The binding of learning to action in motor adaptation

In motor tasks, errors between planned and actual movements generally result in adaptive changes which reduce the occurrence of similar errors in the future. It has commonly been assumed that the motor adaptation arising from an error occurring on a particular movement is specifically associated with the motion that was planned. Here we show that this is not the case. Instead, we demonstrate the binding of the adaptation arising from an error on a particular trial to the motion experienced on that same trial. The formation of this association means that future movements planned to resemble the motion experienced on a given trial benefit maximally from the adaptation arising from it. This reflects the idea that actual rather than planned motions are assigned 'credit' for motor errors because, in a computational sense, the maximal adaptive response would be associated with the condition credited with the error. We studied this process by examining the patterns of generalization associated with motor adaptation to novel dynamic environments during reaching arm movements in humans. We found that these patterns consistently matched those predicted by adaptation associated with the actual rather than the planned motion, with maximal generalization observed where actual motions were clustered. We followed up these findings by showing that a novel training procedure designed to leverage this newfound understanding of the binding of learning to action, can improve adaptation rates by greater than 50%. Our results provide a mechanistic framework for understanding the effects of partial assistance and error augmentation during neurologic rehabilitation, and they suggest ways to optimize their use.     

The role of GABA in human motor learning

GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.     

The role of the striatum in adaptation learning: a computational model

To investigate the functional role of the striatum in visuo-motor adaptation, we extend the DIRECT-model for visuo-motor reaching movements formulated by Bullock et al.(J Cogn Neurosci 5:408–435,1993) through two parallel loops, each modeling a distinct contribution of the cortico–cerebellar–thalamo–cortical and the cortico–striato–thalamo–cortical networks to visuo-motor adaptation. Based on evidence of Robertson and Miall(Neuroreport 10(5): 1029–1034, 1999), we implement the function of the cortico–cerebellar–thalamo–cortical loop as a module that gradually adapts to small changes in sensorimotor relationships. The cortico–striato–thalamo–cortical loop on the other hand is hypothesized to act as an adaptive search element, guessing new sensorimotor-transformations and reinforcing successful guesses while punishing unsuccessful ones. In a first step, we show that the model reproduces trajectories and error curves of healthy subjects in a two dimensional center-out reaching task with rotated screen cursor visual feedback. In a second step, we disable learning processes in the cortico–striato– thalamo–cortical loop to simulate subjects with Parkinson’s disease (PD), and show that this leads to error curves typical of subjects with PD. We conclude that the results support our hypothesis, i.e., that the role of the cortico–striato–thalamo–cortical loop in visuo-motor adaptation is that of an adaptive search element.     

The role of proprioception for motor learning in locust flight

In a muscle-specific flight simulator (simulator driven by muscle action potentials) locusts (Locusta migratoria) show motor learning by which steering performance of the closed-loop muscles is improved. The role of proprioceptive feedback for this motor learning has been studied. Closed-loop muscles were cut in order to disable proprioceptive feedback of their contractions. Since there are no proprioceptors within the muscles, this is a muscle-specific deafferentation. Cut muscles are still activated during flight and their action potentials can be used for controlling the flight simulator. With cut muscles in closed-loop, steering is less reliable as can be seen from the frequent oscillations of the yaw angle. However, periods of stable flight indicate that deafferented muscles are still, in principle, functional for steering. Open-loop yaw stimuli reveal that steering reactions in cut muscles are weaker and have a longer delay than intact muscles. This is responsible for the oscillations observed in closed-loop flight. Intact muscles can take over from cut muscles in order to re-establish stable closed-loop flight. This shows that proprioceptive mechanisms for learning are muscle specific. A hypothetical scheme is presented to explain the role of proprioception for motor learning.     

The role of spatial and temporal information in learning interval time-place tasks

In time-place learning (TPL) paradigms animals are thought to form tripartite memory codes consisting of the spatiotemporal characteristics of biologically significant events. In Phase I, rats were trained on a modified TPL task in which either the spatial or temporal component was constant, while the other component varied randomly. If the memory codes are tripartite then when one aspect of the code is random the rats should have difficulty learning the constant aspect of the code. However, rats that were trained with a fixed spatial sequence of food availability and a random duration did in fact learn the task. Rats that were trained with a fixed duration and a random sequence did not learn the task. In Phase II all rats were placed on a TPL task in which food availability was contingent upon both spatial and temporal information. According to the tripartite theory, prior knowledge of either aspect of the code should have little effect on the acquisition of the task. The rats that received fixed spatial training learned the task relatively more quickly. The use of bipartite, rather than tripartite codes, is better able to explain the results of the current study.     

Reevaluating the role of LTD in cerebellar motor learning

Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.     

Basal ganglia--possible role in motor coordination and learning.

The basal ganglia, with their inhibitory efferents, control motor outputs either directly by their projections to the midbrain motor regions or indirectly through the thalamic nuclei. Neural mechanisms in the basal ganglia act selectively to remove or enhance the inhibition so that different combinations of motor signals, which may act as neural templates for motor learning, are formed.     

Anticipatory postural adjustment in bimanual unloading: role of the motor cortex in motor learning

The role of the motor cortex was investigated during learning unusual postural adjustment. Healthy subjects held their right (postural) forearm in a horizontal position while supporting a 1-kG load via an electromagnet. The postural forearm position was perturbed by the load release triggered by other elbow voluntary movement. Repetition of the imposed unloading test resulted in a progressive reduction of the maximal forearm rotation, accompanied by the anticipatory decrease in m. biceps brachii activity (learning). Control situation consisted of the voluntary forearm loading. Using the transcranial magnetic stimulation we examined changes in the motor evoked potential of the m. biceps brahii at the beginning and at the end of learning. The evoked potential amplitude did not significantly change in process of the decrease of m. biceps brachii activity. At the end of learning, motor evoked potential / baseline electromyogram ratio increased as compared to the beginning of learning and to the control situation. The results highlight the fundamental role of the motor cortex in suppression of synergies which interfere with formation of a new coordination during motor learning.     

The role of individual characteristics and learning in the manifestation of motor asymmetry in rats

Relative role was studied of the initial preference (caused by animals individual properties) and learning in real preference of one limb in rats. After a short-time learning to get food from a narrow horizontal pipe only by the left paw a retrograde amnesia was evoked in rats. At preference determination after three weeks, in conditions which allowed to get food by any paw, in the group of animals without amnesia the number of the left-handed rats was 5.7 times more than of the right-handed ones. In the group of animals with amnesia the numbers of the left-handed, right-handed and ambidextrous were approximately equal. Correlation was revealed between the speed of learning to get food by the left paw and the number of attempts to use the right paw. It has been shown that the initial preference may be stably changed even by a short-time learning (3 food seizures). By the degree of manifestation of the initial preference the rats form a continuum with a gradual transition from pronounced right-handed animals to pronounced left-handed ones. The weaker is the initial preference, the greater the role of learning in the real preference of one of the paws.     

Spontaneous alternation, motor activity, and spatial learning in hot-foot mutant mice

Hot-foot mutant mice, characterized by defective innervation of Purkinje cells and an ataxic gait, were less active than normal mice in a T-maze. In spontaneous alternation testing with either single or multiple trials, hot-foot mutants, contrary to normal mice, did not alternate above chance. Moreover, the mutants had a higher number of errors and higher escape latencies in a water-filled Z-maze. These results indicate that in addition to motor coordination deficits, these cerebellar mutants have deficits in spatial learning and perseverate choices of maze arms.     

The mechanisms of motor learning]

In the paper the general principles of the motor learning are analyzed. A thesis is argued that instrumental conditioning is the basis of the motor learning, but the mechanisms of insight and the apparatus of anticipation of the action result also play an important role. At comparison of some theories of learning a hypothesis is suggested about the possibility of synthetic approach. Two stages can be distinguished in the process of the motor learning: formation of semantic and coordination programs. Formation and realization of learned movements opposite to the initial coordinations are constantly controlled by the motor cortex, which realizes the learned inhibition of the interfering coordinations.     

The effect of spatial structure on adaptation in Escherichia coli

Populations of organisms are generally organized in a given spatial structure. However, the vast majority of population genetic studies are based on populations in which every individual competes globally. Here we use experimental evolution in Escherichia coli to directly test a recently made prediction that spatial structure slows down adaptation and that this cost increases with the mutation rate. This was studied by comparing populations of different mutation rates adapting to a liquid (unstructured) medium with populations that evolved in a Petri dish on solid (structured) medium. We find that mutators adapt faster to both environments and that adaptation is slower if there is spatial structure. We observed no significant difference in the cost of structure between mutator and wild-type populations, which suggests that clonal interference is intense in both genetic backgrounds.     

The cerebellum and motor learning.

Lesions of the cerebellum and its associated circuitry abolish or impair several types of motor learning. It is controversial whether these lesions damage the motor memory or its performance. Recent work is evaluated in the light of the original suggestions by Marr, Albus and Gilbert that the cerebellar cortex is a preferred locus for reflex plasticity and motor learning.     

The role of homeoviscous adaptation in mammalian hibernation

The bulk membrane fluidity of brain synaptosomes and kidney cortex microsomes of hibernating and active mammals have been compared using the steady-state fluorescence polarization technique. No consistent differences were observed indicating that homeoviscous adaptation may not be an important strategy during hibernation.     

The representation of time for motor learning

We have identified factors that control precise motor timing by studying learning in smooth pursuit eye movements. Monkeys tracked a target that moved horizontally for a fixed time interval before changing direction through the addition of a vertical component of motion. After repeated presentations of the same target trajectory, infrequent probe trials of purely horizontal target motion evoked a vertical eye movement around the time when the change in target direction would have occurred. The pursuit system timed the vertical eye movement by keeping track of the duration of horizontal target motion and by measuring the distance the target traveled before changing direction, but not by learning the position in space where the target changed direction. We conclude that high temporal precision in motor output relies on multiple signals whose contributions to timing vary according to task requirements.     

Interference in ballistic motor learning: specificity and role of sensory error signals

Humans are capable of learning numerous motor skills, but newly acquired skills may be abolished by subsequent learning. Here we ask what factors determine whether interference occurs in motor learning. We speculated that interference requires competing processes of synaptic plasticity in overlapping circuits and predicted specificity. To test this, subjects learned a ballistic motor task. Interference was observed following subsequent learning of an accuracy-tracking task, but only if the competing task involved the same muscles and movement direction. Interference was not observed from a non-learning task suggesting that interference requires competing learning. Subsequent learning of the competing task 4 h after initial learning did not cause interference suggesting disruption of early motor memory consolidation as one possible mechanism underlying interference. Repeated transcranial magnetic stimulation (rTMS) of corticospinal motor output at intensities below movement threshold did not cause interference, whereas suprathreshold rTMS evoking motor responses and (re)afferent activation did. Finally, the experiments revealed that suprathreshold repetitive electrical stimulation of the agonist (but not antagonist) peripheral nerve caused interference. The present study is, to our knowledge, the first to demonstrate that peripheral nerve stimulation may cause interference. The finding underscores the importance of sensory feedback as error signals in motor learning. We conclude that interference requires competing plasticity in overlapping circuits. Interference is remarkably specific for circuits involved in a specific movement and it may relate to sensory error signals.     

The peptidergic modulation of learning a motor food-acquiring conditioned-reflex habit]

The experimental data were given obtained at studying the influence of different dozes of synthetic heptapeptide (on tafcine basis) on learning to complex instrumental habit in dogs. Effectiveness of intranasal application of peptide on earlier stages of learning and also its ability to restore the lost habit was shown. Vegetative ensuring of learning at its modulation by peptide was studied.     

Novel role and mechanism of protein inhibitor of activated STAT1 in spatial learning

By using differential display PCR, we have previously identified 98 cDNA fragments from rat dorsal hippocampus, which are expressed differentially between the fast learners and slow learners from water-maze learning task. One cDNA fragment, which showed a higher expression level in fast learners, encodes the rat protein inhibitor of activated STAT1 (pias1) gene. Spatial training induced a significant increase in PIAS1 expression in rat hippocampus. Transient transfection of the wild-type (WT) PIAS1 plasmid to CA1 neurons facilitated, whereas transfection of PIAS1 siRNA impaired spatial learning in rats. Meanwhile, PIAS1WT increased STAT1 sumoylation, decreased STAT1 DNA binding and decreased STAT1 phosphorylation at Tyr-701 associated with spatial learning facilitation. But PIAS1 siRNA transfection produced an opposite effect on these measures associated with spatial learning impairment. Further, transfection of STAT1 sumoylation mutant impaired spatial acquisition, whereas transfection of STAT1 phosphorylation mutant blocked the impairing effect of PIAS1 siRNA on spatial learning. In this study, we first demonstrate the role of PIAS1 in spatial learning. Both posttranslational modifications (increased sumoylation and decreased phosphorylation) mediate the effect of PIAS1 on spatial learning facilitation.