Impairment of saccade adaptation in a patient with a focal thalamic lesion.

The frequent jumps of the eyeballs-called saccades-imply the need for a constant correction of motor errors. If systematic errors are detected in saccade landing, the saccade amplitude adapts to compensate for the error. In the laboratory, saccade adaptation can be studied by displacing the saccade target. Functional selectivity of adaptation for different saccade types suggests that adaptation occurs at multiple sites in the oculomotor system. Saccade motor learning might be the result of a comparison between a prediction of the saccade landing position and its actual postsaccadic location. To investigate whether a thalamic feedback pathway might carry such a prediction signal, we studied a patient with a lesion in the posterior ventrolateral thalamic nucleus. Saccade adaptation was tested for reactive saccades, which are performed to suddenly appearing targets, and for scanning saccades, which are performed to stationary targets. For reactive saccades, we found a clear impairment in adaptation retention ipsilateral to the lesioned side and a larger-than-normal adaptation on the contralesional side. For scanning saccades, adaptation was intact on both sides and not different from the control group. Our results provide the first lesion evidence that adaptation of reactive and scanning saccades relies on distinct feedback pathways from cerebellum to cortex. They further demonstrate that saccade adaptation in humans is not restricted to the cerebellum but also involves cortical areas. The paradoxically strong adaptation for outward target steps can be explained by stronger reliance on visual targeting errors when prediction error signaling is impaired.

Neural substrate of antisaccades: role of subcortical structures.

BACKGROUND: Experimental and clinical studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the superior colliculus (SC) are crucial for the cancellation of reflexive eye movements toward distracting stimuli. However, the contribution of subcortical structures remains unknown. The basal ganglia provide serial tonic inhibitory connections between the DLPFC and the SC, and could therefore be involved in preventing the triggering of unnecessary saccades. The DLPFC could also exert its inhibitory effect on the SC through direct prefronto-tectal pathways that travel in the internal capsule (IC). Since thalamic dysfunction may be responsible for reduced DLPFC activation, it may be hypothesized that the thalamus could also participate in saccadic inhibition. METHODS: The authors recorded reflexive saccade triggering (prosaccade task) and inhibition (antisaccade task) in 29 patients with a single lesion affecting the striatum, the thalamus, or the IC, and compared these results to control subjects. RESULTS: A normal error rate in the antisaccade task was found in patients with 1) a basal ganglia lesion, 2) a thalamic lesion, or 3) a lesion restricted to the posterior half of the posterior limb of the IC. An increased error rate in the antisaccade task was found in patients with a lesion affecting the anterior limb, the genu, or the anterior half of the posterior limb of the IC. CONCLUSION: These results suggest that neither the basal ganglia nor the thalamus plays a major role in reflexive saccade suppression, but support the hypothesis of a direct DLPFC inhibitory control of saccade triggering on the SC.

Eyelid tremor in a patient with a unilateral paramedian thalamic lesion.

A patient with a circumscribed infarction of the right paramedian thalamus developed a tremor of both eyelids on voluntary eye closure. Co-registration of the magnetic resonance image to a stereotactic atlas of the human thalamus revealed that the lesion was confined to a small subgroup of paramedian nuclei, including the parvocellular part of the mediodorsal nucleus. It is concluded that this region provides inhibitory input to cortical and/or subcortical regions controlling eyelid movements. Voluntary eye closure may involve direct cortico-nuclear connections and indirect pathways through the paramedian thalamus, most probably through the mediodorsal nucleus.

Involvement of the cerebellar thalamus in human saccade adaptation.

Saccade adaptation can be experimentally induced by systematically displacing a visual cue during a targeting saccade. Non-human primate studies have highlighted the crucial role of the cerebellum for saccade adaptation, but its neural substrates in humans are poorly understood. Recent physiological experiments suggest that, in addition to cerebellar structures, cortical areas may be involved as well. We have therefore hypothesized that saccade adaptation may rely on a cerebello-cerebral network, in which the cerebellar thalamus may link cerebellar and cerebral structures. To test this hypothesis, we studied saccade adaptation in a group of four patients with a thalamic lesion, with (n = 2) or without (n = 2) involvement of the cerebellar thalamus. Compared to healthy subjects, saccade adaptation was reduced in patients with associated cerebellar syndrome, but normal in patients without cerebellar syndrome. These results are consistent with the hypothesis that cerebello-thalamic pathways contribute to saccade adaptation in humans and suggest that the thalamus relays adaptation-related information from the cerebellum to cerebral cortical oculomotor areas.

Improvement of memory guided saccades in parkinsonian patients by high frequency subthalamic nucleus stimulation.

Recent studies in the monkey suggest that the subthalamic nucleus (STN) is involved in control of eye movement, yet its functional significance in humans is unknown. Saccadic eye movements were studied in eight parkinsonian patients treated by bilateral electrical stimulation of the STN. STN stimulation improved the accuracy of memory guided saccades but not of reflexive visually guided saccades and had no effect on the antisaccade task. This study shows that, by contrast with levodopa, STN stimulation improves memory guided saccade deficits, and illustrates for the first time in humans the role of the STN in the control of purposive saccades.

Vasospastic amaurosis fugax in a patient with overlap collagenosis treated with nimodipine.

Vasospasm has been discussed as a less frequent cause of amaurosis fugax. Since its direct demonstration is difficult, its diagnosis is usually based on the exclusion of other causes and/or response to calcium entry blockers. We describe diagnosis and successful treatment of vasospastic amaurosis fugax in a patient with systemic autoimmune disease: A 54 year-old patient with an overlap collagenosis presented with relapsing episodes of transient monocular blindness. Angiography and transcranial Doppler scanning revealed a high-grade stenosis of the left ophthalmic artery. After administration of oral nimodipine the attacks ceased immediately and repeated Doppler examinations confirmed resolution of the stenosis. We infer that vasospasm of inflammatory altered cerebral vessels may contribute to focal neurological deficits in patients with systemic autoimmune disease. Calcium entry blockers should be discussed as a possible treatment in patients with systemic autoimmune disease and evidence of functional disturbances of cerebral blood flow.