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Biomedical subjects

O Bock

Publications and source records attributed to O Bock.

At least 37 records · Page 2Linked to original sources

Conditions for interference versus facilitation during sequential sensorimotor adaptation.

We investigated how sensorimotor adaptation acquired during one experimental session influenced the adaptation in a subsequent session. The subjects' task was to track a visual target using a joystick-controlled cursor, while the relationship between joystick and cursor position was manipulated to introduce a sensorimotor discordance. Each subject participated in two sessions, separated by a pause of 2 min to 1 month duration. We found that adaptation was achieved within minutes, and persisted in the memory for at least a month, with only a small decay (experiment A). When the discordances administered in the two sessions were in mutual conflict, we found evidence for task interference (experiment B). However, when the discordances were independent, we found facilitation rather than interference (experiment C); the latter finding could not be explained by the use of an "easier" discordance in the second session (experiment D). We conclude that interference is due to an incompatibility between task requirements, and not to a competition of tasks for short-term memory. We further conclude that the ability to adapt to a sensorimotor discordance can be improved by practicing with an unrelated discordance.

Adaptation, Physiological↗

Mechanisms for sensorimotor adaptation to rotated visual input.

Using the multiple-exposure approach, we investigated sensorimotor adaptation by exposing human subjects to different angles of visual rotation in a tracking task. Generally, the tracking error was high at the onset of the visual rotation and gradually declined towards the baseline level during the exposure period. In experiment A, we confirmed that the initial tracking error increases more than proportionally with the angle of rotation. In experiment C, we were unable to confirm intermanual transfer, and attribute this discrepancy with previous literature to details of the experimental tasks. In our main experiment, B, we found that pre-exposure to 45 degrees or 60 degrees of visual rotation facilitated the subsequent adaptation to a 90 degrees rotation, with the facilitatory effect being more pronounced following the 60 degrees rotation. We interpret this finding as evidence that adaptation is achieved by a gradual process, which progresses from small angles of output transformation through intermediate values up to the prescribed angle of rotation.

Adaptation, Physiological↗

Sensorimotor adaptation to rotated visual input: different mechanisms for small versus large rotations.

The present study investigates if sensorimotor adaptation to large visual rotations is achieved by a continuous angular change of the internal representation of space. Human subjects performed manual tracking movements under rotated visual feedback in two sessions; the magnitude of rotation in the second session was 45 degrees larger or smaller than in the first. We found mostly a facilitatory effect of the first adaptation on the second, which supports the view that the internal representation can gradually shift from one angular transformation to another. However, no facilitation was found for visual rotations in the 80-120 degrees range, suggesting that the internal model changes gradually only up to a limiting angle. A subsidiary experiment, employing small stepwise changes of visual rotation throughout a testing session, confirmed this view and placed the limiting angle near 120 degrees for an increasing, and near 70 degrees for a decreasing visual rotation. We conclude that adaptation to large-magnitude rotations may be achieved in two stages: a polarity inversion of both axes (=180 degrees rotation), followed by a "backward" shift toward somewhat smaller angles.

Adaptation, Physiological↗

Demonstration of light chain restricted clonal B-lymphoid infiltrates in archival bone marrow trephines by quantitative real-time polymerase chain reaction.

Assessment of clonality either by demonstrating light chain restriction or showing monoclonal immunoglobulin gene rearrangement is a valuable and indispensable adjunct to diagnosis in hematopathology. The study of light chain restriction by immunohistochemistry on archival material is hampered by a very low sensitivity especially regarding low grade lymphomas of B cell origin. DNA rearrangement studies of the immunoglobulin locus do improve sensitivity markedly but for lymphomas of follicle center origin they are prone to false negative results due to hypermutations. Therefore we developed a new clonality assay based on the quantification of immunoglobulin light chain transcripts using real-time polymerase chain reaction technology, which is also suitable for the analysis of archival bone marrow trephines. We tested the reproducibility and sensitivity of this approach by comparatively analyzing a series of bone marrow trephines with multiple myeloma (n = 26), reactive lymphoid hyperplasia (n = 37), and focal infiltration by low grade B cell lymphoma (n = 29). We could raise the detection rate of clonality from an average of 17% by immunohistochemistry and 66% as assessed by polymerase chain reaction rearrangement studies to 83% by this new technique. Despite false negative results due to light chain hypermutation in some cases, the detection rate of clonality could be improved even for B cell lymphomas of follicle center origin (follicular lymphoma or marginal zone lymphoma) thus making this novel approach a valuable additional tool for the hematopathologist.

B-Lymphocytes↗

Expression of dipeptidyl-peptidase IV (CD26) on CD8+ T cells is significantly decreased in patients with psoriasis vulgaris and atopic dermatitis.

T cells play a major role in inflammatory skin disorders such as psoriasis vulgaris and atopic dermatitis. They are both active on the level of cell-to-cell interaction and by the secretion of pro-inflammatory mediators. CD26 is a lymphocyte membrane-associated dipeptidyl peptidase IV (DPP IV), which is able to inactivate chemokines such as RANTES or eotaxin by cleaving dipeptides from the NH2-terminus of proteins. We investigated the expression of CD26 on CD4+ and CD8+ peripheral blood T cells in patients with psoriasis and atopic dermatitis. In addition PASI and SCORAD as a measure of disease severity were determined in each patient at the time of blood drawing. Thirty patients with psoriasis, 15 with atopic dermatitis and 17 age- and sex-matched healthy persons were investigated by two-colour flow cytometry using epitope-specific monoclonal antibodies. Our results revealed, that there is a significant decrease (P<0.05) of CD26 expression on CD8+ T cells in both psoriasis (7.7%+/-3.3, mean and SD, n=30) and atopic dermatitis patients (7.9%+/-3.7, mean and SD, n=15) compared to the control population (11.58%+/-5.0, mean and SD, n=17). However, there was no correlation to disease severity as determined by PASI and SCORAD, respectively. Since CD26 can be regarded as an anti-inflammatory principle the decreased expression in psoriasis and atopic dermatitis patients may lead to a dysbalance in favour of pro-inflammatory mediators in both clinical conditions.

Adolescent↗

Learning of a new bimanual coordination pattern is governed by three distinct processes.

Learning of a new bimanual coordination pattern was investigated by practicing rhythmical arm movements with a required relative phase of phi=90 degrees. To quantify the learning process, we determined the mean and the standard deviation of the relative phase, and the switching time from a well-established coordination pattern to the to-be-learned pattern. We then calculated for each parameter the time constant of improvement. We found that with practice, all three parameter improved but each following a significantly different time-course. We therefore conclude that the learning of a new bimanual coordination pattern is governed by three separate processes, which can be visualized in a potential landscape of the intrinsic dynamics as distinct topographical features--namely, the location, depth, and steepness of the attractor basin.

Adolescent↗

Human sensorimotor coordination during spaceflight: an analysis of pointing and tracking responses during the "Neurolab" Space Shuttle mission.

BACKGROUND: It has been shown that pointing movements are slowed during microgravity, however there is a paucity of corresponding data for other movement types. METHODS: In our study, subjects pointed at visual targets without seeing their hand, and tracked targets moving around a circular path with and without hand vision, with and without a secondary reaction-time task. RESULTS: Pointing responses were slowed distinctly in microgravity, but the speed of tracking movements was not affected. The secondary task had comparable effects on tracking performance in space and on Earth. CONCLUSIONS: Response slowing in space is not due to an increased dependence on visual feedback, since it persists without hand vision. Differential effects of microgravity on pointing and tracking could be due to subjects' strategic decisions.

Adult↗

Acquisition of a sensorimotor skill in younger and older adults.

The present study compared the learning of sensorimotor transformation rules in young and elderly subjects. In a first experimental session, participants executed manual tracking movements first under normal, and then under left-right reversed visual feedback. Overall, seniors' tracking performance was lower. However, both age groups responded in a quantitatively similar way to the feedback change: Tracking errors increased by a similar amount at the onset of left-right reversal, and then gradually returned to the respective baseline levels. In a second session, visual up-down reversal was added to the left-right reversal. The initial increase of tracking error was substantially smaller than in the first session, and this benefit was even more pronounced in seniors. We interpret the benefit of the second session as learning-to-learn, i.e., as enhancement of a general ability to learn new skills, and conclude that in our study, learning-to-learn was more pronounced in elderly subjects.

Adult↗

The mechanisms of movement preparation: a precuing study.

It is well known that precues about the possible locations of upcoming targets reduce the manual reaction time. The present study investigates at which stage of the sensorimotor system such precues act. Several light dots were displayed as a precue; one of them became the target, and subjects had to produce a manual response to the target as fast as possible. Exp. A varied independently the number of precues and the area of space they occupy; we found that the reaction time of pointing movements depended on spatial extent, but not on the number of choices. The outcome was similar in Exp. B, where subjects produced stereotyped 'tapping' movements irrespective of target position. Taken together, both findings support the view that precues act mainly at a stage concerned with the internal representation of space, rather than with response selection or movement preparation. The effects of precues were preserved when subjects fixated throughout the precuing period (Exp. C), but not when precue and target positions were uncorrelated (Exp. D). These findings do not support the alternative interpretations, that precues act by guiding the eyes into the vicinity of targets, or by elevating the subjects' arousal level.

Adult↗

Quantitative molecular analysis of laser-microdissected paraffin-embedded human tissues.

Laser microdissection enables the contamination-free isolation of morphologically defined pure cell populations from archival formalin-fixed paraffin-embedded tissue specimens. Cells isolated by this method have been characterized by a wide variety of qualitative molecular assays, e.g. loss of heterozygosity, point mutations, clonality and lineage origin. The recently introduced real-time PCR technology renders the reliable quantification of very small amounts of nucleic acids possible. Several groups including our own showed that this technique can be successfully applied for the quantification of DNA and RNA isolated from microdissected archival tissue sections, even after immunohistochemical staining. The exact analysis of quantitative changes of nucleic acids during the course of pathological alterations has thus become possible. In many situations these quantitative changes can be expected to be more important than qualitative changes. The new technology for the quantification of structural genomic alterations and changes in the gene expression pattern in conjunction with microdissection have equipped morphologists with a powerful tool to study reactive and neoplastic changes of tissues.

Cell Separation↗

Is dual-task performance necessarily impaired in space?

Recent single-subject experiments in space have reported impaired dual-task performance that could result from either a direct effect of microgravity on the central nervous system or from the multistressor environment. We sought to distinguish between these hypotheses using 6 astronauts in the 16-day NASA Neurolab mission, testing them at intervals with a dual task consisting of primary pursuit tracking without vision of the hand and secondary reaction time (RT). The participants were highly trained, instructed to maintain a fixed attention strategy, and restrained in the apparatus. The results showed that absolute and variable tracking error, as well as correct RT and the standard deviation of RT, were unimpaired. However, RT errors became more variable, an effect attributed to a decrease in strategic control. We conclude that the impairments observed in previous dual-task space experiments can be attributed to stressors rather than to microgravity and that performance deficits are probably not a necessary concomitant of space flight if attention is paid to task design and astronaut training.

Adult↗

A review of cognitive and perceptual-motor performance in space.

Although a consensus developed early in the space program that complex operations could be performed successfully in space, it appears that humans are slower there than on Earth. Recent experiments aimed at determining the cause of this slowing suggest that central cognitive operations are unaffected but that perceptual-motor performance is degraded under certain circumstances. Two hypotheses have been proposed to account for this degradation-the direct effects of microgravity on the central nervous system and the non-specific effects of multiple stressors. Present evidence can be interpreted as supporting either hypothesis and further experiments are required to settle the question. This issue has practical implications since the countermeasures needed to ameliorate or prevent performance deficits will differ according to which hypothesis is correct. Understanding and ameliorating performance deficits will help ensure safe operations aboard the International Space Station and during a mission to Mars.

Cognition Disorders↗

Reprogramming of grip aperture in a double-step virtual grasping paradigm.

The present study investigated the control of manual prehension movements in humans. Subjects grasped luminous virtual discs with the thumb and index finger, and we recorded the instantaneous grip aperture, defined as the 3-D distance between the thumb and index finger. Target size could remain constant (single-step trials) or unexpectedly change shortly after target appearance (double-step trials). In single-step responses, grip aperture varied throughout the movement in a consistent fashion. Double-step responses exhibited distinct corrective modifications, which followed the target change with a latency similar to the normal reaction time. This suggests that visual size information has a fast and continuous access to the processes involved in grip formation. The grip-aperture profiles of single-step responses had a different shape when the target called for an increase than when it called for a decrease in the initial finger distance. The same asymmetry was observed for aperture corrections in double-step trials. These findings indicate that increases and decreases of grip aperture are controlled through separate processes, engaged equally by the appearance and by the size change of a target. Corrections of grip aperture in double-step trials had a higher peak velocity and reached their maximum as well as their final value earlier than the aperture profiles of single-step trials. Nevertheless, the total duration of double-step trials was prolonged. These response characteristics did not fit with either of the three corrective strategies previously proposed for double-step pointing movements, which could indicate that grasping and pointing movements are controlled by different mechanisms. However, more data are needed to substantiate this view.

Algorithms↗

Dependence of peripheral tremor on mechanical perturbations: a modeling study.

The present study scrutinizes the popular view that tremors of central origin but not those of peripheral origin are largely resistant to mechanical perturbations. We explore the effects of perturbations in a well-established model of peripheral tremor and document that (a) tremor frequency can remain unchanged when spring or weight loads are added, (b) entrainment by external drives can be limited to drives of similar frequency, and (c) resetting of tremor phase by torque pulses can remain fractional. This resistance to mechanical perturbations arises in the model because peripheral neuromuscular dynamics act as a limit-cycle oscillator which, by its very nature, will absorb moderate changes to signals and parameters. We conclude from our study that resistance to mechanical perturbations is not an exclusive property of central tremors, but rather may also be found in peripheral tremors. Other criteria are therefore needed to distinguish between different origins of tremor.

Models, Biological↗

Load dependence of simulated central tremor.

Previous studies have argued that tremors of central versus peripheral origin can be distinguished based on their load dependence: the frequency of peripheral tremor decreases when a weight is added to the tremulous limb, while the frequency of central tremors remains unchanged. The present study scrutinizes the latter statement. We simulated central tremor using a simple network of coupled neural oscillators, which receives proprioceptive feedback from the motor periphery. The network produced a self-sustained, stable oscillation. When the gain of proprioceptive feedback was high, oscillation frequency decreased in the presence of an inertial load. When the gain was low, the oscillation frequency was load independent. We conclude that load dependence is not an exclusive property of peripheral tremors but may be found in tremors of central origin as well. Therefore, the load test is not sufficient to reject a central tremor origin.

Central Nervous System↗

Placebo-controlled multicenter study of oral alendronate in postmenopausal osteoporotic women. FOSIT-Study-Group. Fosamax International Trial.

OBJECTIVES: To evaluate effects on bone mineral density (BMD), safety, and tolerability of a single daily dose of alendronate (10 mg), administered for 1 year to postmenopausal women with osteoporosis. METHODS: This interim analysis includes the first approximately 20% of patients to complete treatment in a large, placebo-controlled study (the Fosamax International Trial (Fosit)), which enrolled 1908 patients from 34 countries. Patients < or = 85-year-old with osteoporosis (lumbar spinal BMD > or = 2 S.D. below mean for mature premenopausal Caucasian women) were randomly assigned to treatment with alendronate or placebo once daily in the morning; all patients received supplemental calcium (500 mg/day). Dual-Energy X-ray Absorptiometry (DXA) was used to measure BMD in spine and proximal femur. RESULTS: A total of 297 patients had BMD data available for analysis. Patients treated with alendronate showed progressive increase of BMD during treatment. At 12 months, mean BMD had increased significantly (P < 0.001) at the lumbar spine (5.6%), trochanter (3.6%), and femoral neck (2.6%) in the alendronate group. Increases in BMD were significantly (P < 0.001) greater than in the placebo group at all sites. Among 442 patients assessed for safety, there were no statistically or clinically significant differences between treatment groups in the incidence of adverse events, including upper gastrointestinal adverse events, or laboratory abnormalities. CONCLUSIONS: Results of this multinational study show that oral alendronate, administered as 10 mg once daily for 1 year, is generally well tolerated and produces significant, progressive increases in BMD at the lumbar spine and proximal femur of postmenopausal women with osteoporosis.

Administration, Oral↗

Problems of sensorimotor coordination in weightlessness.

Previous studies about human sensorimotor coordination in space are inconclusive: it was reported that subjects in weightlessness point too high or too low, too fast or at normal speed, with increased or with normal variability; and that their tracking performance is degraded or normal. A better understanding of human performance in space would be desirable not only from the basic science perspective, but also for operational reasons. We propose a conceptual framework to explain the reported diversity, and to point out avenues for future research. We argue that exposure to weightlessness produces sensorimotor discordance, to which subjects gradually adapt through processes similar to those involved in earthbound adaptation. These processes require substantial information-processing resources in the brain, which may not be easily available during the hectic pace of a space mission. Within this framework, it is not surprising that previous data on sensorimotor performance in space were incongruent, as demand and availability of resources may have differed between missions, or even between subjects. We therefore propose that future work should control resource demand and availability, and study their effects on sensorimotor performance before and during space missions, in order to deconfound their effects from the immediate effects of gravity. A suitable hardware for such research is presented.

Adaptation, Physiological↗

Control of isometric force in hypergravity.

BACKGROUND: Previous work suggests that proprioceptive signals are degraded in hypergravity (hyper-G). We therefore, expected that production of finely graded force is disturbed as well. METHODS: Subjects produced isometric force with their thumb and index finger upon verbal instruction, before, during and after exposure to +1.5 Gz and +3 Gz. Produced force was orthogonal to the direction of gravity. RESULTS: In hyper-G, responses to a given target value were significantly higher (by about 400 pond) than in normal gravity, while the modulation of produced force with target force didn't change. The results in +1.5 Gz and +3 Gz were quantitatively similar, and a positive aftereffect was found. CONCLUSIONS: Subjects underestimate by a constant amount the force they produce in hyper-G. Our results are reminiscent of similar findings with pointing and grasping movements in hyper-G.

Adult↗