The involvement of the fronto-parietal brain network in oculomotor sequence learning using fMRI.

The basis of motor learning involves decomposing complete actions into a series of predictive individual components that form the whole. The present fMRI study investigated the areas of the human brain important for oculomotor short-term learning, by using a novel sequence learning paradigm that is equivalent in visual and temporal properties for both saccades and pursuit, enabling more direct comparisons between the oculomotor subsystems. In contrast with previous studies that have implemented a series of discrete ramps to observe predictive behaviour as evidence for learning, we presented a continuous sequence of interlinked components that better represents sequences of actions. We implemented both a classic univariate fMRI analysis, followed by a further multivariate pattern analysis (MVPA) within a priori regions of interest, to investigate oculomotor sequence learning in the brain and to determine whether these mechanisms overlap in pursuit and saccades as part of a higher order learning network. This study has uniquely identified an equivalent frontal-parietal network (dorsolateral prefrontal cortex, frontal eye fields and posterior parietal cortex) in both saccades and pursuit sequence learning. In addition, this is the first study to investigate oculomotor sequence learning during fMRI brain imaging, and makes significant contributions to understanding the role of the dorsal networks in motor learning

Saccades oculaires, adaptation sensori-motrice et attention visuo-spatiale

The interaction of human beings with their static or dynamic environment requires detailed and precise exploration of objects. For this, our oculomotor system produces fast and accurate eye movements called "saccades" to bring the image of objects of interest on the small central area of the retina (fovea). However, our oculomotor system is frequently exposed to physiological or pathological disturbances. These changes are continuously monitored by sensorimotor processes based on neuronal plasticity and called "saccadic adaptation". The aim of my thesis is to better understand the characteristics of this adaptation and its long-term retention but also the neural networks involved in saccadic adaptation. As saccadic eye movements are closely related to visuo-spatial attention our work has also addressed the interactions that may exist with the networks involved in the control of visuo-spatial attention. A major result revealed that the orientation of the 'covert' exogenous attention -without moving the eyes- in detection and discrimination tasks is improved after adaptation of reactive saccades. These basic data could give rise to the development of new rehabilitation methods in visual-attention deficitsL'interaction des individus avec l'environnement statique ou dynamique nécessite une exploration détaillée et précise des objets. Pour cela, notre système oculomoteur produit des mouvements oculaires rapides et précis appelés « saccades » afin de ramener l’image des objets d’intérêt sur la petite zone centrale de notre rétine (fovéa). Toutefois, notre système oculomoteur est fréquemment exposé à des perturbations physiologiques ou pathologiques. Ces changements sont contrôlés en permanence par des processus sensori moteurs basés sur la plasticité neuronale et appelés adaptation saccadique. L’objectif de mes travaux de thèse est de mieux comprendre les caractéristiques de cette adaptation et sa rétention à long terme mais aussi les réseaux impliqués dans l’adaptation saccadique. Comme les saccades oculaires ont un lien étroit avec l’attention visuo-spatiale, notre intérêt s’est également porté sur les interactions qui peuvent exister avec les réseaux impliqués dans le contrôle de l’attention visuo-spatiale. Un des principaux résultats est que l’orientation de l’attention exogène covert -sans bouger les yeuxdans des taches de détection et de discrimination est améliorée après l’adaptation des saccades réactives. Ces données fondamentales pourraient mener au développement de nouvelles méthodes de rééducation des déficits visuo-attentionnel

How Laminar Frontal Cortex and Basal Ganglia Circuits Interact to Control Planned and Reactive Saccades

The basal ganglia and frontal cortex together allow animals to learn adaptive responses that acquire rewards when prepotent reflexive responses are insufficient. Anatomical studies show a rich pattern of interactions between the basal ganglia and distinct frontal cortical layers. Analysis of the laminar circuitry of the frontal cortex, together with its interactions with the basal ganglia, motor thalamus, superior colliculus, and inferotemporal and parietal cortices, provides new insight into how these brain regions interact to learn and perform complexly conditioned behaviors. A neural model whose cortical component represents the frontal eye fields captures these interacting circuits. Simulations of the neural model illustrate how it provides a functional explanation of the dynamics of 17 physiologically identified cell types found in these areas. The model predicts how action planning or priming (in cortical layers III and VI) is dissociated from execution (in layer V), how a cue may serve either as a movement target or as a discriminative cue to move elsewhere, and how the basal ganglia help choose among competing actions. The model simulates neurophysiological, anatomical, and behavioral data about how monkeys perform saccadic eye movement tasks, including fixation; single saccade, overlap, gap, and memory-guided saccades; anti-saccades; and parallel search among distractors.Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-l-0409, N00014-92-J-1309, N00014-95-1-0657); National Science Foundation (IRI-97-20333)

The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders

The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD

Investigating the effects of psychosocial stress on cerebellar function

Differences in cerebellar structure and function are consistently reported in individuals exposed to early-life stress and individuals with diagnosed stress-related psychopathology. Despite this, current neurobiological models of stress have not considered the role of the cerebellum in the regulation of the stress response. Furthermore, it is unclear the mechanism by which stress may affect cerebellar function. The studies presented in this thesis set out to address these questions by exploring the relationship between acute psychosocial stress and the cerebellum. To achieve this, two putative cerebellar functions were investigated: saccadic adaptation and postural balance control. Chapters 4 and 5 present two studies, which evaluated the effectiveness of each task, as well as individual differences in task performance. Chapter 4 presents evidence demonstrating a linear effect of saccadic adaptation across participants. Chapter 5 revealed improved postural balance control under perturbed balancing conditions. Individual differences in task performance were inconclusive. Each study was followed by an investigation on the effects of acute psychosocial stress on task performance. Particularly, Chapter 6 demonstrated that stress impaired the rate of saccadic adaptation, and that this impairment was associated with the stress-related endocrine response. The study presented in Chapter 7 showed no effect of psychosocial stress on postural balance control. Finally, Chapter 8 explored the effects of non-invasive cerebellar stimulation on saccadic adaptation and cortisol output, revealing that a decrease in cerebellar excitability yielded adaptation rates that were similar to those observed after stress. These findings suggest that psychosocial stress impairs error-driven feedforward computations specifically, via glucocorticoid signalling, thus contributing to the current neurobiological models of stress

Linking brain and behaviour in motor sequence learning tasks

Sequence learning is a fundamental brain function that allows for the acquisition of a wide range of skills. Unlearned movements become faster and more accurate with repetition, due to a process called prediction. Predictive behaviour observed in the eye and hand compensates for the inherent temporal delays in the sensorimotor system and allows for the generation of motor actions prior to visual guidance. We investigated predictive behaviour and the brain areas associated with this processing in (i) the oculomotor system (Eye Only (EO): saccade vs. pursuit) and (ii) during eye and hand coordination (EH). Participants were asked to track a continuous moving target in predictable or random sequence conditions. EO and EH experiments were divided into 1) EO behavioural and 2) EO fMRI findings, and 3) EH behavioural and 4) EH fMRI findings. Results provide new insights into how individuals predict when learning a sequence of target movements, which is not limited to short--‐term memory capacities and that forms a link between shorter and longer--‐term motor skill learning. Furthermore, brain imaging results revealed distinct levels of activation within and between brain areas for repeated and randomized sequences that reflect the distinct timing threshold and adaptation levels needed for the two oculomotor systems. EH results revealed similar predictive behaviour in the eye and the hand, but also demonstrated enhanced coupling between the two motor systems during sequence learning. EH brain imaging findings have provided novel insights into the brain areas involved in coordination, and those areas more associated with sequence learning. Results show evidence of common predictive networks used for the eye and hand during learning