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Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6-OHDA dopamine-depleted (hemi-Parkinson analogue) rats.

L-dopa therapy reverses some but not all of the motor deficits in human Parkinson patients. Although a number rat analogues of human Parkinson's disease have been developed for evaluating the efficacy of drug therapies, it is not known whether L-dopa has a similar selective action on the motor symptoms in the rat models. To examine the effectiveness of L-dopa in reversing the motor deficits in rats, we administered 6-OHDA unilaterally to produce hemi-Parkinson rats, which were then trained to reach for food using either their impaired (contralateral to the lesion) limb or their good (ipsilateral to the lesion) limb. To assess the skill, accuracy and range of limb movement, rats reached for pasta from a horizontal array of 260 vertically orientated pieces of pasta. The number and location of pasta pieces taken from this matrix was calculated and the qualitative aspects of the reaching movements were rated. The quantitative data on pasta sticks retrieved indicated that forelimb extension and movement radius around the shoulder joint was reduced by 6-OHDA treatment and did not improve after chronic L-dopa treatment. The qualitative analysis showed that grasping patterns, paw movements and body movements impaired by the lesion were also not improved by L-dopa treatment. These findings are the first in the rat to suggest that whereas L-dopa has a general activating effect on the rat's whole-body movements, as displayed in contralateral rotation, its effectiveness does not extend to skilled forelimb movements. The results are discussed in relationship to the idea that the restoration of some skilled movements may require normal synaptic function.

Animals↗

Reaching upward is more challenging to dynamic balance than reaching forward.

BACKGROUND: Older adults have less confidence in their ability to reach upward compared to reaching forward. The forward reach test may, therefore, not be ideally suited for detecting functional deficits that directly affect daily activities. METHODS: A new test of upward reach and forward reach (along a 50-degree track) were administered to young and older adults. Reach distance was adjusted for foot length and normalized to stature. The anterior safety margin was calculated by relating the center of pressure to the base of support. The extent to which age, sex, balance confidence, anthropometric, and center of pressure parameters contribute to forward and upward reach performance was assessed. FINDINGS: Reach and anterior safety margin scores were well-correlated between forward and upward reaching, but the upward reach test posed a greater challenge to dynamic balance - eliciting a smaller anterior safety margin from both older and younger subjects. Further, compared to young adults, older adults showed greater limitations in reach distance and balance parameters during upward reach compared with forward reach. An observational measure of reach strategy (whether or not the heels were raised from the platform during the test) differentiated between higher and lower reach performance for older adults. Anthropometric variables accounted for much of the variance in reach performance that would otherwise have been attributed to an age-related loss of functional capacity. Balance confidence scores also contributed to regression models predicting upward - but not forward - reach performance in older adults. INTERPRETATION: Though upward and forward reach performances were well related in this sample, a test of upward reach may be better suited to reveal early signs of functional decline in older adults than a test of forward reach.

Adult↗

Use of the trunk for reaching targets placed within and beyond the reach in adult hemiparesis.

Multijoint movements such as reaching are impaired after brain lesions involving sensorimotor areas and pathways. However, the mechanisms by which such lesions affect motor control are not fully understood. Direct effects of the lesion may be partly compensated by both the system's redundancy and its plasticity. Indeed stroke patients with limited arm movement can reach objects placed within the reach of the arm by using a compensatory strategy involving trunk recruitment. A similar strategy is observed in healthy individuals reaching for objects placed beyond the reach of the arm. Determining the control mechanism(s) governing this compensatory strategy in stroke patients was the goal of this study. Kinematics of reaching movements in hemiparetic and healthy participants to targets placed within and beyond the length of the arm were analysed. Targets were placed sagittally in front of the midline of the body. Two targets (targets 1 and 2) were within reaching distance defined as the length of the stretched arm from axilla to wrist crease. Two others were beyond arm's reach so that one required a forward trunk inclination (target 3) and the other required body raising to a semi-standing position (target 4). Healthy participants used minimal trunk displacement for reaches to targets 1 and 2. For reaches to targets 3 and 4, trunk displacement increased with target distance. Whenever the trunk was involved, there was a stereotyped sequential recruitment of the arm and trunk in that the trunk began moving simultaneously with or before the hand and stopped moving after the end of hand movement. This suggested that the control system predicts that the trunk movement will be needed to extend the reach and includes the trunk, in an anticipatory way, into the reach. In contrast, most hemiparetic participants recruited their trunk for reaches to all four targets, even those placed close to the body. Similar to healthy individuals, the sequence of hand and trunk recruitment was stereotyped, suggesting that temporal planning aspects of the motor program underlying movement coordination were relatively unaffected. In contrast to healthy participants, the contribution of the trunk movement to the endpoint displacement was substantially higher in the hemiparetic group and occurred earlier in the reach. It is suggested that the target distance at which the trunk is integrated into the movement to extend the reach of the arm is attained around the limit of arm extension and that this limit is reduced in hemiparetic individuals.

Adult↗

Application of the GABA antagonist bicuculline to the premotor cortex reduces the ability to withhold reaching movements by well-trained monkeys in visually guided reaching task.

1. A gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BMI, 10 micrograms/microliters, 1 microliter), was locally injected into a total of 32 sites in the right premotor cortex (PM) of two rhesus monkeys that had been well-trained in a visually guided reaching task (VR) for approximately 3 yr. The monkey initiated the task by pressing a central hold lever with its left hand, and this was followed by waiting (1 s), warning (central green square on a computer monitor, 0.5 s), cue (right, upper, or left square), delay (2-5 s), and go (central green square changes to red, < 1.2 s) periods. In the go period, the monkey released the hold lever and reached out to one of three target levers (left, upper, or right) that had been indicated 2-5 s previously in the cue period. 2. At three sites in the dorsal part of the PM, after the local application of BMI, reaching movements of the left forelimb, which were not part of the trained-reaching, occurred 200-300 ms after the onset of a burst of neuronal activity at the BMI injection site. This induced-reaching, which was designated a "forced-reaching" movement, occurred while the monkeys were pressing the hold lever before the cue appeared-i.e., during the waiting or waiting period. No reaching occurred when the burst did not appear. Furthermore, trajectories and electromyograms of the forelimbs during the forced-reaching movements were similar to those in the trained-reaching movements in the VR task. 3. These results suggest that restricted sites in the dorsal PM of monkeys are involved in the initiation and/or execution of trained-reaching movements and that GABAergic inhibition at these sites normally suppresses this initiation/execution unless it is required. By relaxing GABAergic suppression, the dorsal PM might send a command to a neuronal system that is associated with trained reaching to recruit the system, thereby initiating and/or executing the trained reaching.

Animals↗

The parietal reach region codes the next planned movement in a sequential reach task.

Distinct subregions of the posterior parietal cortex contribute to planning different movements. The parietal reach region (PRR) is active during the delay period of a memory-guided reach task but generally not active during a memory-guided saccade task. We explored whether the reach planning activity in PRR is related to remembering targets for reaches or if it is related to specifying the reach that the monkey is about to perform. Monkeys were required to remember two target locations and then reach to them in sequence. Before the movements were executed, PRR neurons predominantly represented the reach about to be performed and only rarely represented the remembered target for the second reach. This indicates the area plays a role in specifying the target for the impending reach and may not contribute to storing the memory of subsequent reach targets.

Animals↗

Manipulation reach and visual reach neurons in the inferior parietal lobule of the rhesus monkey.

The characteristics of inferior parietal lobule (IPL) 'reach cell' responses were studied in the fixating monkey in order to obtain a clue to the function of this area in manipulative behavior. Two subclasses of reach neurons, one showing visual receptive field sensitivity, the other lacking such responsiveness are proposed as correlates of two types of reach behavior, one that takes place with, the other without visual guidance, respectively. Neuronal firing increment and/or firing decrement responses, stimulus-bound to reach behavior were obtained from either type of cell. These were presented as equivalent modes of signal encoding, on the basis of the transformability of neuronal firing increment to firing decrement response as a result of preconditioning stimulation of the oral pulvinar nucleus. Many of the responses obtained were bimodal and some were biphasic, i.e. consisting of incremental and decremental firing phases. As each such component was independently modifiable, they were regarded different signal entities. The multicomponental nature of the visual reach neuronal response was manifested when the reaching movement was into the receptive field of the neuron. Responses consisted then of an initial component, presumably visual, prefixed to a response component stimulus-bound to the reach-invoking stimuli. The early component occupied the same position as the visual response of the cell obtained with visual receptive field stimulation alone. Moreover, the early component could be negated by preconditioning stimulation of the LP and/or pulvinar targets, and then the residual response simulated the response of a non-visual reach neuron.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fields in human motor areas involved in preparation for reaching, actual reaching, and visuomotor learning: a positron emission tomography study.

The purpose of this study was to examine the functional organization of motor cortices in the human brain involved in reaching and visuomotor learning. All subjects were asked to learn the positions of seven circular targets projected on a screen. Each time the targets were turned off, they were required to close their eyes and keep them closed, and, after a delay, to point to the center of the targets in a prescribed order using their right hand. The regional cerebral blood flow (rCBF) was measured with 15O-butanol and positron emission tomography in 20 subjects during a rest state, an initial learning stage, and a later learning stage. Ten subjects constituted the reaching group in which rCBF was measured during actual reaching; the 10 other subjects constituted the preparation group in which rCBF was measured in the delay period between target exposure and actual reaching. Individual subtraction images (each stage minus rest) were calculated and transformed into a standard size and shape brain image by the adjustable computerized brain atlas and averaged, after which significant changes of rCBF were identified. In all reaching and preparation for reaching phases, cortical fields were activated in the left primary motor area (M1) and the left premotor area (PMA). Within M1, fields active in the delay phases were adjacent to the fields active only during actual reaching movements. During the course of learning, additional fields of activity appeared in both M1 and PMA. The results indicate that three types of fields occur in M1 and PMA: (1) fields directly engaged in the efferent control of peripheral muscle contraction, (2) fields engaged in preparatory activity for reaching, and (3) fields appearing after learning of the task has taken place.

Adult↗

Comparing human reaches across three viewing conditions in a step and reach task.

The effects of gaze and step direction on a step and reach task were studied to gain insight to possible motor control strategies used in goal-directed whole-body movements. Head, foot and arm positions were monitored while subjects reached to nine targets in space. In dim light, subjects looked at and reached to actual targets or remembered targets, or reached to remembered targets initially located eccentric to gaze orientation. Final reaching errors were influenced by step and gaze orientations, but gaze direction variables were the largest contributors found to predict reach errors. While spatial memory of target location was initially encoded in eye-centered coordinates, memory of eccentric target location was not updated when subjects stepped and reached. Thus, control strategies were dependent on gaze direction in the dim light conditions.

Arm↗

The pasta matrix reaching task: a simple test for measuring skilled reaching distance, direction, and dexterity in rats.

Skilled forelimb use has been used in many studies to examine motor system status, learning, and recovery from nervous system damage in rats. The dependent measures in many current skilled reaching models rely on endpoint measures, number of successful reaches, or qualitative measures, the movements used in performing a reach. The present study describes a new reaching task, which allows measurement of distance and direction of skilled forelimb movement while also permitting end point and qualitative measurements. Animals reached from a clear Plexiglas box through an aperture to retrieve pieces of straight, uncooked pasta from an array of 260 vertically oriented pieces of pasta arranged in rows distally and laterally away from the aperture (a matrix). By extending the range of a reach, more pasta is obtained. Limb movements, pieces of pasta removed, and the pattern of pasta removal are dependent measures. The usefulness of the test is demonstrated using control, dorsal column lesion, and unilateral dopamine depleted animals. The task uses a desired food, tests learning and skill, the range of limb movement, and the ability to reach for different distances and directions. The task can also be modified to investigate other features of limb use including skill adjustments, laterality, and force.

Adrenergic Agents↗

Reaching beyond reach.

The analysis of errors in two-joint reaching movements has provided clues about sensorimotor processing algorithms. The present study extends this focus to situations where the head, trunk, and legs join with the arm to help reach targets placed slightly beyond arm's length. Subjects reached accurately to touch "real targets" or reached to the remembered locations of "virtual targets" (i.e., targets removed at the start of the reach). Subjects made large errors in the virtual-target condition and these errors were analyzed with the aim of revealing the implications for whole-body coordination. Subjects were found to rotate the head less in the virtual-target condition (when compared with accurate movements to real targets). This resulted in a more limited range of head postures, and the final head angles at the end of the movements were geometrically related to the incorrect hand locations, perhaps accounting for some portion of the errors. This suggests that head-eye-hand coordination plays an important role in the organization of these movements and leads to the hypothesis that a representation of current gaze direction may serve as a reference signal for arm motor control.

Adult↗

Effect of spinal cord lesions on forelimb target-reaching and on visually guided switching of target-reaching in the cat.

Cats were trained to reach to an illuminated tube placed horizontally at shoulder level and retrieve food with the forepaw. The trajectory of an infrared light emitting diode, taped to the wrist dorsum, was recorded with a SELSPOT-like recording system. Movement paths and velocity profiles were compared before and after lesions: (1) in dorsal C5, transecting cortico- and rubrospinal pathways to the forelimb segments so that the cats could only use the C3-C4 propriospinal neurones (PNs) to command reaching, (2) in the ventral part of the lateral funicle in C5, transecting the axons of C3-C4 PNs so that the cats had to use circuitry in the forelimb segments to command reaching. Comparison of trajectories and velocity profiles before and after lesion 1 did not reveal any major qualitative change. After lesion 2, the last third of the movement was fragmented with separate lifting and protraction. Switching of target-reaching occurred when illumination was shifted to another tube during the ongoing movement. The switching latency measured from the time of illumination shift to the earliest change in movement trajectory had a minimal value of 50-60 ms. Short latencies were present after lesion 1 as well as lesion 2 which suggest that fast switching mediated by the C3-C4 PNs and the interneuronal system in the forelimb segments is controlled in parallel by the brain. In order to test a hypothesis that fast switching depends on the tectospinal and tecto-reticulospinal pathways (the tecto-reticulo-spinal system) a ventral lesion was made in C2 aiming at interrupting these pathways. Large ventral C2 lesions tended to block conduction in the more dorsally located rubrospinal (less in corticospinal) axons probably due to compression during surgery. When conduction in the rubrospinal tract was completely interrupted by a ventral C2 lesion which also completely transected the axons of the tecto-reticulo-spinal system, then there was a prolongation of the switching latency with 10-20 ms. After a similar large ventral lesion with remaining conduction in the rubrospinal tract the switching latencies were unchanged. It is postulated that fast visually governed switching does not depend on the tecto-reticulo-spinal system alone but on more dorsally located pathways, presumably the rubrospinal tract, either acting alone or together with the tecto-reticulo-spinal system. It is further postulated that the delayed switching after interruption of conduction both in the rubrospinal tract and the tecto-reticulo-spinal system depends on the corticospinal tract. Visual control of rubrospinal and of corticospinal neurones is considered. It is postulated that target-reaching normally depends on signals in the cortico- and rubrospinal tracts and mechanisms for co-ordination of activity in them as required during switching is discussed in view of the findings now reported.

Animals↗

Sitting balance II: reach direction and thigh support affect the contribution of the lower limbs when reaching beyond arm's length in sitting.

The effects of reach direction and extent of thigh support on the contribution of the lower limbs during seated reaching were examined. Twelve healthy subjects aged 59-79 years performed self-paced reaching forwards and diagonally to both sides and under three thigh support conditions. Vertical ground reaction forces (GRF) and leg muscle activity were monitored bilaterally. Reach direction affected both the magnitude of peak vertical GRF and the relative distribution of vertical GRF through the feet, demonstrating that the lower limbs work cooperatively to control the motion of the body mass. Extent of thigh support also affected the magnitude of peak vertical GRF through the feet. In addition, the EMG data confirmed the active contribution of the lower limbs when reaching beyond arm's length, with muscles in both lower limbs activated in all trials.

Aged↗

Preparatory delay activity in the monkey parietal reach region predicts reach reaction times.

To acquire something that we see, visual spatial information must ultimately result in the activation of the appropriate set of muscles. This sensory to motor transformation requires an interaction between information coding target location and information coding which effector will be moved. Activity in the monkey parietal reach region (PRR) reflects both spatial information and the effector (arm or eye) that will be used in an upcoming reach or saccade task. To further elucidate the functional role of PRR in visually guided movement tasks and to obtain evidence that PRR signals are used to drive arm movements, we tested the hypothesis that increased neuronal activity during a preparatory delay period would lead to faster reach reaction times but would not be correlated with saccade reaction times. This proved to be the case only when the type of movement and not the spatial goal of that movement was known in advance. The correlation was strongest in cells that showed significantly more activity on arm reach compared with saccade trials. No significant correlations were found during delay periods in which spatial information was provided in advance. These data support the idea that PRR constitutes a bottleneck in the processing of spatial information for an upcoming arm reach. The lack of a correlation with saccadic reaction time also supports the idea that PRR processing is effector specific, that is, it is involved in specifying targets for arm movements but not targets for eye movements.

Animals↗

Dynamic illusion effects in a reaching task: evidence for separate visual representations in the planning and control of reaching.

The effects of an orientation illusion on perception and 2 different actions were investigated. An 8-cm x 2-cm cylindrical bar was placed in front of participants at various orientations. A background grating was used to induce an orientation illusion. In a perception task, the illusion affected participants' ability to align the bar with their sagittal planes. In one reaching task, a similar effect of the illusion was found on the choice between 2 possible grasping postures. In a second reaching task involving a single grasping posture, the orientation illusion affected the orientation of the hand at the beginning of the reach but not near its end. The authors argue that reaching trajectories are planned and initiated through a context-dependent representation but are corrected on-line through a context-independent representation. The relation of this model to a more general dichotomy between perception and action is discussed.

Adult↗

Development and validation of a scale for rating motor compensations used for reaching in patients with hemiparesis: the reaching performance scale.

BACKGROUND AND PURPOSE: Recent movement analysis studies have described compensatory movement strategies used by people with hemiparesis secondary to stroke during reaching and grasping tasks. The purpose of this article is to describe the development of a new scale--the Reaching Performance Scale (RPS)--for assessing compensatory movements for upper-extremity reaching in people with hemiparesis secondary to stroke. SUBJECTS: Twenty-eight individuals with hemiparesis, with a mean age of 54.9 years (SD=18.6), participated. METHODS: The study design involved scale development with expert panels and criterion standards for validity. Participants were evaluated on the new scale as well as other clinical tests for validity. They were videotaped while performing reaching and grasping movements. RESULTS: The RPS scores correlated with measurements of grip force and Chedoke-McMaster Stroke Assessment and Upper Extremity Performance Test for the Elderly (TEMPA) scores. The RPS discriminated patients with different impairment levels according to the Chedoke-McMaster Stroke Assessment. Preliminary intrarater and interrater reliability coefficients were acceptable for the whole scale. Mean kappa values on individual scale components for 3 raters represented a mean of 67% (SD=13.5%) agreement. DISCUSSION AND CONCLUSION: Although the RPS shows some types of validity, more rigorous tests of reliability are needed for meaningful conclusions. This study is a first step in validating the scale to assess efficacy of intervention for motor recovery of the arm.

Adult↗

Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent Care and Health.

PURPOSE: To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS: Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS: Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS: The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

ADP-ribosyl Cyclase↗

Immunology and the REACH study: HIV immunology and preliminary findings. Reaching for Excellence in Adolescent Care and Health.

This review paper presents the immunology findings in human immunodeficiency virus (HIV) infected and uninfected youth in the Reaching for Excellence in Adolescent Care and Health (REACH) Project within the context of basic and HIV immunology concepts. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This paper reviews published analyses of cross-sectional data; longitudinal analyses are underway. These preliminary data extend the work of others in demonstrating the potential for substantial thymic reserve in youth. This finding in HIV infected adolescents has implications for a fuller response to antiretroviral or immune-based therapies compared to that seen in adults. Dysregulation in mucosal immunity may appear before systemic HIV effects are seen and requires attention particularly to screening and treatment of genital co-infections. REACH has demonstrated gender differences in immunologic measures irrespective of HIV infection status.

Adolescent↗