Repetition of specific movement biases subsequent actions towards the practiced movement, a phenomenon known as use-dependent learning (UDL). Recent experiments that impose strict constraints on planning time have revealed two sources of use-dependent biases, one arising from dynamic changes occurring during motor planning and another reflecting a stable shift in motor execution. Here, we used a distributional analysis to examine the contribution of these biases in reaching. To create the conditions for UDL, the target appeared at a designated ‘frequent’ location on most trials, and at one of six ‘rare’ locations on other trials. Strikingly, the heading angles were bimodally distributed, with peaks at both frequent and rare target locations. Despite having no constraints on planning time, participants exhibited a robust bias towards the frequent target when movements were self-initiated quickly, the signature of a planning bias; notably, the peak near the rare target was shifted in the frequently practiced direction, the signature of an execution bias. Furthermore, these execution biases were not only replicated in a delayed-response task but were also insensitive to reward. Taken together, these results extend our understanding of how volitional movements are influenced by recent experience.

Errors that result from a mismatch between predicted movement outcomes and sensory afference are used to correct ongoing movements through feedback control and to adapt feedforward control of future movements. The cerebellum has been identified as a critical part of the neural circuit underlying implicit adaptation across a wide variety of movements (reaching, gait, eye movements, and speech). The contribution of this structure to feedback control is less well understood. Although it has recently been shown in the speech domain that individuals with cerebellar degeneration produce larger online corrections for sensory perturbations than control participants, similar behavior has not been observed in other motor domains. Currently, comparisons across domains are limited by different population samples and potential ceiling effects in existing tasks. To assess the relationship between changes in feedforward and feedback control associated with cerebellar degeneration across motor domains, we evaluated adaptive (feedforward) and compensatory (feedback) responses to sensory perturbations in reaching and speech production in human participants of both sexes with cerebellar degeneration and neurobiologically healthy controls. As expected, the cerebellar group demonstrated impaired adaptation in both reaching and speech. In contrast, the groups did not differ in their compensatory response in either domain. Moreover, compensatory and adaptive responses in the cerebellar group were not correlated within or across motor domains. These results point to a general impairment in feedforward control with spared feedback control in cerebellar degeneration. However, the magnitude of feedforward impairments and potential changes in feedback-based control manifest in a domain-specific manner across individuals.SIGNIFICANCE STATEMENTThe cerebellum contributes to feedforward updating of movement in response to sensory errors, but its role in feedback control is less understood. Here, we tested individuals with cerebellar degeneration (CD), using sensory perturbations to assess adaptation of feedforward control and feedback gains during reaching and speech production tasks. The results confirmed that CD leads to reduced adaption in both domains. However, feedback gains were unaffected by CD in either domain. Interestingly, measures of feedforward and feedback control were not correlated across individuals within or across motor domains. Together, these results indicate a general impairment in feedforward control with spared feedback control in CD. However, the magnitude of feedforward impairments manifests in a domain-specific manner across individuals.

Errors that result from a mismatch between predicted movement outcomes and sensory afference are used to correct ongoing movements through feedback control and to adapt feedforward control of future movements. The cerebellum has been identified as a critical part of the neural circuit underlying implicit adaptation across a wide variety of movements (reaching, gait, eye movements, and speech). The contribution of this structure to feedback control is less well understood: although it has recently been shown in the speech domain that individuals with cerebellar degeneration produce even larger online corrections for sensory perturbations than control participants, similar behavior has not been observed in other motor domains. Currently, comparisons across domains are limited by different population samples and potential ceiling effects in existing tasks. To assess the relationship between changes in feedforward and feedback control associated with cerebellar degeneration across motor domains, we evaluated adaptive (feedforward) and compensatory (feedback) responses to sensory perturbations in reaching and speech production in individuals with cerebellar degeneration and neurobiologically healthy controls. As expected, the cerebellar group demonstrated impaired adaptation in both reaching and speech. In contrast, the groups did not differ in their compensatory response in either domain. Moreover, compensatory and adaptive responses in the cerebellar group were not correlated within or across motor domains. Together, these results point to a general impairment in feedforward control with spared feedback control in cerebellar degeneration. However, the magnitude of feedforward impairments and potential changes in feedback-based control manifest in a domain-specific manner across individuals.

Repetition of a specific movement biases subsequent actions towards the recently practiced movement, a phenomenon referred to as use-dependent learning (UDL). UDL has been attributed to shifts in the tuning of neurons in the motor cortex. However, recent studies employing a forced reaction time task, including the eLife article by Marinovic et al (2017), indicate that these biases may also arise from a contaminated motor plan, one that is biased towards the practiced direction. We advanced this line of inquiry, seeking to establish the relative contribution of execution and planning processes to UDL in a center-out reaching task in which participants were able to initiate movements of their own volition. On most trials, the target appeared at a designated “frequent” location; on other trials, the target appeared at one of six “rare” locations. In Experiment 1, participants exhibited a robust movement bias towards the frequent target when movements were self-initiated quickly, but a small movement bias when movements were self-initiated slowly – the signature of a contaminated motor plan. Strikingly, the heading angles were bimodally distributed, with one peak at the frequent target location and the other at the rare target location – a finding reinforced by a re-analysis of two widely cited studies on UDL. Notably, the latter peak was shifted in the frequently practiced direction, a signature of a motor execution bias. To eliminate the contribution of planning-related UDL, we imposed a delay between target onset and movement initiation in Experiment 2. As predicted, the heading angles became unimodally distributed around the rare target. The peak of this distribution was again shifted towards the location of the frequent target, indicative of a persistent bias in motor execution. Taken together, these results highlight two distinct components of UDL even when movements are self-initiated: First, the temporal dynamics underlying movement planning, in which a default plan is progressively overridden by a new plan, produces a pronounced motor planning bias. Second, there is a small, temporally stable bias that may reflect shifts in motor unit tuning.

BACKGROUND: Children with Neurofibromatosis Type 1 (NF1) are at risk for developing gliomas in multiple locations, particularly the optic pathway and brainstem. The goal of this study is to determine if glioma location in NF1 impacts tumor progression and accumulation of neurological deficits over time. METHODS: Retrospective chart review of 98 pediatric patients with NF1-associated gliomas between 1999-2021 at St. Louis Children’s Hospital. Patients who had never received treatment were excluded from analysis. Each glioma was categorized into one of four locations: posterior fossa (PF, n=12, 21%), supratentorial midline (SM, n=33, 57%) supratentorial cortical (SC, n=4, 7%), brainstem (BS, n=9, 15%). Patients with gliomas in different locations had each tumor counted separately (58 total gliomas analyzed). RESULTS: No SC tumors progressed. Time to first progression was comparable across the other 3 locations, and there was no meaningful different in neurologic deficits over time by tumor location. The majority of patients who demonstrated three or more clinical or radiographic progressions had tumors in the SM region. Within the SM tumor group, each tumor was further characterized as a deep extensive glioma (DEG; 36%) or an optic pathway glioma without deep extension (nonDEG; 64%). DEG had a slightly higher number of neurological deficits at baseline (DEG 2.08, nonDEG 1.19), fewer patients with no neurologic deficits (8.3% DEG vs 28.6% nonDEG) and a higher proportion of patients with a first progression event (41% DEG vs 24% nonDEG). However, DEG and nonDEG had similar risk of subsequent progressions after the initial event. CONCLUSION: Among children with NF1 who required glioma treatment, location was not a significant predictor of multiple progression or neurologic morbidity over time. Within the SM location, DEGs represent a newly characterized group that exhibit potentially higher rates of progression and neurological deficits. Multi-institutional analysis is needed to confirm these findings.