Exploring the role of task success in implicit motor adaptation.

Although implicit motor adaptation is driven by sensory-prediction errors (SPEs), recent work has shown that task success modulates this process. Task success has typically been defined as hitting a target, which signifies the goal of the movement. Visuomotor adaptation tasks are uniquely situated to experimentally manipulate task success independently from SPE by changing the target size or the location of the target. These two, distinct manipulations may influence implicit motor adaptation in different ways, so, over four experiments, we sought to probe the efficacy of each manipulation. We found that changes in target size, which caused the target to fully envelop the cursor, only affected implicit adaptation for a narrow range of SPE sizes, while jumping the target to overlap with the cursor more reliably and robustly affected implicit adaptation. Taken together, our data indicate that, while task success exerts a small effect on implicit adaptation, these effects are susceptible to methodological variations. Future investigations of the effect of task success on implicit adaptation could benefit from employing target jump manipulations instead of target size manipulations.NEW & NOTEWORTHY Recent work has suggested that task success, namely, hitting a target, influences implicit motor adaptation. Here, we observed that implicit adaptation is modulated by target jump manipulations, where the target abruptly "jumps" to meet the cursor; however, implicit adaptation was only weakly modulated by target size manipulations, where a static target either envelops or excludes the cursor. We discuss how these manipulations may exert their effects through different mechanisms.

Exploring the role of task success in implicit motor adaptation.

We learn to improve our motor skills using different forms of feedback: sensory-prediction error, task success, and reward/punishment. While implicit motor adaptation is driven by sensory-prediction errors, recent work has shown that task success modulates this process. Task success is often confounded with reward, so we sought to determine if the effects of these two signals on adaptation can be dissociated. To address this question, we conducted five experiments that isolated implicit learning using error-clamp visuomotor reach adaptation paradigms. Task success was manipulated by changing the size and position of the target relative to the cursor providing visual feedback, and reward expectation was established using monetary cues and auditory feedback. We found that neither monetary cues nor auditory feedback affected implicit adaptation, suggesting that task success influences implicit adaptation via mechanisms distinct from conventional reward-related processes. Additionally, we found that changes in target size, which caused the target to either exclude or fully envelop the cursor, only affected implicit adaptation for a narrow range of error sizes, while jumping the target to overlap with the cursor more reliably and robustly affected implicit adaptation. Taken together, our data indicate that, while task success exerts a small effect on implicit adaptation, these effects are susceptible to methodological variations and unlikely to be mediated by reward.

Motor learning without movement.

Prediction errors guide many forms of learning, providing teaching signals that help us improve our performance. Implicit motor adaptation, for instance, is thought to be driven by sensory prediction errors (SPEs), which occur when the expected and observed consequences of a movement differ. Traditionally, SPE computation is thought to require movement execution. However, recent work suggesting that the brain can generate sensory predictions based on motor imagery or planning alone calls this assumption into question. Here, by measuring implicit motor adaptation during a visuomotor task, we tested whether motor planning and well-timed sensory feedback are sufficient for adaptation. Human participants were cued to reach to a target and were, on a subset of trials, rapidly cued to withhold these movements. Errors displayed both on trials with and without movements induced single-trial adaptation. Learning following trials without movements persisted even when movement trials had never been paired with errors and when the direction of movement and sensory feedback trajectories were decoupled. These observations indicate that the brain can compute errors that drive implicit adaptation without generating overt movements, leading to the adaptation of motor commands that are not overtly produced.

Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice.

Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2. Of the many symptoms, motor deterioration is a significant problem for patients. In mice, deleting Mecp2 from the cortex or basal ganglia causes motor dysfunction, hypoactivity, and tremor, which are abnormalities observed in patients. Little is known about the function of Mecp2 in the cerebellum, a brain region critical for motor function. Here we show that deleting Mecp2 from the cerebellum, but not from its neuronal subtypes, causes a delay in motor learning that is overcome by additional training. We observed irregular firing rates of Purkinje cells and altered heterochromatin architecture within the cerebellum of knockout mice. These findings demonstrate that the motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. For Rett syndrome and other neurodevelopmental disorders, our results highlight the importance of understanding which brain regions contribute to disease phenotypes.

A cerebello-olivary signal for negative prediction error is sufficient to cause extinction of associative motor learning.

The brain generates negative prediction error (NPE) signals to trigger extinction, a type of inhibitory learning that is responsible for suppressing learned behaviors when they are no longer useful. Neurons encoding NPE have been reported in multiple brain regions. Here, we use an optogenetic approach to demonstrate that GABAergic cerebello-olivary neurons can generate a powerful NPE signal, capable of causing extinction of conditioned motor responses on its own.

Single-Unit Extracellular Recording from the Cerebellum During Eyeblink Conditioning in Head-Fixed Mice.

This chapter presents a method for performing in vivo single-unit extracellular recordings and optogenetics during an associative, cerebellum-dependent learning task in head-fixed mice. The method uses a cylindrical treadmill system that reduces stress in the mice by allowing them to walk freely, yet it provides enough stability to maintain single-unit isolation of neurons for tens of minutes to hours. Using this system, we have investigated sensorimotor coding in the cerebellum while mice perform learned skilled movements.

Sensitivity to self-administered cocaine within the lateral preoptic-rostral lateral hypothalamic continuum.

The lateral preoptic-rostral lateral hypothalamic continuum (LPH) receives projections from the nucleus accumbens and is believed to be one route by which nucleus accumbens signaling affects motivated behaviors. While accumbens firing patterns are known to be modulated by fluctuating levels of cocaine, studies of the LPH's drug-related firing are absent from the literature. The present study sought to electrophysiologically test whether drug-related tonic and slow-phasic patterns exist in the firing of LPH neurons during a free-access cocaine self-administration task. Results demonstrated that a majority of neurons in the LPH exhibited changes in both tonic and slow-phasic firing rates during fluctuating drug levels. During the maintenance phase of self-administration, 69.6% of neurons exhibited at least a twofold change in tonic firing rate when compared to their pre-drug firing rates. Moreover, 54.4% of LPH neurons demonstrated slow-phasic patterns, specifically "progressive reversal" patterns, which have been shown to be related to pharmacological changes across the inter-infusion interval. Firing rate was correlated with calculated drug level in 58.7% of recorded cells. Typically, a negative correlation between drug level and firing rate was observed, with a majority of neurons showing decreases in firing during cocaine self-administration. A small percentage of LPH neurons also exhibited correlations between locomotor behavior and firing rate; however, correlations with drug level in these same neurons were always stronger. Thus, the weak relationships between LPH firing and locomotor behaviors during cocaine self-administration do not account for the observed changes in firing. Overall, these findings suggest that a proportion of LPH neurons are sensitive to fluctuations in cocaine concentration and may contribute to neural activity that controls drug taking.