Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements

Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a role in motor control, but how the endogenous dopaminergic system influences movement is unknown. Here we examined the relationship between dopaminergic signaling and the timing of reward-related movements in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue; reward was delivered in response to movements initiated after a criterion time. The movement time was variable from trial-to-trial, as expected from previous studies. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement/reward time on single trials. Steeply rising signals preceded early lick-initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movements. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of movement initiation, whereas inhibition caused late-shifting, as if modulating the probability of movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation on single trials. We propose that ramping dopaminergic signals, likely encoding dynamic reward expectation, can modulate the decision of when to move.

Even well-practiced movements benefit from repetition

Professional golf players spend years practicing, but will still perform one or two practice swings without a ball before executing the actual swing. Why do they do this? In this study we tested the hypothesis that repeating a well-practiced movement leads to a reduction of movement variability. To operationalize this hypothesis, participants were tested in a center-out reaching task with four different targets, on four different days. To probe the effect of repetition they performed random sequences from one to six movements to the same target. Our findings show that, with repetition, movements are not only initiated earlier but their variability is reduced across the entire movement trajectory. Furthermore, this effect is present within and across the four sessions. Together, our results suggest that movement repetition changes the tradeoff between movement initiation and movement precision.

Kinetic Monte Carlo method applied to micrometric particle detachment mechanisms by aerodynamic forces

The formulation of a Kinetic Monte Carlo simulation to account for the different possible mechanisms present in the problem of resuspension of aerosol particles is addressed as an extension of a former model [1]. The re-entrainment of micrometer particles to airflow when detached from a surface by aerodynamic forces is modeled using the similitude of the problem with the desorption process from heterogeneous surfaces. Depending on the relative role of the intervening forces, three main mechanisms for movement initiation can be present: rolling, sliding and lifting-off. Three different transition probabilities are defined for each mechanism and the corresponding transition rates calculated for the kinetic process to be simulated. The decisive factor for the development of the model is to set an appropriate dynamical hierarchy to simulate correctly the evolution of the transition rates as the airflow velocity increases, reflecting the stochastic nature of the process, not always fully captured by other Monte Carlo approaches. The model is applied to spherical and elongated particles on a flat surface, reproducing qualitatively well the experimental trends found by other authors for the case of particles with different shapes. It is also demonstrated that, for elongated particles, the main mechanism assisting the detachment is not rolling but sliding, underscoring the need for an adequate choice of the particles shape and detachment mechanism when looking for the critical conditions for particle removal from surfaces.

Dissociating the Impact of Movement Time and Energy Costs on Decision-Making and Action Initiation in Humans

Recent theories and data suggest that adapted behavior involves economic computations during which multiple trade-offs between reward value, accuracy requirement, energy expenditure, and elapsing time are solved so as to obtain rewards as soon as possible while spending the least possible amount of energy. However, the relative impact of movement energy and duration costs on perceptual decision-making and movement initiation is poorly understood. Here, we tested 31 healthy subjects on a perceptual decision-making task in which they executed reaching movements to report probabilistic choices. In distinct blocks of trials, the reaching duration (“Time” condition) and energy (“Effort” condition) costs were independently varied compared to a “Reference” block, while decision difficulty was maintained similar at the block level. Participants also performed a simple delayed-reaching (DR) task aimed at estimating movement initiation duration in each motor condition. Results in that DR task show that long duration movements extended reaction times (RTs) in most subjects, whereas energy-consuming movements led to mixed effects on RTs. In the decision task, about half of the subjects decreased their decision durations (DDs) in the Time condition, while the impact of energy on DDs were again mixed across subjects. Decision accuracy was overall similar across motor conditions. These results indicate that movement duration and, to a lesser extent, energy expenditure, idiosyncratically affect perceptual decision-making and action initiation. We propose that subjects who shortened their choices in the time-consuming condition of the decision task did so to limit a drop of reward rate.

Action planning and control under uncertainty emerge through a desirability-driven competition between parallel encoding motor plans

Living in an uncertain world, nearly all of our decisions are made with some degree of uncertainty about the consequences of actions selected. Although a significant progress has been made in understanding how the sensorimotor system incorporates uncertainty into the decision-making process, the preponderance of studies focus on tasks in which selection and action are two separate processes. First people select among alternative options and then initiate an action to implement the choice. However, we often make decisions during ongoing actions in which the value and availability of the alternatives can change with time and previous actions. The current study aims to decipher how the brain deals with uncertainty in decisions that evolve while acting. To address this question, we trained individuals to perform rapid reaching movements towards two potential targets, where the true target location was revealed only after the movement initiation. We found that reaction time and initial approach direction are correlated, where initial movements towards intermediate locations have longer reaction times than movements that aim directly to the target locations. Interestingly, the association between reaction time and approach direction was independent of the target probability. By modeling the task within a recently proposed neurodynamical framework, we showed that action planning and control under uncertainty emerge through a desirability-driven competition between motor plans that are encoded in parallel.

Functional coupling between target selection and acquisition in the superior colliculus

Survival in unpredictable environments requires that animals continuously evaluate their surroundings for behavioral targets, direct their movements towards those targets, and terminate movements once a target is reached. The ability to select, move toward, and acquire spatial targets depends on a network of brain regions, but it remains unknown how these goal-directed processes are linked by neural circuits. Within this network, common circuits in the midbrain superior colliculus (SC) mediate the selection of, and initiation of movements to, spatial targets. However, SC activity often persists throughout movement, suggesting that the same SC circuits underlying target selection and movement initiation may also contribute to target acquisition: stopping the movement at the selected target. Here, we examine the hypothesis that SC functional circuitry couples target selection and acquisition using a default motor plan generated by selection-related neuronal activity. Recordings from intermediate and deep layer SC neurons in mice performing a spatial choice task demonstrate that choice-predictive neurons, including optogenetically identified GABAergic neurons whose activity mediates target selection, exhibit increased activity during movement to the target. By recording from rostral and caudal SC in separate groups of mice, we also revealed higher activity in rostral than caudal neurons during target acquisition. Finally, we used an attractor model to examine how, invoking only SC circuitry, caudal SC activity related to selecting an eccentric target could generate higher rostral than caudal acquisition-related activity. Overall, our results suggest a functional coupling between SC circuits for target selection and acquisition, elucidating a key mechanism for goal-directed behavior.

First evidence of yawn contagion in a wild monkey species

Yawn contagion occurs when individuals yawn in response to the yawn of others (triggers). This is the first account of yawn contagion in wild geladas (Theropithecus gelada), a monkey species that shows yawn contagion in captivity and is organized in core units (one-male/bachelor groups) forming multilevel associations. In a population of geladas from the Kundi plateau (Ethiopia) we found that the yawning response was highest when geladas could perceive a triggering yawn, which confirms that yawn contagion is present in the wild. Yawn duration, mouth-opening degree and presence/absence of vocalisation (possibly modulating yawn detectability) did not affect the likelihood of contagion. Males and females, known to be both implicated in movement initiation within groups, were similarly powerful as yawn triggers. Instead, group membership and responder sex had a significant role in shaping the phenomenon. Yawn contagion was highest between individuals belonging to different core units and males were most likely to respond to others’ yawns. Because males have a non-negligible role in inter-group coordination, our results suggest that yawn contagion may have a communicative function that goes beyond the basic unit level.

Investigating facilitatory versus inhibitory effects of dynamic social and non-social cues on attention in a realistic space

This study aimed to investigate the facilitatory versus inhibitory effects of dynamic non-predictive central cues presented in a realistic environment. Realistic human-avatars initiated eye contact and then dynamically looked to the left, right or centre of a table. A moving stick served as a non-social control cue and participants localised (Experiment 1) or discriminated (Experiment 2) a contextually relevant target (teapot/teacup). The cues movement took 500 ms and stimulus onset asynchronies (SOA, 150 ms/300 ms/500 ms/1000 ms) were measured from movement initiation. Similar cuing effects were seen for the social avatar and non-social stick cue across tasks. Results showed facilitatory processes without inhibition, though there was some variation by SOA and task. This is the first time facilitatory versus inhibitory processes have been directly investigated where eye contact is initiated prior to gaze shift. These dynamic stimuli allow a better understanding of how attention might be cued in more realistic environments.

Cell-Type Specific Responses to Associative Learning in the Primary Motor Cortex

The primary motor cortex (M1) is known to be a critical site for movement initiation and motor learning. Surprisingly, it has also been shown to possess reward-related activity, presumably to facilitate reward-based learning of new movements. However, whether reward-related signals are represented among different cell types in M1, and whether their response properties change after cue-reward conditioning remains unclear. Here, we performed longitudinal in vivo two-photon Ca2+ imaging to monitor the activity of different neuronal cell types in M1 while mice engaged in a classical conditioning task. Our results demonstrate that most of the major neuronal cell types in M1 showed robust but differential responses to both cue and reward stimuli, and their response properties undergo cell-type specific modifications after associative learning. PV-INs' responses became more reliable to the cue stimulus, while VIP-INs' responses became more reliable to the reward stimulus. PNs only showed robust response to the novel reward stimulus, and they habituated to it after associative learning. Lastly, SOM-IN responses emerged and became more reliable to both conditioned cue and reward stimuli after conditioning. These observations suggest that cue- and reward-related signals are represented among different neuronal cell types in M1, and the distinct modifications they undergo during associative learning could be essential in triggering different aspects of local circuit reorganization in M1 during reward-based motor skill learning.

Cell specific photoswitchable agonist for reversible control of endogenous dopamine receptors

Dopamine controls diverse behaviors and their dysregulation contributes to many disorders. Our ability to understand and manipulate the function of dopamine is limited by the heterogenous nature of dopaminergic projections, the diversity of neurons that are regulated by dopamine, the varying distribution of the five dopamine receptors (DARs), and the complex dynamics of dopamine release. In order to improve our ability to specifically modulate distinct DARs, here we develop a photo-pharmacological strategy using a Membrane anchored Photoswitchable orthogonal remotely tethered agonist for the Dopamine receptor (MP-D). Our design selectively targets D1R/D5R receptor subtypes, most potently D1R (MP-D1ago), as shown in HEK293T cells. In vivo, we targeted dorsal striatal medium spiny neurons where the photo-activation of MP-D1ago increased movement initiation, although further work is required to assess the effects of MP-D1ago on neuronal function. Our method combines ligand and cell type-specificity with temporally precise and reversible activation of D1R to control specific aspects of movement. Our results provide a template for analyzing dopamine receptors.