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Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery.

RATIONALE: 1,1,1-Trichloroethane (TCE), a representative abused solvent, has well described acute behavioral effects in animals. Much less is known about repeated high-concentration exposures as would be encountered in inhalant abusers. Tolerance has been demonstrated in some, but not all, studies with TCE while sensitization has also been seen with other abused solvents. OBJECTIVE: The present study was designed to further characterize changes in the effects of repeated exposure to TCE on a variety of mouse behaviors. METHODS: Mice were tested using locomotor activity as well as a functional observational battery (FOB) both before and after a regimen of daily exposures to various concentrations of TCE. RESULTS: The initial locomotor effects of acute 30-min exposures to TCE were biphasic with concentration-dependent increases in activity at lower concentrations and decreases observed at higher concentrations. The profile of acute effects as measured by the FOB included changes in posture, decreased arousal, disturbances in gait, delayed righting reflexes, and decreased sensorimotor reactivity. Animals were then divided into five groups and exposed 30 min/day to either air or one of four concentrations of TCE (2,000, 6,000, 10,000, or 13,300 ppm) for 15 consecutive days. The TCE concentration used primarily affected the magnitude of change, not whether tolerance or sensitization occurred. Tolerance developed on the measures of forelimb grip strength, inverted screen, and number of rears. Conversely, sensitization developed to measures of locomotor activity. CONCLUSION: Depending on the behavioral measure, both tolerance and sensitization can occur in mice with repeated exposure to TCE. Both of these phenomena are characteristic of drugs of abuse.

Administration, Inhalation↗

Postural control of the trunk in response to lateral support surface translations during trunk movement and loading.

The postural response to translation of the support surface may be influenced by the performance of an ongoing voluntary task. This study was designed to test this proposal by applying lateral perturbations while subjects handled a load in the frontal plane. Measurements were made of medio-lateral displacement of the centre of pressure, angular displacement of the trunk and thigh in the frontal plane and intra-abdominal pressure. Subjects were translated randomly to the left and right in a variety of conditions that involved standing either quietly or with a 5 kg load in their left hand, which they were required either to hold statically or to lift or lower. The results indicate that when the perturbation occurred towards the loaded left side the subjects were able to return their centre of pressure, trunk and thigh rapidly and accurately to the initial position. However, when the perturbation occurred towards the right (away from the load) this correction was delayed and associated with multiple changes in direction of movement, suggesting decreased efficiency of the postural response. This reduced efficiency can be explained by a conflict between the motor commands for the ongoing voluntary task and the postural response, and/or by the mechanical effect of the asymmetrical addition of load to the trunk.

Abdomen↗

Vestibular contributions across the execution of a voluntary forward step.

This work addressed the influence of information arising from the vestibular system on the dynamic control of a forward step. Six subjects performed the stepping task with their eyes closed under three conditions of bipolar, binaural galvanic vestibular stimulation (GVS), including (1) no GVS, (2) GVS with the anode electrode on the side of the swing limb, and (3) GVS with the anode electrode on the side of the stance limb. GVS was delivered 1,500 ms prior to a cue to step. Ground reaction forces were collected from three force platforms and movement was recorded from IRED markers placed bilaterally on the body. The results showed that, following slight deviations caused by GVS onset, the step initiation behaviour was unaffected, but lateral deviations were found during the latter, more dynamic, phases of stepping for centre of mass trajectories, time integrals of the centre of pressure displacement and upper body roll. These findings showed that vestibular information is used differently across the execution of a step without vision. While the initiation phase is run in a feedforward manner without vestibular influence, vestibular information appears to be upregulated during the more dynamic phases. Also, the level of up-regulation may be different across step execution.

Adaptation, Physiological↗

Anticipatory control of center of mass and joint stability during voluntary arm movement from a standing posture: interplay between active and passive control.

Anticipatory control of upright posture is the focus of this study that combines experimental and modeling work. Individuals were asked to raise or lower their arms from two initial postures such that the final posture of the arm was at 90 degrees with respect to the body. Holding different weights in the hand varied the magnitude of perturbation to postural stability generated by the arm movement. Whole body kinematics and ground reaction forces were measured. Inverse dynamic analysis was used to determine the internal joint moments at the shoulder, hip, knee and ankle, and reaction forces at the shoulder. Center of mass (COM) of the arm, posture (rest of the body without the arms) and whole body (net COM) were also determined. Changes in joint moment at the hip, knee and ankle revealed a significant effect of the direction of movement. The polarities of the joint moment response were appropriate for joint stabilization. Net COM change showed a systematic effect of the direction of movement even though the arm COM was displaced by the same amount and in the same direction for both arm raising and lowering conditions. In order to determine the effects of the passive forces and moments on the posture COM, the body was modeled as an inverted pendulum. The model was customized for each participant; the relevant model parameters were estimated from data obtained from each trial. The ankle joint stiffness and viscosity were adjusted to ensure postural equilibrium prior to arm movement. Joint reactive forces and moments generated by the arm movements were applied at the shoulder level of this inverted pendulum; these were the only inputs and no active control was included. The posture COM profile from the model simulation was calculated. Results show that simulated posture COM profile and measured posture COM profile are identical for about 200 ms following the onset of arm movement and then they deviate. Therefore, the initial control of COM is passive in nature and the observed joint moment response is for joint stabilization and not for the control of COM.

Adaptation, Physiological↗

Coexistence of stability and mobility in postural control: evidence from postural compensation for respiration.

This study evaluated the extent to which movement of the lower limbs and pelvis may compensate for the disturbance to posture that results from respiratory movement of the thorax and abdomen. Motion of the neck, pelvis, leg and centre of pressure (COP) were recorded with high resolution in conjunction with electromyographic activity (EMG) of flexor and extensor muscles of the trunk and hip. Respiration was measured from ribcage motion. Subjects breathed quietly, and with increased volume due to hypercapnoea (as a result of breathing with increased dead-space) and a voluntary increase in respiration. Additional recordings were made during apnoea. The relationship between respiration and other parameters was measured from the correlation between data in the frequency domain (i.e. coherence) and from time-locked averages triggered from respiration. In quiet standing, small angular displacements ( approximately 0.5 degrees ) of the trunk and leg were identified in raw data. Correspondingly, there were peaks in the power spectra of the angular movements and EMG. While body movement and EMG were coherent with respiration (>0.5), the coherence between respiration and COP displacement was low (<0.2). The amplitude of movement and coherence was increased when respiration was increased. The present data suggest that the postural disturbance that results from respiratory movement is matched, at least partly, and counteracted by small angular displacements of the lower trunk and lower limbs. Thus, stability in quiet stance is dependent on movement of multiple body segments and control of equilibrium cannot be reduced to control of a single joint.

Abdomen↗

Coordination between equilibrium and hand trajectories during whole body pointing movements.

We examined the coordination between equilibrium and voluntary pointing movements executed from the standing position, using the whole body. It has previously been shown that trunk movement has little effect upon kinematic characteristics of hand pointing when movements are executed in the sitting position. The present study asked if elements of hand trajectory are modified by requirements of large trunk displacements and fine equilibrium control when pointing movements are executed from the standing position. To achieve this, center of pressure (CoP) and center of mass (CoM) displacements were analyzed along with the kinematics of the pointing hand. Results showed that the CoM was not stabilized (it displaced between 23% and 61+/-21% of the foot's length), confirming that instead of a compensation of mechanical perturbations due to arm and trunk movements, the present equilibrium strategy consisted of controlling CoM acceleration towards the target. Hand paths were curved and were not distance or speed invariant. Rather than simple inefficiencies in programming or execution, path curvature suggested that different hand movement strategies were chosen as a function of equilibrium constraints. In light of these results, we hypothesize that postural stability may play a role in the generation of hand trajectory for complex, whole-body pointing movements, in addition to constraints placed upon end-effector kinematics or the dynamic optimization of upper-limb movements. A dependent regulation of equilibrium and spatial components of the movement is proposed.

Acoustic Stimulation↗

Effects of body lean and visual information on the equilibrium maintenance during stance.

Maintenance of equilibrium was tested in conditions when humans assume different leaning postures during upright standing. Subjects ( n=11) stood in 13 different body postures specified by visual center of pressure (COP) targets within their base of support (BOS). Different types of visual information were tested: continuous presentation of visual target, no vision after target presentation, and with simultaneous visual feedback of the COP. The following variables were used to describe the equilibrium maintenance: the mean of the COP position, the area of the ellipse covering the COP sway, and the resultant median frequency of the power spectral density of the COP displacement. The variability of the COP displacement, quantified by the COP area variable, increased when subjects occupied leaning postures, irrespective of the kind of visual information provided. This variability also increased when vision was removed in relation to when vision was present. Without vision, drifts in the COP data were observed which were larger for COP targets farther away from the neutral position. When COP feedback was given in addition to the visual target, the postural control system did not control stance better than in the condition with only visual information. These results indicate that the visual information is used by the postural control system at both short and long time scales.

Adult↗

Role of visual input in nonlinear postural control system.

Stabilometry signals involve irregular and unpredictable components. The purpose of the present study was to investigate these signals with a nonlinear technique to examine how the complexity of the postural control system breaks down under altered visual conditions. We evaluated the dynamical similarities of the postural control system when the eyes were open or closed, or when there was optokinetic stimulation (OKS). A similarity index was calculated by the cross-correlation integral between the two dynamics: eyes open and eyes closed, or eyes open with OKS. Using this technique, dynamical changes were not observed between eyes-open and eyes-closed conditions. This result suggests that the nonvision condition does not produce any striking effect on the postural control system; instead, the eyes-open condition causes a decrease in the stochastic activity of the postural control system, which may originate mainly from the stiffness of the musculoskeletal systems. In contrast, the visual input of OKS affected the dynamics of the postural control system in nearly half of the subjects (group 2) despite showing no significant differences between the eyes-open condition and the other conditions for area as the conventional parameter. However, the other half of the subjects (group 1) did not experience any influence of OKS on their postural dynamics, despite showing significant differences between eyes-open and the other conditions for all traditional parameters. From the results for group 2, we hypothesize that OKS may induce the striking effect on dynamics properties of the multilink network system involving visual and vestibular cortex related to self-motion perception, which acts to decrease the stochastic activity in order to correct disturbed posture.

Adult↗

After-effects of visuo-manual adaptation to prisms on body posture in normal subjects.

Postural equilibrium is known to be controlled by sensorimotor reflexes and automatic control loops but also depends on high-level body representation in space, probably implicating the right temporoparietal cortex. Indeed, short-term prism adaptation to a 10 degrees rightward visual shift has been shown to reduce predominant postural imbalance in patients with right hemisphere damage, as it did for neglect symptoms. These effects are likely to be explained by a high level effect of prism adaptation on body and space representation, rather than by a sensorimotor effect. Cognitive after-effects of prism adaptation to a leftward visual shift, suggesting neglect-like symptoms, have also recently been shown in normal subjects on line bisection tasks. In the present study, we investigated the effect of wedge prism adaptation on postural control in normal subjects. Two groups of seven healthy subjects were either adapted to a leftward or a rightward visual shift. Results showed that our procedure induced changes in lateral postural control in normal subjects. Furthermore, this lateral postural after-effect was dependent on direction of prism adaptation. Indeed, only adaptation to a leftward visual shift induced significant rightward postural bias in normal subjects. The rightward postural lateral displacement was negatively correlated with the visual vertical. Both transfer and direction specific effect of visuo-manual adaptation to prisms on postural control suggest that effects of adaptation act more on high-level postural control linked to body representation in space or at least reveal close interaction between sensorimotor plasticity and body representation.

Adolescent↗

From head orientation to hand control: evidence of both neck and vestibular involvement in hand drawing.

This research investigated the effect of head to trunk relation in a sensorimotor drawing task. In the first experiment, seated participants were asked to reproduce with eyes closed geometric shapes (square or diamond) with the tip of their right index finger in the frontoparallel plane. Their head was either aligned with the trunk or tilted 25 degrees towards the left or right shoulder. Results showed that drawings were subjected to an overall rotation of a few degrees in the opposite direction to the tilt. In two subsequent experiments, the respective contribution of both otoliths and neck receptors to this head tilt effect was investigated. In Experiment 2, seated participants kept their head straight but were subjected to 2.5 mA vestibular galvanic stimulation (GVS). Results indicated that GVS induced a small but significant deviation of the drawings towards the anode. Finally, in Experiment 3, subjects performed the drawing task either seated upright (seated condition) or lying on their back (supine condition). Unlike in the seated condition, tilting the head towards the shoulders in a supine posture does not modulate afferents from the otolith stimulation and therefore mainly stimulates neck receptors. Head tilt induced rotations of hand-drawn reproductions in both seated and supine conditions, suggesting a significant contribution of neck afferents in the control of hand motion in space in the absence of vision. Overall the data provided evidence for a strong head-hand linkage during kinaesthetically guided drawing movements.

Adult↗

Movement sway: changes in postural sway during voluntary shifts of the center of pressure.

We introduce a method for quantification of movement sway--spontaneous migrations of the center of pressure (COP) during its voluntary shifts. Subjects stood on a force platform or on a board with a narrow support surface ("unstable board") and performed voluntary cyclic shifts of the COP at different frequencies. Movement sway was typically higher than postural sway; sway in the mediolateral direction was particularly increased. Movement sway showed a drop with the frequency of voluntary COP shifts. During standing on the unstable board, postural sway increased while movement sway decreased. The effects of task parameters were stronger on the sway component in the direction of the voluntary COP shift than in the orthogonal direction. We interpret changes in movement sway with task parameters as partly resulting from modulation of the search function of sway during voluntary COP shifts.

Adult↗

Reciprocal error behavior in estimated body position and subjective visual vertical.

This study investigated the reciprocal relation between estimation of body tilt and visual vertical by using self-controlled passive body tilts at constant velocity (slow tilts with no semicircular canal activation) or constant acceleration (rapid tilts with canal activation). In both conditions, the visual vertical was overestimated in the luminous line setting paradigm, whereas body tilt was underestimated in the position estimation paradigm. These errors were larger after slow than rapid tilts. During slow tilts, the range of actually reached positions was on average underestimated by about 25% with respect to the desired positions. Interestingly, there were no significant differences in the estimated positions for tilts in the roll and pitch plane. Most remarkably, in the range of +/-45 degrees the resulting means of position and luminous line setting errors of the velocity and acceleration paradigms as a function of the desired roll positions were close to zero. Furthermore, the resulting means of the two paradigms showed a high correlation in the tested range of +/-90 degrees. We conclude that: (a). the otoliths provide the main information for the spatial reference for both the estimation of body positions and the luminous line settings, at least in the range of about +/-45 degrees where the resulting mean errors between the two paradigms are close to zero, and (b). coactivation of semicircular canals improves the estimations.

Acceleration↗

The integration of multiple proprioceptive information: effect of ankle tendon vibration on postural responses to platform tilt.

Previous studies have looked at co-processing of multiple proprioceptive inputs but few have investigated the effect of separate dynamic and tonic predominantly proprioceptive disruptions applied concurrently at the same segment. The purpose of the present study was to investigate how simultaneous ankle tendon vibration, a tonic stimulus, with a dynamic toes-up (TU) or toes-down (TD) platform perturbation (1) affects postural stability and (2) influences the adaptation process. Sixteen normal subjects (ten male, six female, mean age 26 +/- 4.8 years) stood blindfolded on a moving platform with vibrators attached bilaterally over the Achilles tendons. Participants were tested in quiet stance (QS), and with five successive TU and TD tilts. All tests were conducted both with (QS+V, TU+V, TD+V) and without vibration. Centre of pressure (CoP) displacements and pitch angular trunk velocity were recorded. Results for QS+V showed a significant 1.02-cm backward CoP displacement (P<0.01) and a significant increase in trunk velocity (peak-to-peak amplitude, P<0.05; SD of trunk velocity, P<0.05). TU+V resulted in a non-significant increase of maximum backwards CoP displacement when compared to TU alone. In addition, no notable effect of vibration on other measures of CoP (pre-tilt position, SD and area of sway) and trunk velocity (peak-to-peak, SD and area of sway) indicates that TU+V does not introduce significantly greater instability compared to tilt alone. In the TD condition, vibration was found to be a stabilising influence, causing a significant shift of the mean pre-tilt position 0.85 cm backwards (P<0.01) and a substantial decrease in the area of forward CoP displacement (P<0.01). However, maximum forwards CoP displacement and trunk velocity measures were not significantly altered during TD+V. Furthermore, in neither TU nor TD was the time-course or pattern of adaptation disrupted by the additional application of vibration. In conclusion, although vibration significantly affects postural measures when applied in isolation, this finding does not hold when it is applied in combination with a more dynamic stimulus. Instead it seems that once postural stability has been disrupted the central nervous system can rapidly assess information from a weaker tonic input and utilise or suppress it appropriately, depending on its effect towards overall postural control. It can be concluded that postural responses to the concurrent application of different predominantly proprioceptive stimuli are dependent upon the type of stimulus and the ability of the central nervous system to rapidly assess and re-weigh available sensory inputs.

Adaptation, Physiological↗

Referent configuration of the body: a global factor in the control of multiple skeletal muscles.

In addition to local biomechanical and reflex factors influencing muscle activation, global factors may be used by the nervous system to control all muscles in a coherent and task-specific way. It has been hypothesized that a virtual or referent (R) configuration of the body determined by muscle recruitment thresholds specified by neural control levels is such a factor. Due to the threshold nature of the R configuration, the activity of each muscle depends on the difference between the actual (Q) and the R configuration of the body. The nervous system modifies the R configuration to produce movement. One prediction of this hypothesis is that the Q and R configurations may match each other, most likely in movements with reversals in direction, resulting in a minimum in the electromyographic (EMG) activity level of muscles involved. The depth of the minima is constrained by the degree of coactivation of opposing muscle groups. Another prediction is that EMG minima in the activity of multiple muscles may occur not only when the movement is assisted but also when it is opposed by external forces (e.g., gravity). To verify these predictions, we analyzed EMG patterns of 16-21 functionally diverse muscles of the legs, trunk, and arms during jumping and stepping in place. One EMG minimum in the activity of all muscles regularly occurred near the apex of the jump. A minimum was also observed near the point of transition of the body from flexion to extension leading to a jump. During stepping in place, the activity of muscles of each side of the body was usually minimized near the beginning and near the end of the stance phase as well as during the maximum elevation of the foot. Since EMG minima occurred not only during gravity-assisted but also gravity-opposed movement reversals, it is concluded that neural factors (such as matching between the Q and R) rather than mechanical factors are responsible for minimizing the EMG activity in these movements.

Adult↗

Long-lasting body leanings following neck muscle isometric contractions.

Our objective was to investigate the neural mechanisms and the functional relevance of motor effects that develop involuntarily following the release of a sustained isometric muscle contraction. The few data available in the literature deal only with post-contractions occurring in a body segment. Although these data emphasise the role of proprioceptive input, the question as to whether this phenomenon is of central or peripheral origin remains unclear. Given the leading role of neck muscle proprioceptive input in body orientation and posture regulation, we designed two experiments to test for postural posteffects after voluntary and involuntary neck muscle contraction. The spatiotemporal characteristics of the posteffects were analysed by means of stabilometric recordings following 30-s isometric contraction of splenius, trapezius and levator muscle groups, and 30-s electrically-induced contraction of the levator muscle group. Results show that a postural response occurred after voluntary contraction of each muscle group tested, which was oriented in the plane of action of the muscle, and lasted 14 min at least. In contrast, no clearly oriented body leanings were found after electrical stimulation of the levator muscle, except for a slight increase in natural postural instability. Data are interpreted as a change in the postural reference resulting from an increase in proprioceptive inflow accompanying mainly the voluntary muscle contraction.

Adult↗

Evidence for reflex and perceptual vestibular contributions to postural control.

Vestibular signals are known to have an important role in stance under specific conditions. Potentially these effects could be modulated by vestibular reflexes or by voluntary responses to perceived vestibular signals. Our preliminary aim was to confirm that vestibulospinal reflexes change in parallel with sway under different postural conditions, and then to determine whether any relationship was present between these reflexes and body sway within fixed postural conditions. Sixteen subjects (eight male, eight female) were tested in conditions assessing the effects of vision (eyes open or closed), support surface (firm or compliant), external support (with or without) and stance width (feet apart or together). Sway (centre of pressure) in the anteroposterior (AP) and mediolateral planes was measured using a force platform. A subgroup of 11 subjects (five male, six female) underwent testing to measure short (SL) and medium latency (ML) reflexes from soleus. Bipolar, transmastoid galvanic stimulation (1 mA, 200 ms) was administered while subjects stood in the most unstable of our conditions (eyes closed, compliant surface and feet together). In the final part, to assess possible perceptual contributions to body sway, short duration AP sway levels were measured and expressed in angular terms (sway in mrad, velocity in mrad s(-1)) in the 11 subjects for both our baseline (eyes open, firm surface and feet apart) and most unstable conditions. Average sway levels increased more than seven-fold between conditions and had significant, positive correlations with reported changes in mean vestibulospinal reflexes under similar conditions (overall r = 0.75, P < 0.001). However, the SL reflex for the subgroup of 11 subjects had a significant negative correlation (r = -0.71; P = 0.014) with the degree of AP sway in the condition with maximum reliance on vestibular inputs (eyes closed, compliant surface, and feet together). Under baseline conditions, 5/125 (4%) of the short-term AP sway displacements were above the threshold previously reported for the detection of imposed sway. In the unstable condition, when sway was increased, 43/138 (31%) of the short-term AP sway movements were above the threshold for perception of imposed body sway based on vestibular signals. Our results confirm that vestibulospinal reflexes appear to be acutely facilitated as body sway increases. For the most unstable condition, when non-vestibular information was absent or attenuated, subjects with larger SL reflexes had less AP sway, suggesting that the SL reflex acted to attenuate sway. Under the same condition, short duration sway levels increased such that 31% were above the previously published threshold for detection using vestibular afferents. We conclude that both vestibular reflexes and perceptual signals appear to have a specific role in the maintenance of upright stance, under conditions in which other sources of postural information are attenuated or absent.

Adult↗

Nonlinear postural control in response to visual translation.

Recent models of human postural control have focused on the nonlinear properties inherent to fusing sensory information from multiple modalities. In general, these models are underconstrained, requiring additional experimental data to clarify the properties of such nonlinearities. Here we report an experiment suggesting that new or multiple mechanisms may be needed to capture the integration of vision into the postural control scheme. Subjects were presented with visual displays whose motion consisted of two components: a constant-amplitude, 0.2 Hz oscillation, and constant-velocity translation from left to right at velocities between 0 cm/s and 4 cm/s. Postural sway variability increased systematically with translation velocity, but remained below that observed in the eyes-closed condition, indicating that the postural control system is able to use visual information to stabilize sway even at translation velocities as high as 4 cm/s. Gain initially increased as translation velocity increased from 0 cm/s to 1 cm/s and then decreased. The changes in gain and variability provided a clear indication of nonlinearity in the postural response across conditions, which were interpreted in terms of sensory reweighting. The fact that gain did not decrease at low translation velocities suggests that the postural control system is able to decompose relative visual motion into environmental motion and self-motion. The eventual decrease in gain suggests that nonlinearities in sensory noise levels (state-dependent noise) may also contribute to the sensory reweighting involved in postural control. These results provide important constraints and suggest that multiple mechanisms may be required to model the nonlinearities involved in sensory fusion for upright stance control.

Adult↗

Testing hypotheses and the advancement of science: recent attempts to falsify the equilibrium point hypothesis.

Criticisms of the equilibrium point (EP) hypothesis have recently appeared that are based on misunderstandings of some of its central notions. Starting from such interpretations of the hypothesis, incorrect predictions are made and tested. When the incorrect predictions prove false, the hypothesis is claimed to be falsified. In particular, the hypothesis has been rejected based on the wrong assumptions that it conflicts with empirically defined joint stiffness values or that it is incompatible with violations of equifinality under certain velocity-dependent perturbations. Typically, such attempts use notions describing the control of movements of artificial systems in place of physiologically relevant ones. While appreciating constructive criticisms of the EP hypothesis, we feel that incorrect interpretations have to be clarified by reiterating what the EP hypothesis does and does not predict. We conclude that the recent claims of falsifying the EP hypothesis and the calls for its replacement by EMG-force control hypothesis are unsubstantiated. The EP hypothesis goes far beyond the EMG-force control view. In particular, the former offers a resolution for the famous posture-movement paradox while the latter fails to resolve it.

Electromyography↗