Cerebellar GABA change during visuomotor adaptation relates to adaptation performance and cerebellar network connectivity: A Magnetic Resonance Spectroscopic Imaging study.

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum that underpin human motor adaptation remain unknown. We used a novel Magnetic Resonance Spectroscopic Imaging (MRSI) technique to measure changes in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the human cerebellum during visuomotor adaptation. Participants used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We were able to spatially resolve adaptation-driven GABA changes at the cerebellar nuclei and in the cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple movement of the right hand increases GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found an increase in GABA in the left cerebellar nuclei and a decrease in GABA in the right cerebellar nuclei during adaptation. Early adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance: Participants showing greater GABA decrease adapted better, suggesting that this early GABA change is behaviourally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network: Participants showing a greater decrease in GABA also showed greater strength increase in cerebellar network connectivity. These results were specific to GABA, specific to adaptation and specific to the cerebellar network. This study provides the first evidence for plastic changes in cerebellar neurochemistry during a motor adaptation task. Characterising these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate neurochemical changes in the cerebellum that can improve human motor adaptation.

Increased cognitive load in immersive virtual reality during visuomotor adaptation is associated with decreased long-term retention and context transfer

Background: Complex motor tasks in immersive virtual reality using a head-mounted display (HMD-VR) have been shown to increase cognitive load and decrease motor performance compared to conventional computer screens (CS). Separately, visuomotor adaptation in HMD-VR has been shown to recruit more explicit, cognitive strategies, resulting in decreased implicit mechanisms thought to contribute to motor memory formation. However, it is unclear whether visuomotor adaptation in HMD-VR increases cognitive load and whether cognitive load is related to explicit mechanisms and long-term motor memory formation.Methods: We randomized 36 healthy participants into three equal groups. All groups completed an established visuomotor adaptation task measuring explicit and implicit mechanisms, combined with a dual-task probe measuring cognitive load. Then, all groups returned after 24-hours to measure retention of the overall adaptation. One group completed both training and retention tasks in CS (measuring long-term retention in a CS environment), one group completed both training and retention tasks in HMD-VR (measuring long-term retention in an HMD-VR environment), and one group completed the training task in HMD-VR and the retention task in CS (measuring context transfer from an HMD-VR environment). A Generalized Linear Mixed-Effect Model (GLMM) was used to compare cognitive load between CS and HMD-VR during visuomotor adaptation, t-tests were used to compare overall adaptation and explicit and implicit mechanisms between CS and HMD-VR training environments, and ANOVAs were used to compare group differences in long-term retention and context transfer.Results: Cognitive load was found to be greater in HMD-VR than in CS. This increased cognitive load was related to decreased use of explicit, cognitive mechanisms early in adaptation. Moreover, increased cognitive load was also related to decreased long-term motor memory formation. Finally, training in HMD-VR resulted in decreased long-term retention and context transfer.Conclusions: Our findings show that cognitive load increases in HMD-VR and relates to explicit learning and long-term motor memory formation during motor learning. Future studies should examine what factors cause increased cognitive load in HMD-VR motor learning and whether this impacts HMD-VR training and long-term retention in clinical populations.

Coherent theta oscillations in the cerebellum and supplementary motor area mediate visuomotor adaptation

The cerebellum and its interaction with cortical areas play a key role in our ability to flexibly adapt a motor program in response to sensory input. Current knowledge about specific neural mechanisms underlying the process of visuomotor adaptation is however lacking. Using a novel placement of EEG electrodes to record electric activity from the cerebellum, we studied local cerebellar activity, as well as its coupling with neocortical activity to obtain direct neurophysiological markers of visuomotor adaptation in humans. We found increased theta (4-8Hz) power in cerebellar as well as cortical electrodes, when subjects first encountered a visual perturbation. Theta power decreased as subjects adapted to the perturbation, and rebounded when the perturbation was suddenly removed. This effect was observed in two distinct locations: a cerebellar cluster and a central cluster, which were localized in left cerebellar crus I (lCB) and right supplementary motor area (rSMA) using linear constrained minimum variance beamforming. Importantly, we found that better adaptation was associated with increased theta power in left cerebellar electrodes and a right sensorimotor cortex electrode. Finally, increased rSMA -> lCB connectivity was significantly decreased with adaptation. These results demonstrate that: (1) cerebellar theta power is markedly modulated over the course of visuomotor adaptation and (2) theta oscillations could serve as a key mechanism for communication within a cortico-cerebellar loop.

Visuomotor adaptation modulates the clustering of sleep spindles into trains

Sleep spindles are thought to promote memory consolidation. Recently, we have shown that visuomotor adaptation (VMA) learning increases the density of spindles and promotes the coupling between spindles and slow oscillations, locally, with the level of spindle-SO synchrony predicting overnight memory retention. Yet, growing evidence suggests that the rhythmicity in spindle occurrence may also influence the stabilization of declarative and procedural memories. Here, we examined if VMA learning promotes the temporal organization of sleep spindles into trains. We found that VMA increased the proportion of spindles and spindle-SO couplings in trains. In agreement with our previous work, this modulation was observed over the contralateral hemisphere to the trained hand, and predicted overnight memory retention. Interestingly, spindles grouped in a cluster showed greater amplitude and duration than isolated spindles. The fact that these features increased as a function of train length, provides evidence supporting a biological advantage of this temporal arrangement. Our work opens the possibility that the periodicity of NREM oscillations may be relevant in the stabilization of procedural memories.

Aging Effect on Visuomotor Adaptation: Mediated by Cognitive Decline

The question of whether and how aging affects humans’ visuomotor adaptation remains controversial. This study investigates how the effect of aging on visuomotor adaptation is related to age-related cognitive declines. We compared the performance of 100 older people (age: 55–82 years) and 20 young adults (age: 18–27 years) on a visuomotor adaptation task and three cognition tasks. A decline in visuomotor adaptation of older people was well observed. However, this decline was not strongly correlated with chronological age increase but was associated to the age-related declines of cognitive functions and speed of motor planning. We then constructed a structural mediation model in which the declined cognitive resources mediated the effect of age increase on the decline in visuomotor adaptation. The data from the present study was well-explained by the mediation model. These findings indicate that the aging effect on visuomotor adaptation mainly reflects the age-related decline of cognitive functions, which results in insufficient explicit processing on visual perturbation during visuomotor control.

Dynamic changes in spatial representation within the posterior parietal cortex in response to visuomotor adaptation

Recent studies used fMRI population receptive field (pRF) mapping to demonstrate that retinotopic organization extends from primary visual cortex to ventral and dorsal visual pathways by quantifying visual field maps, receptive field size, and laterality throughout multiple areas. Visuospatial representation in the posterior parietal cortex (PPC) is modulated by attentional deployment, raising the question of whether spatial representation in the PPC is dynamic and flexible and that this flexibility contributes to visuospatial learning. To answer this question, changes in spatial representation within PPC, as measured with pRF mapping, were recorded before and after visuomotor adaptation. Visuospatial input was laterally manipulated, rightward or leftward, via prism adaptation, a well-established visuomotor technique that modulates visuospatial performance. Based on existing models of prism adaptation mechanism of action, we predicted left prism adaptation to produce a right visuospatial bias via an increasing pRF size in the left parietal cortex. However, our hypothesis was agnostic as to whether right PPC will show an opposite effect given the bilateral bias to right visual field. Findings show that adaptation to left-shifting prisms increases pRF size in both PPCs, while leaving space representation in early visual cortex unchanged. This is the first evidence that prism adaptation drives a dynamic reorganization of response profiles in the PPC. Our results show that spatial representation in the PPC not only reflects changes driven by attentional deployment but dynamically changes in response to visuomotor adaptation. Furthermore, our results provide support for using prism adaptation as a tool to rehabilitate visuospatial deficits.

Composition and decomposition of visuomotor maps during manual tracking

Adapting hand movements to changes in our body or the environment is essential for skilled motor behavior, as is the ability to flexibly combine experience gathered in separate contexts. However it has been shown that when adapting hand movements to two different visuomotor perturbations in succession, interference effects can occur. Here we investigate whether these interference effects compromise our ability to adapt to the superposition of the two perturbations. Participants tracked with a joystick a visual target that followed a smooth but unpredictable trajectory. Four separate groups of participants (total n = 83) completed one block of 50 trials under each of three mappings: one in which the cursor was rotated by 90° (ROTATION), one in which the cursor mimicked the behavior of a mass-spring system (SPRING), and one in which the SPRING and ROTATION mappings were superimposed (SPROT). The order of the blocks differed across groups. Although interference effects were found when switching between SPRING and ROTATION, participants who performed these blocks first performed better in SPROT than participants who had no prior experience with SPRING and ROTATION (i.e., composition). Moreover, participants who started with SPROT exhibited better performance under SPRING and ROTATION than participants who had no prior experience with each of these mappings (i.e., decomposition). Additional analyses confirmed that these effects resulted from components of learning that were specific to the rotational and spring perturbations. These results show that interference effects do not preclude the ability to compose/decompose various forms of visuomotor adaptation.

Implicit adaptation to mirror-reversal is in the correct coordinate system but the wrong direction

Learning in visuomotor adaptation tasks is the result of both explicit and implicit processes. Explicit processes, operationalized as re-aiming an intended movement to a new goal, account for a significant proportion of learning. However, implicit processes, operationalized as error-dependent learning that gives rise to aftereffects, appear to be highly constrained. The limitations of implicit learning are highlighted in the mirror-reversal task, where implicit corrections act in opposition to performance. This is surprising given the mirror-reversal task has been viewed as emblematic of implicit learning. One potential issue not being considered in these studies is that both explicit and implicit processes were allowed to operate concurrently, which may interact, potentially in opposition. Therefore, we sought to further characterized implicit learning in a mirror-reversal task with a clamp design to isolate implicit learning from explicit strategies. We confirmed that implicit adaptation is in the wrong direction for mirror-reversal and operates as if the perturbation were a rotation, and only showed a moderate attenuation after three days of training. This result raised the question of whether implicit adaptation blindly operates as though perturbations were a rotation. In a separate experiment, which directly compared a mirror-reversal and a rotation, we found that implicit adaptation operates in a proper coordinate system for different perturbations: adaptation to a mirror-reversal and rotational perturbation is more consistent with Cartesian and polar coordinate systems, respectively. It remains an open question why implicit process would be flexible to the coordinate system of a perturbation but continue to be directed inappropriately.