Muriel Panouillères

Sensorimotor adaptation of saccadic eye movements.

Sensory-motor adaptation mechanisms play a pivotal role in maintaining the performance of goal-directed movements. The saccadic system, used to explore the visual environment through fast and accurate shifts of the eyes (saccades), is a valuable model for studying adaptation mechanisms. Significant progresses have been recently made in identifying the properties and neural substrates of saccadic adaptation elicited by the double-step target paradigm. Behavioural data collected in healthy and brain-damaged subjects, and neurophysiological data from non human primates, will be reviewed in an attempt to build a coherent picture of saccadic adaptation mechanisms. Emphasis will further be put on the contextual factors of saccadic adaptation, and on the link between adaptive changes of oculomotor commands and visual perception. It will be shown that saccadic adaptation relies on multiple mechanisms according to experimental contexts, time-scales, saccade categories, and direction of adaptive changes of saccade amplitude (shortening versus lengthening). Taking into account this complexity will be a key toward a comprehensive understanding of the physiopathology of saccadic adaptation and toward the development of possible rehabilitation procedures.

Behavioral Evidence of Separate Adaptation Mechanisms Controlling Saccade Amplitude Lengthening and Shortening

The accuracy of saccadic eye movements is maintained over the long term by adaptation mechanisms that decrease or increase saccade amplitude. It is still unknown whether these opposite adaptive changes rely on common mechanisms. Here, a double-step target paradigm was used to adaptively decrease (backward second target step) or increase (forward step) the amplitude of reactive saccades in one direction only. To test which sensorimotor transformation stages are subjected to these adaptive changes, we measured their transfer to antisaccades in which sensory and motor vectors are spatially dissociated. In the backward adaptation condition, all subjects showed a significant amplitude decrease for adapted prosaccades and a significant transfer of adaptation to antisaccades performed in the adapted direction, but not to oppositely directed antisaccades elicited by a target jump in the adapted direction. In the forward adaptation condition, only 14 of 19 subjects showed a significant amplitude increase for prosaccades and no significant adaptation transfer to antisaccades was detected in either the adapted or nonadapted direction. These findings suggest that, whereas the level(s) of forward adaptation cannot be resolved, the mechanisms involved in backward adaptation of reactive saccades take place at a sensorimotor level downstream from the vector inversion process of antisaccades and differ markedly from those involved in forward adaptation.

Transcranial Magnetic Stimulation and Motor Plasticity in Human Lateral Cerebellum: Dual Effect on Saccadic Adaptation

The cerebellum is a key area for movement control and sensory‐motor plasticity. Its medial part is considered as the exclusive cerebellar center controlling the accuracy and adaptive calibration of saccadic eye movements. However, the contribution of other zones situated in its lateral part is unknown. We addressed this question in healthy adult volunteers by using magnetic resonance imaging (MRI)‐guided transcranial magnetic stimulation (TMS). The double‐step target paradigm was used to adaptively lengthen or shorten saccades. TMS pulses over the right hemisphere of the cerebellum were delivered at 0, 30, or 60 ms after saccade detection in separate recording sessions. The effects on saccadic adaptation were assessed relative to a fourth session where TMS was applied to Vertex as a control site. First, TMS applied upon saccade detection before the adaptation phase reduced saccade accuracy. Second, TMS applied during the adaptation phase had a dual effect on saccadic plasticity: adaptation after‐effects revealed a potentiation of the adaptive lengthening and a depression of the adaptive shortening of saccades. For the first time, we demonstrate that TMS on lateral cerebellum can influence plasticity mechanisms underlying motor performance. These findings also provide the first evidence that the human cerebellar hemispheres are involved in the control of saccade accuracy and in saccadic adaptation, with possibly different neuronal populations concerned in adaptive lengthening and shortening. Overall, these results require a reappraisal of current models of cerebellar contribution to oculomotor plasticity. Hum Brain Mapp, 2011.

Sensory Processing of Motor Inaccuracy Depends on Previously Performed Movement and on Subsequent Motor Corrections: A Study of the Saccadic System

When goal-directed movements are inaccurate, two responses are generated by the brain: a fast motor correction toward the target and an adaptive motor recalibration developing progressively across subsequent trials. For the saccadic system, there is a clear dissociation between the fast motor correction (corrective saccade production) and the adaptive motor recalibration (primary saccade modification). Error signals used to trigger corrective saccades and to induce adaptation are based on post-saccadic visual feedback. The goal of this study was to determine if similar or different error signals are involved in saccadic adaptation and in corrective saccade generation. Saccadic accuracy was experimentally altered by systematically displacing the visual target during motor execution. Post-saccadic error signals were studied by manipulating visual information in two ways. First, the duration of the displaced target after primary saccade termination was set at 15, 50, 100 or 800 ms in different adaptation sessions. Second, in some sessions, the displaced target was followed by a visual mask that interfered with visual processing. Because they rely on different mechanisms, the adaptation of reactive saccades and the adaptation of voluntary saccades were both evaluated. We found that saccadic adaptation and corrective saccade production were both affected by the manipulations of post-saccadic visual information, but in different ways. This first finding suggests that different types of error signal processing are involved in the induction of these two motor corrections. Interestingly, voluntary saccades required a longer duration of post-saccadic target presentation to reach the same amount of adaptation as reactive saccades. Finally, the visual mask interfered with the production of corrective saccades only during the voluntary saccades adaptation task. These last observations suggest that post-saccadic perception depends on the previously performed action and that the differences between saccade categories of motor correction and adaptation occur at an early level of visual processing.

A Role for the Parietal Cortex in Sensorimotor Adaptation of Saccades

Sensorimotor adaptation ensures movement accuracy despite continuously changing environment and body. Adaptation of saccadic eye movements is a classical model of sensorimotor adaptation. Beside the well-established role of the brainstem-cerebellum in the adaptation of reactive saccades (RSs), the cerebral cortex has been suggested to be involved in the adaptation of voluntary saccades (VSs). Here, we provide direct evidence for a causal involvement of the parietal cortex in saccadic adaptation. First, the posterior intraparietal sulcus (pIPS) was identified in each subject using functional magnetic resonance imaging (fMRI). Then, a saccadic adaptation paradigm was used to progressively reduce the amplitude of RSs and VSs, while single-pulse transcranial magnetic stimulation (spTMS) was applied over the right pIPS. The perturbations of pIPS resulted in impairment for the adaptation of VSs, selectively when spTMS was applied 60 ms after saccade onset. In contrast, the adaptation of RSs was facilitated by spTMS applied 90 ms after saccade initiation. The differential effect of spTMS relative to saccade types suggests a direct interference with pIPS activity for the VS adaptation and a remote interference with brainstem-cerebellum activity for the RS adaptation. These results support the hypothesis that the adaptation of VSs and RSs involves different neuronal substrates.

Reversing motor adaptation deficits in the ageing brain using non-invasive stimulation

Healthy ageing in man is associated with a decline in motor adaptation. Transcranial direct current stimulation (TDCS) over the primary motor cortex (M1) or the lateral cerebellum can improve motor adaptation in young and older adults, but as yet no direct comparisons of TDCS effects exist between the two age groups and the two stimulation sites. TDCS over M1 enhanced the motor adaptation in both age groups by ∼30% relative to their respective non‐stimulated groups and improved the performance of older adults to the extent that it compared with that of young adults without stimulation. The study suggests that the plastic mechanisms activated by TDCS that underpin improvements in motor behaviour in young adults remain available in older adults. The results indicate that TDCS may be a useful tool to help combat the normal decline in motor performance seen in normal healthy ageing.

Effects of structural and functional cerebellar lesions on sensorimotor adaptation of saccades

The cerebellum is critically involved in the adaptation mechanisms that maintain the accuracy of goal-directed acts such as saccadic eye movements. Two categories of saccades, each relying on different adaptation mechanisms, are defined: reactive (externally triggered) saccades and voluntary (internally triggered) saccades. The contribution of the medio-posterior part of the cerebellum to reactive saccades adaptation has been clearly demonstrated, but the evidence that other parts of the cerebellum are also involved is limited. Moreover, the cerebellar substrates of voluntary saccades adaptation have only been marginally investigated. Here, we addressed these two questions by investigating the adaptive capabilities of patients with cerebellar or pre-cerebellar stroke. We recruited three groups of patients presenting focal lesions located, respectively, in the supero-anterior cerebellum, the infero-posterior cerebellum and the lateral medulla (leading to a Wallenberg syndrome including motor dysfunctions similar to those resulting from lesion of the medio-posterior cerebellum). Adaptations of reactive saccades and of voluntary saccades were tested during separate sessions in all patients and in a group of healthy participants. The functional lesion of the medio-posterior cerebellum in Wallenberg syndrome strongly impaired the adaptation of both reactive and voluntary saccades. In contrast, patients with lesion in the supero-anterior part of the cerebellum presented a specific adaptation deficit of voluntary saccades. Finally, patients with an infero-posterior cerebellar lesion showed mild adaptation deficits. We conclude that the medio-posterior cerebellum is critical for the adaptation of both saccade categories, whereas the supero-anterior cerebellum is specifically involved in the adaptation of voluntary saccades.

Saccades and Eye–Head Coordination in Ataxia with Oculomotor Apraxia Type 2

Ataxia with oculomotor apraxia type 2 (AOA2) is one of the most frequent autosomal recessive cerebellar ataxias. Oculomotor apraxia refers to horizontal gaze failure due to deficits in voluntary/reactive eye movements. These deficits can manifest as increased latency and/or hypometria of saccades with a staircase pattern and are frequently associated with compensatory head thrust movements. Oculomotor disturbances associated with AOA2 have been poorly studied mainly because the diagnosis of oculomotor apraxia was based on the presence of compensatory head thrusts. The aim of this study was to characterise the nature of horizontal gaze failure in patients with AOA2 and to demonstrate oculomotor apraxia even in the absence of head thrusts. Five patients with AOA2, without head thrusts, were tested in saccadic tasks with the head restrained or free to move and their performance was compared to a group of six healthy participants. The most salient deficit of the patients was saccadic hypometria with a typical staircase pattern. Saccade latency in the patients was longer than controls only for memory-guided saccades. In the head-free condition, head movements were delayed relative to the eye and their amplitude and velocity were strongly reduced compared to controls. Our study emphasises that in AOA2, hypometric saccades with a staircase pattern are a more reliable sign of oculomotor apraxia than head thrust movements. In addition, the variety of eye and head movements’ deficits suggests that, although the main neural degeneration in AOA2 affects the cerebellum, this disease affects other structures.

Brain Processing of Visual Information during Fast Eye Movements Maintains Motor Performance

Movement accuracy depends crucially on the ability to detect errors while actions are being performed. When inaccuracies occur repeatedly, both an immediate motor correction and a progressive adaptation of the motor command can unfold. Of all the movements in the motor repertoire of humans, saccadic eye movements are the fastest. Due to the high speed of saccades, and to the impairment of visual perception during saccades, a phenomenon called “saccadic suppression”, it is widely believed that the adaptive mechanisms maintaining saccadic performance depend critically on visual error signals acquired after saccade completion. Here, we demonstrate that, contrary to this widespread view, saccadic adaptation can be based entirely on visual information presented during saccades. Our results show that visual error signals introduced during saccade execution–by shifting a visual target at saccade onset and blanking it at saccade offset–induce the same level of adaptation as error signals, presented for the same duration, but after saccade completion. In addition, they reveal that this processing of intra-saccadic visual information for adaptation depends critically on visual information presented during the deceleration phase, but not the acceleration phase, of the saccade. These findings demonstrate that the human central nervous system can use short intra-saccadic glimpses of visual information for motor adaptation, and they call for a reappraisal of current models of saccadic adaptation.

Adaptation of scanning saccades co-occurs in different coordinate systems

Plastic changes of saccades (i.e., following saccadic adaptation) do not transfer between oppositely directed saccades, except when multiple directions are trained simultaneously, suggesting a saccadic planning in retinotopic coordinates. Interestingly, a recent study in human healthy subjects revealed that after an adaptive increase of rightward-scanning saccades, both leftward and rightward double-step, memory-guided saccades, triggered toward the adapted endpoint, were modified, revealing that target location was coded in spatial coordinates (Zimmermann et al. 2011). However, as the computer screen provided a visual frame, one alternative hypothesis could be a coding in allocentric coordinates. Here, we questioned whether adaptive modifications of saccadic planning occur in multiple coordinate systems. We reproduced the paradigm of Zimmermann et al. (2011) using target light-emitting diodes in the dark, with and without a visual frame, and tested different saccades before and after adaptation. With double-step, memory-guided saccades, we reproduced the transfer of adaptation to leftward saccades with the visual frame but not without, suggesting that the coordinate system used for saccade planning, when the frame is visible, is allocentric rather than spatiotopic. With single-step, memory-guided saccades, adaptation transferred to leftward saccades, both with and without the visual frame, revealing a target localization in a coordinate system that is neither retinotopic nor allocentric. Finally, with single-step, visually guided saccades, the classical, unidirectional pattern of amplitude change was reproduced, revealing retinotopic coordinate coding. These experiments indicate that the same procedure of adaptation modifies saccadic planning in multiple coordinate systems in parallel-each of them revealed by the use of different saccade tasks in postadaptation.