Rat models of upper extremity impairment in stroke

Stroke remains the leading cause of adult disability, with upper extremity motor impairments being the most prominent functional deficit in surviving stroke victims. The development of animal models of upper extremity dysfunction after stroke has enabled investigators to examine the neural mechanisms underlying rehabilitation-dependent motor recovery as well as the efficacy of various adjuvant therapies for enhancing recovery. Much of this research has focused on rat models of forelimb motor function after experimentally induced ischemic or hemorrhagic stroke. This article provides a review of several different methods for inducing stroke, including devascularization, photothrombosis, chemical vasoconstriction, and hemorrhagia. We also describe a battery of sensorimotor tasks for assessing forelimb motor function after stroke. The tasks range from measures of gross motor performance to fine object manipulation and kinematic movement analysis, and we offer a comparison of the sensitivity for revealing motor deficits and the amount of time required to administer each motor test. In addition, we discuss several important methodological issues, including the importance of testing on multiple tasks to characterize the nature of the impairments, establishing stable baseline prestroke motor performance measures, dissociating the effects of acute versus chronic testing, and verifying lesion location and size. Finally, we outline general considerations for conducting research using rat models of stroke and the role that these models should play in guiding clinical trials.     

Look What I Am Doing: Does Observational Learning Take Place in Evocative Task-Sharing Situations?

Two experiments were conducted to investigate whether physical and observational practice in task-sharing entail comparable implicit motor learning. To this end, the social-transfer-of-learning (SToL) effect was assessed when both participants performed the joint practice task (Experiment 1 - complete task-sharing), or when one participant observed the other performing half of the practice task (Experiment 2 - evocative task-sharing). Since the inversion of the spatial relations between responding agent and stimulus position has been shown to prevent SToL, in the present study we assessed it in both complete and evocative task-sharing conditions either when spatial relations were kept constant or changed from the practice to the transfer session. The same pattern of results was found for both complete and evocative task-sharing, thus suggesting that implicit motor learning in evocative task-sharing is equivalent to that obtained in complete task-sharing. We conclude that this motor learning originates from the simulation of the complementary (rather than the imitative) action.     

Motor Cost Influences Perceptual Decisions

Perceptual decision making has been widely studied using tasks in which subjects are asked to discriminate a visual stimulus and instructed to report their decision with a movement. In these studies, performance is measured by assessing the accuracy of the participants’ choices as a function of the ambiguity of the visual stimulus. Typically, the reporting movement is considered as a mere means of reporting the decision with no influence on the decision-making process. However, recent studies have shown that even subtle differences of biomechanical costs between movements may influence how we select between them. Here we investigated whether this purely motor cost could also influence decisions in a perceptual discrimination task in detriment of accuracy. In other words, are perceptual decisions only dependent on the visual stimulus and entirely orthogonal to motor costs? Here we show the results of a psychophysical experiment in which human subjects were presented with a random dot motion discrimination task and asked to report the perceived motion direction using movements of different biomechanical cost. We found that the pattern of decisions exhibited a significant bias towards the movement of lower cost, even when this bias reduced performance accuracy. This strongly suggests that motor costs influence decision making in visual discrimination tasks for which its contribution is neither instructed nor beneficial.     

Motor skill impairment in SIV-infected rhesus macaques with rapidly and slowly progressing disease.

A number of studies have shown that simian immunodeficiency virus (SIV) infection in rhesus macaques parallels many aspects of HIV disease in humans. The purpose of this study was to further characterize the rhesus macaque infected with neurovirulent SIV as a model of neuroAIDS. Using a motor skill task, our objective was to detect SIV-related movement impairments in behaviorally trained macaques. The motor skill task required retrieval of a food pellet from a cup in a rotating turntable across a range of speeds. Nine monkeys were infected with neurovirulent strains of SIVmac (R71/17E): four monkeys served initially as controls pre-inoculation. Seven monkeys developed simian AIDS within 4 months of inoculation (rapid progressors), and two survived more than 18 months post-inoculation (slow progressors). Of the rapid progressors, five exhibited significant deficits in this task, most showing a gradual decline in performance terminating in a sharp drop to severely impaired levels of performance. One slow progressor (AQ15) showed no performance declines. The other slow progressor (AQ94) showed a significant decrease in maximum speed that was concurrent with the onset of clinical signs. For AQ94, the role of sickness behavior related to late stage simian AIDS could not be ruled out. These results demonstrate that motor system impairment can be detected early in the course of SIV infection in rhesus macaques, further establishing the SIVmac-infected macaque monkey as a viable model of neuroAIDS.     

Quantifying deficits in the 3D force capabilities of a digit caused by selective paralysis: application to the thumb with simulated low ulnar nerve palsy

We present the development of a vision-feedback method to characterize how selective paralysis distorts the three-dimensional (3D) volume representing digit-tip force production capability and its application to healthy individuals producing thumb-tip force with and without simulated low ulnar nerve palsy (LUNP). Subjects produced maximal static voluntary force spanning the transverse, sagittal and frontal planes of the thumb (16, 15 and 10 subjects, respectively). Subjects produced thumb-tip force tasks in guided and self-selected directions. The envelope (convex hull) of extreme forces in each plane approximated that cross-section of the 3D volume of force capability. Some subjects repeated the tasks with a temporary ulnar nerve block applied at the wrist to simulate complete acute LUNP. Three geometric properties of the force convex hull characterized each cross-section's shape: the ratios of its principal moments of inertia (RPMIs), the orientation of its principal axis (OPA), and its centroid location. Our results show that force production in the thumb's sagittal plane may be a reproducible and objective test to grade motor impairment in LUNP: paired t-tests of the larger RPMI in this plane best distinguished the nerve-blocked cases from the control cases in the guided task (p = 0.012), and Discriminant Analysis of the centroid location for the self-selected task in this plane correctly classified 94.7% of subjects into the control and ulnar nerve-blocked groups. We show that our method measures and detects changes in a digit's force production capabilities. Towards a clinical test of motor impairment in LUNP, this biomechanical study dictates which 3D thumb-tip forces to measure (those in the sagittal plane) and how to measure them (using the self-selected task).     

An estimation of joint kinematics for a standing reach task using ground reaction data

The objective of this work was to derive a procedure able to estimate joint kinematics, relative to a simple, yet functionally relevant, motor task, starting from ground reaction data. The minimum number of input data has been used: force platform data, few and simple measurements relative to the subject, and protocol-specific parameters. Standing reach (SR) is the motor task analysed. The biomechanical model is a two degrees-of-freedom inverted pendulum moving on the vertical sagittal plane. Joint kinematics has been estimated solving the related direct dynamic problem stated in function of ground reaction data. The original nonlinear differential equation system of the model showed a high sensitivity to errors affecting initial conditions and experimental input data. Consequently, an approximate solution has been looked for in order to reduce the coupling between the model differential equations. This was possible taking into account the peculiar characteristics of the motor task. An optimization procedure has been deemed necessary in order to minimize the effects of the assumed approximation. The method has been tested both with simulated and with experimental data. In this latter case the validation of the angular kinematics estimated by the proposed method has been performed by means of data obtained by a stereophotogrammetric system. Results show a satisfactory behaviour of the whole optimization procedure. Very good results have been obtained in the case of slow reaching tasks.     

Organization of voluntary movement.

There have recently been a number of advances in our knowledge of the organization of complex, multi-joint movements. Promising starts have been made in our understanding of how the motor system translates information about the location of external targets into motor commands encoded in a body-based coordinate system. Two simplifying strategies for trajectory control that are discussed are parallel specification of response features and the programming of equilibrium trajectories. New insights have also been gained into how neural systems process sensory information to plan and assist with task performance. A number of recent papers emphasize the feedforward use of sensory input, which is mediated through models of the external world, the body's physical plant, and the task structure. These models exert their influence at both reflex and higher levels and permit the preparation of predictive default parameters of trajectories as well as strategies for resolving task demands.     

Determining Pain Detection and Tolerance Thresholds Using an Integrated,Multi-Modal Pain Task Battery

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug''s pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.     

Effects of Physical Practice and Imagery Practice on Bilateral Transfer in Learning a Sequential Tapping Task

Recent research on bilateral transfer suggests that imagery training can facilitate the transfer of motor skill from a trained limb to that of an untrained limb above and beyond that of physical practice. To further explore this effect, the present study examined the influence of practice duration and task difficulty on the extent to which imagery training and physical training influences bilateral transfer of a sequential key pressing task. In experiment 1, participants trained on the key pressing task using their non-dominant arm under one of three conditions (physical practice, imagery practice, and no practice). In a subsequent bilateral transfer test, participants performed the sequential task using their untrained dominant arm in either an original order or mirror-ordered sequence. In experiment 2, the same procedures were followed as in experiment 1 except that participants trained with their dominant arm and performed the bilateral transfer task with their non-dominant arm. Results indicated that with extended practice beyond what has been employed in previous studies, physical practice is more effective at facilitating bilateral transfer compared to training with imagery. Interestingly, significant bilateral transfer was only observed for transfer from the non-dominant to the dominant arm with no differences observed between performing the task in an original or mirror ordered sequence. Overall, these findings suggest that imagery training may benefit bilateral transfer primarily at the initial stages of learning, but with extended training, physical practice leads to larger influences on transfer.     

The roles of motor activity and environmental enrichment in intellectual disability

In people with intellectual disabilities, an enriched environment can stimulate the acquisition of motor skills and could partially repair neuronal impairment thanks to exploration and motor activity. A deficit in environmental and motor stimulation leads to low scores in intelligence tests and can cause serious motor skill problems. Although studies in humans do not give much evidence for explaining basic mechanisms of intellectual disability and for highlighting improvements due to enriched environmental stimulation, animal models have been valuable in the investigation of these conditions. Here, we discuss the role of environmental enrichment in four intellectual disabilities: Foetal Alcohol Spectrum Disorder (FASD), Down, Rett, and Fragile X syndromes.     

Event-related covariances during a bimanual visuomotor task. I. Methods and analysis of stimulus- and response-locked data

A new method that measures between-channel, event-related covariances (ERCs) from scalp-recorded brain signals has been developed. The method was applied to recordings of 26 EEG channels from 7 right-handed men performing a bimanual visuomotor judgment task that required fine motor control. Covariance and time-delay measures were derived from pairs of filtered, laplacian-derived, averaged wave forms, which were enhanced by rejection of outlying trials, in intervals spanning event-related potential components. Stimulus- and response-locked ERC patterns were consistent with functional neuroanatomical models of visual stimulus processing and response execution. In early post-stimulus intervals, ERC patterns differed according to the physical properties of the stimulus; in later intervals, the patterns differed according to the subjective interpretation of the stimulus. The response-locked ERC patterns suggested 4 major cortical generators for the voluntary fine motor control required by the task: motor, somesthetic, premotor and/or supplementary motor, and prefrontal. This new method may thus be an advancement toward characterizing, both spatially and temporally, functional cortical networks in the human brain responsible for perception and action.     

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis

Background

The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive.

Objective

To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis.

Methods

A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed.

Results

We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status.

Conclusions

Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis.     

A single bout of exercise improves motor memory

Regular physical activity has a positive impact on cognition and brain function. Here we investigated if a single bout of exercise can improve motor memory and motor skill learning. We also explored if the timing of the exercise bout in relation to the timing of practice has any impact on the acquisition and retention of a motor skill. Forty-eight young subjects were randomly allocated into three groups, which practiced a visuomotor accuracy-tracking task either before or after a bout of intense cycling or after rest. Motor skill acquisition was assessed during practice and retention was measured 1 hour, 24 hours and 7 days after practice. Differences among groups in the rate of motor skill acquisition were not significant. In contrast, both exercise groups showed a significantly better retention of the motor skill 24 hours and 7 days after practice. Furthermore, compared to the subjects that exercised before practice, the subjects that exercised after practice showed a better retention of the motor skill 7 days after practice. These findings indicate that one bout of intense exercise performed immediately before or after practicing a motor task is sufficient to improve the long-term retention of a motor skill. The positive effects of acute exercise on motor memory are maximized when exercise is performed immediately after practice, during the early stages of memory consolidation. Thus, the timing of exercise in relation to practice is possibly an important factor regulating the effects of acute exercise on long-term motor memory.     

Music Attenuates Excessive Visual Guidance of Skilled Reaching in Advanced but Not Mild Parkinson's Disease

Parkinson''s disease (PD) results in movement and sensory impairments that can be reduced by familiar music. At present, it is unclear whether the beneficial effects of music are limited to lessening the bradykinesia of whole body movement or whether beneficial effects also extend to skilled movements of PD subjects. This question was addressed in the present study in which control and PD subjects were given a skilled reaching task that was performed with and without accompanying preferred musical pieces. Eye movements and limb use were monitored with biomechanical measures and limb movements were additionally assessed using a previously described movement element scoring system. Preferred musical pieces did not lessen limb and hand movement impairments as assessed with either the biomechanical measures or movement element scoring. Nevertheless, the PD patients with more severe motor symptoms as assessed by Hoehn and Yahr (HY) scores displayed enhanced visual engagement of the target and this impairment was reduced during trials performed in association with accompanying preferred musical pieces. The results are discussed in relation to the idea that preferred musical pieces, although not generally beneficial in lessening skilled reaching impairments, may normalize the balance between visual and proprioceptive guidance of skilled reaching.     

Improved Behavioral Response as a Valid Biomarker for Drug Screening Program in Transgenic Rodent Models of Tauopathies

Neurodegenerative tauopathies are defined as a group of dementia and movement disorders characterized by prominent filamentous tau inclusions and degeneration located within certain brain regions. Their common sign is a presence of proteinaceous aggregates composed of hyperphosphorylated and truncated tau proteins. The molecular mechanisms of the disease still remain unresolved, therefore transgenic organisms displaying tau-related neurodegenerative cascade have been created to allow decoding of individual pathways involved in human pathological conditions. Moreover, use of transgenic model organisms enables the application of potential therapeutic approaches. The expression of mutated or misfolded tau as a transgene in vivo leads to significant alteration of neurobehavioral features of experimental animal, therefore detailed classification of behavioral phenotype become one of the first crucial analyses, while it functionally correlates with central nervous system impairment. Currently, two major types of behavioral impairment have been described in transgenic rodent models of tauopathies, (1) progressive motor impairment associated with muscular weakness and premature death and (2) age-related impairment of cognitive functions attended with unaffected motor status. Up to the present, only transgenic models displaying motor impairment were successfully applied into the drug trials targeting misfolded tau protein, despite their behavioral inconsistence with clinical profile of progressive human tauopathy. The aim of this study was, therefore, to summarize the pros and cons of used transgenic rodent models mimicking human tauopathies in connection with development of therapeutic strategies.     

Predictive Models to Determine Imagery Strategies Employed by Children to Judge Hand Laterality

A commonly used paradigm to study motor imagery is the hand laterality judgment task. The present study aimed to determine which strategies young children employ to successfully perform this task. Children of 5 to 8 years old (N = 92) judged laterality of back and palm view hand pictures in different rotation angles. Response accuracy and response duration were registered. Response durations of the trials with a correct judgment were fitted to a-priori defined predictive sinusoid models, representing different strategies to successfully perform the hand laterality judgment task. The first model predicted systematic changes in response duration as a function of rotation angle of the displayed hand. The second model predicted that response durations are affected by biomechanical constraints of hand rotation. If observed data could be best described by the first model, this would argue for a mental imagery strategy that does not involve motor processes to solve the task. The second model reflects a motor imagery strategy to solve the task. In line with previous research, we showed an age-related increase in response accuracy and decrease in response duration in children. Observed data for both back and palm view showed that motor imagery strategies were used to perform hand laterality judgments, but that not all the children use these strategies (appropriately) at all times. A direct comparison of response duration patterns across age sheds new light on age-related differences in the strategies employed to solve the task. Importantly, the employment of the motor imagery strategy for successful task performance did not change with age.