Effects of hyperbaric oxygen pre-exposure on the motor learning acquisition phase.

Hyperbaric oxygen (HBO) exposure has recently been reported to be effective in spatial learning and memory. Additionally, HBO exposure considerably improves performance on motor tasks. These findings suggest that HBO exposure may facilitate motor learning. However, the specific effects of HBO exposure on motor learning remain largely unexplored. The present study aimed to investigate the effects of HBO exposure on motor learning tasks. In the experimental animal models (control n = 8, HBO n = 8), the HBO environment was exposed to 100 % oxygen with the chamber at 2.0 atmosphere absolute (ATA) for 90 min/day for 20 days. The motor learning task was an accelerated rotating bar task (bar width, 3 and 6 cm; rotation speed, 4-40 rpm; acceleration, 0.4, 0.6, and 0.8 rpm/s). The learning task was performed for 3 consecutive days. The HBO group showed a main effect of the day factor on the bar with a width of 6 cm, and significant differences were observed for each day comparison. However, no main effect of the day factor was observed in the control group. Additionally, significant differences were found in the bar with a width of 3 cm for both groups between days 1 and 2 and between days 1 and 3. In conclusion, these findings suggest that HBO exposure has a positive effect on more challenging motor learning tasks.

Effects of online and offline trigeminal nerve stimulation on visuomotor learning.

Introduction: A current thrust in neurology involves using exogenous neuromodulation of cranial nerves (e.g, vagus, trigeminal) to treat the signs and symptoms of various neurological disorders. These techniques also have the potential to augment cognitive and/or sensorimotor functions in healthy individuals. Although much is known about the clinical effects of trigeminal nerve stimulation (TNS), effects on sensorimotor and cognitive functions such as learning have received less attention, despite their potential impact on neurorehabilitation. Here we describe the results of experiments aimed at assessing the effects of TNS on motor learning, which was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. Objective: Assessing the effects of TNS on motor learning. Methods: Motor learning was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. In Experiment 1, effects of offline TNS using clinically tested frequencies (120 and 60 Hz) were characterized. Sixty-three healthy young adults received TNS before performing a task that involved reaching with perturbed hand visual feedback. In Experiment 2, the effects of 120 and 60 Hz online TNS were characterized with the same task. Sixty-three new participants received either TNS or sham stimulation concurrently with perturbed visual feedback. Results: Experiment 1 results showed that 60 Hz stimulation was associated with slower rates of learning than both sham and 120 Hz stimulation, indicating frequency-dependent effects of TNS. Experiment 2 however showed no significant differences among stimulation groups. A post-hoc, cross-study comparison of the 60 Hz offline and online TNS results showed a statistically significant improvement in learning rates with online stimulation relative to offline, pointing to timing-dependent effects of TNS on visuomotor learning. Discussion: The results indicate that both the frequency and timing of TNS can influence rates of motor learning in healthy adults. This suggests that optimization of one or both parameters could potentially increase learning rates, which would provide new avenues for enhancing performance in healthy individuals and augmenting rehabilitation in patients with sensorimotor dysfunction resulting from stroke or other neurological disorders.

Blending motor learning approaches for short-term adjustments to gait in people with Parkinson disease.

Rhythmic auditory cueing (RAC) using an isochronous metronome is an effective approach to immediately enhance spatiotemporal aspects of gait for people with Parkinson disease (PwPD). Whereas entraining to RAC typically occurs subconsciously via cerebellar pathways, the use of metronome frequencies that deviate from one's typical cadence, such as those used in rehabilitation, may require conscious awareness. This heightened awareness may increase cognitive load and limit the persistence of gait training gains. Here, we explore the immediate effects of incorporating an implicit motor learning approach (i.e., error-based recalibration) to gait training with RAC. Twenty older adults (10 with PD and 10 controls) were asked to match their footfalls to both isochronous and subtly varying metronomes while walking on a treadmill and overground. Our findings revealed intriguing differences between treadmill and overground walking. During treadmill walking to a slower metronome frequency, both groups reduced their cadence and increased step lengths, but did not make the necessary adjustments to match the subtly varying metronome. During overground walking, both groups modified their cadence in response to a 3-4% change in metronome frequency (p < 0.05). Both metronomes yielded evidence of implicit and explicit retention during overground and treadmill walking. Furthermore, during overground walking the PD group showed greater implicit retention of cadence changes following the varying metronome, compared to the isochronous metronome. Our results suggest that incorporating implicit motor learning approaches to gait training during a single session of overground walking may enhance short term implicit retention of gait behaviors for PwPD.

The affective response to positive performance feedback is associated with motor learning.

Motor skill learning and performance are improved when successful actions are paired with extrinsic rewards, such as money. Positive feedback indicating successful task performance is thought to induce intrinsic reward associated with goal attainment, evidenced by increases in positive affect that correlate with neural reward signaling. However, it is not clear whether the subjective, internal reward processes elicited by positive feedback promote motor learning and performance.Here, we tested the hypothesis that intrinsic reward elicited by positive feedback promotes motor learning and performance. Participants practiced a visuomotor interception task using a joystick, and received feedback during practice indicating success or failure depending on their accuracy. During practice, the accuracy demands were adapted to control and vary the frequency of positive feedback across randomly ordered blocks of practice at either 50%, 70%, or 90%. Performance was measured for each condition as the average accuracy during practice. Learning was estimated by measuring the accuracy pre and post practice in the absence of feedback. We queried participants periodically on their enjoyment of the task to index affective responses to performance feedback.The intrinsic reward elicited by positive feedback, operationalized by the increase in enjoyment immediately following positive versus negative feedback, was positively correlated with learning from pre to post practice. However, increasing the overall amount of positive feedback by lower accuracy demands did not improve performance. These results suggest that experiencing intrinsic reward due to positive feedback benefits motor learning only when it is contingent on good performance.

Corrigendum: Contribution of thyrotropin-releasing hormone to cerebellar long-term depression and motor learning.

[This corrects the article DOI: 10.3389/fncel.2018.00490.].

Cortical drive may facilitate enhanced use of the paretic leg induced by random constraint force to the non-paretic leg during walking in chronic stroke.

The goal of this study was to determine the effects of applying random vs. constant constraint force to the non-paretic leg during walking on enhanced use of the paretic leg in individuals post-stroke, and examine the underlying brain mechanisms. Twelve individuals with chronic stroke were tested under two conditions while walking on a treadmill: random vs. constant magnitude of constraint force applied to the non-paretic leg during swing phase of gait using a custom designed robotic system. Leg kinematics, muscle activity of the paretic leg, and electroencephalography (EEG) were recorded during treadmill walking. Paretic step length and muscle activity of the paretic ankle plantarflexors significantly increased after walking with random and constant constraint forces. Cortico-cortical connectivity between motor cortices and cortico-muscular connectivity from the lesioned motor cortex to the paretic ankle plantarflexors significantly increased for the random force condition but not for the constant force condition. In addition, individuals post-stroke with greater baseline gait variability showed greater improvements in the paretic step length after walking with random force condition but not with the constant force condition. In conclusion, application of random constraint force to the non-paretic leg may enhance the use of the paretic leg during walking by facilitating cortical drive from the lesioned motor cortex to the paretic ankle plantarflexors. Results from this study may be used for the development of constraint induced locomotor intervention approaches aimed at improving locomotor function in individuals after stroke.

Muscular, Temporal, and Spatial Responses to Shoulder Exosuit Assistance During Functional Tasks.

Shoulder exosuits are a promising new technology that could enable individuals with neuromuscular impairments to independently perform activities of daily living, however, scarce evidence exists to evaluate their ability to support such activities. Consequently, it is not understood how humans adapt motion in response to assistance from a shoulder exosuit. In this study, we developed a cable-driven shoulder exosuit and evaluated its effect on reaching and drinking tasks within a cohort of 18 healthy subjects to quantify changes to muscle activity and kinematics as well as trial-to-trial learning in duration and actuator switch timing. The exosuit successfully reduced mean muscle activity in the middle (reaching: 23.4±26.3%, drinking: 20.0±25.1%) and posterior (reaching: 12.8±10.3%, drinking: 4.0±7.2%) deltoid across both functional tasks. Likewise, the exosuit reduced integrated muscle activity in the middle deltoid (reaching: 22.2±22.7%, drinking: 14.9±27.0%). Exosuit assistance also altered kinematics such that individuals allowed their arms to follow forces applied by the exosuit. In terms of learning, subjects reduced movement duration by 15.6±11.9% as they practiced using the exosuit. Reducing movement duration allowed subjects to reduce integrated muscle activity in the anterior (15.2±10.3%), middle (14.7±9.7%), and posterior (14.8±9.7%) deltoids. Similarly, subjects activated the actuator switch earlier over the course of many assisted trials. The muscle activity reductions during both reaching and drinking demonstrate the promise of shoulder exosuits to enable independent function among individuals with neuromuscular impairments. The kinematic response to assistance and learning features observed in movement duration provide insight into human-exosuit interaction principles that could inform future exosuit development.

Differential impact of optogenetic stimulation of direct and indirect pathways from dorsolateral and dorsomedial striatum on motor symptoms in Huntington's disease mice.

The alterations in the basal ganglia circuitry are core pathological hallmark in Huntington's Disease (HD) and traditionally linked to its sever motor symptoms. Recently it was shown that optogenetic stimulation of cortical afferences to the striatum is able to reverse motor symptoms in HD mice. However, the specific contribution of the direct and indirect striatal output pathways from the dorsolateral (DLS) and dorsomedial striatum (DMS) to the motor phenotype is still not clear. Here, we aim to uncover the contributions of these striatal subcircuits to motor control in wild type (WT) and HD mice by using the symptomatic R6/1 mice. We systematically evaluated locomotion, exploratory behavior, and motor learning effects of the selective optogenetic stimulation of D1 or A2A expressing neurons (direct and indirect pathway, respectively), in DLS or DMS. Bilateral optogenetic stimulation of the direct pathway from DLS and the indirect pathway from DMS resulted in subtle locomotor enhancements, while unaltering exploratory behavior. Additionally, bilateral stimulation of the indirect pathway from the DLS improved performance in the accelerated rotarod task, suggesting a role in motor learning. In contrast, in HD mice, stimulation of these pathways did not modulate any of these behaviors. Overall, this study highlights that selective stimulation of direct and indirect pathways from DLS and DMS have subtle impact in locomotion, exploratory activity or motor learning. The lack of responses in HD mice also suggests that strategies involving cortico-striatal circuits rather than striatal output circuits might be a better strategy for managing motor symptoms in movement disorders.

Use your imagination for better performance. Effects of analogy instruction in motor skills. A systematic review and Meta-Analysis.

This systematic review and meta-analysis examined the effects of analogy instruction (ANA) on motor performance and knowledge declared (KD) compared with explicit learning (EXP) and control conditions. Five databases were included. The study analyzed 16 randomized controlled trials. Subsequent analysis was performed for moderators variables as age, skill, retention, stress situations number of rules, specificity and number of trials. The ANA instruction demonstrated greater efficacy than the control (ES = 0.32, p=0.03) or EXP condition (ES = 0.29, p=0.02) in motor tasks performance in general terms. ANA instructions also showed superiority in motor performance when compared to control conditions in retention (ES = 5.72, p=0.004), and a trend towards significance was found under stress (ES = 1.18, p=0.05). ANA also showed superiority in motor performance when compared to EXP instruction (ES = 0.29, p=0.02). ANA demonstrated greater effects than EXP in retention (ES = 7.25, p=0.01), but not under stress (ES = 0.62, p=0.18). Sub-analyses demonstrated that children (all p < 0.01) and novices (all p < 0.01) are more likely to benefit from ANA instruction when compared to control or EXP. A subgroup analysis based on quantity of information comparing ANA versus EXP condition shows that ANA is more effective for enhancing motor performance than EXP when the number of rules are similar. Sub-analyses comparing ANA versus CNT shows that as the number of repetitions increases and the task becomes less specific, ANA instruction significantly improves performance. A comparison between ANA and EXP indicates no significant differences in performance regarding the number of repetitions and task specificity. A secondary analysis examined KD of different instructions. KD was greater in EXP instructions (ES = -1.48, p < 0.001) when compared to ANA. Findings suggest that analogy instruction may improve motor performance, especially in novice and child populations. However, caution is needed due to concerns when comparing with other instructional types and environments, as well as due to high heterogeneity in most of the comparisons and high risk of bias in included studies.

Intra- and interlimb effects of gait retraining in individuals with knee hyperextension.

BACKGROUND: Gait retraining, which typically focuses on the most severely affected limb or joint, has shown promising results in treating faulty running and walking patterns. The closed-chain nature of gait during the stance phase may influence kinematic changes in the adjacent joints of the trained leg. In addition, the coupled nature of the lower extremity motion of gait suggests that changes in one leg may transfer to the other. This study aimed to assess the intra- and inter-limb transfer of kinematic changes following gait retraining to reduce knee extension in individuals with hyperextension walking patterns. METHODS: Seventeen women with knee hyperextension gait patterns participated in six treadmill retraining sessions. All participants received verbal and real-time visual kinematic feedback in the form of knowledge of results. This intervention study took place at the Gait Analysis Laboratory at the University of Iowa. Mean peak sagittal-plane lower extremity joint kinematics during overground walking at pretraining, post-training, and 1- and 8-month follow-ups were calculated for analysis and comparisons. FINDINGS: The post-training changes in ankle range of motion returned to baseline values by the 8-month follow-up. There was a significant transfer effect of kinematic changes to the untrained knee following gait retraining. INTERPRETATION: Training one knee did not result in long-term compensatory kinematic changes in the other joints. In addition, the improvements in knee extension range of motion were transferred to the untrained knee and retained at the 8-month follow-up. This study supports the use of gait retraining as an effective clinical intervention.

Comparing the effects of anodal and cathodal transcranial direct current stimulation of primary motor cortex at varying intensities on motor learning in healthy young adults.

Inconsistent results are observed in the effects of transcranial direct current stimulation (tDCS) with different montages on motor learning. This study aimed to compare the effects of anodal and cathodal tDCS (c-tDCS) over primary motor cortex (M1) at different intensities on motor learning in healthy young adults. The participants were randomly divided into: (1) 1 mA M1 c-tDCS, (2) 1 mA M1 anodal tDCS (a-tDCS), (3) 2 mA M1 c-tDCS, (4) 2 mA M1 a-tDCS and (5) M1 sham tDCS groups. The groups received 20-min stimulation with serial reaction time task (SRTT) incidentally, while the tDCS was turned off after 30 s in the sham tDCS group. Response time (RT) and error rate (ER) during SRTT were assessed prior, during and 72 h after the intervention. The results of the paired t-test indicated that online learning occurred in all groups (p < 0.05), except in M1 c-tDCS (1 mA) (p > 0.05). One-way ANOVA analysis also indicated that there were differences in offline learning (RT (F(DF) = 5.19(4); p < 0.001; and ER (F(DF) = 9(4), p < 0.0001) among groups, with more offline learning in 1 mA M1 a-tDCS, 2 mA M1 c-tDCS and 2 mA M1 a-tDCS groups (p < 0.05). On the other hand, the 1 mA M1 c-tDCS group did not indicate any consolidation effect or even a trend toward negative offline learning. M1 a-tDCS with different intensities and also 2 mA M1 c-tDCS may be helpful for the enhancement of motor learning in young healthy adults. This study enhances our understanding of tDCS intensity and polarity effects on motor learning, with potential for optimizing therapeutic protocols.

Determining the optimal challenge point for learning motor skills in children with attention deficit/hyperactivity disorder.

The purpose of this study was to investigate the optimal challenge point for learning motor skills in children with and without attention deficit/hyperactivity disorder (ADHD). Ninety-six 9- to 10-year-old children, including 48 children with ADHD and 48 neurotypical children, were randomly assigned to one of four practice groups with varying levels of nominal and functional task difficulty. They performed 63 trials of a dart throwing task in the acquisition phase and 18 trials in the retention and transfer tests a day later. The results showed that neurotypical children outperformed children with ADHD in all phases of the study. Both groups improved in the acquisition phase and performed better in the retention and transfer tests. Interestingly, low nominal task difficulty was associated with better learning for both groups, despite lower average performance for children with ADHD. Thus, despite their performance differences, we did not find a difference in the effective challenge point between children with ADHD and their neurotypical peers.

Acquiring musculoskeletal skills with curriculum-based reinforcement learning.

Efficient musculoskeletal simulators and powerful learning algorithms provide computational tools to tackle the grand challenge of understanding biological motor control. Our winning solution for the inaugural NeurIPS MyoChallenge leverages an approach mirroring human skill learning. Using a novel curriculum learning approach, we trained a recurrent neural network to control a realistic model of the human hand with 39 muscles to rotate two Baoding balls in the palm of the hand. In agreement with data from human subjects, the policy uncovers a small number of kinematic synergies, even though it is not explicitly biased toward low-dimensional solutions. However, selectively inactivating parts of the control signal, we found that more dimensions contribute to the task performance than suggested by traditional synergy analysis. Overall, our work illustrates the emerging possibilities at the interface of musculoskeletal physics engines, reinforcement learning, and neuroscience to advance our understanding of biological motor control.

Using interactive computer play in physical therapy and occupational therapy clinical practice: an explanatory sequential mixed methods study.

Introduction: This study explored the extent to which an interactive computer play system, Bootle Blast, supports motor learning in a clinical context and examined clinicians' perceptions of their therapeutic role in the system's use as an intervention tool. Methods: In this observational sequential explanatory mixed methods study, five children with cerebral palsy [mean age 9.4 years (SD, 0.5), Gross Motor Function Classification System Levels I-III] used Bootle Blast during a single video-recorded therapy session with their treating clinicians (physical therapists, occupational therapists, and therapy assistants). Children played one Bootle Blast mini game independently (without clinician involvement) before clinicians carried out therapy sessions with the game as per usual care. The type and extent of motor learning strategies (MLS) delivered by Bootle Blast and clinicians were rated from video recordings by a trained assessor using the 22-item Motor Learning Strategies Rating Instrument. Semi-structured interviews with clinicians were conducted to gain insights into MLS use and clinicians' perceived role during Bootle Blast use. Interviews were audio recorded, transcribed verbatim, and analyzed independently by two researchers using thematic analysis. Quantitative and qualitative data were merged and reported using narrative and joint display approaches. Results: Bootle Blast provided eight MLS, with clinicians adding or enhancing another eight. Four themes reflected clinicians' perspectives: (1) Bootle Blast disguises therapy as play, (2) clinicians give Bootle Blast the human touch; (3) home use of Bootle Blast is promising; and (4) Bootle Blast is not always the right fit but some shortcomings could be addressed. Agreement was found for nine MLS and disagreement for four MLS when quantitative and qualitative findings were merged. Discussion: Bootle Blast delivers several MLS as part of game play and clinicians can enhance and provide additional MLS to suit the child's needs/abilities. Further game refinements that were identified in this study may optimize its clinical use.

Effectiveness of intensive motor learning approaches from working on a vertical surface on hemiplegic children's upper limb motor skills, a randomized controlled trial.

PURPOSE: This study compares the effect of intensive motor learning approaches on improving the quality of upper extremity skills in children with unilateral cerebral palsy (UCP) by working on vertical surfaces versus horizontal surfaces during rehabilitation sessions. MATERIALS AND METHODS: Forty UCP children of both sexes were randomized into two equal groups. All participants received 60 min of intensive motor learning approaches three days/week for three successive months. These approaches included constraint-induced movement therapy (CIMT), in which children wore a splint or sling on the unaffected upper limb, as well as hand-arm bimanual intensive training (HABIT) that requires the use of both hands during specific play-based activities. The control group received training on a horizontal surface while the child sat in front of an elbow-height table while the study group (vertical surface training) sat or stood in front of a wall/mirror/board. The task requirements were graded to ensure success. RESULTS: Statistically significant differences were detected between the mean values of post-treatment of all scorers, with a greater percentage of improvement in favor of the study group. CONCLUSIONS: This study revealed that working on a vertical surface improved upper limb motor skills more significantly than working on a horizontal surface.

This study compares the effect of intensive motor learning approaches on improving the quality of upper extremity skills in children with unilateral cerebral palsy by working on vertical surfaces versus horizontal surfaces during rehabilitation sessions.Incorporating occupational therapy tasks on a vertical surface may increase the control of proximal muscles and ease graphomotor performance.Working on a vertical surface can make activities fun for children and make challenging tasks, like writing, more interesting.Working on a vertical surface during rehabilitation sessions can particularly help children with unilateral cerebral palsy to further develop essential fine, visual, and gross motor skills more than training on horizontal surfaces.

Development of a low-cost upper-body rehabilitation robot for home use.

The inability to use one's hands or arms greatly restricts the ability to perform daily activities. After a developmental or acquired injury, the intensity and frequency of rehabilitation exercises are essential. To alleviate the burden on the healthcare system, robotic systems have been developed to support clinicians' interventions. However, these systems are often bulky and expensive, limiting their use to specific clinical settings and making them impractical for home use. This paper presents the development of an affordable and easy to install 2-DOF five-bar linkage robot designed to be used at home. This work aims to reduce the cost of the robot through actuation optimization, mechanical optimization and 3D printing. The architecture and links length are chosen to optimize the robot's performance in the required workspace. Using sensor feedback, impedance control algorithms and multiple types of exercise such as virtual walls guidance are implemented. Finally, a user interface was programmed to facilitate the robot's use.

Enhancing Cough Motor Learning in Parkinson's Disease Through Variable Practice During Skill Training.

BACKGROUND: When re-learning a motor skill, practicing a variety of treatment targets promotes error processing and the exploration of motor control strategies, which initially disrupts accuracy during training (motor performance), but ultimately enhances generalization, retention, and transfer (motor learning). Cough skill training (CST) is feasible and efficacious to improve cough strength; however, previous studies have used the same practice target during training. OBJECTIVES: Our goal was to examine the impact of CST with variable practice on motor performance, motor learning, and respiratory system adaptations. METHOD: The study was a prospective three-visit single group design. Twenty individuals with Parkinson's disease (PD) and concomitant dysphagia and dystussia completed two sessions of CST involving three randomized practice targets. Cough, lung volume, and airway clearance outcomes were assessed before and after treatment sessions with long-term retention evaluated after 1 month. RESULTS: Peak expiratory flow rate improved after CST with variable practice for voluntary single (ß = 0.35 L/s) and sequential (ß = 0.22 L/s) cough, which were maintained after 1 month without treatment. The ability to expel material from the upper airway demonstrated a small magnitude of improvement (ß = -1.87%). During CST, participants altered lung volume based on the treatment target and lung volume decreased during reflex cough after completing CST. CONCLUSIONS: Individuals with PD demonstrated improvements in several aspects of motor learning after two sessions of CST with variable practice. Increasing lung volume may not be an implicit strategy to upregulate voluntary cough strength in this treatment paradigm. The findings support the need for larger investigations exploring the potential benefits of this CST approach.

Implicit motor sequence learning using three-dimensional reaching movements with the non-dominant left arm.

Interlimb differences in reach control could impact the learning of a motor sequence that requires whole-arm movements. The purpose of this study was to investigate the learning of an implicit, 3-dimensional whole-arm sequence task with the non-dominant left arm compared to the dominant right arm. Thirty-one right-hand dominant adults completed two consecutive days of practice of a motor sequence task presented in a virtual environment with either their dominant right or non-dominant left arm. Targets were presented one-at-a-time alternating between Random and Repeated sequences. Task performance was indicated by the time to complete the sequence (response time), and kinematic measures (hand path distance, peak velocity) were used to examine how movements changed over time. While the Left Arm group was slower than the Right Arm group at baseline, both groups significantly improved response time with practice with the Left Arm group demonstrating greater gains. The Left Arm group improved performance by decreasing hand path distance (straighter path to targets) while the Right Arm group improved performance through a smaller decrease in hand path distance combined with increasing peak velocity. Gains made during practice on Day 1 were retained on Day 2 for both groups. Overall, individuals reaching with the non-dominant left arm learned the whole-arm motor sequence task but did so through a different strategy than individuals reaching with the dominant right arm. The strategy adopted for the learning of movement sequences that require whole-arm movements may be impacted by differences in reach control between the nondominant and dominant arms.

KCTD1 regulation of Adenylyl cyclase type 5 adjusts striatal cAMP signaling.

Dopamine transfers information to striatal neurons, and disrupted neurotransmission leads to motor deficits observed in movement disorders. Striatal dopamine converges downstream to Adenylyl Cyclase Type 5 (AC5)-mediated synthesis of cAMP, indicating the essential role of signal transduction in motor physiology. However, the relationship between dopamine decoding and AC5 regulation is unknown. Here, we utilized an unbiased global protein stability screen to identify Potassium Channel Tetramerization Domain 1 (KCTD1) as a key regulator of AC5 level that is mechanistically tied to N-linked glycosylation. We then implemented a CRISPR/SaCas9 approach to eliminate KCTD1 in striatal neurons expressing a Förster resonance energy transfer (FRET)-based cAMP biosensor. 2-photon imaging of striatal neurons in intact circuits uncovered that dopaminergic signaling was substantially compromised in the absence of KCTD1. Finally, knockdown of KCTD1 in genetically defined dorsal striatal neurons significantly altered motor behavior in mice. These results reveal that KCTD1 acts as an essential modifier of dopaminergic signaling by stabilizing striatal AC5.

Learning to Control Complex Robots Using High-Dimensional Body-Machine Interfaces.

When individuals are paralyzed from injury or damage to the brain, upper body movement and function can be compromised. While the use of body motions to interface with machines has shown to be an effective noninvasive strategy to provide movement assistance and to promote physical rehabilitation, learning to use such interfaces to control complex machines is not well understood. In a five session study, we demonstrate that a subset of an uninjured population is able to learn and improve their ability to use a high-dimensional Body-Machine Interface (BoMI), to control a robotic arm. We use a sensor net of four inertial measurement units, placed bilaterally on the upper body, and a BoMI with the capacity to directly control a robot in six dimensions. We consider whether the way in which the robot control space is mapped from human inputs has any impact on learning. Our results suggest that the space of robot control does play a role in the evolution of human learning: specifically, though robot control in joint space appears to be more intuitive initially, control in task space is found to have a greater capacity for longer-term improvement and learning. Our results further suggest that there is an inverse relationship between control dimension couplings and task performance.