Biology subjects

Holland, P. J.

Publications and source records attributed to Holland, P. J..

7 recordsLinked to original sources

bioRxiv2021

Purkinje Cell Activity During Suppression of Voluntary Eye Movements in Rhesus Macaques

Volitional suppression of responses to distracting external stimuli enables us to achieve our goals. This volitional inhibition of a specific behavior is supposed to be mainly mediated by the cerebral cortex. However, recent evidence supports the involvement of the cerebellum in this process. It is currently not known whether different parts of the cerebellar cortex play differential or synergistic roles in planning and execution of this behavior. Here, we measured Purkinje cell (PC) responses in the medial and lateral cerebellum in two rhesus macaques during a pro- and antisaccade task. During an antisaccade trial, non-human primates were instructed to make a saccadic eye movement away from a target, rather than towards it, as in prosaccade trials. Our data shows that the cerebellum plays an important role not only during execution of the saccades, but also during the volitional inhibition of eye movements towards the target. Simple Spike (SS) modulation during the instruction and execution period of pro- and antisaccades was prominent in PCs of both medial and lateral cerebellum. However, only the SS activity in the lateral cerebellar cortex contained information about trial identity and showed a stronger reciprocal interaction with complex spikes. Moreover, SS activity of different PC groups modulated bidirectionally in both regions, but the PCs that showed facilitating and suppressive activity were predominantly associated with instruction and execution, respectively. These findings show that different cerebellar regions and PC groups contribute to goal-directed behavior and volitional inhibition, but with different propensities, highlighting the rich repertoire of cerebellar control in executive functions. Significance StatementThe antisaccade task is commonly used in research and clinical evaluation as a test of volitional and flexible control of behavior. It requires volitional suppression of prosaccades, a function that has been attributed to the neocortex. However, recent findings indicate that cerebellum also contributes to this behavior. We recorded from neurons in the medial and lateral cerebellum to evaluate their responses in this task. We found that both regions significantly modulated their activity during this task, but only cells in the lateral cerebellum encoded the stimulus identity in each trial. These results indicate that the cerebellum actively contributes to the control of flexible behavior and that lateral and medial cerebellum play different roles during volitional eye movements.

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bioRxiv2020

Reward-driven enhancements in motor control are robust to TMS manipulation

A wealth of evidence describes the strong positive impact that reward has on motor control at the behavioural level. However, surprisingly little is known regarding the neural mechanisms which underpin these effects, beyond a reliance on the dopaminergic system. In recent work, we developed a task that enabled the dissociation of the selection and execution components of an upper limb reaching movement. Our results demonstrated that both selection and execution are concommitently enhanced by immediate reward availability. Here, we investigate what the neural underpinnings of each component may be. To this end, we disrupted activity of the ventromedial prefrontal cortex and supplementary motor area using continuous theta-burst transcranial magnetic stimulation (cTBS) in a within-participant design (N=23). Both cortical areas are involved in reward processing and motor control, and we hypothesised that disruption of their activity would result in disruption of the reward-driven effects on action selection and execution, respectively. To increase statistical power, participants were pre-selected based on their sensitivity to reward in the reaching task. While reward did lead to enhanced perforance during the cTBS sessions and a control sham session, cTBS was ineffective in altering these effects. These results may provide evidence that other areas, such as the primary motor cortex or the premotor area, may drive the reward-based enhancements of motor performance.

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bioRxiv2019

Reward-based improvements in motor control are driven by multiple error-reducing mechanisms

Reward has a remarkable ability to invigorate motor behaviour, enabling individuals to select and execute actions with greater precision and speed. However, if reward is to be exploited in applied settings such as rehabilitation, a thorough understanding of its underlying mechanisms is required. Although reward-driven enhancement of movement execution has been proposed to occur through enhanced feedback control, an untested alternative is that it is driven by increased arm stiffness, an energy-consuming process that increases limb stability. First, we demonstrate that during reaching reward improves selection and execution performance concomitantly without interference. Computational analysis revealed that reward led to both an increase in feedback correction during movement and a reduction in motor noise near the target. We provide novel evidence that this noise reduction is driven by a reward-dependent increase in arm stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate motor performance without compromising accuracy.

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bioRxiv2019

A neuroanatomically grounded optimal control model of the compensatory eye movement system

We present a working model of the compensatory eye movement system. We challenge the model with a data set of eye movements in mice (n=34) recorded in 4 different sinusoidal stimulus conditions with 36 different combinations of frequency (0.1-3.2 Hz) and amplitude (0.5-8{degrees}) in each condition. The conditions included vestibular stimulation in the dark (vestibular-ocular reflex, VOR), optokinetic stimulation (optokinetic reflex, OKR), and two combined visual/vestibular conditions (the visual-vestibular ocular reflex, vVOR, and visual suppression of the VOR, sVOR). The model successfully reproduced the eye movements in all conditions, except for minor failures to predict phase when gain was very low. Most importantly, it could explain the non-linear summation of VOR and OKR when the two reflexes are activated simultaneously during vVOR stimulation. In addition to our own data, we also reproduced the behavior of the compensatory eye movement system found in the existing literature. These include its response to sum-of-sines stimuli, its response after lesions of the nucleus prepositus hypoglossi or the flocculus, characteristics of VOR adaptation, and characteristics of drift in the dark. Our model is based on ideas of state prediction and forward modeling that have been widely used in the study of motor control. However, it represents one of the first quantitative efforts to simulate the full range of behaviors of a specific system. The model has two separate processing loops, one for vestibular stimulation and one for visual stimulation. Importantly, state prediction in the visual processing loop depends on a forward model of residual retinal slip after vestibular processing. In addition, we hypothesize that adaptation in the system is primarily adaptation of this model. In other words, VOR adaptation happens primarily in the OKR loop.

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bioRxiv2019

Domain-specific working memory, but not dopamine-related genetic variability, shapes reward-based motor learning

The addition of rewarding feedback to motor learning tasks has been shown to increase the retention of learning, spurring interest in the possible utility for rehabilitation. However, laboratory-based motor tasks employing rewarding feedback have repeatedly been shown to lead to great inter-individual variability in performance. Understanding the causes of such variability is vital for maximising the potential benefits of reward-based motor learning. Thus, in this pre-registered study, we assessed whether spatial (SWM), verbal (VWM) and mental rotation (RWM) working memory capacity as well as dopamine-related genetic profiles could predict performance in two reward-based motor tasks, using a large cohort of participants (N=241). The first task assessed participants ability to follow a hidden and slowly shifting reward region based on hit/miss (binary) feedback. The second task investigated participants capacity to preserve performance with binary feedback after adapting to the shift with full visual feedback. Our results demonstrate that SWM strongly predicts a participants capacity to reliably reproduce a successful motor action, measured as change in reach angle following reward, while RWM predicted a participants propensity to express an explicit strategy when required to make large adjustments in reach angle. Therefore, both SWM and RWM were reliable predictors of success during reward-based motor learning. Change in reach direction following failure was also a strong predictor of success rate, although we observed no consistent relationship with any type of working memory. Surprisingly, no dopamine-related genotypes predicted performance. Therefore, working memory capacity plays a pivotal in determining individual ability in reward-based motor learning.\n\nSignificance statementReward-based motor learning tasks have repeatedly been shown to lead to idiosyncratic behaviours that cause varying degrees of task success. Yet, the factors determining an individuals capacity to use reward-based feedback are unclear. Here, we assessed a wide range of possible candidate predictors, and demonstrate that domain-specific working memory plays an essential role in determining individual capacity to use reward-based feedback. Surprisingly, genetic variations in dopamine availability were not found to play a role. This is in stark contrast with seminal work in the reinforcement and decision-making literature, which show strong and replicated effects of the same dopaminergic genes in decision-making. Therefore, our results provide novel insights in reward-based motor learning, highlighting a key role for domain-specific working memory capacity.

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bioRxiv2017

The role of explicit strategies during reinforcement-based motor learning

Despite increasing interest in the role of reward in motor learning, the underlying mechanisms remain ill-defined. In particular, the relevance of explicit strategies to reward-based motor learning is unclear. To address this, we examined subjects (n=30) ability to learn to compensate for a gradually introduced 25{degrees} visuomotor rotation with only reward-based feedback (binary success/failure). Only two-thirds of subjects (n=20) were successful at the maximum angle. The remaining subjects initially follow the rotation but after a variable number of trials begin to reach at an insufficiently large angle and subsequently return to near baseline performance (n=10). Furthermore, those that were successful accomplished this largely via the use of strategies, evidenced by a large reduction in reach angle when asked to remove any strategy they employed. However, both groups display a small degree of remaining retention even after the removal of strategies. All subjects made greater and more variable changes in reach angle following incorrect (unrewarded) trials. However, subjects who failed to learn showed decreased sensitivity to errors, even in the initial period in which they followed the rotation, a pattern previously found in Parkinsonian patients. In a second experiment, the addition of a secondary mental rotation task completely abolished learning (n=10), whilst a control group replicated the results of the first experiment (n=10). These results emphasize a pivotal role of strategy-use during reinforcement-based motor learning and the susceptibility of this form of learning to disruption has important implications for its potential therapeutic benefits.

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bioRxiv2017

The relationship between reinforcement and explicit strategies during visuomotor adaptation

The motor systems ability to adapt to changes in the environment is essential for maintaining accurate movements. During such adaptation several distinct systems are recruited: cerebellar sensory-prediction error learning, success-based reinforcement, and explicit strategy-use. Although much work has focused on the relationship between cerebellar learning and strategy-use, there is little research regarding how reinforcement and strategy-use interact. To address this, participants first learnt a 20{degrees} visuomotor displacement. After reaching asymptotic performance, binary, hit-or-miss feedback (BF) was introduced either with or without visual feedback, the latter promoting reinforcement. Subsequently, retention was assessed using no-feedback trials, with half of the participants in each group being instructed to stop using any strategy. Although BF led to an increase in retention of the visuomotor displacement, instructing participants to remove their strategy nullified this effect, suggesting strategy-use is critical to BF-based reinforcement. In a second experiment, we prevented the expression or development of a strategy during BF performance, by either constraining participants to a short preparation time (expression) or by introducing the displacement gradually (development). As both strongly impaired BF performance, it suggests reinforcement requires both the development and expression of a strategy. These results emphasise a pivotal role of strategy-use during reinforcement-based motor learning.

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