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Diffusion MRI in neurofibromatosis type 1: ADC evaluations of the optic pathways, and a comparison with normal individuals.

In a control group of 12 normal children (ages ranging from 9 months to 3 years; mean=1.6 years) the mean apparent diffusion coefficient (ADC) value of the normal white matter, obtained from automatically generated ADC maps, was 0.84 +/- 0.14 x 10(-3)mm(2)/s. A patient with neurofibromatosis type 1 with bilateral optic gliomas, and extensive optic pathway involvement was evaluated by diffusion MRI. Multiple measurements of ADC values throughout the involved optic radiations revealed a higher mean value: 1.16 +/- 0.06 x 10(-3)mm(2)/s than that of the normal white matter, suggesting relatively high molecular motion in these regions, probably representing myelin vacuolization. ADC evaluation of a thalamic hamartoma revealed a lower value (=1.06 x 10(-3)mm(2)/s) than this. The mean ADC value obtained from multiple measurements of the enlarged optic chiasm, and intraorbital portions of the nerve was similar (=0.81+/- 0.09 x 10(-3)mm(2)/s) to that of the normal cerebral white matter of the control cases. It appears that diffusion imaging can be useful in evaluation of optic pathway involvement in NF1, and might contribute to differentiating optic gliomas from hamartomas, and myelin vacuolization, however, further studies will be required for assessing the role of diffusion imaging in such lesions.

Case-Control Studies↗

Adaptive control: a review of the ability to acquire and maintain high sensorimotor performance.

When the relationship which relates us to the environment through vision, often named visual mapping, is durably modified, our behaviour is altered at sensory, motor and cognitive levels. The brain has the ability through the so-called adaptive control to progressively decrease the motor errors despite visual image alteration. Adaptive control in both the visuo-manual and the vestibulo-ocular systems is reviewed. A parallel is tentatively made between adaptation to ordinary optical alterations (resulting from the use of refraction-corrective glasses) in the visual mapping of these two systems and the adaptation to more complex visuo-motor relationships experienced by people working in virtual environments.

Adaptation, Ocular↗

Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice.

Voltage-sensitive dye imaging resolves the spatiotemporal dynamics of supragranular subthreshold cortical activity with millisecond temporal resolution and subcolumnar spatial resolution. We used a flexible fiber optic image bundle to visualize voltage-sensitive dye dynamics in the barrel cortex of freely moving mice while simultaneously filming whisker-related behavior to generate two movies matched frame-by-frame with a temporal resolution of up to 2 ms. Sensory responses evoked by passive whisker stimulation lasted longer and spread further across the barrel cortex in awake mice compared to anesthetized mice. Passively evoked sensory responses were large during behaviorally quiet periods and small during active whisking. However, as an exploring mouse approached an object while whisking, large-amplitude, propagating cortical sensory activity was evoked by active whisker-touch. These experiments demonstrate that fiber optics can be used to image cortical sensory activity with high resolution in freely moving animals. The results demonstrate differential processing of sensory input depending upon behavior.

Anesthesia, General↗

Mapping retinal projections from double nasal and double temporal compound eyes to dually innervated tectum in Xenopus.

Right double nasal (NN) and left double temporal (TT) compound eyes were formed in the same animal by the fusion of two similar halves at early embryonic stages in Xenopus. After metamorphosis either the right or left optic nerve was sectioned to induce optic fiber regeneration from one of the two eyes to both tecta. Retinal projections from each eye to the monocularly and dually innervated tecta were later investigated by visuotectal mapping and by [3H]proline autoradiography. Visuotectal and autoradiographic maps from NN and TT eyes showed the restoration of typical compound eye projections where each of the hemiretinal projections extended across the entire contralateral (monocularly innervated) tectum. In contrast, the tectum ipsilateral to the optic nerve section was dually innervated by fibers from the TT and NN eyes. The rostral and caudal poles of the tectum were innervated by fibers from the TT and NN eyes respectively, whereas the middle third received partially overlapping projections from both eyes. Thus the full expansion of the hemiretinal projection across the dually innervated tectum was prevented by fiber-fiber interactions between optic fibers from the TT and NN eyes. It is concluded that tectal polarity cues determine the proper orientation, and fiber-fiber interaction the extent and orderliness of the retinotectal map. The formation of the latter two features of the retinotectal map does not require the existence of independent tectal positional markers.

Animals↗

Optical recording of the rat piriform cortex activity.

The piriform cortex (PCx) is a phylogenetically old brain structure which presents characteristics of a content-addressable memory. Taking into account its particular anatomo-functional organization, we hypothesized that this cortex could behave rather as an assembly of different functional units than as a functionally homogeneous structure. This hypothesis was tested by using both anatomical and functional approaches. Immunohistological and tracing experiments demonstrated that both the connections of the PCx with the higher nervous centres, and its monoaminergic and cholinergic modulatory afferents exhibited a heterogeneous distribution. Then, optical monitoring of its neuronal activity with a voltage-sensitive dye pointed out that the PCx is a functionally heterogeneous structure. Electrical stimulations of the olfactory bulb showed that the inhibitory processes which control the cortical responsiveness were not identical in all the PCx area. Two different functional areas at least could be distinguished: in the ventromedial PCx, the afferent activity is privileged since the level of inhibition of disynaptic activation remained large during repetitive stimuli. Contrarily, in the posterior PCx, the disynaptic activity remained unchanged in response to successive stimulations and the responses of neighbouring sites were statistically more synchronized than in its anterior part. Moreover, a late depolarization wave was significantly larger in the posterior PCx. These data are in good agreement with the results provided by computational models of the PCx. In the future, theoretical and experimental investigations of this cortex will be useful for understanding olfactory information processing and as a model of brain functioning at the neocortical level as well.

Animals↗

Morphometric study of the optic nerve of adult normal mice and mice heterozygous for the Small eye mutation (Sey/+).

The Small eye (Sey) gene, which has been mapped to chromosome 2 in the mouse, is known to cause variable malformations of the eye and nose. The effect of the gene in the heterozygous state is mainly on the eye. A combined electron microscopy and morphometric analysis of the optic nerve in adult littermates with a normal (+/+) and heterozygous mutant (Sey/+) genotype was carried out. The optic nerve could be dissected from the posterior pole of the eyeball to the optic chiasma in all the mice examined. The results of morphometric analyses carried out in this study show that the Sey gene indirectly affects the normal morphogenesis of the optic nerve in the heterozygous mutant Sey male mouse to a significant degree compared with its male normal littermate. The heterozygous mutant Sey female mouse is also affected, but not significantly so when compared with its normal female littermate. The mean nerve cross-sectional area and mean nerve fibre counts for the Sey strain are lower than those observed in other strains of mice that have been studied. The nerve fibre densities and the spectrum of nerve fibre sizes encountered are, however, similar to those seen in other strains of mice. We believe that the findings indicate that the smaller mean nerve fibre counts observed in the heterozygous mutant (Sey/+) mice compared to their normal (+/+) siblings is unlikely to have resulted from primary retinal dysgenesis, but is a consequence of the reduced size of their neural retina, and total retinal ganglion cell population.

Animals↗

Leber hereditary optic neuropathy: involvement of the mitochondrial ND1 gene and evidence for an intragenic suppressor mutation.

A large Queensland family has an extreme form of Leber hereditary optic neuropathy (LHON) in which several neurological abnormalities and an infantile encephalopathy are present in addition to the characteristic ophthalmological changes. Sequence analysis of the seven mitochondrial genes encoding subunits of respiratory chain complex I (NADH-ubiquinone oxidoreductase) reveals two novel features of the etiology of this mitochondrial genetic disease. The first conclusion from these studies is that the ophthalmological and neurological deficits in this family are produced by a mutation at nucleotide 4160 of the ND1 gene. This nucleotide alteration results in the substitution of proline for the highly conserved leucine residue at position 285 of the ND1 protein. Secondary-structure analysis predicts that the proline replacement disrupts a small alpha helix in a hydrophilic loop. All nine family members analyzed were homoplasmic for this mutation. The second major result from these studies is that the members of one branch of this family carry, at nucleotide 4136 of the same gene, a second mutation, also homoplasmic, which produces a cysteine-for-tyrosine replacement at position 277. The clinical and biochemical phenotypes of the family members indicate that this second nucleotide substitution may function as an intragenic suppressor mutation which ameliorates the neurological abnormalities and complex I deficiency.

Amino Acid Sequence↗

Ultraresolution in optical imaging using spatiotemporal scanning.

Spatial information exceeding the passband of an imaging system can be captured by using the optics to generate a spatiotemporal multiple beam interference pattern that is scanned over the object, rather than using it to image the object directly. The modulation of the higher temporal harmonics of the signal resulting from collecting the scattered light represents a mapping in the time domain of higher spatial harmonics of the data. Upon reconstruction, the additional temporal degrees of freedom are mapped back in the spatial domain where they represent spatial frequencies exceeding the passband of the optics. The spatial resolution is thus not limited by the spatial passband, but rather by the temporal bandwidth of the detection system. Due to hardware limitations, experimental demonstration is provided only for a one-dimensional scan of Ronchi gratings with 50 and 200 lines per inch.

Journal Article↗

Plasticity in the developing visual system: the effects of retinal lesions made in young rats.

The central visual pathways of the rat have been used as a model for investigating the significance of axonal interactions in mammalian neural development. Attention is restricted largely to the aberrant distribution of optic axons to the ipsilateral side of the brain and their distribution in the superior colliculus after early unilateral eye damage. The normal ipsilateral retinotectal pathway in pigmented rats appears as a series of patches located anteriorly and laterally in the stratum opticum, whereas in albino animals it is a small area lying anteromedially. In both, a few axons are often found at the extreme posterior border of the superior colliculus. After unilateral eye enucleation at birth, an aberrant ipsilateral pathway from the remaining eye arises at the optic chiasm. It originates from all parts of the retina and terminates in the ipsilateral superior colliculus in a topographic fashion such that the upper retina projects laterally and the lower retina, medially. The pathway is heaviest anteromedially (from lower temporal retina) and lightest posterolaterally (from upper nasal retina). There is always a heavy projection to the extreme posterior border of the superior colliculus. In only two animals of a large series was direct intertectal sprouting found. After partial retinal lesions, there is again an ipsilateral pathway from the unlesioned eye which fills the projection area of the lesion. As after total enucleation, the pathway arises from most of the ipsilateral retina, not just that region homotypic to the lesion site, being heaviest from the lower temporal and lightest (or deficient) from the upper retina. There is suggestion of ordering of the projection into the deafferented region in that the ipsilateral degeneration after lesions in the intact eye is compact but does not fill the gap in the crossed projection completely. There is also indication that some intact parts of the retina lesioned at birth may also project in an inappropriate retinotopic fashion to the deafferented region. The corticotectal pathway shows a normal map. Study of the ipsilateral retinotectal pathway indicates that the axons terminating at the extreme posterior border of the superior colliculus arise from the lower temporal retina. The results are interpreted as indicating that the aberrant uncrossed pathways after complete or local retinal lesions, compare very closely in most features. Both distribute to the deafferented area of the superior colliculus -- in one, this is the whole surface, while in the other it is a small area. The fact that in the latter case axons are ending in quite inappropriate parts of the tectal map, may be explained more simply in terms of interactions between adjacent axons in the optic pathway rather than by an hypothesis involving a change in the cell labels across the tectal map.

Age Factors↗

Intrinsic signal recording from a monkey whose behavior was maintained by a schedule of reinforcement.

Optical recording of cortical activity in awake monkeys has enhanced our understanding of the functional anatomy of the primary visual cortex (V1). However, cortical representation of visual cognition has not been studied by optical recording, even though the greatest merit of using awake animals is that they can offer advantages in studying cognitive function that anesthetized animals cannot. Thus far, the optical recording method has not been combined with tasks that accompany body movements because of concern about movement noise, although behavioral tasks are helpful in the study of animal cognition. Here, I tested the influence of body movements during the signal acquisition period on the resultant images. I recorded the intrinsic signals associating with different orientations from V1 of a monkey who was emitting behavior during the signal acquisition period. Although the monkey's behavior was maintained on a variable-interval schedule that typically induces a high rate of response, orientation maps were consistently obtained. Therefore, a successful recording under this operant regimen implies the applicability of the optical recording method to other behavioral tasks. Several constraints in applying optical recording to studies using behaving animals are also discussed.

Analysis of Variance↗

Scanning X-ray microdiffraction with submicrometer white beam for strain/stress and orientation mapping in thin films.

Scanning X-ray microdiffraction (microSXRD) combines the use of high-brilliance synchrotron sources with the latest achromatic X-ray focusing optics and fast large-area two-dimensional-detector technology. Using white beams or a combination of white and monochromatic beams, this technique allows for the orientation and strain/stress mapping of polycrystalline thin films with submicrometer spatial resolution. The technique is described in detail as applied to the study of thin aluminium and copper blanket films and lines following electromigration testing and/or thermal cycling experiments. It is shown that there are significant orientation and strain/stress variations between grains and inside individual grains. A polycrystalline film when investigated at the granular (micrometer) level shows a highly mechanically inhomogeneous medium that allows insight into its mesoscopic properties. If the microSXRD data are averaged over a macroscopic range, results show good agreement with direct macroscopic texture and stress measurements.

Journal Article↗

Alignment maps of tissues: I. Microscopic elliptical polarimetry.

An automated method for generating a fiber alignment map in tissues, tissue-equivalents, and other fibrillar materials exhibiting linear and circular optical properties and scattering is presented. This method consists of interrogating the sample with elliptically polarized light from a rotated quarter-wave plate and an effective circular analyzer, and implementing nonlinear regression techniques to estimate parameters defining the optical properties of the optic train and the sample. Thus, an account is made for imperfect and misaligned optic elements. The optic train was modeled using the Mueller matrix representation and the combined sample properties by an exponential matrix. Because a sample's Mueller matrix does not uniquely determine the linear, circular, or scattering properties, the circular properties and effective scattering are estimated for a matched isotropic sample to determine and correct for the linear birefringence of an aligned sample. The method's utility is demonstrated by generating an alignment map of an arterial media-equivalent, a relevant test case because of its circumferential alignment and thus showing the method's sample orientation independence.

Animals↗

Suprathreshold auditory cortex activation visualized by intrinsic signal optical imaging.

The suprathreshold tonotopic organization of rat and guinea pig auditory cortex was investigated using intrinsic signal optical imaging through a thinned skull. Optical imaging revealed that suprathreshold pure sine wave tone stimulation (25-80 dB) evoked activity over large cortical areas that were tonotopically organized. Three-dimensional surface plots of the activated areas revealed "patchy' auditory-evoked activity consisting of numerous local peaks and valleys building to a maximum. Subsequent detailed electrophysiological mapping in the same subjects confirmed the localization of auditory-evoked activity based on optical imaging, including responses to a test frequency at cortical loci more than 2 octaves away from the threshold-defined isofrequency contour. The success of this technique in visualizing auditory cortex functional organization at suprathreshold stimulus levels will allow for future investigations of auditory cortex frequency representation, including representational plasticity induced by a variety of experimental manipulations.

Acoustic Stimulation↗

Intertectal commissural projection in the lizard Gallotia stehlini: origin and midline topography.

The retinotectal projection of reptiles is largely crossed. The intertectal commissure is an important pathway that interconnects directly the two sides of the optic tectum. The rostrocaudal topography of intertectal commissural fibers at the dorsal midplane was examined by means of the in vitro horseradish peroxidase (HRP) labelling technique in the lizard Gallotia stehlini. Unilateral large deposits of tracer in the optic tectum as well as smaller deposits restricted to one quadrant were used to map the intertectal fibers anterogradely. Most commissural axons reached the contralateral side grouped into a dense bundle at the transition between two structurally distinct parts of the midbrain dorsal midline. The smaller rostral zone relates laterally to the griseum tectale, whereas the larger caudal zone relates to the tectum. The intertectal fibers seem to converge on the rostralmost part of the latter midline region, even though they originate throughout the optic tectum. A rough rostrocaudal tectotopic order was detected at the midline. Retrogradely labelled neurons were best obtained by depositing HRP directly within the compact commissure at the midline. These belong to pyriform cells in the periventricular layers 3 and 5. Axons labelled from the tectum did not enter the posterior commissure nor the intervening commissural region related to the griseum tectale.

Animals↗

Noninvasive transcutaneous access flow measurement before and after hemodialysis: impact of hematocrit and blood pressure.

BACKGROUND/AIMS: The dialysis outcome is strongly affected by the function of the vascular access. It has been suggested that access clotting may be related to increased hematocrit (Hct) or excessive ultrafiltration during dialysis. The present study was designed to evaluate the changes of vascular access flow during hemodialysis in 18 end-stage renal disease patients with native arteriovenous fistulas and the possible correlations with Hct and mean arterial pressure (MAP). METHODS: We utilized a noninvasive vascular access flow measurement technique, based on a transcutaneous optical sensor, to evaluate the flow in the access before and after a single hemodialysis session. At the beginning and at the end of the session, the blood flow was measured noninvasively, placing the sensor approximately 2 in from the point of insertion of the arterial needle. At the same time, Hct and MAP were measured directly. All patients were on hemodialysis for more than 3 months. RESULTS: There was a significant increase in Hct, likely due to ultrafiltration and consequent hemoconcentration, from the beginning to the end of the dialysis session. In detail, the Hct increased from 32.6 +/- 1.9 to 35.4 +/- 1.8% (p < 0.001), while the MAP did not present significant variations. The blood flow did not show significant variations, increasing from 780 +/- 312 to 919 +/- 411 ml/min after the session. Because of the stability of the MAP, we could dissociate the effects of the Hct from those of the MAP on blood flow variations. CONCLUSION: Our study suggests that the blood flow in native fistulas is not affected by the acute rise in Hct due to ultrafiltration during hemodialysis. The transcutaneous access flow measurement technique appears to be reliable and accurate, and it could represent an important diagnostic tool.

Arteriovenous Fistula↗

Imaging of somatotopic representation of sensory cortex with intrinsic optical signals as guides for brain tumor surgery.

OBJECT: Intrinsic optical signals in response to somatosensory stimuli were intraoperatively recorded during brain tumor surgery. In the present study, the authors report on the use of this technique as an intraoperative guide for the safe resection of tumors adjacent to or within the sensorimotor cortex. METHODS: In 14 patients with tumors adjacent to or within the sensorimotor cortex, intrinsic optical signals in response to somatosensory stimuli were recorded by illuminating the brain surface with Xe white light and imaging the reflected light passing through a bandpass filter (605 nm). Results were compared with intraoperative recordings of sensory evoked potentials in all 14 patients and with noninvasive mapping modalities such as magnetoencephalography and positron emission tomography in selected patients. In all but two patients, the somatosensory optical signals were recorded on the primary sensory cortex. Optical signals elicited by stimulation of the first and fifth digits and the three branches of the trigeminal nerve were recorded at different locations on the sensory strip. This somatotopic information was useful in determining the resection border in patients with glioma located in the sensorimotor cortex. CONCLUSIONS: Optical imaging of intrinsic signals is a useful technique with superior spatial resolution for delineating the somatotopic representation of human primary sensory cortex. Furthermore, it can be used as an intraoperative monitoring tool to improve the safety and accuracy of resections of brain tumors adjacent to or within the sensorimotor cortex.

Adult↗