequencies, the Scheimpflug system had poor agreement with the videokeratoscope; thus, caution should be used when interpreting these corneal aberrations with the Scheimpflug system.

One-year clinical outcomes of a two-step surgical management for keratoconus-topography-guided photorefractive keratectomy/cross-linking after intrastromal corneal ring implantation

PURPOSE - To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK) and corneal collagen cross-linking (CXL) after intrastromal corneal ring (ISCR) implantation in patients with keratoconus. METHODS - Thirty-three patients (41 eyes) aged between 19 and 45 years were included in this prospective study. All patients underwent a femtosecond laser-enabled (Intralase FS; Abbott Medical Optics, Inc.) placement of intracorneal ring segments (Kerarings; Mediphacos, Brazil). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings remained stable for 6 months. Same-day PRK and CXL was subsequently performed in all patients. RESULTS - After 12 months of completion of the procedure, mean UDVA in log of minimal angle of resolution was significantly improved (0.74±0.54-0.10±0.16); CDVA did not improve significantly but 85% of eyes maintained or gained multiple lines of CDVA; mean refraction spherical equivalent improved (from -3.03±1.98 to -0.04±0.99 D), all keratometry readings were significantly reduced, from preoperative values, but coma did not vary significantly from preoperative values. Central corneal thickness and corneal thickness at the thinnest point were significantly (P<0.0001) reduced from 519.76±29.33 and 501.87±31.50 preoperatively to 464.71±36.79 and 436.55±47.42 postoperatively, respectively. Safety and efficacy indices were 0.97 and 0.88, respectively. From 6 months up until more than 1 year of follow-up, further significant improvement was observed only for UDVA (P<0.0001). CONCLUSIONS - Same-day combined TG-PRK and CXL after ISCR implantation is a safe and effective option for improving visual acuity and visual function, and it halts the progression of the keratoconus. The improvements recorded after 6 months of follow-up were maintained or improved upon 1 year after the procedure.

Neural routing circuits for forming invariant representations of visual objects

This thesis presents a biologically plausible model of an attentional mechanism for forming position- and scale-invariant representations of objects in the visual world. The model relies on a set of control neurons to dynamically modify the synaptic strengths of intra-cortical connections so that information from a windowed region of primary visual cortex (Vl) is selectively routed to higher cortical areas. Local spatial relationships (i.e., topography) within the attentional window are preserved as information is routed through the cortex, thus enabling attended objects to be represented in higher cortical areas within an object-centered reference frame that is position and scale invariant. The representation in V1 is modeled as a multiscale stack of sample nodes with progressively lower resolution at higher eccentricities. Large changes in the size of the attentional window are accomplished by switching between different levels of the multiscale stack, while positional shifts and small changes in scale are accomplished by translating and rescaling the window within a single level of the stack. The control signals for setting the position and size of the attentional window are hypothesized to originate from neurons in the pulvinar and in the deep layers of visual cortex. The dynamics of these control neurons are governed by simple differential equations that can be realized by neurobiologically plausible circuits. In pre-attentive mode, the control neurons receive their input from a low-level "saliency map" representing potentially interesting regions of a scene. During the pattern recognition phase, control neurons are driven by the interaction between top-down (memory) and bottom-up (retinal input) sources. The model respects key neurophysiological, neuroanatomical, and psychophysical data relating to attention, and it makes a variety of experimentally testable predictions.

Expression of eph-family receptor tyrosine kinases and ephrins in the tadpole of the frog Xenopus laevis, and possible roles in the development of retinotectal topography

Assembling a nervous system requires exquisite specificity in the construction of neuronal connectivity. One method by which such specificity is implemented is the presence of chemical cues within the tissues, differentiating one region from another, and the presence of receptors for those cues on the surface of neurons and their axons that are navigating within this cellular environment.

Connections from one part of the nervous system to another often take the form of a topographic mapping. One widely studied model system that involves such a mapping is the vertebrate retinotectal projection-the set of connections between the eye and the optic tectum of the midbrain, which is the primary visual center in non-mammals and is homologous to the superior colliculus in mammals. In this projection the two-dimensional surface of the retina is mapped smoothly onto the two-dimensional surface of the tectum, such that light from neighboring points in visual space excites neighboring cells in the brain. This mapping is implemented at least in part via differential chemical cues in different regions of the tectum.

The Eph family of receptor tyrosine kinases and their cell-surface ligands, the ephrins, have been implicated in a wide variety of processes, generally involving cellular movement in response to extracellular cues. In particular, they possess expression patterns-i.e., complementary gradients of receptor in retina and ligand in tectum- and in vitro and in vivo activities and phenotypes-i.e., repulsive guidance of axons and defective mapping in mutants, respectively-consistent with the long-sought retinotectal chemical mapping cues.

The tadpole of Xenopus laevis, the South African clawed frog, is advantageous for in vivo retinotectal studies because of its transparency and manipulability. However, neither the expression patterns nor the retinotectal roles of these proteins have been well characterized in this system. We report here comprehensive descriptions in swimming stage tadpoles of the messenger RNA expression patterns of eleven known Xenopus Eph and ephrin genes, including xephrin-A3, which is novel, and xEphB2, whose expression pattern has not previously been published in detail. We also report the results of in vivo protein injection perturbation studies on Xenopus retinotectal topography, which were negative, and of in vitro axonal guidance assays, which suggest a previously unrecognized attractive activity of ephrins at low concentrations on retinal ganglion cell axons. This raises the possibility that these axons find their correct targets in part by seeking out a preferred concentration of ligands appropriate to their individual receptor expression levels, rather than by being repelled to greater or lesser degrees by the ephrins but attracted by some as-yet-unknown cue(s).