Estimating the Relevance of World Disturbances to Explain Savings, Interference and Long-Term Motor Adaptation Effects

Recent studies suggest that motor adaptation is the result of multiple, perhaps linear processes each with distinct time scales. While these models are consistent with some motor phenomena, they can neither explain the relatively fast re-adaptation after a long washout period, nor savings on a subsequent day. Here we examined if these effects can be explained if we assume that the CNS stores and retrieves movement parameters based on their possible relevance. We formalize this idea with a model that infers not only the sources of potential motor errors, but also their relevance to the current motor circumstances. In our model adaptation is the process of re-estimating parameters that represent the body and the world. The likelihood of a world parameter being relevant is then based on the mismatch between an observed movement and that predicted when not compensating for the estimated world disturbance. As such, adapting to large motor errors in a laboratory setting should alert subjects that disturbances are being imposed on them, even after motor performance has returned to baseline. Estimates of this external disturbance should be relevant both now and in future laboratory settings. Estimated properties of our bodies on the other hand should always be relevant. Our model demonstrates savings, interference, spontaneous rebound and differences between adaptation to sudden and gradual disturbances. We suggest that many issues concerning savings and interference can be understood when adaptation is conditioned on the relevance of parameters

Active lead-in variability affects motor memory formation and slows motor learning

Rapid learning can be critical to ensure elite performance in a changing world or to recover basic movement after neural injuries. Recently it was shown that the variability of follow-through movements afects the rate of motor memory formation. Here we investigate if lead-in movement has a similar efect on learning rate. We hypothesized that both modality and variability of lead-in movement would play critical roles, with simulations suggesting that only changes in active lead-in variability would exhibit slower learning. We tested this experimentally using a two-movement paradigm, with either visual or active initial lead-in movements preceeding a second movement performed in a force feld. As predicted, increasing active lead-in variability reduced the rate of motor adaptation, whereas changes in visual lead-in variability had little efect. This demonstrates that distinct neural tuning activity is induced by diferent lead-in modalities, subsequently infuencing the access to, and switching between, distinct motor memories

Long-term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

It is well established that unilateral motor practice can lead to increased performance in the opposite non-trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long-term skill training with the dominant right hand increase performance and corticomotor excitability of the left non-trained hand. Subjects practiced a visuomotor tracking task engaging right digit V for 6 weeks with either progressively increasing task difficulty (PT) or no progression (NPT). Corticospinal excitability (CSE) was evaluated from the resting motor threshold (rMT) and recruitment curve parameters following application of transcranial magnetic stimulation (TMS) to the ipsilateral primary motor cortex (iM1) hotspot of the left abductor digiti minimi muscle (ADM). PT led to significant improvements in left-hand motor performance immediately after 6 weeks of training (63 ± 18%, P < 0.001) and 8 days later (76 ± 14%, P < 0.001). In addition, PT led to better task performance compared to NPT (19 ± 15%, P = 0.024 and 27 ± 15%, P = 0.016). Following the initial training session, CSE increased across all subjects. After 6 weeks of training and 8 days later, only PT was accompanied by increased CSE demonstrated by a left and upwards shift in the recruitment curves, e.g. indicated by increased MEPmax (P = 0.012). Eight days after training similar effects were observed, but 14 months later motor performance and CSE were similar between groups. We suggest that progressively adjusting demands for timing and accuracy to individual proficiency promotes motor skill learning and drives the iM1-CSE resulting in enhanced performance of the non-trained hand. The results underline the importance of increasing task difficulty progressively and individually in skill learning and rehabilitation training

Representation and Interaction of Sensorimotor Learning Processes

Human sensorimotor control is remarkably adept at utilising contextual information to learn and recall systematic sensorimotor transformations. Here, we investigate the motor representations that underlie such learning, and examine how motor memories acquired based on different contextual information interact. Using a novel three-dimensional robotic manipulandum, the 3BOT, we examined the spatial transfer of learning across various movement directions in a 3D environment, while human subjects performed reaching movements under velocity-dependent force field. The obtained pattern of generalisation suggested that the representation of dynamic learning was most likely defined in a target-based, rather than an extrinsic, coordinate system. We further examined how motor memories interact when subjects adapt to force fields applied in orthogonal dimensions. We found that, unlike opposing fields, learning two spatially orthogonal force fields led to the formation of separate motor memories, which neither interfered with nor facilitated each other. Moreover, we demonstrated a novel, more general aspect of the spontaneous recovery phenomenon using a two-dimensional force field task: when subjects learned two orthogonal force fields consecutively, in the following phase of clamped error feedback, the expression of adaptation spontaneously rotated from the direction of the second force field, towards the direction of the first force field. Finally, we examined the interaction of sensorimotor memories formed based on separate contextual information. Subjects performed reciprocating reaching and object manipulation tasks under two alternating contexts (movement directions), while we manipulated the dynamics of the task in each context separately. The results suggested that separate motor memories were formed for the dynamics of the task in different contexts, and that these motor memories interacted by sharing error signals to enhance learning. Importantly, the extent of interaction was not fixed between the context-dependent motor memories, but adaptively changed according to the task dynamics to potentially improve overall performance. Together, our experimental and theoretical results add to the understanding of mechanisms that underlie sensorimotor learning, and the way these mechanisms interact under various tasks and different dynamics.The thesis was funded by Wellcome Trust and the Yousef Jameel scholarship via Cambridge Trust

Coordinate representations for interference reduction in motor learning

When opposing force fields are presented alternately or randomly across trials for identical reaching movements, subjects learn neither force field, a behavior termed 'interference'. Studies have shown that a small difference in the endpoint posture of the limb reduces this interference. However, any difference in the limb's endpoint location typically changes the hand position, joint angles and the hand orientation making it ambiguous as to which of these changes underlies the ability to learn dynamics that normally interfere. Here we examine the extent to which each of these three possible coordinate systems--Cartesian hand position, shoulder and elbow joint angles, or hand orientation--underlies the reduction in interference. Subjects performed goal-directed reaching movements in five different limb configurations designed so that different pairs of these configurations involved a change in only one coordinate system. By specifically assigning clockwise and counter-clockwise force fields to the configurations we could create three different conditions in which the direction of the force field could only be uniquely distinguished in one of the three coordinate systems. We examined the ability to learn the two fields based on each of the coordinate systems. The largest reduction of interference was observed when the field direction was linked to the hand orientation with smaller reductions in the other two conditions. This result demonstrates that the strongest reduction in interference occurred with changes in the hand orientation, suggesting that hand orientation may have a privileged role in reducing motor interference for changes in the endpoint posture of the limb

Cerebellar Motor Learning Deficits: Structural mapping, neuromodulation and training-related interventions

Movement allows us to interact with our direct environment, manipulate objects and communicate with each other. Moreover, we can adjust our movements to fit a remarkable range of situations and circumstances. The ability to adjust movements in response to changes in the environment and task demands is referred to as motor learning. The cerebellum is a key neural structure for motor learning. As such, disease of the cerebellum, in addition to the clinical symptom of ataxia, results in various motor learning deficits. There is a consensus that supportive therapy (e.g. physiotherapy, occupational therapy or speech therapy) can reduce ataxia symptoms of cerebellar patients, but little is known about the mechanisms underlying the improvements, and how patients can benefit most. Additionally, motor learning deficits are associated with reduced efficacy of supportive therapy. With the work described in this thesis, we sought to unravel the structural components of cerebellar disease and the relationship between cerebellar integrity and motor learning. Furthermore, we investigated whether motor learning deficits in cerebellar patients could be ameliorated with neuromodulation or training-related interventions, under experimental conditions, hoping to support the development of interventions relevant for application in a clinical setting

Children and adolescents with chronic pain: parental factors, functioning, and neurodevelopmental comorbidity

Background: Pediatric chronic pain affects between 11 and 38% of all children. Although pain may result from injury or disease, the cause of chronic pain is commonly unclear. The interaction between biological, psychological, and social aspects has been emphasized as key to the understanding of the chronic pain experience, as well as risk and resilience factors. Pediatric chronic pain may result in significant impairment affecting both child and family functioning, and addressing family factors such as parental distress and protective behaviors, are generally considered important to pediatric chronic pain management. However, there is still a need to identify resilience factors that can be targeted in parental support programs, and to develop and evaluate effective parent support interventions. The complexity of the pain experience in pediatric chronic pain is well known with a large number of patients suffering from co-occurring disorders such as depression or insomnia. However, despite a considerable number of clinical observations suggesting an elevated prevalence of attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) among children with chronic pain, and similarities in terms of clinical correlates, the empirical support has been scarce. More research on the co-occurrence of pediatric chronic pain, ADHD, and ASD, including relationships with functioning, is therefore warranted. Purpose and aims: The purpose of the present research project was to identify and assess parental and child factors of importance for functioning and treatment effects in pediatric chronic pain. More specifically, the aims of the project were to: validate an instrument for parental psychological flexibility (Study I); evaluate the effects of a brief parental ACTintervention on parent outcomes (Study II); assess the prevalence of clinically significant traits and symptoms of ASD and ADHD in children, and relations to pain- and demographic variables (Study III); and, to explore the relationships between traits and symptoms of ASD and ADHD, functioning, and health-related quality of life (HRQoL) (Study IV). Methods: In Study 1, utilizing a cross-sectional design, the Parent Psychological Flexibility Questionnaire (PPFQ) was translated and psychometrically evaluated in a sample of parents (n=263) of children with chronic pain using principal component analysis (PCA), correlation and regression analyses, and analysis of internal consistency. In Study II, the effects of individual and group ACT-interventions for adolescents (n=48) with chronic pain, and a brief support program for their parents (n=28), were evaluated using a randomized (group/individual) uncontrolled pilot design and non-parametric analyses of differences between groups and over time. In Study III, the prevalence of clinically significant ASD-traits and ADHD-symptoms was evaluated in a descriptive cross-sectional study on children with chronic pain (n=146) and their parents (n=146). Differences in painand demographic variables between children below and above cutoff for clinically significant traits and symptoms of ADHD or ASD were also assessed. Study IV, using the same sample as Study III, examined the relationships between ASD-traits and ADHDsymptoms, functioning (depression and pain interference), and HRQoL in correlation- and regression analyses and with independent t-tests, and assessed the indirect effects of insomnia and psychological inflexibility on the relationships between ASD-traits or ADHD-symptoms as predictors and functioning and HRQoL as dependents. Results: In Study 1, results supported a three-factor solution for the PPFQ with 10 items (PPFQ-10), showing good internal consistency and explaining a significant amount of variance in the criteria variables anxiety (29%) and depression (35.6%). In Study II, significant improvements in parental pain reactivity and psychological flexibility were found with clinically significant changes in the direction of better functioning for 54-76% of parents, with no differences between individual and group formats. In Study III, 13.7% of the sample presented with clinically significant ASD-traits and 19.9% of the sample presented with clinically significant ADHD-symptoms. The combined prevalence of clinically significant ASD/ADHD-traits and symptoms was 26%. Children with clinically significant ASD-traits were more likely to be girls and clinically significant ADHDsymptoms showed no gender differences. In Study IV, children with clinically significant ASD-traits and ADHD-symptoms presented with significantly higher levels of depressive symptoms and pain interference, and significantly lower HRQoL, compared to the rest of the sample. ASD-traits and ADHD-symptoms explained a significant amount of variance in pain interference and depressive symptoms, as well as in HRQoL. Psychological inflexibility was shown to mediate the influence of both ADHD-symptoms and ASD-traits, and insomnia the effect of ADHD-symptoms, on depression, pain interference, and HRQoL. Conclusions: Although tentative, the results suggests the utility of addressing parental psychological flexibility in relation to pediatric chronic pain. However, more research is warranted and future studies should e.g. evaluate the predictive utility of the PPFQ for child treatment outcomes, and evaluate if parental support programs that increase parental psychological flexibility also have positive effects on the children. Also, the results provide empirical support regarding elevated levels of clinically significant ADHD-symptoms and ASD-traits in pediatric chronic pain, and illustrate significant relationships between such traits and symptoms and functioning in children. Children with debilitating chronic pain, particularly girls, may be at risk for having a comorbid, and possibly undetected highfunctioning neurodevelopmental disorder. Results thus suggest the utility of screening for neurodevelopmental disorders in children with chronic pain, and may indicate insomnia, and psychological flexibility as potential treatment targets to improve functioning and HRQoL. The results also warrant further research to e.g. validate these findings in larger studies, evaluate the utility of tailored interventions, and examine the shared neuropathophysiology of chronic pain and neurodevelopmental disorders, including dopamine function and sensory abnormalities

The role of error-based learning in movement and stillness

When people and other animals perform a movement that produces an unexpected outcome, they learn from the resulting error and retain a portion of this learning over time. Curiously, for reaching movements of the arm, errors that occur solely during periods of movement cause changes to both the way we move and also the way we hold the arm still. Here, we explore the way the brain corrects for error after a single occurrence, how this response to error changes with experience, and finally, how these responses to error change the way we maintain stillness of the arm. In Chapter 2, we consider mechanisms that guide learning after a single error. Here we provide evidence that the brain uses its past corrections as a model for its future movement plans. This learning response does not remain fixed over time, but is augmented with experience. In Chapter 3, we describe a new algorithm that can be used to extract mathematical properties of adaptation. With this tool, we show that savings (faster rate of re-learning) is caused by an increase in the brain’s sensitivity to error, specifically within fast motor learning processes. Next, we show that reemergence of earlier memories is caused by the decay of fast learning processes. In Chapter 4, we show that anterograde interference (slower rate of re-learning) is caused by a reduction in one’s sensitivity to error, that recovers over time. Finally, in Chapter 5, we demonstrate that modulation of error sensitivity not only changes the rate at which we acquire motor memories, but also the point at which the learning process saturates. Lastly, in Chapter 6, we revisit our initial observation, that adaptation changes not only the way we move, but also the way we hold still. In a series of experiments in human and non-human primates, we report a surprising relationship between movement and posture: on a within-trial basis, the commands that hold the arm and finger at a target location depend in part on the mathematical integration of the commands that moved the limb to that location