Mariam Alaverdashvili

Similar hand shaping in reaching-for-food (skilled reaching) in rats and humans provides evidence of homology in release, collection, and manipulation movements.

Many animal species use their forelimbs to assist in eating, such as occurs in a reach-to-eat task (skilled reaching) in which a forelimb is extended to grasp food that is placed in the mouth for eating. It is unclear the extent to which the skilled reaching movements of different species share common ancestry and so are homologous or evolved independently and so are analogous (homoplasy). Here hand shaping (the movements of the hand and digits) that occur as the hand is transported to the target, were examined using high-speed (1000 frames/s) video recording and kinematic measurement (Peak Motus) in the rat (Rattus norvegicus) and human (Homo sapiens). Ten movement similarities were identified from the point that the limb initiated transport towards the food item to the point that the food was grasped. The digits were closed and semi-flexed as the hand was lifted (released from a substrate) and supinated. They closed further as the hand was collected for aiming. They then extended as the hand was transported to the target and then opened in conjunction with pronation to orient the hand for grasping (manipulation). Finally the digits were flexed and closed for grasping. These movements occurred at approximately the same point of limb transport in both species even though the rat used a whole paw grasp and the humans used a pincer grasp. Bushbabies (Galago garnettii), titi monkeys (Callicebus brunneus), rhesus monkeys (Macaca mulatta) and the bonobo (Pan paniscus) displayed similar hand shaping in skilled reaching despite species differences in grasping movements. Homologous hand shaping in the rodent clade and the primate clade and within the primate lineage is discussed in relation to its possible derivation from hand shaping movements associated with stepping.

The problem of relating plasticity and skilled reaching after motor cortex stroke in the rat

The plasticity of the nervous system is illustrated in the many new neuronal connections that are formed during the acquisition of behavioral skills, loss of function after brain injury, and subsequent recovery of function. The present review describes the acquisition of skilled reaching, the act of reaching for food with a forelimb, and the changes that take place in skilled reaching following motor cortex stroke. The review then discusses the difficulty in associating plastic changes with specific aspects of behavioral change. Skilled reaching behavior is complex and consists of a number of oppositions (stimulus response relationships), between the rat and the food target, a number of forelimb gestures (non-weight supporting movements), which are performed to obtain food, and a complex series of segmental movements (of the limb, head, and trunk), all of which influence the success of the act. Measures of these four aspects of skilled reaching behavior following motor cortex stroke reveal that there are a number of learned changes that take place at different times, including learned nonuse, learned bad-use, and forgetting. The widespread dendritic proliferation, axonal growth, and synaptic formation that take place both before and after stroke are difficult to precisely relate to these behavioral changes. Whereas plasticity is usually proposed to be associated with improved performance it is suggested that future work should attempt to better relate plastic changes to the details of behavioral changes.

Compensation aids skilled reaching in aging and in recovery from forelimb motor cortex stroke in the rat.

Compensatory movements mediate success in skilled reaching for food after stroke to the forelimb region of motor cortex (MtCx) in the rat. The present study asks whether the neural plasticity that enables compensation after motor stroke is preserved in aging. In order to avoid potential confounding effects of age-related negative-learning, rats were trained in a single pellet reaching task during young-adulthood. Subgroups were retested before and after contralateral forelimb MtCx stroke via pial stripping given at 3, 18, or 23 months of age. Over a two-month post-stroke rehabilitation period, end point measures were made of learned nonuse, recovery, retention, and performance ratings were made of reaching movement elements. Prior to stroke, young and aged rats maintained equivalent end point performance but older rats displayed compensatory changes in limb use as measured with ratings of the elements of forelimb movement. Following stroke, the aged groups of rats were more impaired on end point, movement, and anatomical measures. Nevertheless, the aged rats displayed substantial recovery via the use of compensatory movements. Thus, this study demonstrates that the neural plasticity that mediates compensatory movements after stroke in young adults is preserved prior to and following stroke in aging.

Both compensation and recovery of skilled reaching following small photothrombotic stroke to motor cortex in the rat

Large lesions produced by stroke to the forelimb region of motor cortex of the rat feature post-stroke improvement that in the main is due to compensation. The present study describes both recovery and compensation of forelimb use in a reach-to-eat (skilled reaching) task following small photothrombotic stroke. The rats were pretrained before stroke, and then assessed using endpoint measures and biometric movement analysis during rehabilitation in the acute and chronic post-stroke periods. Histological and MRI analysis indicated that the stroke consisted of a small lesion surrounded by cortex featuring scattered cell loss, likely of the large pyramidal cells that characterize the forelimb region of motor cortex. The stroke reduced reaching success, especially on the most demanding measure of success on first reach attempts, in the acute period, but with rehabilitation, performance returned to pre-stroke levels. Reach movements as assessed by biometric measures were severely impaired acutely but displayed significant recovery chronically although this recovery was not complete. The results suggest that not only do rats show post-stroke compensation in skilled reaching but they can also display functional recovery. It is suggested that recovery is mediated by the spared neurons in the peri-infarct region of forelimb motor cortex. The results demonstrate the utility of a small lesion model for studying post-stroke neural and behavioral change and support the view that optimal post-stroke treatment should be directed toward limiting tissue loss.

Motor cortex stroke impairs individual digit movement in skilled reaching by the rat

Over 30 years ago, Castro [(1972) Brain Res., 37, 173–185] proposed that motor cortex (MtCx) ablation produced deficits in digital usage that contributed to the rat’s impairments in a reach‐to‐eat task, but the impairment was not directly documented. The present study examined digit use in control rats and rats with MtCx lesions using high‐speed (1000 f/s) video recording. Temporal and spatial characteristics of individual digits were evaluated by digitizing the tip of the digits and digital joints using the motion measurement system Peak Motus. Control rats displayed differential digital use during grasping actions and MtCx damage reduced individual digit movement, both as the paw was pre‐shaped for grasping and in the grasping action itself. The findings show that although grasping is retained following MtCx damage, MtCx is essential for dexterous movement. The results are discussed in relation to the idea that rodent MtCx is not only necessary for rotatory movements of the limb, but also for digital control and in relation to the similarities of rodent digit use to that described for primates.

A behavioral method for identifying recovery and compensation: Hand use in a preclinical stroke model using the single pellet reaching task

One objective of preclinical animal models of stroke is to distinguish behavioral compensation from behavioral recovery. In compensation, a new behavior is substituted for a lost behavior, whereas in recovery, the original behavior is restored. Distinguishing between these processes is important because: (1) compensation can be mistaken for recovery, (2) compensatory strategies can disrupt performance, (3) the behavioral methods, therapy, and neural changes associated with enhancing compensation can be different from those associated with recovery, (4) under different conditions both compensation and recovery can be desirable outcomes. The review describes a behavioral method for assessing hand use in reaching (skilled reaching or reach-to-eat) by the rat, a behavior analogous to single handed prehension in humans. The method consists of seven separate assessments obtained with end point, movement notation, and biometric measures. The method highlights the importance of using multiple measures to identify behavioral change during acute, early, and chronic poststroke periods. Distinguishing between compensation and recovery refines the interpretation of preclinical behavioral findings and expands opportunities for developing therapies for stroke.

Cineradiographic (video X-ray) analysis of skilled reaching in a single pellet reaching task provides insight into relative contribution of body, head, oral, and forelimb movement in rats

The forelimb movements (skilled reaching) used by rats to reach for a single food pellet to place into the mouth have been used to model many neurological conditions. They have been described as a sequence of oppositions of head-pellet, paw-pellet and pellet-mouth that can be described as movements of the distal portion of body segments in relation to their fixed proximal joints. Movement scoring is difficult, however, because the location and movement of body segments is estimated through the overlying fur and skin, which is pliable and partially obscures movement. Using moderately high-speed cineradiographic filming from lateral, dorsal, and frontal perspectives, the present study describes how forelimb and skeletal bones move during the skilled reaching act. The analysis indicates that: (i) head movements for orienting to food, enabled by the vertical orientation of the rostral spinal cord, are mainly independent of trunk movement, (ii) skilled reaching consists of a sequence of upper arm and extremity movements each involving a number of concurrent limb segment and joint movements and (iii) food pellets are retrieved from the paw using either the incisors and/or tongue. The findings are discussed in relation to the idea that X-ray cinematography is valuable tool for assisting descriptive analysis and can contribute to understanding general principles of the relations between whole body, head, oral, and upper extremity movement.

No improvement by amphetamine on learned non-use, attempts, success or movement in skilled reaching by the rat after motor cortex stroke.

Amphetamine (AMPH) has been proposed as a treatment for post‐stroke motor deficits when coupled with symptom‐relevant physical rehabilitation. Whereas a number of experimental studies report improvements in endpoint measures of skilled reaching for food by rats, there has been no assessment of whether beneficial effects extend to overcoming learned non‐use of the limb in the acute post‐stroke period or to the qualitative deficits in movement in the chronic post‐stroke period. In addition to evaluating the effects of AMPH on success, these were the objectives of the present study. In three different reaching experiments, groups of rats were pre‐trained in skilled reaching for food prior to receiving a motor cortex stroke via pial removal. Postoperatively the rats received periodic AMPH treatment and daily rehabilitation. In the acute post‐stroke period, AMPH failed to prevent the development of learned non‐use of the limb, and in the acute and chronic period failed to improve recovery of reaching success, and also failed to improve the qualitative aspects of reaching movements. Nevertheless, AMPH did enhance adjunct non‐reaching movements of locomotion, rearing and turning. The results are discussed in relation to the idea that the beneficial effects of post‐stroke AMPH treatment do not extend to all movements, especially the movements of a forelimb in retrieving and consuming food.

Thinning, movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis

Plasticity of residual cortical tissue has been identified as an important mediator of functional post-stroke recovery. Many studies have been directed toward describing biochemical, electrophysiological, and cytoarchitectural changes in residual cortex and correlating them with functional changes. Additionally, after neonatal stroke the thickness of residual tissue can change, the tissue can move, and tissue can fill in the stroke core. The purpose of the present study was to systematically investigate and document possible gross morphological changes in peri-infarct tissue after forelimb motor cortex stroke in the adult rat. Rats received a unilateral forelimb motor cortex stroke of equivalent size by pial strip devascularization or photothrombotic occlusion and were then examined using histology or magnetic resonance imaging (MRI) at 1 h, 1, 3, 7, 14, or 31 days post-stroke. Middle cerebral artery occlusion was used as a control stroke procedure. Decreases in cortical thickness, volume, and neural density were found to extend far beyond the stroke infarct and included most of the sensorimotor regions of the stroke and intact hemispheres. Movement of residual tissue towards the infarct was observed and confirmed using anatomical markers placed in intact cortical tissue at the time of stroke induction. The results are discussed in relation to the idea that extensive time-dependent morphological changes that occur in residual tissue must be considered when evaluating plasticity-related cortical changes associated with post-stroke recovery of function.

Nicotine does not improve recovery from learned nonuse nor enhance constraint-induced therapy after motor cortex stroke in the rat

Nicotine, a cholinergic agonist, rapidly crosses the blood-brain barrier, promotes neuronal plasticity and has been suggested to enhance behavior in a variety of neurological conditions. Nicotine has also been suggested to benefit functional recovery in rodent models of stroke. At present there has been no systematic investigation of the potential benefits of nicotine therapy in both the acute and chronic post-stroke period. This was the objective of the present study and to that end, the effects of nicotine administration prior to and following motor cortex stroke were examined in a skilled reaching task. The task provides a thorough assessment of learned nonuse and constraint-induced recovery of behavior as determined by both end-point and movement element analysis. Nicotine (0.3 mg/kg p.o.) was administered twice daily during reach training and following motor cortex stroke. Rats were divided into four groups based on their pre-/post-stroke treatment: nicotine/nicotine, nicotine/vehicle, vehicle/nicotine, vehicle/vehicle. After stroke, nicotine did not counteract learned nonuse, facilitate constraint-induced therapy, or improve long-term recovery as measured by end-point analysis and movement element analysis. The results are discussed in relation to the problem of identifying pharmacotherapeutic agents that augment rehabilitation following stroke.