[Emotional-affective reactions evokec by electrostimulation of the ventrolateral nucleus of the optic thalamus].
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Brain Mapping↗
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[Naming and recognizing. Clinical and anatomical report of a case of optic aphasia, alexia and optic agnosia].
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Agnosia↗
Topographic changes in corneal asphericity and effective optical zone after laser in situ keratomileusis.
PURPOSE: To determine the relationship between the spherical refractive change after myopic excimer laser surgery and the effective optical zone (EOZ) and corneal asphericity determined by corneal topography. SETTING: Baylor College of Medicine, Houston, Texas, USA. METHODS: Preoperative and postoperative topographies along with refractions were evaluated in all patients who had had laser in situ keratomileusis since January 1999 and had at least 6 months of follow-up. The VISX Smoothscan S2 excimer laser and the Hansatome microkeratome (Bausch & Lomb) were used in all cases. Because optical zones are oval with astigmatic treatments with the VISX laser, only patients with spherical refractions and treatments were included. Thirty-nine cases met the criteria; their treatments ranged from -1.50 to -18.00 diopters (D). The preoperative and postoperative corneal asphericities (Q-values) were taken directly from the Holladay Diagnostic Summary Report on the EyeSys 2000, version 4.0. The mean diameter of the optical zone was measured on the local radius of curvature map using the outer edge of the yellow zone, which corresponds to 2 color changes or approximately 0.50 D steepening from the mean central radius (green). RESULTS: The EOZ decreased as the amount of treatment increased. The decrease was slightly nonlinear, decreasing slightly more rapidly at higher treatments. For an "intended" 6.0 mm optical zone, the nominal EOZs from the least-squares second-order polynomial regression were 6.0 mm for -1.5 D, 5.4 mm for -5.0 D, 4.6 mm for -10.0 D, 3.8 mm for -15.0 D, and 3.2 mm for -18.0 D. The least-squares second-order polynomial regression yielded a standard error of the estimate (SEE) of +/- 0.22 mm (R(2) = 0.90). The asphericity increased nonlinearly in a positive direction (oblate) with the amount of treatment, indicating greater amounts of correction produced progressively more oblate corneal surfaces. The least-squares second-order polynomial regression yielded an SEE of +/- 0.42 (R(2) = 0.55). CONCLUSIONS: The EOZ decreased and the Q-value increased with the amount of myopic excimer laser treatment. The optical zone was approximately 4.3 mm with a spherical treatment of -12.0 D. These findings may explain the clinical studies that indicate high myopic treatments (above -12.0 D) are associated with poor visual outcomes.
Cornea↗
Visual mechanisms of spatial disorientation in Alzheimer's disease.
Impaired optic flow perception may contribute to the visuospatial disorientation of Alzheimer's disease (AD). We find that 36% of AD patients have elevated perceptual thresholds for left/right outward radial optic flow discrimination. This impairment is related to independent visual motion processing deficits affecting the perception of left/right motion-defined boundaries and in/out radial motion. Elevated optic flow thresholds in AD are correlated with greater difficulty in the Road Map test of visuospatial function (r = -0.5) and in on-the-road driving tests (r = -0.83). When local motion cues are removed from optic flow, subjects must rely on the global pattern of motion. This reveals global pattern perceptual deficits that affect most AD patients (85%) and some normal elderly subjects (21%). This deficit might combine with impaired local motion processing to undermine the alternative perceptual strategies for visuospatial orientation. The greater prevalence of global pattern deficits suggests that it might precede local motion processing impairments, possibly relating to the sequence of early hippocampal and later posterior cortical damage that is typical of AD.
Adult↗
Relationship between the ocular dominance and orientation maps in visual cortex of monocularly deprived cats.
The significance of functional maps for cortical plasticity was investigated by imaging of intrinsic optical signals together with single-unit recording in kittens. After even a brief period of monocular deprivation during the height of the critical period, only isolated patches of visual cortex continued to respond strongly to the closed eye. These deprived-eye patches were located on the pinwheel center singularities of the orientation map and consisted of neurons that were poorly selective for stimulus orientation. Neurons in regions surrounding the deprived-eye patches responded only weakly to the deprived eye but were well tuned for the same stimulus orientation that optimally excited them when presented to the open, nondeprived eye. The coincidence of deprived-eye patches with pinwheel center singularities, and the selective loss of orientation tuning within the deprived-eye patches, indicate that the orientation and ocular dominance maps are functionally linked and provide compelling evidence that pinwheel center singularities are important for cortical plasticity.
Animals↗
An automated simultaneous transmural cardiac mapping system.
The origin and propagation sequence of cardiac depolarization in situ requires accurate simultaneous three-dimensional information from multiple sites. Likewise, the mechanism underlying an arrhythmia can often be elucidated by determining the course of impulse propagation through the heart, particularly if information can be obtained from multiple sites simultaneously, allowing analysis of transient or rapidly occurring events. The most significant problem with obtaining such detailed continuous information is the large amount of data storage required as well as the need for rapid analysis. In the present system these problems are overcome by immediate conversion of all electrograms from analog to digital for all subsequent storage and processing. The bipolar electrogram information is acquired from 240 cardiac sites simultaneously at a sampling rate of 2 kHz with continuous and total data storage of up to 60 min. Rapid two-dimensional isochronic maps at multiple depths (effective 3-dimensional information) are presented via computer-generated interactive graphics. System design permits easy expansion to almost 2,000 simultaneous sites. Surgical electrophysiological intraoperative studies in humans are performed at an operating room located 2,000 ft from the computer facility with all communications carried by a fiber-optic link. The system allows both experimental and clinical cardiac mapping from multiple sites from a single cardiac depolarization, minimal redundancy of costly hardware, and direct rapid visualization of all original electrogram data.
Arrhythmias, Cardiac↗
Near-field mapping of the emission distribution in semiconductor microdiscs.
We have used a scanning near-field optical microscope to study the fluorescent light distribution in the near- and far-fields with two types of microdiscs, InGaP and GaN, fabricated in our laboratory. The InGaP microdisc has a radius of 2.5-5.0 microm, a thickness of 0.15-0.2 microm and a circular shape and the GaN disc has a radius of 5-8 microm with a thickness of 0.5-2 microm. Spontaneous emission enhancement in these microdiscs has been observed with emitting wavelengths of 650 and 550 nm respectively In both types of microdisc, the whispering-gallery mode (WCM) has been observed on the top surface using near-field optical and far-field microscopic methods. However, due to the different disc structures and optical confinements, the light distributions of the type types of disc are quite different. In the case of the InGaP disc, WGM is the dominant mode with a mixture of other modes. Interference-like ring intensities have been observed both inside the disc surface and outside, with a period ratio of 1:2. In addition, the propagating waves emitted from the side of the disc have been collected for the first time by using near-field optical microscopy. A theoretical calculation based on the theory of optical modes in microdisc lasers confirmed this observation. It also predicted the behaviour of the electric field distribution (transverse electric) inside and outside the disc, as well as the period of the wave propagation. In contrast, the near-field mapping of the GaN fluorescence showed not only a ring-like emission intensity along the circumference of the disc, an indication of WGM, but also an even intensity distribution inside the disc. This can be explained as the combination of the WGM with the Fabry-Perot mode of multi-reflection between the GaN layer and the substrate. The results also demonstrate the potential application of near-field optics to explore the light emission mode of a microdisc on a nanometre scale.
Journal Article↗
Combined physiological-anatomical approaches to study lateral inhibition.
In the visual cortex, large basket cells form the cellular basis of long-range lateral inhibition. The present paper focuses on combinations of methods with which large basket cells can be studied in the context of extensive neuronal representations. In the first approach, the topographic relationship between large basket axons and known functional representations such as orientation, direction, and ocular dominance is analysed. Functional mapping is carried out using extracellular electrode recordings or optical imaging of intrinsic signals followed by 3-dimensional anatomical reconstruction of biocytin stained large basket cells in the same regions. In the second approach, the contribution of lateral inhibition to orientation and direction selectivity is assessed using the GABA inactivation paradigm and direct inhibitory projections from the inactivation to recording sites are demonstrated with biocytin staining and injections of [3H]nipecotic acid, a radioactive marker for GABAergic cells. The limitation of these approaches is that they can only be used in cortical regions which lie on the surface of the brain.
Animals↗
Altered map of visual space in the superior colliculus of mice lacking early retinal waves.
During the development of the mammalian retinocollicular projection, a coarse retinotopic map is set up by the graded distribution of axon guidance molecules. Subsequent refinement of the initially diffuse projection has been shown to depend on the spatially correlated firing of retinal ganglion cells. In this scheme, the abolition of patterned retinal activity is not expected to influence overall retinotopic organization, but this has not been investigated. We used optical imaging of intrinsic signals to visualize the complete retinotopic map in the superior colliculus (SC) of mice lacking early retinal waves, caused by the deletion of the beta2 subunit of the nicotinic acetylcholine receptor. As expected from previous anatomical studies in the SC of beta2(-/-) mice, regions activated by individual visual stimuli were much larger and had less sharp borders than those in wild-type mice. Importantly, however, we also found systematic distortions of the entire retinotopic map: the map of visual space was expanded anteriorly and compressed posteriorly. Thus, patterned neuronal activity in the early retina has a substantial influence on the coarse retinotopic organization of the SC.
Animals↗
Combinatorial materials synthesis and high-throughput screening: an integrated materials chip approach to mapping phase diagrams and discovery and optimization of functional materials.
Combinatorial materials synthesis methods and high-throughput evaluation techniques have been developed to accelerate the process of materials discovery and optimization and phase-diagram mapping. Analogous to integrated circuit chips, integrated materials chips containing thousands of discrete different compositions or continuous phase diagrams, often in the form of high-quality epitaxial thin films, can be fabricated and screened for interesting properties. Microspot x-ray method, various optical measurement techniques, and a novel evanescent microwave microscope have been used to characterize the structural, optical, magnetic, and electrical properties of samples on the materials chips. These techniques are routinely used to discover/optimize and map phase diagrams of ferroelectric, dielectric, optical, magnetic, and superconducting materials.
Combinatorial Chemistry Techniques↗
V2 thin stripes contain spatially organized representations of achromatic luminance change.
A considerable amount of research over the last decades has focused on the apparent specialization of V2 thin stripes for the processing of color in diurnal primates. However, because V2 thin stripes are functionally heterogeneous in that they consist of largely separate color- and luminance-preferring domains and because the color-preferring domains contain a systematic representation of hue, we hypothesized that they contained functional maps that subserve luminance processing. Here we show, using optical imaging of intrinsic cortical signals and microelectrode recording, that the V2 thin stripe luminance-preferring domains contain spatially segregated modules that encode the direction of relative luminance change. Quantitative analysis of the cortical responses to luminance increments or decrements indicates that these luminance-sensitive modules also encode the magnitude of the luminance change by the magnitude of the evoked cortical response. These results demonstrate an important role of V2 thin stripes in the processing of luminance and thus suggest that thin stripes are involved in the overall processing of the surface properties of objects rather than simply the processing of color.
Animals↗
OPA1 (Kjer type) dominant optic atrophy: a novel mitochondrial disease.
Dominant optic atrophy (DOA) is the most common form of inherited optic neuropathy. Although heterogeneous, a major locus has been mapped to chromosome 3q28 and the responsible gene, OPA1, was recently identified. OPA1 is a mitochondrial dynamin-related GTPase implicated in the formation and maintenance of the mitochondrial network. To date, 62 mutations have been identified in a total of 201 DOA patients. Most of them (90%) are distributed from exons 8 to 28 with a majority in the GTPase domain (54%). None were found in the alternatively spliced exons 4, 4b, and 5b. Half of them are truncative mutations (50%) with a frequent recurrent allele, c.2708delTTAG. Most missense mutations (81%) cluster within the putative GTPase domain. Various pathogenic mechanisms may play a role in OPA1 DOA. Truncative mutations in the N-terminal region and perhaps missense mutations in the GTPase domain lead to a loss of function of the encoded protein and haplotype insufficiency. However, there is a cluster of truncation mutations in the in C-terminus, a putative dimerization domain, that could act through a dominant negative effect. The findings that OPA1-type DOA, as Leber optic neuropathy, is caused by the impairment of a mitochondrial protein address the question of the vulnerability of the retinal ganglion cell in response to mitochondrial defects.
Animals↗
Three-dimensional optical tomographic brain imaging in small animals, part 1: hypercapnia.
In this study, we explore the potential of diffuse optical tomography for brain oximetry. While several groups have already reported on the sensitivity of optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood volume, these studies were often limited to single source-detector geometries or topographic maps, where signals obtained from within the brain are projected onto 2-D surface maps. In this two-part study, we report on our efforts toward developing a volumetric optical imaging system that allows one to spatially resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the instrumentation, optical probe design, and the model-based iterative image reconstruction algorithm employed in this work. Consideration of how a priori anatomical knowledge can be incorporated in the reconstruction process is presented. This system is then used to monitor global hemodynamic changes that occur in the brain under various degrees of hypercapnia. The physiologic cerebral response to hypercapnia is well known and therefore allows an initial performance assessment of the imaging system. As expected, we observe global changes in blood volume and oxygenation, which vary linearly as a function of the concentration of the inspired carbon dioxide. Furthermore, experiments are designed to determine the sensitivity of the reconstructions of only 1 mm to inaccurate probe positioning. We determine that shifts can significantly influence the reconstructions. In part 2 we focus on more local hemodynamic changes that occur during unilateral carotid occlusion performed at lower-than-normal systemic blood pressure. In this case, the occlusion leads to a predominantly monohemispherically localized effect, which is well described in the literature. Having explored the system with a well-characterized physiologic effect, we investigate and discuss the complex compensatory cerebrovascular hemodynamics that occur at normotensive blood pressure. Overall, these studies demonstrate the potential and limitations of our diffuse optical imager for visualizing global and focal hemodynamic phenomenon three dimensionally in the brains of small animals.
Algorithms↗
Activity sharpens the regenerating retinotectal projection in goldfish: sensitive period for strobe illumination and lack of effect on synaptogenesis and on ganglion cell receptive field properties.
The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the contralateral tectum and then sharpens it. Disruption of visual activity, either by blocking activity with intraocular tetrodotoxin (TTX; Schmidt and Edwards, 1983) or by synchronizing activity with strobe illumination (Schmidt and Eisele, 1985), disrupts the sharpening process: the map is correctly oriented but the multiunit receptive fields at each point average 25-40 degrees in diameter. In order to test whether strobe and TTX interfere with the same mechanism, we have tested whether their sensitive periods are the same, and whether strobe, like TTX treatment, does not affect either ganglion cell receptive field properties or synaptogenesis. In parallel studies, we exposed fish to 2 weeks of either strobe illumination or intraocular TTX beginning at various times after crush and determined via electrophysiological recordings that the periods of sensitivity were nearly identical. There was no effect of either treatment during the first 2 weeks (before the fibers arrive at the tectum), maximal disruption of sharpening between 14 and 50 days (the period of rapid synaptogenesis), decreasing disruption between 50 and 125 days, and no effect beyond that point or in the normal projection. In addition, long strobe exposures of up to 142 days produced no greater disruptions than shorter 2-3-week exposures, indicating no cumulative effect. The reestablishment of synaptic transmission in tectum, assayed by recording field potentials elicited by optic nerve shock, was not affected by stroboscopic illumination. Finally, individual ganglion cells, recorded intraretinally following long-term strobe exposure, had receptive fields that were normal both in size and in their characteristic responses to light-on, to light-off, or to both on and off. These findings support the hypothesis that strobe-like TTX prevents retinotopic refinement by preventing the correction of errors initially made by the ingrowing optic axons (Schmidt et al., 1988).
Animals↗
Component-dependent urine responses in the rat accessory olfactory bulb.
To investigate how pheromonal information is processed in the rat accessory olfactory bulb, we optically imaged intrinsic signals to obtain high-resolution maps of activation induced by urinary stimulation. Application of volatile components in male urine mainly induced activation in the anterior accessory olfactory bulb, irrespective of the sex, whereas volatile female urine elicited activation not only in the anterior but also to some extent in the caudal part of the posterior accessory olfactory bulb of male, but not female, rats. Nonvolatile components of both male and female urine induced activation mainly in the rostral part of the posterior and to a lesser extent in the anterior accessory olfactory bulb, irrespective of the sex. These results indicate that volatile and nonvolatile urinary components activate the anterior and posterior subdivisions of the accessory olfactory bulb, respectively.
Animals↗
Dynamical MCG mapping with an atomic vapor magnetometer.
We have developed a magnetometer based on magnetic resonance in cesium vapor optically pumped by resonant laser radiation, which has the sensitivity and bandwidth to record human magnetocardiograms. The device is operated as a first-order gradiometer in a weakly shielded environment and allows us to record 2-dimensional field maps by shifting the subject with respect to a single sensor and making time-sequential measurements. We discuss the magnetometer technique and its performance as well as obtained results, which include a comparison of MCG data recorded with our single channel optical magnetometer with SQUID measurements from a commercial multi-channel device as well as from SQUID reference data. The results obtained so far in the detection of cardiomagnetic signals using the optical magnetometer make us confident that the technique has a high potential to serve as an alternative to SQUID detection.
Body Surface Potential Mapping↗
Simultaneous recording of task-induced changes in blood oxygenation, volume, and flow using diffuse optical imaging and arterial spin-labeling MRI.
Increased neural activity in brain tissue is accompanied by an array of supporting physiological processes, including increases in blood flow and the rates at which glucose and oxygen are consumed. These responses lead to secondary effects such as alterations in blood oxygenation and blood volume, and are ultimately the primary determinants of the amplitude and temporal signature of the blood oxygenation level-dependent (BOLD) signal used prevalently to map brain function. We have performed experiments using a combination of optical and MRI-based imaging methods to develop a more comprehensive picture of the physiological events accompanying activation of primary motor cortex during a finger apposition task. Temporal profiles for changes in tissue hemoglobin concentrations were qualitatively similar to those observed for MRI-based flow and oxygenation signals. Quantitative analysis of these signals revealed peak changes of +16 +/- 2% for HbO, -13 +/- 2% for HbR, +8 +/- 3% for total Hb, +83 +/- 9% for cerebral blood flow, and +1.4 +/- 0.1% for the BOLD MRI signal. A mass balance model was used to estimate the change in rate of oxidative metabolism implied by the optical and flow measurements, leading to a computed value of +47 +/- 5%. It should be noted that the optical and MRI observations may in general reflect changes over different volumes of tissue. The ratio of fractional changes in oxidative metabolism to fractional change in blood flow was found to be 0.56 +/- 0.08, in general agreement with previous studies of flow-metabolism coupling.
Arousal↗
Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy.
Dominant optic atrophy (DOA) is the commonest form of inherited optic neuropathy. Although heterogeneous, a major locus has been mapped to chromosome 3q28 and the gene responsible, OPA1, was recently identified. We therefore screened a panel of 35 DOA patients for mutations in OPA1. This revealed 14 novel mutations and a further three known mutations, which together accounted for 20 of the 35 families (57%) included in this study. This more than doubles the number of OPA1 mutations reported in the literature, bringing the total to 25. These are predominantly null mutations generating truncated proteins, strongly suggesting that the mechanism underlying DOA is haploinsufficiency. The mutations are largely family-specific, although a common 4 bp deletion in exon 27 (eight different families) and missense mutations in exons 8 (two families) and 9 (two families) have been identified. Haplotype analysis of individuals with the exon 27 2708del(TTAG) mutation suggests that this is a mutation hotspot and not an ancient mutation, thus excluding a major founder effect at the OPA1 locus. The mutation screening in this study also identified a number of asymptomatic individuals with OPA1 mutations. A re-calculation of the penetrance of this disorder within two of our families indicates figures as low as 43 and 62% associated with the 2708del(TTAG) mutation. If haploinsufficiency is the mechanism underlying DOA it is unlikely that this figure will be mutation-specific, indicating that the penetrance in DOA is much lower than the 98% reported previously. To investigate whether Leber's hereditary optic neuropathy (LHON) could be caused by mutations in OPA1 we also screened a panel of 28 LHON patients who tested negatively for the three major LHON mutations. No mutations were identified in any LHON patients, indicating that DOA and LHON are genetically distinct.
Alternative Splicing↗