Behavioral Effects of Chronic Melatonin and Pregnenolone Injections in a Myelin Mutant Rat (taiep)

The taiep (tremor, ataxia, immobility, epilepsy, and paralysis) myelin mutant displays a number of locomotor deficits. Taiep rat gait is characterized by shorter stride and step lengths as well as by larger stride widths. Thirty-day-old taiep mutants were placed under a regimen of daily hormone injections for 60 days. Animals in Condition 1 received melatonin, those in Condition 2 received pregnenolone sulfate, and those in a third control condition received injections of saline. Following the injections, each taiep mutant's gait was analyzed. The animals that received melatonin and pregnenolone displayed significantly larger stride and step lengths than did the controls. In addition, the animals that received hormones displayed shorter stride widths than did the controls. These experimental effects are consistent with a normalization of gait. Possible cellular mechanisms of this behavioral effect are discussed.     

Locomotor analysis of the taiep rat

Locomotor activity (tremor, ataxia, immobility, epilepsy, and paralysis) in the taiep rat, which suffers from a myelin deficient disorder, has not been previously documented. This study used walking track analysis of footprints to analyze locomotor activity in the taiep rat in comparison to normal, age-matched controls. The results confirmed differences between normal and taiep rats in terms of stride length, step length, and stride width. In addition, we found significant interactions between age and condition for stride and step length. The results suggest that locomotor analysis is a sensitive indicator of myelin deficiency. The results are discussed in terms of the underlying myelin deficiency and possible treatment regimens.     

Domestic cat walking parallels human constrained optimization: Optimization strategies and the comparison of normal and sensory deficient individuals

To evaluate how fundamental gait parameters used in walking (stride length, frequency, speed) are selected by cats we compared stride characteristics selected when walking on a solid surface to those selected when they were constrained to specific stride lengths using a pedestal walkway. Humans spontaneously select substantially different stride length–stride frequency–speed relationships in walking when each of these parameters is constrained, as in walking to a metronome beat (frequency constrained), evenly spaced floor markers (stride length constrained) or on a treadmill (speed constrained). In humans such adjustments largely provide energetic economy under the prescribed walking conditions. Cats show a similar shift in gait parameter selection between conditions as observed in humans. This suggests that cats (and by extension, quadrupedal mammals) also select gait parameters to optimize walking cost-effectiveness. Cats with a profound peripheral sensory deficit (from pyridoxine overdose) appeared to parallel the optimization seen in healthy cats, but without the same level of precision. Recent studies in humans suggest that gait optimization may proceed in two stages – a fast perception-based stage that provides the initial gait selection strategy which is then fine-tuned by feedback. The sensory deficit cats appeared unable to accomplish the feedback-dependent aspect of this process.     

Spatial and temporal variability of movement parameters in individuals with Down syndrome

This investigation compared spatial and temporal gait movement parameters of a sample of individuals with Down syndrome (n=12) and one of individuals without disabilities (n=12). All participants were evaluated on responses to a preferred pace and fast walk with the GAITRite Electronic Walkway. Spatial outcomes included step and stride length, step and stride width, toe-in/toe-out, and base of support. Temporal outcomes included step time, velocity, single and double leg support time, stance, and swing time. There were significant group differences for step length, step width, stride length, and velocity in the preferred walk condition. Significant group differences for step length, step width, and stride length were observed in the fast walk condition. Percentage differences also indicated lower scores for all spatial and temporal variables in relation to the control group. The ability to control gait movements appears to reflect earlier movement experiences, so it may be possible to use variable sensory feedback and specific training to modify and adjust movement responses and improve gait performance in Down syndrome.     

Treadmill gait analysis does not detect motor deficits in animal models of Parkinson's disease or amyotrophic lateral sclerosis

Computerized treadmill gait analysis in models of toxicant exposure and neurodegenerative disorders holds much potential for detection and therapeutic intervention in these models, and researchers must validate the technology that assists in that data collection and analysis. The present authors used a commercially available computerized gait analysis system that used (a) a motorized treadmill on retired breeder male C57BL/6J mice, (b) the toxicant-induced (1-methyl-1-, 2-, 3-, 6-tetrahydropyridine) MPTP mouse model of Parkinson's disease (PD), and (c) the superoxide dismutase 1 (SOD1) G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS). The authors compared the detection of deficits by computerized treadmill gait analysis in MPTP-treated mice with inked-paw stride length and correlated these measures to dopamine (DA) loss. The authors found that the computerized treadmill gait analysis system did not distinguish MPTP-treated mice from vehicle controls, despite a nearly 90% deficit of striatal DA. In contrast, decreases in inked-paw stride length correlated strongly with DA losses in these same animals. Computerized treadmill gait analysis could neither reliably distinguish SOD1 G93A mutant mice from controls from 6 to 12 weeks of age nor detect any consistent early motor deficits in these mice. On the basis of the authors' findings, they inferred that computerized gait analysis on a motorized treadmill is not suited to measuring motor deficits in either the MPTP mouse model of PD or the SOD1 G93A mouse model of ALS.     

Treadmill Gait Analysis Does Not Detect Motor Deficits in Animal Models of Parkinson's Disease or Amyotrophic Lateral Sclerosis

Computerized treadmill gait analysis in models of toxicant exposure and neurodegenerative disorders holds much potential for detection and therapeutic intervention in these models, and researchers must validate the technology that assists in that data collection and analysis. The present authors used a commercially available computerized gait analysis system that used (a) a motorized treadmill on retired breeder male C57BL/6J mice, (b) the toxicant-induced (1-methyl-1-, 2-, 3-, 6-tetrahydropyridine) MPTP mouse model of Parkinson's disease (PD), and (c) the superoxide dismutase 1 (SOD1) G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS). The authors compared the detection of deficits by computerized treadmill gait analysis in MPTP-treated mice with inked-paw stride length and correlated these measures to dopamine (DA) loss. The authors found that the computerized treadmill gait analysis system did not distinguish MPTP-treated mice from vehicle controls, despite a nearly 90% deficit of striatal DA. In contrast, decreases in inked-paw stride length correlated strongly with DA losses in these same animals. Computerized treadmill gait analysis could neither reliably distinguish SOD1 G93A mutant mice from controls from 6 to 12 weeks of age nor detect any consistent early motor deficits in these mice. On the basis of the authors' findings, they inferred that computerized gait analysis on a motorized treadmill is not suited to measuring motor deficits in either the MPTP mouse model of PD or the SOD1 G93A mouse model of ALS.     

Biofeedback augmenting lower limb loading alters the underlying temporal structure of gait following anterior cruciate ligament reconstruction

Biofeedback has recently been explored to target deviant lower extremity loading mechanics following anterior cruciate ligament reconstruction (ACLR) to mitigate the development of post traumatic osteoarthritis. The impact this feedback has on the structure of the stride interval dynamics—a barometer of gait system health—however, have yet to be examined. This study was designed to assess how feedback, used to alter lower-extremity loading during gait, affects the structure of stride interval variability by examining long-range stride-to-stride correlations during gait in those with unilateral ACLR. Twelve participants walked under three separate loading conditions: (1) control (i.e., no cue) (2) high loading, and (3) low loading. Baseline vertical ground reaction force (vGRF) data was used to calculate a target 5% change in vGRF for the appropriate loading condition (i.e., high loading was +5% vGRF, low loading was −5% vGRF). The target for the load condition was displayed on a screen along with real-time vGRF values, prescribing changes in stride-to-stride peak vertical ground reaction forces of each limb. From time-series of stride intervals (i.e., duration), we analyzed the mean and standard deviation of stride-to-stride variability and, via detrended fluctuation analysis (i.e., DFA α), temporal persistence for each feedback condition. Both the high and low loading conditions exhibited a change toward more temporally persistent stride intervals (high loading: α =0.92, low loading: α = 0.98) than walking under the control condition (α = 0.78; high vs. control: p = .026, low vs. control: p = .001). Overall, these results indicate that altering lower extremity load changes the temporal persistence of the stride internal dynamics in ACLR individuals, demonstrating the implications of the design of gait training interventions and the influence feedback has on movement strategies.     

Evaluating the Acute Contributions of Dopaminergic Replacement to Gait With Obstacles in Parkinson's Disease

The influence of dopaminergic replacement (DR) on gait in people with Parkinson's disease (PD) is well documented. However, little is known about the acute effects of dopamine on more complex locomotor tasks that require visual guidance to avoid obstacles during gait. The authors investigated the influence of DR on locomotor behavior in a task where movement planning and control might be challenged by the height of the obstacle. The PD group included patients diagnosed with idiopathic PD (n = 12), as well as healthy controls (n = 12). Patients walked and stepped over obstacles of different heights before (OFF) and after (ON) levodopa intake. Spatial adjustments were not modulated by DR, but the step time to perform these anticipatory gait adjustments was longer only in PD-OFF (compared with healthy controls) when approaching the highest obstacle, but not PD-ON. During the crossing phase, trail limb toe clearance of PD patients was shorter than healthy controls only during the OFF state. ON-OFF comparisons were significantly different only for the time to reach the lead foot clearance over the highest obstacle. In summary, DR partially improved movement slowness but did not directly affect movement amplitude of lower limb regulation in this gait task.     

Muscimol Induces Retrograde Amnesia for Changes in Reward Magnitude

These experiments examined the effect of the GABA_A, agonist, muscimol (MUS), on memory for changes in reward magnitude. In Experiment 1 rats were trained to run a straight alley for either a large or small food reward. After reaching asymptotic performance rats in the high reward group were shifted to the small food reward. Half the animals received 1.0 or 3.0 mg/kg (ip) of MUS or the equivalent volume of saline immediately after training. Shifted training continued for 3 more days and no further injections were given. Shifted saline animals displayed an increase in response latencies compared to unshifted controls with a sharp peak on the day after the shift. Shifted MUS receiving 1.0 mg/kg performed comparably to shifted saline animals. In contrast, shifted MUS animals receiving 3.0 mg/kg displayed performance comparable to shifted saline animals on the day of the shift but displayed a sharp increase in response latencies on the second day after the shift. These findings indicate that post-training systemic MUS injections delay the peak increase in response latencies and suggest that MUS induces retrograde amnesia for reward reduction. Experiment 2 examined the effect of MUS on the memory of a reward increase. Rats were first trained as in Experiment 1 and rats under the high reward condition were then shifted to the small reward. On the next training session, the large food reward was reinstated. Immediately after the session all animals were injected with saline or 3.0 mg/kg of MUS. The large food reward was continued for the remainder of training and no further injections were given. On the following session, the performance of the shifted saline animals was comparable to that of the unshifted controls while shifted MUS animals displayed significantly higher response latencies. The findings that MUS prevented the reduction in response latencies seen in saline-injected animals suggest that MUS also induces retrograde amnesia for reward increases.     

The influence of aging on the spatial and temporal variables of gait during usual and fast speeds in older adults aged 60 to 102 years

BackgroundWith increases in life expectancy, it is important to understand the influence of aging on gait, given that this activity is related to the independence of older adults and may help in the development of health strategies that encourage successful aging in all phases of this process.Research questionTo compare gait parameters with usual and fast speeds for independent and autonomous older adults throughout the aging process (60 to 102 years old), and also to identify which of the gait variables are best for identifying differences across the different age groups.MethodsTwo hundred older adults aged between 60 and 102 years were evaluated. The sample was divided into 3 age groups: 60 to 79 years, 80 to 89 years and 90 years and over. The analyzed gait variables were: speed (meters/s), cadence (steps/min), stride time (seconds), step length (centimeters), double support (percentage of the gait cycle), swing (percentage of the gait cycle), step length variability (CoV%) and stride time variability (CoV%).ResultsGroup comparison regarding usual gait and fast gait revealed a significant difference in all gait variables. In addition, it can be seen that variables such as gait speed and step length showed greater effect sizes in intergroup comparison (usual gait: 0.48 and 0.47; fast gait: 0.36 and 0.40; respectively), possibly showing that these variables can better detect the changes observed with increasing age.ConclusionThere are differences in the gait performance of older adults from different age groups for usual and fast gait speeds, which is more evident regarding gait speed and step length variables. We recommend the use of usual gait for the identification of the effects of aging because, besides showing a higher effect size values it is more comfortable and requires less effort from older subjects.     

Stepping Responses in Young and Older Adults Following a Perturbation to the Support Surface During Gait

The objective of this work was to investigate the influence perturbation direction has on postural responses during overground gait, and whether these responses are age related. Differences in stepping patterns following perturbations of the support surface were examined in the frontal and sagittal planes during forward walking. Eleven young and 10 older adults completed Mini BESTest, hip strength tests, and 45 perturbed walking trials, triggered on heel contact. Lateral perturbations were more challenging to postural stability for both groups. Step length measures showed young adults recovered in the step proceeding the perturbation, while older adults needed additional steps to regain balance. Young adults arrested center of mass movement by producing larger step widths than older adults following the support surface perturbation.     

Musical pleasure beneficially alters stride and arm swing amplitude during rhythmically-cued walking in people with Parkinson's disease

Entrainment of walking to rhythmic auditory cues (e.g., metronome and/or music) improves gait in people with Parkinson's disease (PD). Studies on healthy individuals indicate that entrainment to pleasant musical rhythm can be more beneficial for gait facilitation than entrainment to isochronous rhythm, potentially as a function of emotional/motivational responses to music and their associated influence on motor function. Here, we sought to investigate how emotional attributes of music and isochronous cues influence stride and arm swing amplitude in people with PD. A within-subjects experimental trial was completed with persons with PD serving as their own controls. Twenty-three individuals with PD walked to the cue of self-chosen pleasant music cue, pitch-distorted unpleasant music, and an emotionally neutral isochronous drumbeat. All music cues were tempo-matched to individual walking pace at baseline. Greater gait velocity, stride length, arm swing peak velocity and arm swing range of motion (RoM) were found when patients walked to pleasant music cues compared to baseline, walking to unpleasant music, and walking to isochronous cues. Cued walking in general marginally increased variability of stride-to-stride time and length compared with uncued walking. Enhanced stride and arm swing amplitude were most strongly associated with increases in perceived enjoyment and pleasant musical emotions such as power, tenderness, and joyful activation. Musical pleasure contributes to improvement of stride and arm swing amplitude in people with PD, independent of perceived familiarity with music, cognitive demands of music listening, and beat salience. Our findings aid in understanding the role of musical pleasure in invigorating gait in PD, and inform novel approaches for restoring or compensating impaired motor circuits.     

Failure to acquire an inhibitory task following seizure-induced brain damage

Male rats that had displayed limbic seizures following a single pair of systemic injections of lithium and pilocarpine were trained 2 months later on an operant schedule that required differential low rates of responding (DRL). The seizured rats never acquired schedules that required either 6-sec. or 12-sec. inhibition of responses following a reward; these rats displayed more perseverative responding and shorter interresponse times than controls. Histomorphology indicated severe brain damage primarily within the entorhinal cortices (and adjacent amygdala) and dorsal thalamus.     

Effects of a 12-month pedometer walking program on gait, body mass index, and lower extremity function in obese women

This study evaluated the effects of a self-reported pedometer-walking program on gait, lower extremity function, and Body Mass Index for 33 obese women, ages 31-65 years (M = 48.0, SD = 8.0) and whose initial average Body Mass Index was 40.30 +/- 9.60 kg/m2. During the 12-mo. intervention participants wore pedometers and reported the number of daily steps walked. Body Mass Index, three gait parameters, steps/day, and lower extremity function were taken over 3-mo. intervals. All participants increased in gait velocity, % single-leg support, and lower extremity function, and decreased in Body Mass Index over time. Those whose steps/day increased by 2000 over 6 mo. had significantly faster velocities and longer step lengths than those whose steps/day did not increase. The 1-yr. walking program stimulated changes in gait, Body Mass Index, and lower extremity function for these obese women. Ultimately, these changes may reduce the risk of falls for this group of women.     

The effect of dividing attention between walking and auxiliary tasks in people with Parkinson's disease

This controlled study examined the effects of dividing attention between walking and the performance of a secondary cognitive task in people with mild to moderate Parkinson's disease (Hoehn and Yahr stages 2-3.5). Participants in the training group (n=6) received 30 min divided attention training in taking big steps while simultaneously performing serial three subtractions. Participants in the control group (n=6) received no training. Stride length, gait velocity and accurate enumeration rate were measured at baseline, immediate after training and 30 min after training under single-task (walk only or subtract only) and dual-task (walk and subtract) conditions. Data were also collected at training in the training group. Immediate improvement in stride length and gait velocity was found when instruction was given to participants to pay equal attention to gait and subtractions (p=0.001, p=0.05) compared to baseline. Short-term improvement in the gait variables was also found after training when compared to the controls (p=0.001, p=0.001). Nevertheless, there was no significant difference in the accurate enumeration rate. Based on the findings, we conclude that divided attention can be used as a strategy to improve slow and short-stepped gait under dual-task conditions. Divided attention can also be used in gait training for short term stride length and gait velocity improvement.     

TWO-TO-ONE versus ONE-TO-ONE STUDENT-TEACHER RATIOS IN THE OPERANT VERBAL TRAINING OF RETARDED CHILDREN1

The operant training of two retarded children simultaneously on a picture-naming task was investigated as an alternative to the more commonly reported one-to-one student-teacher ratio. In Experiment I, two conditions were compared in which the children received primary reinforcement on a fixed-ratio schedule for responding correctly on prompt and probe trials in a standardized picture-naming procedure. During the “Group Condition”, the experimenter alternated from one child to the other after each primary reinforcement, after each incorrect response, after each response omission, and after each 10-sec period in which a child did not “attend” (by making a trial-initiating response) when it was his or her turn to be worked with. During the “Individual Condition”, the experimenter worked with only one child, and presented trials whenever the child made attending responses. Experiment I demonstrated that the Group Condition was more efficient than the Individual Condition in terms of total correct responses and total pictures learned per unit of training time. Incidental learning was also found in that the children learned some of each others' pictures as well as their own, thus indicating a further advantage of the larger student-teacher ratio. In Experiment II, an attempt was made to equate the two conditions, except for the presence of two children in the Group Condition, by ignoring the child in the Individual Condition for brief periods equal to those that occurred in the Group Condition when the experimenter presented training trials to the other child. The results demonstrated that the greater efficiency of the Group Condition was not due to the manner in which training time was allocated to the two members of a group. It also replicated the finding that the children learned some of each others' words in the Group Condition.     

Age-dependent variability in spatiotemporal gait parameters and the walk-to-run transition

Adolescents tend to exhibit more variability in their gait patterns than adults, suggesting a lack of gait maturity during this period of ongoing musculoskeletal growth and development. However, there is a lack of consensus over the age at which mature gait patterns are achieved and the factors contributing to gait maturation. Therefore, the purpose of this study was to investigate gait control and maturity in adolescents by determining if differences existed between adolescents and adults in a) the amount of spatiotemporal variability of walking and running patterns across a range of speeds, and b) how swiftly gait patterns are adapted to increasing gait speed during the walk-to-run transition. Forty-six adolescents (10–12-year-olds, n = 17; 13–14-year-olds, n = 12; and 15–17-year-olds, n = 17) and 12 young adults completed an incrementally ramped treadmill test (+0.2 km·h⁻¹ every 30 s) to determine the preferred transition speed (PTS) during a walk-to-run transition. Age-related differences in the variability of stride lengths and stride durations were assessed across 4 speeds (self-selected walking speed, PTS − 0.06 m·s⁻¹, PTS + 0.06 m·s⁻¹, PTS + 0.83 m·s⁻¹). Repeated measures ANOVAs (p < 0.05) compared coefficients of variation for these spatiotemporal parameters, while a one-way ANOVA compared the numbers of gait transitions and speed increments used to identify PTS between the adolescent groups and young adults. Compared to adults, 10–12yo exhibited more spatiotemporal variability during all gait conditions, while 13–17yo only exhibited more variability at PTS + 0.06 m·s⁻¹. No age-dependent pattern was observed in PTS values, but 10–12yo completed more gait transitions over more speed increments than 15–17yo and adults. The development of mature gait patterns is thus a progressive process, with walking maturing at an earlier age than running. As 10-12yo were unable to swiftly adapt gait patterns to the changing task demands, their control mechanisms of gait may not have fully matured yet.     

Kinematic assessment of treadmill running using different body-weight support harnesses

10 male collegiate runners (M age = 21.4, SD = 1.5 yr.) ran on a treadmill with no body-weight support (BWS), 20% BWS, and 40% BWS conditions. In addition, they wore three different commercially available harnesses at the 20% and 40% BWS conditions. The aim was to run on the treadmill at a fast speed while maintaining an adequate step length. The purpose was to investigate how each harness changed running gait, and the differences in running gait between the harnesses with various body-weight support. Analysis of variance indicated significant restriction of upper body torso rotation between the harnesses at the 40% BWS conditions. Body-weight support resulted in a longer stride, decreased cadence, less vertical displacement of the center of mass, and diminished hip and ankle joint excursions. These changes indicated that increased body-weight support results in longer steps with the foot contacting the belt for a shorter period of time with less leg angular changes throughout the running cycling.     

Gender differences in the variability of lower extremity kinematics during treadmill locomotion

The authors examined whether there were gender differences in the variability of basic gait parameters (stride length, stride time) and 3-dimensional (3D) rotations of the hip, knee, and ankle joints during treadmill locomotion of 18 men and 15 women at 4 different gait speeds (walking at 5 km/hr, running at 8, 10, and 12 km/hr). The authors used 2-way analyses of variance to assess the data. No gender differences in the mean values or variability of basic gait parameters were detected. However, the women exhibited lower variability than did the men for 6 individual joint rotations: (a) transverse plane rotations of the ankle joint at 8, 10, and 12 km/hr, (b) transverse plane rotations of the hip and knee joints at 12 km/hr, and (c) sagittal plane rotations of the ankle joint at 12 km/hr. When collapsed across all 3D lower extremity rotations, the data showed that the women had lower variability than did the men at 12 km/hr. Reduced variability may result in more localized mechanical stress on anatomical structures and could therefore be a risk factor for injury in women at high gait speeds. The results also suggested that gender differences in variability may not be consistent across different levels of the motor system.     

The effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage

Clozapine is an atypical antipsychotic drug that has been shown to improve spatial memory in some animal models; however its efficacy in reversing spatial memory impairment in rats with hippocampal lesions is unknown. To address this issue, we tested the effects of clozapine on delayed spatial alternation deficits in rats with hippocampal damage in three separate experiments. In each experiment, adult male rats received sham surgery or direct stereotaxic infusions of the excitotoxin, NMDA, into the hippocampus. In the first study, seven days after surgery, the sham control animals received daily saline injections while the lesioned animals were split into two groups that received daily saline or clozapine (2.0 mg/kg, sc) injections. During the fifth week of injections, all animals were tested in a food-motivated delayed spatial alternation task. Saline-treated rats with excitotoxic hippocampal damage displayed significant deficits in delayed spatial alternation. Daily clozapine injections completely reversed this deficit. In a second experiment, it was found that clozapine treatment limited to the testing days only did not improve alternation performance in lesioned rats. Finally, in a third experiment, chronic clozapine treatment did not improve alternation performance in lesioned rats that were pre-trained in the alternation task prior to surgery. These results suggest that chronic, but not acute, clozapine treatment enables rats with hippocampal damage to develop new spatial learning, but can not rescue old spatial learning established prior to damage. These results may have implications for the treatment of cognitive deficits caused by hippocampal dysfunction in disorders such as schizophrenia, Alzheimer's disease, and others.