Primate memory, from simple associations to abstract concepts.

The hippocampus is a neural structure central to the formation of memories and wayfinding. To understand the neural mechanisms at work during memory formation over multiple episodes, Electrophysiological recordings show that neurons in the macaque hippocampus encode complex conjunctions of traits relevant to the navigational task during virtual navigation. While a majority encode environment-specific cues, about one third exhibit correlated firing across different environments sharing the same spatial structure. The similarity of firing appeared to encode the logic of the task in a way akin to a schema. The existence of the schema cells offers a foundation for abstraction in the monkey and suggests that memory storage in the primate could proceed in a similar way from simple cue associations up to conceptual thinking.

L'hippocampe est une structure neuronale essentielle à la formation des souvenirs et à l'orientation spatiale. Afin de comprendre les mécanismes neuronaux qui sous-tendent la mémorisation au cours d'expériences multiples, nous avons réalisé des enregistrements électrophysiologiques dans l'hippocampe du macaque, alors que les animaux se prêtaient à une série de tâches de navigation virtuelle. Nos résultats montrent que les neurones encodent des conjonctions complexes d'éléments pertinents pour la navigation, liées aux repères visuels, la position du singe et aux actions à venir. Si la majorité des neurones encodent une information spécifique à chaque environnement, environ un tiers d'entre eux présentent une activité corrélée dans des environnements différents qui partagent la même structure spatiale : ces cellules semblent coder la logique d'organisation de l'environnement et plus généralement, de la tâche, indépendamment des détails propres à chaque environnement, d'une manière proche d'un schéma mental. Ces cellules de schéma pourraient être un fondement de l'abstraction chez le singe et leur existence suggère un mécanisme relationnel général pour le stockage de la mémoire chez le primate, depuis de simples associations de repères spatiaux jusqu'à une pensée conceptuelle.

Gaze-informed, task-situated representation of space in primate hippocampus during virtual navigation.

To elucidate how gaze informs the construction of mental space during wayfinding in visual species like primates, we jointly examined navigation behavior, visual exploration, and hippocampal activity as macaque monkeys searched a virtual reality maze for a reward. Cells sensitive to place also responded to one or more variables like head direction, point of gaze, or task context. Many cells fired at the sight (and in anticipation) of a single landmark in a viewpoint- or task-dependent manner, simultaneously encoding the animal's logical situation within a set of actions leading to the goal. Overall, hippocampal activity was best fit by a fine-grained state space comprising current position, view, and action contexts. Our findings indicate that counterparts of rodent place cells in primates embody multidimensional, task-situated knowledge pertaining to the target of gaze, therein supporting self-awareness in the construction of space.

Direct Two-Dimensional Access to the Spatial Location of Covert Attention in Macaque Prefrontal Cortex.

Direct access to motor cortical information now enables tetraplegic patients to precisely control neuroprostheses and recover some autonomy. In contrast, explicit access to higher cortical cognitive functions, such as covert attention, has been missing. Indeed, this cognitive information, known only to the subject, can solely be inferred by an observer from the subject's overt behavior. Here, we present direct two-dimensional real-time access to where monkeys are covertly paying attention, using machine-learning decoding methods applied to their ongoing prefrontal cortical activity. Decoded attention was highly predictive of overt behavior in a cued target-detection task. Indeed, monkeys had a higher probability of detecting a visual stimulus as the distance between decoded attention and stimulus location decreased. This was true whether the visual stimulus was presented at the cued target location or at another distractor location. In error trials, in which the animals failed to detect the cued target stimulus, both the locations of attention and visual cue were misencoded. This misencoding coincided with a specific state of the prefrontal cortical population in which the shared variability between its different neurons (or noise correlations) was high, even before trial onset. This observation strongly suggests a functional link between high noise-correlation states and attentional failure. Overall, this real-time access to the attentional spotlight, as well as the identification of a neural signature of attentional lapses, open new perspectives both to the study of the neural bases of attention and to the remediation or enhancement of the attentional function using neurofeedback.

Slowness in Movement Initiation is Associated with Proactive Inhibitory Network Dysfunction in Parkinson's Disease.

BACKGROUND: Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. OBJECTIVE: Testing this hypothesis on the basis of direct neural-based evidence. METHODS: Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. RESULTS: For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients with regard to controls was associated with pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). CONCLUSIONS: These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia.

Neural representations of ethologically relevant hand/mouth synergies in the human precentral gyrus.

Complex motor responses are often thought to result from the combination of elemental movements represented at different neural sites. However, in monkeys, evidence indicates that some behaviors with critical ethological value, such as self-feeding, are represented as motor primitives in the precentral gyrus (PrG). In humans, such primitives have not yet been described. This could reflect well-known interspecies differences in the organization of sensorimotor regions (including PrG) or the difficulty of identifying complex neural representations in peroperative settings. To settle this alternative, we focused on the neural bases of hand/mouth synergies, a prominent example of human behavior with high ethological value. By recording motor- and somatosensory-evoked potentials in the PrG of patients undergoing brain surgery (2-60 y), we show that two complex nested neural representations can mediate hand/mouth actions within this structure: (i) a motor representation, resembling self-feeding, where electrical stimulation causes the closing hand to approach the opening mouth, and (ii) a motor-sensory representation, likely associated with perioral exploration, where cross-signal integration is accomplished at a cortical site that generates hand/arm actions while receiving mouth sensory inputs. The first finding extends to humans' previous observations in monkeys. The second provides evidence that complex neural representations also exist for perioral exploration, a finely tuned skill requiring the combination of motor and sensory signals within a common control loop. These representations likely underlie the ability of human children and newborns to accurately produce coordinated hand/mouth movements, in an otherwise general context of motor immaturity.

Comparison of classifiers for decoding sensory and cognitive information from prefrontal neuronal populations.

Decoding neuronal information is important in neuroscience, both as a basic means to understand how neuronal activity is related to cerebral function and as a processing stage in driving neuroprosthetic effectors. Here, we compare the readout performance of six commonly used classifiers at decoding two different variables encoded by the spiking activity of the non-human primate frontal eye fields (FEF): the spatial position of a visual cue, and the instructed orientation of the animal's attention. While the first variable is exogenously driven by the environment, the second variable corresponds to the interpretation of the instruction conveyed by the cue; it is endogenously driven and corresponds to the output of internal cognitive operations performed on the visual attributes of the cue. These two variables were decoded using either a regularized optimal linear estimator in its explicit formulation, an optimal linear artificial neural network estimator, a non-linear artificial neural network estimator, a non-linear naïve Bayesian estimator, a non-linear Reservoir recurrent network classifier or a non-linear Support Vector Machine classifier. Our results suggest that endogenous information such as the orientation of attention can be decoded from the FEF with the same accuracy as exogenous visual information. All classifiers did not behave equally in the face of population size and heterogeneity, the available training and testing trials, the subject's behavior and the temporal structure of the variable of interest. In most situations, the regularized optimal linear estimator and the non-linear Support Vector Machine classifiers outperformed the other tested decoders.

A common optimization principle for motor execution in healthy subjects and parkinsonian patients.

Recent research on Parkinson's disease (PD) has emphasized that parkinsonian movement, although bradykinetic, shares many attributes with healthy behavior. This observation led to the suggestion that bradykinesia in PD could be due to a reduction in motor motivation. This hypothesis can be tested in the framework of optimal control theory, which accounts for many characteristics of healthy human movement while providing a link between the motor behavior and a cost/benefit trade-off. This approach offers the opportunity to interpret movement deficits of PD patients in the light of a computational theory of normal motor control. We studied 14 PD patients with bilateral subthalamic nucleus (STN) stimulation and 16 age-matched healthy controls, and tested whether reaching movements were governed by similar rules in these two groups. A single optimal control model accounted for the reaching movements of healthy subjects and PD patients, whatever the condition of STN stimulation (on or off). The choice of movement speed was explained in all subjects by the existence of a preset dynamic range for the motor signals. This range was idiosyncratic and applied to all movements regardless of their amplitude. In PD patients this dynamic range was abnormally narrow and correlated with bradykinesia. STN stimulation reduced bradykinesia and widened this range in all patients, but did not restore it to a normal value. These results, consistent with the motor motivation hypothesis, suggest that constrained optimization of motor effort is the main determinant of movement planning (choice of speed) and movement production, in both healthy and PD subjects.

When one size does not fit all: a simple statistical method to deal with across-individual variations of effects.

In science, it is a common experience to discover that although the investigated effect is very clear in some individuals, statistical tests are not significant because the effect is null or even opposite in other individuals. Indeed, t-tests, Anovas and linear regressions compare the average effect with respect to its inter-individual variability, so that they can fail to evidence a factor that has a high effect in many individuals (with respect to the intra-individual variability). In such paradoxical situations, statistical tools are at odds with the researcher's aim to uncover any factor that affects individual behavior, and not only those with stereotypical effects. In order to go beyond the reductive and sometimes illusory description of the average behavior, we propose a simple statistical method: applying a Kolmogorov-Smirnov test to assess whether the distribution of p-values provided by individual tests is significantly biased towards zero. Using Monte-Carlo studies, we assess the power of this two-step procedure with respect to RM Anova and multilevel mixed-effect analyses, and probe its robustness when individual data violate the assumption of normality and homoscedasticity. We find that the method is powerful and robust even with small sample sizes for which multilevel methods reach their limits. In contrast to existing methods for combining p-values, the Kolmogorov-Smirnov test has unique resistance to outlier individuals: it cannot yield significance based on a high effect in one or two exceptional individuals, which allows drawing valid population inferences. The simplicity and ease of use of our method facilitates the identification of factors that would otherwise be overlooked because they affect individual behavior in significant but variable ways, and its power and reliability with small sample sizes (<30-50 individuals) suggest it as a tool of choice in exploratory studies.

Optimal and suboptimal use of postsaccadic vision in sequences of saccades.

Saccades are imprecise, due to sensory and motor noise. To avoid an accumulation of errors during sequences of saccades, a prediction derived from the efference copy can be combined with the reafferent visual feedback to adjust the following eye movement. By varying the information quantity of the visual feedback, we investigated how the reliability of the visual information affects the postsaccadic update in humans. Two elements of the visual scene were manipulated, the saccade target or the background, presented either together or in isolation. We determined the weight of the postsaccadic visual information by measuring the effect of intrasaccadic visual shifts on the following saccade. We confirmed that the weight of visual information evolves with information quantity as predicted for a statistically optimal system. In particular, we found that the visual background alone can guide the postsaccadic update, and that information from target and background are optimally combined. Moreover, these visual weights are adjusted dynamically and on a trial-to-trial basis to the level of visual noise determined by target eccentricity and reaction time. In contrast, we uncovered a dissociation between the visual signals used to update the next planned saccade (main saccade) and those used to generate an involuntary corrective saccade. The latter was exclusively based on visual information about the target, and discarded all information about the background: a suboptimal use of visual evidence.

What are they up to? The role of sensory evidence and prior knowledge in action understanding.

Explaining or predicting the behaviour of our conspecifics requires the ability to infer the intentions that motivate it. Such inferences are assumed to rely on two types of information: (1) the sensory information conveyed by movement kinematics and (2) the observer's prior expectations--acquired from past experience or derived from prior knowledge. However, the respective contribution of these two sources of information is still controversial. This controversy stems in part from the fact that "intention" is an umbrella term that may embrace various sub-types each being assigned different scopes and targets. We hypothesized that variations in the scope and target of intentions may account for variations in the contribution of visual kinematics and prior knowledge to the intention inference process. To test this hypothesis, we conducted four behavioural experiments in which participants were instructed to identify different types of intention: basic intentions (i.e. simple goal of a motor act), superordinate intentions (i.e. general goal of a sequence of motor acts), or social intentions (i.e. intentions accomplished in a context of reciprocal interaction). For each of the above-mentioned intentions, we varied (1) the amount of visual information available from the action scene and (2) participant's prior expectations concerning the intention that was more likely to be accomplished. First, we showed that intentional judgments depend on a consistent interaction between visual information and participant's prior expectations. Moreover, we demonstrated that this interaction varied according to the type of intention to be inferred, with participant's priors rather than perceptual evidence exerting a greater effect on the inference of social and superordinate intentions. The results are discussed by appealing to the specific properties of each type of intention considered and further interpreted in the light of a hierarchical model of action representation.

Proximodistal gradient in the perception of delayed stiffness.

Proximal and distal muscles are different in size, maximum force, mechanical action, and neuromuscular control. In the current study we explore the perception of delayed stiffness when probing is executed using movement of different joints. We found a proximodistal gradient in the amount of underestimation of delayed stiffness in the transition between probing with shoulder, elbow, and wrist joints. Moreover, there was a similar gradient in the optimal weighting between estimation of stiffness and the inverse of estimation of compliance that predicted the perception of the subjects. These gradients could not be ascribed to differences in movement amplitude, duration, velocity, and force amplitude because these variables were not significantly modulated by the joint used for probing. Mean force did not follow a similar gradient either. Therefore we suggest that the observed gradient in perception reveals a proximodistal gradient in control, such that proximal joints are dominated by force control, whereas distal joints are dominated by position control.

Computational motor control: feedback and accuracy.

Speed/accuracy trade-off is a ubiquitous phenomenon in motor behaviour, which has been ascribed to the presence of signal-dependent noise (SDN) in motor commands. Although this explanation can provide a quantitative account of many aspects of motor variability, including Fitts' law, the fact that this law is frequently violated, e.g. during the acquisition of new motor skills, remains unexplained. Here, we describe a principled approach to the influence of noise on motor behaviour, in which motor variability results from the interplay between sensory and motor execution noises in an optimal feedback-controlled system. In this framework, we first show that Fitts' law arises due to signal-dependent motor noise (SDN(m)) when sensory (proprioceptive) noise is low, e.g. under visual feedback. Then we show that the terminal variability of non-visually guided movement can be explained by the presence of signal-dependent proprioceptive noise. Finally, we show that movement accuracy can be controlled by opposite changes in signal-dependent sensory (SDN(s)) and SDN(m), a phenomenon that could be ascribed to muscular co-contraction. As the model also explains kinematics, kinetics, muscular and neural characteristics of reaching movements, it provides a unified framework to address motor variability.

Optimality, stochasticity, and variability in motor behavior.

Recent theories of motor control have proposed that the nervous system acts as a stochastically optimal controller, i.e. it plans and executes motor behaviors taking into account the nature and statistics of noise. Detrimental effects of noise are converted into a principled way of controlling movements. Attractive aspects of such theories are their ability to explain not only characteristic features of single motor acts, but also statistical properties of repeated actions. Here, we present a critical analysis of stochastic optimality in motor control which reveals several difficulties with this hypothesis. We show that stochastic control may not be necessary to explain the stochastic nature of motor behavior, and we propose an alternative framework, based on the action of a deterministic controller coupled with an optimal state estimator, which relieves drawbacks of stochastic optimality and appropriately explains movement variability.

Saccadic adaptation without retinal postsaccadic error.

Primary saccades undershoot their target. Corrective saccades are then triggered by retinal postsaccadic information. We tested whether primary saccades still undershoot when no postsaccadic visual information is available. Participants saccaded to five targets (10-34 degrees) that were either constantly illuminated (ON) or extinguished at saccade onset (OFF(Onset)). In OFF(Onset), few corrective saccades were observed. The saccadic gain increased over trials for the furthest (34 degrees) target. Terminal eye position after glissades or microsaccades progressively converged to the values observed in ON (targets over 16 degrees). Target extinction during the saccade only did not elicit any change. The results show that (i) postsaccadic retinal signals stabilize the saccadic gain and (ii) adaptive changes that reduce terminal error can take place without visual information.

Coding of movement- and force-related information in primate primary motor cortex: a computational approach.

Coordinated movements result from descending commands transmitted by central motor systems to the muscles. Although the resulting effect of the commands has the dimension of a muscular force, it is unclear whether the information transmitted by the commands concerns movement kinematics (e.g. position, velocity) or movement dynamics (e.g. force, torque). To address this issue, we used an optimal control model of movement production that calculates inputs to motoneurons that are appropriate to drive an articulated limb toward a goal. The model quantitatively accounted for kinematic, kinetic and muscular properties of planar, shoulder/elbow arm-reaching movements of monkeys, and reproduced detailed features of neuronal correlates of these movements in primate motor cortex. The model also reproduced qualitative spatio-temporal characteristics of movement- and force-related single neuron discharges in non-planar reaching and isometric force production tasks. The results suggest that the nervous system of the primate controls movements through a muscle-based controller that could be located in the motor cortex.

Functional anatomy of motor urgency.

This PET H(2)(15)O study uses a reaching task to determine the neural basis of the unconscious motor speed up observed in the context of urgency in healthy subjects. Three conditions were considered: self-initiated (produce the fastest possible movement toward a large plate, when ready), externally-cued (same as self-initiated but in response to an acoustic cue) and temporally-pressing (same as externally-cued with the plate controlling an electromagnet that prevented a rolling ball from falling at the bottom of a tilted ramp). Results show that: (1) Urgent responses (Temporally-pressing versus Externally-cued) engage the left parasagittal and lateral cerebellar hemisphere and the sensorimotor cortex (SMC) bilaterally; (2) Externally-driven responses (Externally-cued versus Self-initiated) recruit executive areas within the contralateral SMC; (3) Volitional responses (Self-initiated versus Externally-cued) involve prefrontal cortical areas. These observations are discussed with respect to the idea that neuromuscular energy is set to a submaximal threshold in self-determined situations. In more challenging tasks, this threshold is raised and the first answer of the nervous system is to optimize the response of the lateral (i.e. crossed) corticospinal tract (contralateral SMC) and ipsilateral cerebellum. In a second step, the anterior (i.e. uncrossed) corticospinal tract (ipsilateral SMC) and the contralateral cerebellum are recruited. This recruitment is akin to the strategy observed during recovery in patients with brain lesions.

Computational motor control: redundancy and invariance.

The nervous system controls the behavior of complex kinematically redundant biomechanical systems. How it computes appropriate commands to generate movements is unknown. Here we propose a model based on the assumption that the nervous system: 1) processes static (e.g., gravitational) and dynamic (e.g., inertial) forces separately; 2) calculates appropriate dynamic controls to master the dynamic forces and progress toward the goal according to principles of optimal feedback control; 3) uses the size of the dynamic commands (effort) as an optimality criterion; and 4) can specify movement duration from a given level of effort. The model was used to control kinematic chains with 2, 4, and 7 degrees of freedom [planar shoulder/elbow, three-dimensional (3D) shoulder/elbow, 3D shoulder/elbow/wrist] actuated by pairs of antagonist muscles. The muscles were modeled as second-order nonlinear filters and received the dynamics commands as inputs. Simulations showed that the model can quantitatively reproduce characteristic features of pointing and grasping movements in 3D space, i.e., trajectory, velocity profile, and final posture. Furthermore, it accounted for amplitude/duration scaling and kinematic invariance for distance and load. These results suggest that motor control could be explained in terms of a limited set of computational principles.

"Paradoxical kinesis" is not a hallmark of Parkinson's disease but a general property of the motor system.

Although slowness of movement is a typical feature of Parkinson's disease (PD), it has been suggested that severely disabled patients remained able to produce normal motor responses in the context of urgent or externally driven situations. To investigate this phenomenon (often designated "paradoxical kinesis"), we required PD patients and healthy subjects to press a large switch under three main conditions: Self Generated, produce the fastest possible movement; External Cue, same as Self Generated but in response to an acoustic cue; Urgent External Cue, same as External Cue with the switch controlling an electromagnet that prevented a ball falling at the bottom of a tilted ramp. Task difficulty was equalized for the two experimental groups. Results showed that external cues and urgent conditions decreased movement duration (Urgent External Cue < External Cue < Self Generated) and reaction time (Urgent External Cue < External Cue). The amount of reduction was identical in PD patients and healthy subjects. These observations show that paradoxical kineses are not a hallmark of PD or a byproduct of basal ganglia dysfunctions, but a general property of the motor system.

Consolidation of dynamic motor learning is not disrupted by rTMS of primary motor cortex.

Motor skills, once learned, are often retained over a long period of time. However, such learning first undergoes a period of consolidation after practice. During this time, the motor memory is susceptible to being disrupted by the performance of another motor-learning task. Recently, it was shown that repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex could disrupt the retention of a newly learned ballistic task in which subjects had to oppose their index finger and thumb as rapidly as possible. Here we investigate whether the motor cortex is similarly involved during the consolidation that follows learning novel dynamics. We applied rTMS to primary motor cortex shortly after subjects had either learned to compensate for a dynamic force field applied to their index finger or learned a ballistic finger abduction task. rTMS severely degraded the retention of the learning for the ballistic task but had no effect on retention of the dynamic force-field learning. This suggests that, unlike learning of simple ballistic skills, learning of dynamics may be stored in a more distributed manner, possibly outside the primary motor cortex.