Catch-Up Saccades in Vestibular Hypofunction: A Contribution of the Cerebellum?

Long-term deficits of the vestibulo-ocular reflex (VOR) elicited by head rotation can be partially compensated by catch-up saccades (CuS). These saccades are initially visually guided, but their latency can greatly decrease resulting in short latency CuS (SL-CuS). It is still unclear what triggers these CuS and what are the underlying neural circuits. In this study, we aimed at evaluating the impact of cerebellar pathology on CuS by comparing their characteristics between two groups of patients with bilateral vestibular hypofunction, with or without additional cerebellar dysfunction. We recruited 12 patients with both bilateral vestibular hypofunction and cerebellar dysfunction (BVH-CD group) and 12 patients with isolated bilateral vestibular hypofunction (BVH group). Both groups were matched for age and residual VOR gain. Subjects underwent video head impulse test recording of the horizontal semicircular canals responses as well as recording of visually guided saccades in the step, gap, and overlap paradigms. Latency and gain of the different saccades were calculated. The mean age for BVH-CD and BVH was, respectively, 67.8 and 67.2 years, and the mean residual VOR gain was, respectively, 0.24 and 0.26. The mean latency of the first catch-up saccade was significantly longer for the BVH-CD group than that for the BVH group (204 ms vs 145 ms, p < 0.05). There was no significant difference in the latency of visually guided saccades between the two groups, for none of the three paradigms. The gain of covert saccades tended to be lower in the BVH-CD group than in BVH group (t test; p = 0.06). The mean gain of the 12° or 20° visually guided saccades were not different in both groups. Our results suggest that the cerebellum plays a role in the generation of compensatory SL-CuS observed in BVH patients.

A triple distinction of cerebellar function for oculomotor learning and fatigue compensation.

The cerebellum implements error-based motor learning via synaptic gain adaptation of an inverse model, i.e. the mapping of a spatial movement goal onto a motor command. Recently, we modeled the motor and perceptual changes during learning of saccadic eye movements, showing that learning is actually a threefold process. Besides motor recalibration of (1) the inverse model, learning also comprises perceptual recalibration of (2) the visuospatial target map and (3) of a forward dynamics model that estimates the saccade size from corollary discharge. Yet, the site of perceptual recalibration remains unclear. Here we dissociate cerebellar contributions to the three stages of learning by modeling the learning data of eight cerebellar patients and eight healthy controls. Results showed that cerebellar pathology restrains short-term recalibration of the inverse model while the forward dynamics model is well informed about the reduced saccade change. Adaptation of the visuospatial target map trended in learning direction only in control subjects, yet without reaching significance. Moreover, some patients showed a tendency for uncompensated oculomotor fatigue caused by insufficient upregulation of saccade duration. According to our model, this could induce long-term perceptual compensation, consistent with the overestimation of target eccentricity found in the patients' baseline data. We conclude that the cerebellum mediates short-term adaptation of the inverse model, especially by control of saccade duration, while the forward dynamics model was not affected by cerebellar pathology.

Task-independent neural bases of peer presence effect on cognition in children and adults.

There is ample behavioral evidence that others' mere presence can affect any behavior in human and non-human animals, generally facilitating the expression of mastered responses while impairing the acquisition of novel ones. Much less is known about i) how the brain orchestrates the modulation of such a wide array of behaviors by others' presence and ii) when these neural underpinnings mature during development. To address these issues, fMRI data were collected in children and adults alternately observed and unobserved by a familiar peer. Subjects performed a numerosity comparison task and a phonological comparison task. While the former involves number-processing brain areas, the latter involves language-processing areas. Consistent with previous behavioral findings, adults' and children's performance improved in both tasks when observed by a peer. Across all participants, task-specific brain regions showed no reliable change in activity under peer observation. Rather, we found task-independent changes in domain-general brain regions typically involved in mentalizing, reward, and attention. Bayesian analyses singled out the attention network as the exception to the close child-adult resemblance of peer observation neural substrates. These findings suggest that i) social facilitation of some human education-related skills is primarily orchestrated by domain-general brain networks, rather than by task-selective substrates, and ii) apart from attention, peer presence neural processing is largely mature in children.

Cerebellar signals drive motor adjustments and visual perceptual changes during forward and backward adaptation of reactive saccades.

Saccadic adaptation ($SA$) is a cerebellar-dependent learning of motor commands ($MC$), which aims at preserving saccade accuracy. Since $SA$ alters visual localization during fixation and even more so across saccades, it could also involve changes of target and/or saccade visuospatial representations, the latter ($CDv$) resulting from a motor-to-visual transformation (forward dynamics model) of the corollary discharge of the $MC$. In the present study, we investigated if, in addition to its established role in adaptive adjustment of $MC$, the cerebellum could contribute to the adaptation-associated perceptual changes. Transfer of backward and forward adaptation to spatial perceptual performance (during ocular fixation and trans-saccadically) was assessed in eight cerebellar patients and eight healthy volunteers. In healthy participants, both types of $SA$ altered $MC$ as well as internal representations of the saccade target and of the saccadic eye displacement. In patients, adaptation-related adjustments of $MC$ and adaptation transfer to localization were strongly reduced relative to healthy participants, unraveling abnormal adaptation-related changes of target and $CDv$. Importantly, the estimated changes of $CDv$ were totally abolished following forward session but mainly preserved in backward session, suggesting that an internal model ensuring trans-saccadic localization could be located in the adaptation-related cerebellar networks or in downstream networks, respectively.

Neural substrates of saccadic adaptation: Plastic changes versus error processing and forward versus backward learning.

Previous behavioral, clinical, and neuroimaging studies suggest that the neural substrates of adaptation of saccadic eye movements involve, beyond the central role of the cerebellum, several, still incompletely determined, cortical areas. Furthermore, no neuroimaging study has yet tackled the differences between saccade lengthening ("forward adaptation") and shortening ("backward adaptation") and neither between their two main components, i.e. error processing and oculomotor changes. The present fMRI study was designed to fill these gaps. Blood-oxygen-level-dependent (BOLD) signal and eye movements of 24 healthy volunteers were acquired while performing reactive saccades under 4 conditions repeated in short blocks of 16 trials: systematic target jump during the saccade and in the saccade direction (forward: FW) or in the opposite direction (backward: BW), randomly directed FW or BW target jump during the saccade (random: RND) and no intra-saccadic target jump (stationary: STA). BOLD signals were analyzed both through general linear model (GLM) approaches applied at the whole-brain level and through sensitive Multi-Variate Pattern Analyses (MVPA) applied to 34 regions of interest (ROIs) identified from independent 'Saccade Localizer' functional data. Oculomotor data were consistent with successful induction of forward and backward adaptation in FW and BW blocks, respectively. The different analyses of voxel activation patterns (MVPAs) disclosed the involvement of 1) a set of ROIs specifically related to adaptation in the right occipital cortex, right and left MT/MST, right FEF and right pallidum; 2) several ROIs specifically involved in error signal processing in the left occipital cortex, left PEF, left precuneus, Medial Cingulate cortex (MCC), left inferior and right superior cerebellum; 3) ROIs specific to the direction of adaptation in the occipital cortex and MT/MST (left and right hemispheres for FW and BW, respectively) and in the pallidum of the right hemisphere (FW). The involvement of the left PEF and of the (left and right) occipital cortex were further supported and qualified by the whole brain GLM analysis: clusters of increased activity were found in PEF for the RND versus STA contrast (related to error processing) and in the left (right) occipital cortex for the FW (BW) versus STA contrasts [related to the FW (BW) direction of error and/or adaptation]. The present study both adds complementary data to the growing literature supporting a role of the cerebral cortex in saccadic adaptation through feedback and feedforward relationships with the cerebellum and provides the basis for improving conceptual frameworks of oculomotor plasticity and of its link with spatial cognition.

Saccadic Adaptation Boosts Ongoing Gamma Activity in a Subsequent Visuoattentional Task.

Attention and saccadic adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy toward them. Recent studies propelled the hypothesis of a tight functional coupling between these mechanisms, possibly due to shared neural substrates. Here, we used magnetoencephalography to investigate for the first time the neurophysiological bases of this coupling and of SA per se. We compared visual discrimination performance of 12 healthy subjects before and after SA. Eye movements and magnetic signals were recorded continuously. Analyses focused on gamma band activity (GBA) during the pretarget period of the discrimination and the saccadic tasks. We found that GBA increases after SA. This increase was found in the right hemisphere for both postadaptation saccadic and discrimination tasks. For the latter, GBA also increased in the left hemisphere. We conclude that oculomotor plasticity involves GBA modulation within an extended neural network which persists after SA, suggesting a possible role of gamma oscillations in the coupling between SA and attention.

A cortical substrate for the long-term memory of saccadic eye movements calibration.

How movements are continuously adapted to physiological and environmental changes is a fundamental question in systems neuroscience. While many studies have elucidated the mechanisms which underlie short-term sensorimotor adaptation (∼10-30 min), how these motor memories are maintained over longer-term (>3-5 days) -and thanks to which neural systems-is virtually unknown. Here, we examine in healthy human participants whether the temporo-parietal junction (TPJ) is causally involved in the induction and/or the retention of saccadic eye movements' adaptation. Single-pulse transcranial magnetic stimulation (spTMS) was applied while subjects performed a ∼15min size-decrease adaptation task of leftward reactive saccades. A TMS pulse was delivered over the TPJ in the right hemisphere (rTPJ) in each trial either 30, 60, 90 or 120 msec (in 4 separate adaptation sessions) after the saccade onset. In two control groups of subjects, the same adaptation procedure was achieved either alone (No-TMS) or combined with spTMS applied over the vertex (SHAM-TMS). While the timing of spTMS over the rTPJ did not significantly affect the speed and immediate after-effect of adaptation, we found that the amount of adaptation retention measured 10 days later was markedly larger (42%) than in both the No-TMS (21%) and the SHAM-TMS (11%) control groups. These results demonstrate for the first time that the cerebral cortex is causally involved in maintaining long-term oculomotor memories.

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.

Plastic modification of anti-saccades: adaptation of saccadic eye movements aimed at a virtual target.

Saccades allow us to visually explore our environment. Like other goal-directed movements, their accuracy is permanently controlled by adaptation mechanisms that, in the laboratory, can be induced by systematic displacement of the "real" visual target during the saccade. However, in an anti-saccade (AS) task, the target is "virtual" because gaze has to be shifted away from the "real" visual target toward its mentally defined mirror position. Here, we investigated whether the brain can adapt movements aimed at a virtual target by trying, for the first time, to adapt AS. Healthy human volunteers produced leftward AS during three different exposure phases in which a visual target provided feedback after the AS. In the adaptation condition, the feedback target appeared after completion of the AS response at a location shifted outward from final eye position (immediate non-veridical feedback). In the two control conditions, adaptation was prevented by delaying (800 ms) the shifted feedback target (delayed-shift) or by providing an immediate but veridical feedback at the mirror position of the visual target (no-shift). Results revealed a significant increase of AS gain only in the adaptation condition. Moreover, testing pro-saccades (PS) before and after exposure revealed a significant increase of leftward PS gain in the adaptation condition. This transfer of adaptation supports the hypotheses of a motor level of AS adaptation and of a visual level of AS vector inversion. Together with data from the literature, these results also provide new insights into adaptation and planning mechanisms for AS and for other subtypes of voluntary saccades.

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.

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.

Persistent visual impairment in multiple sclerosis: prevalence, mechanisms and resulting disability.

OBJECTIVE: The objective of this article is to evaluate in multiple sclerosis (MS) patients the prevalence of persistent complaints of visual disturbances and the mechanisms and resulting functional disability of persistent visual complaints (PVCs). METHODS: Firstly, the prevalence of PVCs was calculated in 303 MS patients. MS-related data of patients with or without PVCs were compared. Secondly, 70 patients with PVCs performed an extensive neuro-ophthalmologic assessment and a vision-related quality of life questionnaire, the National Eye Institute Visual Functionary Questionnaire (NEI-VFQ-25). RESULTS: PVCs were reported in 105 MS patients (34.6%). Patients with PVCs had more frequently primary progressive MS (30.5% vs 13.6%) and more neuro-ophthalmologic relapses (1.97 vs 1.36) than patients without PVCs. In the mechanisms/disability study, an afferent visual and an ocular-motor pathways dysfunction were respectively diagnosed in 41 and 59 patients, mostly related to bilateral optic neuropathy and bilateral internuclear ophthalmoplegia. The NEI-VFQ 25 score was poor and significantly correlated with the number of impaired neuro-ophthalmologic tests. CONCLUSION: Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.

Developmental Trajectory of Anticipation: Insights from Sequential Comparative Judgments.

Reaction time (RT) is a critical measure of performance, and studying its distribution at the group or individual level provides useful information on the cognitive processes or strategies used to perform a task. In a previous study measuring RT in children and adults asked to compare two successive stimuli (quantities or words), we discovered that the group RT distribution was bimodal, with some subjects responding with a mean RT of around 1100 ms and others with a mean RT of around 500 ms. This bimodal distribution suggested two distinct response strategies, one reactive, the other anticipatory. In the present study, we tested whether subjects' segregation into fast and slow responders (1) extended to other sequential comparative judgments (2) evolved from age 8 to adulthood, (3) could be linked to anticipation as assessed using computer modeling (4) stemmed from individual-specific strategies amenable to instruction. To test the first three predictions, we conducted a distributional and theoretical analysis of the RT of 158 subjects tested earlier using four different sequential comparative judgment tasks (numerosity, phonological, multiplication, subtraction). Group RT distributions were bimodal in all tasks, with the two strategies differing in speed and sometimes accuracy too. The fast strategy, which was rare or absent in 8- to 9-year-olds, steadily increased through childhood. Its frequency in adolescence remained, however, lower than in adulthood. A mixture model confirmed this developmental evolution, while a diffusion model corroborated the idea that the difference between the two strategies concerns anticipatory processes preceding decision processes. To test the fourth prediction, we conducted an online experiment where 236 participants made numerosity comparisons before and after an instruction favoring either reactive or anticipatory responses. The results provide out-of-the-lab evidence of the bimodal RT distribution associated with sequential comparisons and demonstrated that the proportions of fast vs. slow responders can be modulated simply by asking subjects to anticipate or not the future result of the comparison. Although anticipation of the future is as important for cognition as memory of the past, its evolution after the first year of life is much more poorly known. The present study is a step toward meeting this challenge. It also illustrates how analyzing individual RT distributions in addition to group RT distributions and using computational models can improve the assessment of decision making cognitive processes.

Virtual reality set-up for studying vestibular function during head impulse test.

Objectives: Virtual reality (VR) offers an ecological setting and the possibility of altered visual feedback during head movements useful for vestibular research and treatment of vestibular disorders. There is however no data quantifying vestibulo-ocular reflex (VOR) during head impulse test (HIT) in VR. The main objective of this study is to assess the feasibility and performance of eye and head movement measurements of healthy subjects in a VR environment during high velocity horizontal head rotation (VR-HIT) under a normal visual feedback condition. The secondary objective is to establish the feasibility of VR-HIT recordings in the same group of normal subjects but under altered visual feedback conditions. Design: Twelve healthy subjects underwent video HIT using both a standard setup (vHIT) and VR-HIT. In VR, eye and head positions were recorded by using, respectively, an imbedded eye tracker and an infrared motion tracker. Subjects were tested under four conditions, one reproducing normal visual feedback and three simulating an altered gain or direction of visual feedback. During these three altered conditions the movement of the visual scene relative to the head movement was decreased in amplitude by 50% (half), was nullified (freeze) or was inverted in direction (inverse). Results: Eye and head motion recording during normal visual feedback as well as during all 3 altered conditions was successful. There was no significant difference in VOR gain in VR-HIT between normal, half, freeze and inverse conditions. In the normal condition, VOR gain was significantly but slightly (by 3%) different for VR-HIT and vHIT. Duration and amplitude of head impulses were significantly greater in VR-HIT than in vHIT. In all three altered VR-HIT conditions, covert saccades were present in approximatively one out of four trials. Conclusion: Our VR setup allowed high quality recording of eye and head data during head impulse test under normal and altered visual feedback conditions. This setup could be used to investigate compensation mechanisms in vestibular hypofunction, to elicit adaptation of VOR in ecological settings or to allow objective evaluation of VR-based vestibular rehabilitation.

Functional activation of the cerebral cortex related to sensorimotor adaptation of reactive and voluntary saccades.

Potentially dangerous events in the environment evoke automatic ocular responses, called reactive saccades. Adaptation processes, which maintain saccade accuracy against various events (e.g. growth, aging, neuro-muscular lesions), are to date mostly relayed to cerebellar activity. Here we demonstrate that adaptation of reactive saccades also involves cerebral cortical areas. Moreover, we provide the first identification of the neural substrates of adaptation of voluntary saccades, representing the complement to reactive saccades for the active exploration of our environment. An fMRI approach was designed to isolate adaptation from saccade production: an adaptation condition in which the visual target stepped backward 50 ms after saccade termination was compared to a control condition where the same target backstep occurred 500 ms after saccade termination. Subjects were tested for reactive and voluntary saccades in separate sessions. Multi-voxel pattern analyses of fMRI data from previously-defined regions of interests (ROIs) significantly discriminated between adaptation and control conditions for several ROIs. Some of these areas were revealed for adaptation of both saccade categories (cerebellum, frontal cortex), whereas others were specifically related to reactive saccades (temporo-parietal junction, hMT+/V5) or to voluntary saccades (medial and posterior areas of intra-parietal sulcus). These findings critically extend our knowledge on brain motor plasticity by showing that saccadic adaptation relies on a hitherto unknown contribution of the cerebral cortex.

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.

Consensus paper: roles of the cerebellum in motor control--the diversity of ideas on cerebellar involvement in movement.

Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.

Impaired saccadic adaptation in DYT11 dystonia.

BACKGROUND: Recent neuroimaging studies point to a possible pathophysiological role of cerebellar dysfunction in dystonia. The authors investigated the association between sensorimotor adaptation, cerebellar dysfunction and the myoclonus-dystonia phenotype. METHODS: The authors prospectively analysed reactive saccade adaptation in a genetically homogeneous group of 14 patients with DYT11 dystonia owing to a mutation of the SGCE gene. The authors used a backward reactive saccade adaptation task, a well-characterised experimental oculomotor paradigm involving the cerebellum. The principle of this paradigm is to simulate a spatial error in saccade generation by systematically shifting a visual target during saccade execution. Repetition of this systematic error induces a gradual decrease in the initial saccade amplitude, reflecting an adaptive phenomenon. RESULTS: Saccade adaptation was significantly lower in the DYT11 patients than in healthy controls (mean value: 8.9%±4.5% vs 21.6%±4.5%; p=8.3×10(-6)). The time course of adaptation also differed between the patients and controls (p=0.002), reflecting the slower saccadic adaptation in the patients. CONCLUSIONS: This study provides the first neurophysiological evidence of cerebellar dysfunction in DYT11 dystonia and supports a role of cerebellar dysfunction in the myoclonus-dystonia phenotype.

Unusual monocular pendular nystagmus in multiple sclerosis.

Two unusual cases of monocular pendular nystagmus in patients with multiple sclerosis are reported. One patient showed regular horizontal oscillations of the right eye in abduction, associated with right abduction paresis. The second patient had a similar abnormal eye movement of the left eye in adduction, with partial left internuclear ophthalmoplegia. Such eye position-dependent monocular pendular nystagmus provides new insights into pathogenic mechanism for acquired pendular nystagmus. Different mechanisms are discussed such as the combination of paresis and commonly accepted hypothesis of dysfunction of visual and/or motor feedback loops in the ocular motor neural network.