Movement variability can be modulated in speech production.

Although movement variability is often attributed to unwanted noise in the motor system, recent work has demonstrated that variability may be actively controlled. To date, research on regulation of motor variability has relied on relatively simple, laboratory-specific reaching tasks. It is not clear how these results translate to complex, well-practiced tasks. Here, we test how variability is regulated during speech production, a complex, highly overpracticed, and natural motor behavior that relies on auditory and somatosensory feedback. Specifically, in a series of four experiments, we assessed the effects of auditory feedback manipulations that modulate perceived speech variability, shifting every production either toward (inward pushing) or away from (outward pushing) the center of the distribution for each vowel. Participants exposed to the inward-pushing perturbation (experiment 1) increased produced variability while the perturbation was applied as well as after it was removed. Unexpectedly, the outward-pushing perturbation (experiment 2) also increased produced variability during exposure, but variability returned to near-baseline levels when the perturbation was removed. Outward-pushing perturbations failed to reduce participants' produced variability both with larger perturbation magnitude (experiment 3) and after their variability had increased above baseline levels as a result of the inward-pushing perturbation (experiment 4). Simulations of the applied perturbations using a state-space model of motor behavior suggest that the increases in produced variability in response to the two types of perturbations may arise through distinct mechanisms. Together, these results suggest that motor variability is actively monitored and can be modulated even in complex and well-practiced behaviors such as speech.NEW & NOTEWORTHY By implementing a novel auditory feedback perturbation that modulates participants' perceived trial-to-trial variability without affecting their overall mean behavior, we show that variability in the speech motor system can be modulated. By assaying speech production, we expand our current understanding of variability to a well-practiced, complex behavior outside of the limb control system. Our results additionally highlight the need to incorporate the active control of variability in models of speech motor control.

Sensitivity to error during visuomotor adaptation is similarly modulated by abrupt, gradual, and random perturbation schedules.

It has been suggested that sensorimotor adaptation involves at least two processes (i.e., fast and slow) that differ in retention and error sensitivity. Previous work has shown that repeated exposure to an abrupt force field perturbation results in greater error sensitivity for both the fast and slow processes. Although this implies that the faster relearning is associated with increased error sensitivity, it remains unclear what aspects of prior experience modulate error sensitivity. In the present study, we manipulated the initial training using different perturbation schedules, thought to differentially affect fast and slow learning processes based on error magnitude, and then observed what effect prior learning had on subsequent adaptation. During initial training of a visuomotor rotation task, we exposed three groups of participants to either an abrupt, a gradual, or a random perturbation schedule. During a testing session, all three groups were subsequently exposed to an abrupt perturbation schedule. Comparing the two sessions of the control group who experienced repetition of the same perturbation, we found an increased error sensitivity for both processes. We found that the error sensitivity was increased for both the fast and slow processes, with no reliable changes in the retention, for both the gradual and structural learning groups when compared to the first session of the control group. We discuss the findings in the context of how fast and slow learning processes respond to a history of errors.NEW & NOTEWORTHY We investigated what aspects of prior experience modulate error sensitivity, within the framework of a two-state model of short-term sensorimotor adaptation. We manipulated initial training on a visuomotor adaptation reaching task using specific perturbation schedules that are thought to differentially affect fast and slow learning processes, and we tested what effect these had on subsequent adaptation. We found that sensitivity to adaptation error was similarly modulated by abrupt, gradual, and random perturbation schedules.

The Origins of Anterograde Interference in Visuomotor Adaptation.

Anterograde interference refers to the negative impact of prior learning on the propensity for future learning. There is currently no consensus on whether this phenomenon is transient or long lasting, with studies pointing to an effect in the time scale of hours to days. These inconsistencies might be caused by the method employed to quantify performance, which often confounds changes in learning rate and retention. Here, we aimed to unveil the time course of anterograde interference by tracking its impact on visuomotor adaptation at different intervals throughout a 24-h period. Our empirical and model-based approaches allowed us to measure the capacity for new learning separately from the influence of a previous memory. In agreement with previous reports, we found that prior learning persistently impaired the initial level of performance upon revisiting the task. However, despite this strong initial bias, learning capacity was impaired only when conflicting information was learned up to 1 h apart, recovering thereafter with passage of time. These findings suggest that when adapting to conflicting perturbations, impairments in performance are driven by two distinct mechanisms: a long-lasting bias that acts as a prior and hinders initial performance and a short-lasting anterograde interference that originates from a reduction in error sensitivity.

Behavioural and neural basis of anomalous motor learning in children with autism.

Autism spectrum disorder is a developmental disorder characterized by deficits in social and communication skills and repetitive and stereotyped interests and behaviours. Although not part of the diagnostic criteria, individuals with autism experience a host of motor impairments, potentially due to abnormalities in how they learn motor control throughout development. Here, we used behavioural techniques to quantify motor learning in autism spectrum disorder, and structural brain imaging to investigate the neural basis of that learning in the cerebellum. Twenty children with autism spectrum disorder and 20 typically developing control subjects, aged 8-12, made reaching movements while holding the handle of a robotic manipulandum. In random trials the reach was perturbed, resulting in errors that were sensed through vision and proprioception. The brain learned from these errors and altered the motor commands on the subsequent reach. We measured learning from error as a function of the sensory modality of that error, and found that children with autism spectrum disorder outperformed typically developing children when learning from errors that were sensed through proprioception, but underperformed typically developing children when learning from errors that were sensed through vision. Previous work had shown that this learning depends on the integrity of a region in the anterior cerebellum. Here we found that the anterior cerebellum, extending into lobule VI, and parts of lobule VIII were smaller than normal in children with autism spectrum disorder, with a volume that was predicted by the pattern of learning from visual and proprioceptive errors. We suggest that the abnormal patterns of motor learning in children with autism spectrum disorder, showing an increased sensitivity to proprioceptive error and a decreased sensitivity to visual error, may be associated with abnormalities in the cerebellum.

Attenuation of implicit motor learning with consecutive exposure to visual errors.

Visual errors induced by movement drive implicit corrections of that movement. When similar errors are experienced consecutively, does sensitivity to the error remain consistent each time? This study aimed to investigate the modulation of implicit error sensitivity through continuous exposure to the same errors. In the reaching task using visual error-clamp feedback, participants were presented with the same error in direction and magnitude for four consecutive trials. We found that implicit error sensitivity decreased after exposure to the second error. These results indicate that when visual errors occur consecutively, the sensorimotor system exhibits different responses, even for identical errors. The continuity of errors may be a factor that modulates error sensitivity.

Evaluation of a complementary metal oxide semiconductor detector as a tool for stereotactic body radiotherapy plan quality assurance.

Background and purpose: A sub-mm resolution Complementary Metal Oxide Semiconductor sensor has been developed for stereotactic radiotherapy quality assurance. Herein we evaluate its basic dosimetric performance and its application for linac C-arm stereotactic body radiotherapy (SBRT) plan quality assurance. Materials and methods: The detector was integrated into its accompanying phantom or in Water Equivalent Plastic (WEP). The measurement reproducibility, stability, dose linearity and dependence on angularity, dose rate and field size were investigated. Clinical plan measurements were compared to our radiotherapy treatment planning system and radiochromic film. Sensitivity to introduced Multi Leaf Collimator (MLC) offsets was evaluated by simulating single MLC offsets in SBRT plans and comparing measurements to expected doses. Results: Signal reproducibility was within ± 0.1 % and output calibration was stable over a 6 month period. Detector showed good linearity with dose (r2 = 1). Signal decreased by 5 % when dose rate was decreased from 1300 MU/min to 300 MU/min. Output factors agreed within 0.5 % of chamber measurements for 1x1 cm field sizes or greater. Angularity measurements showed good agreement with reference. For measurement of planned clinical doses, gamma pass-rates were 98.5 % ± 2.3 % (treatment planning system reference, 2 %/2mm) and 99.2 % ± 1.0 % (film reference, 2 %,2mm). The detector also showed sensitivity to errors of 1 mm offsets in MLC positioning. Conclusion: The detector performed well when used for pre-treatment SBRT plan quality assurance, offering a good alternative to radiochromic film.

Adaptive control of a wheelchair mounted robotic arm with neuromorphically integrated velocity readings and online-learning.

Wheelchair-mounted robotic arms support people with upper extremity disabilities with various activities of daily living (ADL). However, the associated cost and the power consumption of responsive and adaptive assistive robotic arms contribute to the fact that such systems are in limited use. Neuromorphic spiking neural networks can be used for a real-time machine learning-driven control of robots, providing an energy efficient framework for adaptive control. In this work, we demonstrate a neuromorphic adaptive control of a wheelchair-mounted robotic arm deployed on Intel's Loihi chip. Our algorithm design uses neuromorphically represented and integrated velocity readings to derive the arm's current state. The proposed controller provides the robotic arm with adaptive signals, guiding its motion while accounting for kinematic changes in real-time. We pilot-tested the device with an able-bodied participant to evaluate its accuracy while performing ADL-related trajectories. We further demonstrated the capacity of the controller to compensate for unexpected inertia-generating payloads using online learning. Videotaped recordings of ADL tasks performed by the robot were viewed by caregivers; data summarizing their feedback on the user experience and the potential benefit of the system is reported.

Experience of After-Effect of Memory Update Reduces Sensitivity to Errors During Sensory-Motor Adaptation Task.

Motor learning is the process of updating motor commands in response to a trajectory error induced by a perturbation to the body or vision. The brain has a great capability to accelerate learning by increasing the sensitivity of the memory update to the perceived trajectory errors. Conventional theory suggests that the statistics of perturbations or the statistics of the experienced errors induced by the external perturbations determine the learning speeds. However, the potential effect of another type of error perception, a self-generated error as a result of motor command updates (i.e., an aftereffect), on the learning speeds has not been examined yet. In this study, we dissociated the two kinds of errors by controlling the perception of the aftereffect using a channel-force environment. One group experienced errors due to the aftereffect of the learning process, while the other did not. We found that the participants who perceived the aftereffect of the memory updates exhibited a significant decrease in error-sensitivity, whereas the participants who did not perceive the aftereffect did not show an increase or decrease in error-sensitivity. This suggests that the perception of the aftereffect of learning attenuated updating the motor commands from the perceived errors. Thus, both self-generated and externally induced errors may modulate learning speeds.

The Bat-and-Ball Problem: Stronger evidence in support of a conscious error process.

Traditional accounts of reasoning have characterized human error response to be an unconscious process whereby cognitive misers blindly neglect the critical information that would lead to problem solution, thereby substituting an easier problem for the actual problem (e.g., Kahneman & Frederick, 2002). For the bat-and-ball problem, the unconscious substitution hypothesis is challenged on two fronts in the present study: (1) testing for conscious representation of the error-inducing semantic content of the problem (i.e., the "more than" phrase, "The bat costs $1.00 more than the ball."); and (2) comparing experimentally response confidence differences between standard versions of the problem and isomorphic controls (without that phrase) to verify post-decision sensitivity to the errors, following De Neys, Rossi, and Houdé (2013). Crucially, even when interference questions were included between testing and memory response, incorrect reasoners largely had accurate recall and recognition of the problem's error inducing phrase. Incorrect reasoners' intra-individual error sensitivity was replicated and extended via the introduction of a social-metacognitive measurement, which was found to be correlated with intra-individual post-decision confidence and also yielded an error sensitivity effect. Finally, latency responses verify the relationship between time spent reasoning and post-decision confidence. Implications and future directions are discussed.

Changes of signal transductivity and robustness of gene regulatory network in the carcinogenesis of leukemic subtypes via microarray sample data.

Mutation accumulation and epigenetic alterations in genes are important for carcinogenesis. Because leukemogenesis-related signal pathways have been investigated and microarray sample data have been produced in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and normal cells, systems analysis in coupling pathways becomes possible. Based on system modeling and identification, we could construct the coupling pathways and their associated gene regulatory networks using microarray sample data. By applying system theory to the estimated system model in coupling pathways, we can then obtain transductivity sensitivity, basal sensitivity and error sensitivity of each protein to identify the potential impact of genetic mutations, epigenetic alterations and the coupling of other pathways from the perspective of energy, respectively. By comparing the results in AML, MDS and normal cells, we investigated the potential critical genetic mutations and epigenetic alterations that activate or repress specific cellular functions to promote MDS or AML leukemogenesis. We suggested that epigenetic modification of ß-catenin and signal integration of CSLs, AP-2α, STATs, c-Jun and ß-catenin could contribute to cell proliferation at AML and MDS. Epigenetic regulation of ERK and genetic mutation of p53 could lead to the repressed apoptosis, cell cycle arrest and DNA repair in leukemic cells. Genetic mutation of JAK, epigenetic regulation of ERK, and signal integration of C/EBPα could result in the promotion of MDS cell differentiation. According to the results, we proposed three drugs, decitabine, genistein, and monorden for preventing AML leukemogenesis, while three drugs, decitabine, thalidomide, and geldanamycin, for preventing MDS leukemogenesis.

Alteration of a motor learning rule under mirror-reversal transformation does not depend on the amplitude of visual error.

Human's sophisticated motor learning system paradoxically interferes with motor performance when visual information is mirror-reversed (MR), because normal movement error correction further aggravates the error. This error-increasing mechanism makes performing even a simple reaching task difficult, but is overcome by alterations in the error correction rule during the trials. To isolate factors that trigger learners to change the error correction rule, we manipulated the gain of visual angular errors when participants made arm-reaching movements with mirror-reversed visual feedback, and compared the rule alteration timing between groups with normal or reduced gain. Trial-by-trial changes in the visual angular error was tracked to explain the timing of the change in the error correction rule. Under both gain conditions, visual angular errors increased under the MR transformation, and suddenly decreased after 3-5 trials with increase. The increase became degressive at different amplitude between the two groups, nearly proportional to the visual gain. The findings suggest that the alteration of the error-correction rule is not dependent on the amplitude of visual angular errors, and possibly determined by the number of trials over which the errors increased or statistical property of the environment. The current results encourage future intensive studies focusing on the exact rule-change mechanism.