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Functional magnetic resonance imaging of motor, sensory, and posterior parietal cortical areas during performance of sequential typing movements.

We investigated the activation of sensory and motor areas involved in the production of typing movements using functional magnetic resonance imaging (fMRI). Eleven experienced typists performed tasks, in which the spatial and temporal requirements as well as the number of digits involved were varied. These included a simple uni-digit repetitive task, a uni-digit sequential task, a dual-digit sequential task, a multi-digit sequential task, and typing text from memory. We found that the production of simple repetitive keypresses with the index finger primarily involved the activation of contralateral primary motor cortex (M1), although a small activation of the supplementary motor area (SMA) and other regions was sometimes observed as well. The sequencing of keypresses involved bilateral M1 and a stronger activation of the SMA and to a lesser extent the premotor area, cingulate gyrus, caudate, and lentiform nuclei. However, the activation of these areas did not exclusively depend on the complexity of the movements, since they were often activated during more simple movements, such as alternating two keypresses repeatedly. Somatosensory and parietal regions were also found to be activated during typing sequences. The activation of parietal areas did not exclusively depend on the spatial requirements of the task, since similar activation was observed during movements within intra-personal space (finger-thumb opposition) and may instead be related to the temporal requirements of the task. Our findings suggest that the assembly of well-learned, goal-directed finger movement sequences involves the SMA and other secondary motor areas as well as somatosensory and parietal areas.

Adult↗

Dynamic competition between contour integration and contour segmentation probed with moving stimuli.

Line-ends, corners and junctions are important singularities for form analysis, object recognition, depth ordering or motion processing. In this study, we investigate the extent to which processing the motion of line ends depends on the spatial configuration of their immediate surround. To that aim, we used two vertical collinear line segments, translating clockwise or anti-clockwise along a circular path, together with a direction discrimination task. Direction discrimination was measured independently for outer line-ends--at both segments extremities--and inner line-ends--in between collinear segments--using line segments partially occluded by invisible masks such that the direction of either inner or outer line-ends' motion was restricted to a sinusoidal translation along a horizontal axis, and thus irrelevant for the motion task. Under these conditions, access to the direction of inner line-ends is longer and more difficult than it is for outer line-ends. Subsequent experiments show that these effects depend on the degree of collinearity between line segments. Similar experiments were performed after volunteers took a dose of Lorazepam, a benzodiazepine that facilitates the fixation of GABA on GABAA receptors. The results show that the differences between the processing of inner and outer line-ends is reduced, suggesting that the effect of the surround is modulated by inhibitory mechanisms. Using a simple model, we propose that this effect can be explained by a competition between a segmentation process based on surround suppression and contour integration through long-range horizontal connections, at or prior to motion processing stages.

Adult↗

Expression and regulation of vascular endothelial growth factor in a first trimester trophoblast cell line.

Embryo implantation and development are critically dependent upon the spatial and temporal regulation of angiogenesis and localized vascular permeability. A key mediator of these effects is the endothelial cell mitogen vascular endothelial growth factor (VEGF). VEGF has been shown to promote endometrial vascular permeability, fetal vasculogenesis and placental, fetal and maternal angiogenesis. However, the mechanism through which this regulation occurs in the placenta is poorly understood. This study was conducted to determine if the pro-angiogenic cytokines, TNF-alpha and TGF-beta1, affect VEGF expression in human first trimester trophoblasts. Culture of a first trimester trophoblast cell line (HTR-8/SVneo), in the presence of either TNF-alpha or TGF-beta1, resulted in the expression of significant levels of VEGF in culture. The trophoblast cell line also showed a time-dependent and a dose-dependent increase in VEGF mRNA levels when cultured in the presence of either TNF-alpha or TGF-beta1. These results suggest that both TNF-alpha and TGF-beta1 may regulate the production of VEGF in early gestational trophoblasts and may therefore serve to modulate placental vascular permeability and angiogenesis that are necessary for embryo implantation and placentation.

Adult↗

Local calcium changes regulate the length of growth cone filopodia.

Previous studies have demonstrated that the free intracellular calcium concentration ([Ca(2+)](i)) in growth cones can act as an important regulator of growth cone behavior. Here we investigated whether there is a spatial and temporal correlation between [Ca(2+)](i) and one particular aspect of growth cone behavior, namely the regulation of growth cone filopodia. Calcium was released from the caged compound NP-EGTA (o-nitrophenyl EGTA tetrapotassium salt) to simulate a signaling event in the form of a transient increase in [Ca(2+)](i). In three different experimental paradigms, we released calcium either globally (within an entire growth cone), regionally (within a small area of the lamellipodium), or locally (within a single filopodium). We demonstrate that global photolysis of NP-EGTA in growth cones caused a transient increase in [Ca(2+)](i) throughout the growth cone and elicited subsequent filopodial elongation that was restricted to the stimulated growth cone. Pharmacological blockage of either calmodulin or the Ca(2+)-dependent phosphatase, calcineurin, inhibited the effect of uncaging calcium, suggesting that these enzymes are acting downstream of calcium. Regional uncaging of calcium in the lamellipodium caused a regional increase in [Ca(2+)](i), but induced filopodial elongation on the entire growth cone. Elevation of [Ca(2+)](i) locally within an individual filopodium resulted in the elongation of only the stimulated filopodium. These findings suggest that the effect of an elevation of [Ca(2+)](i) on filopodial behavior depends on the spatial distribution of the calcium signal. In particular, calcium signals within filopodia can cause filopodial length changes that are likely a first step towards directed filopodial steering events seen during pathfinding in vivo.

Animals↗

Cerebellar vermis involvement in monkey saccadic eye movements: microstimulation.

The cerebellar vermis (lobules V to VII) was focally stimulated (maximum current = 300 microA) through microelectrodes in alert monkeys trained to fixate on visual targets located at different positions in the eye movement field. Microstimulation of this area evoked saccades whose direction and amplitude were dependent on the spatial locus of the vermal point stimulated and on the position of the eye at the time of stimulation. Stimulation evoked saccades on most (70%) of the electrode penetrations. By alternatively stimulating and recording through the electrode as it advanced through the depth of the vermis, it was possible to map the threshold for evoking saccades along a penetration as well as to ascertain the type of tissue (white matter or Purkinje cell layer) situated at the stimulation points. On penetrations where saccades were evoked, there was generally one (90%) and sometimes two (10%) low-threshold region(s). These low-threshold regions were located in fiber tracks and not in the Purkinje or other cellular layers of the cerebellar cortex. The direction and size of the evoked saccades were dependent on position of the eye in the orbit. At a few sites, even the presence or the absence of an evoked saccade depended on the initial eye position. Postsaccadic drifts after termination of evoked saccades were also a common feature (50% of the tracks) associated with vermal microstimulation. The presence or absence as well as the direction of the postsaccadic drift were also dependent on initial eye position. These observations suggest that the vermal stimulations evoked saccades by the antidromic activation of mossy fiber afferent inputs that emanate from the brain stem saccadic burst generator. Furthermore, stimulation in this manner would actually bypass the cerebellar circuitry and produce saccades without the usual modifying influence of the cerebellum.

Animals↗

Spatial-gradient limit on perception of multiple motion.

Motion is perceived whenever a subject is presented with an appropriate spatiotemporal visual pattern. Like many other visual tasks, motion perception involves both local and global processing, and thus might be subject to the well-known paradox that arises from the fact that local features and observations form the basis for global perception, but sometimes this global percept can not be easily derived from any single local observation, as is best exemplified by the aperture problem. Globally, dual (transparent) motion can be readily perceived. Spatial limits on the local ability to perceive multiple motion are sought. By using the framework of apparent motion, it is found that dual, orthogonally oriented motion can be perceived only when the dots that constitute the two motions are separated by some spatial limit. For short-range apparent motion, the limit is found to be comparable to D(max), and the visual system cannot perceive more than a single coherent motion in a local "patch" of radius D(max). It was also found that this spatial limit on local-motion perception is not constant, but depends linearly on the spatial organisation of the stimuli, and vanishes for stimuli having reverse contrast. The lower bound on the ability to perceive multiple motion is compared with some well-known bounds in stereopsis, and a cortical columnar architecture that might account for it is proposed.

Adult↗

Spatial phase-shift interferometry--a wavefront analysis technique for three-dimensional topometry.

We describe a new wavefront analysis method, in which certain wavefront manipulations are applied to a spatially defined area in a certain plane along the optical axis. These manipulations replace the reference-beam phase shifting of existing methods, making this method a spatial phase-shift interferometry method. We demonstrate the system's dependence on a defined spatial Airy number, which is the ratio of the characteristic dimension of the manipulated area and the Airy disk diameter of the optical system. We analytically obtain the resulting intensity data of the optical setup and develop various methods to accurately reconstruct the inspected wavefront out of the data. These reconstructions largely involve global techniques, in which the entire wavefront's pattern affects the reconstruction of the wavefront in any given position. The method's noise sensitivity is analyzed, and actual reconstruction results are presented.

Journal Article↗

Three dimensional spatial memory and learning in real and virtual environments.

Human orientation and spatial cognition partly depends on our ability to remember sets of visual landmarks and imagine their relationship to us from a different viewpoint. We normally make large body rotations only about a single axis which is aligned with gravity. However, astronauts who try to recognize environments rotated in 3 dimensions report that their terrestrial ability to imagine the relative orientation of remembered landmarks does not easily generalize. The ability of human subjects to learn to mentally rotate a simple array of six objects around them was studied in 1-G laboratory experiments. Subjects were tested in a cubic chamber (n = 73) and a equivalent virtual environment (n = 24), analogous to the interior of a space station node module. A picture of an object was presented at the center of each wall. Subjects had to memorize the spatial relationships among the six objects and learn to predict the direction to a specific object if their body were in a specified 3D orientation. Percent correct learning curves and response times were measured. Most subjects achieved high accuracy from a given viewpoint within 20 trials, regardless of roll orientation, and learned a second view direction with equal or greater ease. Performance of the subject group that used a head mounted display/head tracker was qualitatively similar to that of the second group tested in a physical node simulator. Body position with respect to gravity had a significant but minor effect on performance of each group, suggesting that results may also apply to weightless situations. A correlation was found between task performance measures and conventional paper-and-pencil tests of field independence and 2&3 dimensional figure rotation ability.

Adolescent↗

Residual cornea and the degenerate eye of the cryptophthalmic Typhlotriton spelaeus.

The cave-dwelling Typhlotriton spelaeus larvas live in daylight. The larvas undergo a metamorphosis when the thyroxin level (T3 and T4) increases. They leave aquatic life for terrestrial and subterranean aphotic life. The larval eyes are normal and show good vision response to tests. On the contrary, in the oldest larva and the adult, the eyes are small with poor vision or no vision at all. The lens can disappear but in any case the eyelids grow over the eye. The retinal degeneration takes place during and after metamorphosis. The admitted statement that "after metamorphosis . . . the developing lids close over the eye and invade the cornea" is not confirmed concerning the invasion, because it is now evident that the eyelids separate spatially from the residual cornea. Consequently, the fibroblasts of the eyelids are not able to invade the corneal stroma. In fact, the periocular tissues do not invade the cornea but invade the eyelids' tissues. We are able to confirm that the development of the larval eyes is complete and apparently normal. After metamorphosis, the eyes decrease in size. The cornea "sinks" with the eye into orbit tissues. The eyelids cover the eye and are themselves replaced by a supraocular skin. This fits the description of the human cryptophthalmia. We also demonstrate that even in the degenerate eye the residual cornea retains the main structure of a normal salamander cornea. The preservation of the endothelium and of the Descemet membrane is exceptional in blind cave-dwelling vertebrates because in the other degenerate corneas the edema of the stroma depends on the spatial disjunction of the underepithelial stroma and the supraendothelial stroma. Perhaps, the very advanced development of the eye and the late start of the degenerative processes could explain the relative preservation of the cornea. Thus, the arguments put forward tend to prove that the thyroxinic metamorphosis sets off the growth and fusion of the eyelids but that the eye degeneration is related to hereditary processes.

Animals↗

Temporal bone dynamics, the hard way. Formation, growth, modeling, repair and quantum type bone remodeling in the otic capsule.

This review presents studies in which temporal bone dynamics were monitored in undecalcified human and animal materials by combined microradiography and osteofluorochromic time labeling. The results are interpreted in accordance with modern concepts of spatial and temporal organization of bone behavior in an attempt to contribute to a new basis for understanding the structure and function of the bony otic capsule. In postcartilaginous development, perilabyrinthine bone formed a separate functional unit in which growth and modeling were absent. Consequently, all drift movements bypassed the bone present inside a narrow perilabyrinthine zone, which in effect maintained a so-called drift barrier enclosing the entire inner ear. In baseline bone remodeling and repair-associated remodeling transients, secondary osteons were distributed centrifugally with respect to inner ear spaces, and the average osteonal size decreased towards the inner ear, suggesting a progressive inhibition of bone resorption towards inner ear spaces. No histological capsular component proved resistant to bone resorption during modeling and remodeling. Instead the dynamic behaviour of any moiety of capsular bone appeared to depend on its spatial relation to the membranous labyrinth rather than on histological characteristics. This spatial organization of perilabyrinthine bone development and turnover is responsible for the unique histology of capsular bone and may explain the accumulation of fatigue micro-cracks which can be found in human perila byrinthine bone. These findings suggests the role of inner ear tissues as a functional matrix in control of capsular bone dynamics even beyond fetal life.

Animals↗

Steady state visual evoked potentials in the alert primate.

Macaque monkeys were trained to fixate a small spot while we recorded epidural steady state visual evoked potentials (SSVEP) in response to counterphase modulated sinusoidal gratings. This led to the following results: (1) the SSVEP can show either broad or narrow spatial frequency tuning, depending on electrode location, temporal frequency, contrast and method of analysis. (2) The SSVEP can also show narrow temporal frequency tuning, as narrow as 0.5 octave at half height. (3) Contrast functions relating VEP amplitude to log contrast were highly nonlinear. We propose that they are the composite of at least two distinct linear functions, one with a shallow slope for low contrasts and one with a significantly steeper slope for the higher contrasts. (4) Extrapolation of the low contrast function to zero voltage can lead to an excellent match with psychophysical functions. A similar extrapolation of the high contrast function, however, leads to a contrast value much higher than the psychophysical threshold. These findings suggest that the SSVEP can reflect the activity of two distinct neural mechanisms responsive to pattern stimulation. The degree to which either mechanism is evident determines the spatial and temporal frequency tuning of the VEP.

Animals↗

Cholesterol feeding modulates spatial expression of TGF-beta 1 and beta 2 in aortas of Watanabe rabbits.

Several cytokines have been identified as markers of early atherosclerotic disease during vascular injury and remodelling. Of particular importance, transforming growth factor-beta (TGF-beta 1) has been found to be crucial in promoting connective tissue deposition resulting in both intimal and medial hyperplasia. However, the expression of TGF-beta 1 and beta 2 during cholesterol feeding in the Watanabe rabbit, an established model of hypercholesterolemia, has not been evaluated. Accordingly, we examined the expression of TGF-beta 1 and beta 2 signal from aortic segments of 10 heterozygous Watanabe rabbits with the use of reverse transcription-polymerase chain reaction (RT-PCR) amplification during normal non-supplemental diet and during 0.5% supplemental cholesterol feeding for a period of two months. TGF-beta transcripts from the aortic tissue were quantified at the end of the feeding interval. For Watanabe rabbits fed regular chow, the expression of both TGF-beta 1 and beta 2 is reduced in the aortic arch as compared with the descending aorta. In contrast, Watanabe rabbits fed high cholesterol diets manifested a differential expression of TGF-beta isoforms depending on the spatial location within the aorta. In the aortic arch, increased transcript signals for both TGF-beta 1 and beta 2 were noted as compared with rabbits on normal chow. The lesions found in the aortic arch are typified by abundant foam cells and proliferating smooth muscle cells. Analysis of the TGF-beta 1 and 2 profile on these same cell elements in vitro results in a similar expression of increased mRNA isoforms for TGF-beta 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

How spatial orientation of Japanese text affects fixation points in patients with bilateral macular atrophy.

PURPOSE: To ascertain the retinal area used by patients with bilateral macular atrophy when reading Japanese text of different character sizes written horizontally or vertically. In addition, to determine fixation points as part of the first of a series of studies designed ultimately to enhance the quality of life of these patients through the improvement of reading acuity. METHODS: Seventeen patients (34 eyes) with bilateral macular atrophy were tested to determine the retinal area employed for reading (R fixation point). Sentences were arranged either horizontally or vertically and projected onto the retina using a scanning laser ophthalmoscope. We also determined the fixation point using microperimetry (M fixation point). The positional relationships between these two fixation points and the scotoma were examined. RESULTS: The R and M fixation points were the same in 20 of the 34 eyes. Multiple R fixation points were found in 11 eyes. The R fixation point was frequently positioned above the lesion when reading horizontally (nine eyes), while it was often positioned in the area nasal to (eight eyes) or temporal to (six eyes) the lesion when reading vertically. CONCLUSIONS: Fixation points changed frequently in these patients with bilateral macular atrophy depending on the spatial orientation of the text. These data should be used in the future to help patients learn how to use the preferred retinal locus to improve their reading skills and enhance their quality of life.

Adolescent↗

Oculomotor readiness and covert orienting: differences between central and peripheral precues.

The costs produced by invalid precues can depend on the spatial relationship between the cued location and the target location. If oculomotor programs mediate attention shifts, then the effect of varying the spatial relation between the cue and target should be the same for covert orienting (indexed by manual responses) and saccadic responses. We found this to be true only for central precues. With central precues, both manual and saccadic costs were greater when cue and target occurred on opposite sides of the vertical meridian than when they occurred on the same side. With peripheral precues, there were no meridian effects in either response condition, but there was a significant dissociation in the pattern of saccadic and manual costs. For manual responses costs were greater when the target was eccentric relative to the cue, whereas for saccades costs were greater when the cue was eccentric to the target. These results provide additional support for the idea that different orienting mechanisms are engaged by central and peripheral precues. They further suggest that the relationship between oculomotor and attentional orienting may depend on the nature of the precue, with the potential for interdependence being greater with central precues.

Adult↗

The metabotropic glutamate receptor, mGluR5, is a key determinant of good and bad spatial learning performance and hippocampal synaptic plasticity.

Hippocampal synaptic plasticity is expressed to very different extents in distinct rat strains in vivo. This may correlate with differences in learning ability. We investigated whether the metabotropic glutamate receptor mGluR5 contributes to differences in long-term potentiation (LTP) and learning in freely moving hooded Lister (HL) and Wistar rats. High-frequency tetanization (HFT) generated robust CA1 LTP in Wistar rats (> 24 h) and incremental potentiation in HL rats. The mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP; 1.8 microg), applied intracerebrally, impaired LTP from approximately 60 min onwards in Wistar and from 24 h in HL rats. HFT generated LTP in the dentate gyrus (DG) of Wistar rats (> 24 h), which was blocked by MPEP, and MPEP-resistant short-term depression in HL rats. Training for 10 days in an eight-arm radial maze revealed no working memory differences, but better reference memory performance in Wistar compared with HL rats. Daily application of MPEP (1.8 microg) impaired working and reference memory in Wistar rats. In HL rats, working memory was impaired but reference memory was unaffected. Western blot analysis revealed lower expression of mGluR5 in HL compared with Wistar rats. MGluR1 expression was equivalent. These data reveal striking mGluR5-dependent differences in spatial learning in different rat strains, which correlate to synaptic plasticity and mGluR5 expression levels.

Animals↗

Stereopsis and disparity vergence in monkeys with subnormal binocular vision.

The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.

Amblyopia↗

Adaptive temporal integration of motion in direction-selective neurons in macaque visual cortex.

Direction-selective neurons in the primary visual cortex (V1) and the extrastriate motion area MT/V5 constitute a critical channel that links early cortical mechanisms of spatiotemporal integration to downstream signals that underlie motion perception. We studied how temporal integration in direction-selective cells depends on speed, spatial frequency (SF), and contrast using randomly moving sinusoidal gratings and spike-triggered average (STA) analysis. The window of temporal integration revealed by the STAs varied substantially with stimulus parameters, extending farther back in time for slow motion, high SF, and low contrast. At low speeds and high SF, STA peaks were larger, indicating that a single spike often conveyed more information about the stimulus under conditions in which the mean firing rate was very low. The observed trends were similar in V1 and MT and offer a physiological correlate for a large body of psychophysical data on temporal integration. We applied the same visual stimuli to a model of motion detection based on oriented linear filters (a motion energy model) that incorporated an integrate-and-fire mechanism and found that it did not account for the neuronal data. Our results show that cortical motion processing in V1 and in MT is highly nonlinear and stimulus dependent. They cast considerable doubt on the ability of simple oriented filter models to account for the output of direction-selective neurons in a general manner. Finally, they suggest that spike rate tuning functions may miss important aspects of the neural coding of motion for stimulus conditions that evoke low firing rates.

Action Potentials↗

Linking richness, community variability, and invasion resistance with patch size.

The influence of community dynamics on the success or failure of an invasion is of considerable interest. What has not been explored is the influence of patch size on the outcomes of invasions for communities with the same species pool. Here we use an empirically validated spatial model of a marine epibenthic community to examine the effects of patch size on community variability, species richness, invasion, and the relationships between these variables. We found that the qualitative form of the relationship between community variability and species richness is determined by the size of the model patch. In small patches, variability decreases with species richness, but beyond a critical patch size, variability increases with increasing richness. This occurs because in large patches large, long-lived colonies attain sufficient size to minimize mortality and dominate the community, leading to decreased species richness and community variability. This mechanism cannot operate on smaller patches where the size of colonies is limited by the patch size and mortality is high irrespective of species identity. Further, invasion resistance is strongly correlated with community variability. Thus, the relationship between species richness and invasion resistance is also determined by patch size. These patterns are generated largely by an inverse relationship between colony size and mortality, and they depend on the spatial nature and patch size of the community. Our results suggest that a continuum of possible relationships can exist between species richness, community variability, invasion resistance, and area. These relationships are emergent behaviors generated by the individual properties of the particular component species of a community.

Biodiversity↗