Competition between parallel sensorimotor learning systems

Sensorimotor learning is supported by at least two parallel systems: A strategic process that benefits from explicit knowledge, and an implicit process that adapts subconsciously. How do these systems interact? Does one system's contributions suppress the other, or do they operate independently? Here we illustrate that during reaching, implicit and explicit systems both learn from visual target errors. This shared error leads to competition such that an increase in the explicit system's response siphons away resources that are needed for implicit adaptation, thus reducing its learning. As a result, steady-state implicit learning can vary across experimental conditions, due to changes in strategy. Furthermore, strategies can mask changes in implicit learning properties, such as its error sensitivity. These ideas, however, become more complex in conditions where subjects adapt using multiple visual landmarks, a situation which introduces learning from sensory prediction errors in addition to target errors. These two types of implicit errors can oppose each other, leading to another type of competition. Thus, during sensorimotor adaptation, implicit and explicit learning systems compete for a common resource: error

Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease.

Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in proteins and their functions. Some downregulated proteins such as DPYSL2, TPI1, ALDH, and UCHL1 were found to play critical roles in the neurological disease and PSMA1, PSMA3, PSMC2, PSMD11, and UCHL1 in protein homeostasis. Taken together, we have provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in SVZ neurogenesis for the early detection of differences in gene expression and the potential risk of neurological disease, which is beneficial in the prevention of the diseases

fMRI Supports the Sensorimotor Theory of Motor Resonance

The neural mechanisms mediating the activation of the motor system during action observation, also known as motor resonance, are of major interest to the field of motor control. It has been proposed that motor resonance develops in infants through Hebbian plasticity of pathways connecting sensory and motor regions that fire simultaneously during imitation or self movement observation. A fundamental problem when testing this theory in adults is that most experimental paradigms involve actions that have been overpracticed throughout life. Here, we directly tested the sensorimotor theory of motor resonance by creating new visuomotor representations using abstract stimuli (motor symbols) and identifying the neural networks recruited through fMRI. We predicted that the network recruited during action observation and execution would overlap with that recruited during observation of new motor symbols. Our results indicate that a network consisting of premotor and posterior parietal cortex, the supplementary motor area, the inferior frontal gyrus and cerebellum was activated both by new motor symbols and by direct observation of the corresponding action. This tight spatial overlap underscores the importance of sensorimotor learning for motor resonance and further indicates that the physical characteristics of the perceived stimulus are irrelevant to the evoked response in the observer

Sensorimotor adaptation as a behavioural biomarker of early spinocerebellar ataxia type 6.

Early detection of the behavioural deficits of neurodegenerative diseases may help to describe the pathogenesis of such diseases and establish important biomarkers of disease progression. The aim of this study was to identify how sensorimotor adaptation of the upper limb, a cerebellar-dependent process restoring movement accuracy after introduction of a perturbation, is affected at the pre-clinical and clinical stages of spinocerebellar ataxia type 6 (SCA6), an inherited neurodegenerative disease. We demonstrate that initial adaptation to the perturbation was significantly impaired in the eighteen individuals with clinical motor symptoms but mostly preserved in the five pre-clinical individuals. Moreover, the amount of error reduction correlated with the clinical symptoms, with the most symptomatic patients adapting the least. Finally both pre-clinical and clinical individuals showed significantly reduced de-adaptation performance after the perturbation was removed in comparison to the control participants. Thus, in this large study of motor features in SCA6, we provide novel evidence for the existence of subclinical motor dysfunction at a pre-clinical stage of SCA6. Our findings show that testing sensorimotor de-adaptation could provide a potential predictor of future motor deficits in SCA6

Reduction in Learning Rates Associated with Anterograde Interference Results from Interactions between Different Timescales in Motor Adaptation

Prior experiences can influence future actions. These experiences can not only drive adaptive changes in motor output, but they can also modulate the rate at which these adaptive changes occur. Here we studied anterograde interference in motor adaptation – the ability of a previously learned motor task (Task A) to reduce the rate of subsequently learning a different (and usually opposite) motor task (Task B). We examined the formation of the motor system's capacity for anterograde interference in the adaptive control of human reaching-arm movements by determining the amount of interference after varying durations of exposure to Task A (13, 41, 112, 230, and 369 trials). We found that the amount of anterograde interference observed in the learning of Task B increased with the duration of Task A. However, this increase did not continue indefinitely; instead, the interference reached asymptote after 15–40 trials of Task A. Interestingly, we found that a recently proposed multi-rate model of motor adaptation, composed of two distinct but interacting adaptive processes, predicts several key features of the interference patterns we observed. Specifically, this computational model (without any free parameters) predicts the initial growth and leveling off of anterograde interference that we describe, as well as the asymptotic amount of interference that we observe experimentally (R2 = 0.91). Understanding the mechanisms underlying anterograde interference in motor adaptation may enable the development of improved training and rehabilitation paradigms that mitigate unwanted interference

Visuomotor adaptive improvement and aftereffects are impaired differentially following cerebellar lesions in SCA and PICA territory

The aim of the present study was to elucidate the contribution of the superior and posterior inferior cerebellum to adaptive improvement and aftereffects in a visuomotor adaptation task. Nine patients with ischemic lesions within the territory of the posterior inferior cerebellar artery (PICA), six patients with ischemic lesions within the territory of the superior cerebellar artery (SCA) and 17 age-matched controls participated. All subjects performed center-out reaching movements under 60° rotation of visual feedback. For the assessment of aftereffects, we tested retention of adaptation and de-adaptation under 0° visual rotation. From this data we also quantified five measures of motor performance. Cerebellar lesion-symptom mapping was performed using magnetic resonance imaging subtraction analysis. Adaptive improvement during 60° rotation was significantly degraded in PICA patients and even more in SCA patients. Subtraction analysis revealed that posterior (Crus I) as well as anterior cerebellar regions (lobule V) showed a common overlap related to deficits in adaptive improvement. However, for aftereffect measures as well as for motor performance variables only SCA patients, but not PICA patients showed significant differences to control subjects. Subtraction analysis showed that affection of lobules V and VI were more common in patients with impaired retention and de-adaptation, respectively. Data shows that areas both within the superior and posterior inferior cerebellum are involved in adaptive improvement. However, only the superior cerebellum including lobules V and VI appears to be important for aftereffects and therefore true adaptive ability

Perceiving What Is Reachable Depends on Motor Representations: Evidence from a Transcranial Magnetic Stimulation Study

Background: Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space. Methodology: Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80 % of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90 % of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms). Principal Findings: Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space. Conclusion: This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possibl

Assessing the Influence of Different ROI Selection Strategies on Functional Connectivity Analyses of fMRI Data Acquired During Steady-State Conditions

In blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), assessing functional connectivity between and within brain networks from datasets acquired during steady-state conditions has become increasingly common. However, in contrast to connectivity analyses based on task-evoked signal changes, selecting the optimal spatial location of the regions of interest (ROIs) whose timecourses will be extracted and used in subsequent analyses is not straightforward. Moreover, it is also unknown how different choices of the precise anatomical locations within given brain regions influence the estimates of functional connectivity under steady-state conditions. The objective of the present study was to assess the variability in estimates of functional connectivity induced by different anatomical choices of ROI locations for a given brain network. We here targeted the default mode network (DMN) sampled during both resting-state and a continuous verbal 2-back working memory task to compare four different methods to extract ROIs in terms of ROI features (spatial overlap, spatial functional heterogeneity), signal features (signal distribution, mean, variance, correlation) as well as strength of functional connectivity as a function of condition. We show that, while different ROI selection methods produced quantitatively different results, all tested ROI selection methods agreed on the final conclusion that functional connectivity within the DMN decreased during the continuous working memory task compared to rest

Optimizing Preprocessing and Analysis Pipelines for Single-Subject fMRI: 2. Interactions with ICA, PCA, Task Contrast and Inter-Subject Heterogeneity

A variety of preprocessing techniques are available to correct subject-dependant artifacts in fMRI, caused by head motion and physiological noise. Although it has been established that the chosen preprocessing steps (or “pipeline”) may significantly affect fMRI results, it is not well understood how preprocessing choices interact with other parts of the fMRI experimental design. In this study, we examine how two experimental factors interact with preprocessing: between-subject heterogeneity, and strength of task contrast. Two levels of cognitive contrast were examined in an fMRI adaptation of the Trail-Making Test, with data from young, healthy adults. The importance of standard preprocessing with motion correction, physiological noise correction, motion parameter regression and temporal detrending were examined for the two task contrasts. We also tested subspace estimation using Principal Component Analysis (PCA), and Independent Component Analysis (ICA). Results were obtained for Penalized Discriminant Analysis, and model performance quantified with reproducibility (R) and prediction metrics (P). Simulation methods were also used to test for potential biases from individual-subject optimization. Our results demonstrate that (1) individual pipeline optimization is not significantly more biased than fixed preprocessing. In addition, (2) when applying a fixed pipeline across all subjects, the task contrast significantly affects pipeline performance; in particular, the effects of PCA and ICA models vary with contrast, and are not by themselves optimal preprocessing steps. Also, (3) selecting the optimal pipeline for each subject improves within-subject (P,R) and between-subject overlap, with the weaker cognitive contrast being more sensitive to pipeline optimization. These results demonstrate that sensitivity of fMRI results is influenced not only by preprocessing choices, but also by interactions with other experimental design factors. This paper outlines a quantitative procedure to denoise data that would otherwise be discarded due to artifact; this is particularly relevant for weak signal contrasts in single-subject, small-sample and clinical datasets