Decreased Movement Speed Research Articles

In vivo and molecular docking studies of the pathological mechanism underlying adriamycin cardiotoxicity

Adriamycin (ADR), one of the most effective broad-spectrum antitumor chemotherapeutic agents in clinical practice, is used to treat solid tumors as well as hematological malignancies in adults and children. However, long-term ADR use causes several adverse reactions, including time- and dose-dependent cardiotoxicity, which limit its clinical application. In addition, the mechanism by which ADR induces cardiotoxicity remains unclear. Therefore, we used zebrafish as animal models to evaluate ADR toxicity during embryonic heart development owing to the similarity of this process in zebrafish to that in humans. Exposure of zebrafish embryos to 1.25, 2.5, and 5 mg/L ADR induced abnormal embryonic development, with the occurrence of cardiac malformations, pericardial edema, decreased movement speed and activity, and increased distance between the venous sinus and the arterial bulb (SV-BA). ADR exposure induced dysregulated cardiogenesis during the precardiac mesoderm formation period. We also observed irregular expression of cardiac-related genes, an upregulation of apoptotic gene expression, and a dose-dependent increase in oxidative stress levels. Furthermore, oxidative stress-induced apoptosis exerted deleterious effects on cardiac development in zebrafish embryos, and treatment with astaxanthin (ATX) alleviated these heart defects. ADR- and Wnt pathway-related genes exhibited good energy and spatial matching, and ADR upregulated the Wnt signaling pathway in zebrafish. Moreover, IWR-1 effectively alleviated ADR-induced heart defects. In conclusion, we demonstrated that the toxic effects of ADR on cardiac development in zebrafish embryos could provide a theoretical basis for explaining the pathogenesis of ADR-induced cardiotoxicity, which occurs through the upregulation of oxidative stress and Wnt signaling pathway, as well as its prevention and treatment in humans. These findings will help develop effective treatment strategies to combat ADR-induced cardiotoxicity and broaden the application of ADR for clinical practice.

Quantitative assessment of finger motor performance: Normative data.

BackgroundFinger opposition movements are the basis of many daily living activities and are essential in general for manipulating objects; an engineered glove quantitatively assessing motor performance during sequences of finger opposition movements has been shown to be useful to provide reliable measures of finger motor impairment, even subtle, in subjects affected by neurological diseases. However, the obtained behavioral parameters lack published reference values.ObjectiveTo determine mean values for different motor behavioral parameters describing the strategy adopted by healthy people in performing repeated sequences of finger opposition movements, examining associations with gender and age.MethodsNormative values for finger motor performance parameters were obtained on a sample of 255 healthy volunteers executing sequences of finger-to-thumb opposition movements, stratified by gender and over a wide range of ages. Touch duration, inter-tapping interval, movement rate, correct sequences (%), movements in advance compared with a metronome (%) and inter-hand interval were assessed.ResultsIncreasing age resulted in decreased movement speed, advance movements with respect to a cue, correctness of sequences, and bimanual coordination.No significant performance differences were found between male and female subjects except for the duration of the finger touch, the interval between two successive touches and their ratio.ConclusionsWe report age- and gender-specific normal mean values and ranges for different parameters objectively describing the performance of finger opposition movement sequences, which may serve as useful references for clinicians to identify possible deficits in subjects affected by diseases altering fine hand motor skills.

Walking through an aperture with visual information obtained at a distance.

The present study addressed whether visual information about the width of an aperture, obtained at a distance, would be sufficient to guide walking through the aperture without collision. For this purpose, we asked twelve young participants to walk while holding a 66-cm horizontal bar (bar length needs to be considered in order to perceive space necessary for crossing) and pass through an aperture without vision from 3m in front of the aperture. Participants performed the tasks under each of four visual conditions, which differed in how vision was available: observation for 1.5s while standing (static vision), observation during two forward steps and stopping (dynamic vision), observation during two forward steps and not stopping (dynamic vision with nonstop walking), and full vision. The results showed that, for narrow apertures (the widths were 0.8 and 1.0 times the bar length), the rate of collision without vision was about 40-50%. This was mainly due to the maladaptive planning of body rotation. For the aperture 1.0 times the bar length, the percentage of trials with no body rotation was high, suggesting that at least some participants underestimated the space necessary for crossing. The location at which maximum body rotation occurred became farther from the obstacle, which may have been related to decreased movement speed. The availability of dynamic visual sampling during two forward steps did not contribute to improving collision avoidance. These results suggest that, while fundamental locomotor patterns are maintained even without online vision, both the underestimation of space required for crossing and the lack of fine-tuning of behavior prior to crossing increased collision rates.

Distinct ensembles of medial prefrontal cortex neurons are activated by threatening stimuli that elicit excitation vs. inhibition of movement.

Neural circuits controlling defensive behavior were investigated by recording single units in medial prefrontal cortex (mPFC) and dorsolateral periaqueductal gray (dlPAG) while rats expressed conditioned fear responses to an auditory conditioned stimulus (CS; 20-s train of white noise pips) previously paired with an aversive unconditioned stimulus (US; 2-s train of periorbital shocks). The CS elicited conditioned movement inhibition (CMI; characterized by decreased movement speed and freezing) when rats had not recently encountered the US, whereas the CS elicited conditioned movement excitation (CME; characterized by increased movement speed and flight behavior) after recent US encounters. Many mPFC neurons were "strategy-selective" cells that changed their firing rates only when the CS elicited CME (15/71) or CMI (13/71) responses, whereas few mPFC cells (4/71) responded nonselectively to the CS during either response. By contrast, many dlPAG neurons (20/74) responded nonselectively to the CS, but most (40/74) were excited by the CS selectively during CME trials (and none during CMI trials). CME-selective neurons in dlPAG responded phasically after CS pips that elicited CME responses, whereas CME-selective neurons in mPFC showed tonically elevated activity before and after pips that evoked CME responses. These findings suggest that, at the time when the CS occurs, tonic firing rates of CME- and CMI-selective mPFC neurons may bias the rat's choice of whether to express CME vs. CMI responses, perhaps via projections to downstream structures (such as amygdala and PAG) that influence how sensory stimuli are mapped onto motor circuits that drive the expression of competing behaviors.

Origins of Balance Disorders during a Daily Living Movement in Obese: Can Biomechanical Factors Explain Everything?

Obese people suffer from postural deficits and are more subject to falls than their lean counterpart. To improve prevention and post-fall rehabilitation programs, it seems important to better understand the posturo-kinetic disorders in daily life situations by determining the contribution of some key factors, mainly morphological characteristics and physical activity level, in the apparition of these disorders.Twelve severe android obese and eight healthy non obese adults performed a reaching task mobilizing the whole body. To further determine the origin of the postural and motor behavior differences, non obese individuals also performed an experimental session with additional constraints which simulated some of the obese morphological characteristics. Impact of the sedentary lifestyle was also studied by dissociation of the obese in two subgroups: physically « active » and physically « inactive ». Movement kinetics and kinematics were characterized with an optoelectronic system synchronized to a force platform. The mechanical equilibrium pattern was evaluated through the displacements of the Centre of Mass (CoM) and the centre of foot pressure within the Base of Support (BoS).Results showed that obesity decreased movement speed (≈−23%, p<0.01), strongly increased CoM displacement (≈+30%, p<0.05) and induced an important spatio-temporal desynchronization (≈+40%, p<0.05) of the focal and postural components of the movement during the transition between the descending and ascending movements.The role of some morphological characteristics and of physical activity on obese patients' postural control disorder is discussed and set back in the more general context of overall factors contributing to postural deficits with obesity.

MCAK facilitates chromosome movement by promoting kinetochore microtubule turnover

Mitotic centromere-associated kinesin (MCAK)/Kif2C is the most potent microtubule (MT)-destabilizing enzyme identified thus far. However, MCAK's function at the centromere has remained mechanistically elusive because of interference from cytoplasmic MCAK's global regulation of MT dynamics. In this study, we present MCAK chimeras and mutants designed to target centromere-associated MCAK for mechanistic analysis. Live imaging reveals that depletion of centromere-associated MCAK considerably decreases the directional coordination between sister kinetochores. Sister centromere directional antagonism results in decreased movement speed and increased tension. Sister centromeres appear unable to detach from kinetochore MTs efficiently in response to directional switching cues during oscillatory movement. These effects are reversed by anchoring ectopic MCAK to the centromere. We propose that MCAK increases the turnover of kinetochore MTs at all centromeres to coordinate directional switching between sister centromeres and facilitate smooth translocation. This may contribute to error correction during chromosome segregation either directly via slow MT turnover or indirectly by mechanical release of MTs during facilitated movement.

Temporal coordination of the arms during bilateral simultaneous and sequential movements in patients with chronic hemiparesis

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.

Decreased Movement Speed in Girls with Turner Syndrome: A Problem in Motor Planning or Muscle Initiation?

In three experiments with graphical tasks we examined whether the decreased movement speed in girls with Turner Syndrome (TS) is caused either by a diminished planning capacity or by more peripheral motor execution problems. Fourteen girls with TS and 14 matched controls (mean age 11.6 years) participated. Task difficulty addressed the muscle-initiation, size-control, and shape-programming level (Van Galen, 1991). The influence of task difficulty on accuracy, velocity, velocity profile and dwell time was analyzed and confirmed that girls with TS do not plan and program their movements differently from normals. We conclude that the decreased movement speed in TS is caused by problems at the muscle initiation level.

Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats

Spontaneous locomotor activity was measured in young (6–8 months) and aged (24–26 months) Fischer 344 (F344) rats. Following habituation to the activity monitors, aged rats demonstrated significantly diminished motor activity as quantified by total distance traveled and vertical activity. Movement speed did not differ significantly between the two groups. Following habituation, rats were administered acute doses of fluoxetine, sertraline, or nomifensine (1.0, 3.0, and 10.0 mg/kg). Fluoxetine diminished all three behavioral measures in the young rats, while in the old rats, fluoxetine's effects were limited to a robust attenuation of vertical activity. Sertraline decreased movement speed and vertical activity, but not total distance traveled, in the young rats. Unlike fluoxetine, sertraline produced no significant effects on any of the three behavioral variables in the old rats. Nomifensine increased behavioral scores for both age groups. The results are discussed in relation to acute motor side effects of selective serotonin reuptake inhibitors (SSRIs) in motor-impaired aged individuals, as these effects may influence their eventual use in the clinic.

Accuracy of movement speed and error detection skills in adolescents with cerebral palsy.

People with cerebral palsy (CP) usually have decreased ability to learn new movements and decreased movement speed. This study examined the ability of 10 adolescents with CP (M age = 16.2 yr., SD = 1.9 yr.) to achieve a target speed on an tipper extremity ballistic task and to detect speed errors in their movements, compared to the performance of 10 adolescents with no disability (M age = 15.7 yr., SD = 1.7 yr.). Subjects were instructed to slide a lever along a track in 150 msec., then guess their movement time. Knowledge of results feedback was provided on the first 50 trials except for Trials 11-20 on Day 1. Knowledge of results feedback was withheld on Day 2, Trials 51-60, to assess learning and retention of the skill. Speed Error and Error Detection were compared for two groups of adolescents on Trials 51-60. Independent t tests indicated a significant difference between the two groups for both Speed Error and Error Detection. Examination of individual scores of the adolescents with CP indicated that half scored within the range of the control group, and variability of skills within the group with CP was high. Some individuals with CP have deficits in accuracy of movement speed and error detection unrelated to their severity of CP which may affect their ability to learn new movements.

ACCURACY OF MOVEMENT SPEED AND ERROR DETECTION SKILLS IN ADOLESCENTS WITH CEREBRAL PALSY

People with cerebral palsy (CP) usually have decreased ability to learn new movements and decreased movement speed. This study examined the ability of 10 adolescents with CP (M age= 16.2 yr., SD = 1.9 yr.) to achieve a target speed on an upper extremity ballistic task and to detect speed errors in their movements, compared to the performance of 10 adolescents with no disability (M age=15.7 yr., SD = 1.7 yr.). Subjects were instructed to slide a lever along a track in 150 msec, then guess their movement time. Knowledge of results feedback was provided on the first 50 trials except for Trials 11–20 on Day 1. Knowledge of results feedback was withheld on Day 2, Trials 51–60, to assess learning and retention of the skill. Speed Error and Error Detection were compared for two groups of adolescents on Trials 51–60. Independent t tests indicated a significant difference between the two groups for both Speed Error and Error Detection. Examination of individual scores of the adolescents with CP indicated that half scored within the range of the control group, and variability of skills within the group with CP was high. Some individuals with CP have deficits in accuracy of movement speed and error detection unrelated to their severity of CP which may affect their ability to learn new movements.

Compensatory strategies for reaching in stroke.

A major prerequisite for successful rehabilitation therapy after stroke is the understanding of the mechanisms underlying motor deficits common to these patients. Studies have shown that in stroke patients multijoint pointing movements are characterized by decreased movement speed and increased movement variability, by increased movement segmentation and by spatial and temporal incoordination between adjacent arm joints with respect to healthy subjects. We studied how the damaged nervous system recovers or compensates for deficits in reaching, and correlated reaching deficits with the level of functional impairment. Nine right-hemiparetic subjects and nine healthy subjects participated. All subjects were right-hand dominant. Data from the affected arm of hemiparetic subjects were compared with those from the arm in healthy subjects. Seated subjects made 40 pointing movements with the right arm in a single session. Movements were made from an initial target, for which the arm was positioned alongside the trunk. Then the subject lifted the arm and pointed to the final target, located in front of the subject in the contralateral workspace. Kinematic data from the arm and trunk were recorded with a three-dimensional analysis system. Arm movements in stroke subjects were longer, more segmented, more variable and had larger movement errors. Elbow-shoulder coordination was disrupted and the range of active joint motion was decreased significantly compared with healthy subjects. Some aspects of motor performance (duration, segmentation, accuracy and coordination) were significantly correlated with the level of motor impairment. Despite the fact that stroke subjects encountered all these deficits, even subjects with the most severe motor impairment were able to transport the end-point to the target. All but one subject involved the trunk to accomplish this motor task. In others words, they recruited new degrees of freedom typically not used by healthy subjects. The use of compensatory strategies may be related to the degree of motor impairment: severely to moderately impaired subjects recruited new degrees of freedom to compensate for motor deficits while mildly impaired subjects tended to employ healthy movement patterns. We discuss the possibility that there is a critical level of recovery at which patients switch from a strategy employing new degrees of freedom to one in which motor recovery is produced by improving the management of degrees of freedom characteristic of healthy performance. Our data also suggest that stroke subjects may be able to exploit effectively the redundancy of the motor system.