Andreas Sprenger

Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study.

Smooth pursuit eye movements are evoked by retinal image motion of visible moving objects and can also be driven by the internal representation of a target due to extraretinal mechanisms (e.g. efference copy). To delineate the corresponding neuronal correlates, functional magnetic resonance imaging at 1.5 T was applied during smooth pursuit at 10 °/s with continuous target presentation and target blanking for 1 s to 16 right‐handed healthy males. Eye movements were assessed during scanning sessions by infra‐red reflection oculography. Smooth pursuit performance was optimal when the target was visible but decreased to a residual velocity of about 30% of the velocity observed during continuous target presentation. Random effects analysis of the imaging data yielded an activation pattern for smooth pursuit in the absence of a visual target (in contrast to continuous target presentation) which included a number of cortical areas in which extraretinal information is available such as the frontal eye field, the superior parietal lobe, the anterior and the posterior intraparietal sulcus and the premotor cortex, and also the supplementary and the presupplementary eye field, the supramarginal gyrus, the dorsolateral prefrontal cortex, cerebellar areas and the basal ganglia. We suggest that cortical mechanisms such as prediction, visuo‐spatial attention and transformation, multimodal visuomotor control and working memory are of special importance for maintaining smooth pursuit eye movements in the absence of a visible target.

Cerebellar activation in opsoclonus An fMRI study

It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose opsoclonus largely disappeared on eye closure underwent fMRI. A comparison of these two states revealed neither vermal nor brainstem activation but rather a bilateral activation in the deep cerebellar nuclei in excess of what the authors found in healthy subjects. The results support a crucial role of the fastigial nucleus in opsoclonus.

Parametric modulation of cortical activation during smooth pursuit with and without target blanking. an fMRI study.

Smooth pursuit eye movements (SPEM) are performed to track slowly moving visual targets and are accompanied by saccades whenever foveal representation is lost. In the present study, we correlated the cerebral activation as assessed by functional magnetic resonance imaging with parameters of eye movement performance in order to determine the cortical areas involved in the retinal and extraretinal processing of maintaining smooth pursuit velocity (SPV) and generating saccades in 16 healthy males. The stimulus consisted of a target moving at a constant velocity of 10 degrees/s with and without target blanking. During constant target presentation, SPV was positively correlated with the BOLD signal in the right V5 complex and negatively correlated with the BOLD response in the left dorsolateral prefrontal cortex (DLPFC). In the condition with target blanking, additional negative correlations with SPV were found in the left frontal eye field (FEF), the left parietoinsular vestibular cortex (PIVC) and the left angular gyrus. Saccadic frequency was negatively correlated with activations of the right mesial intraparietal sulcus (IPS) during both conditions and the right premotor area during continuous target presentation. We conclude that V5 is directly related to the maintenance of an optimal smooth pursuit velocity during visual feedback, whereas the FEF, PFC, angular gyrus and PIVC are involved in reconstitution and prediction whenever SPV decreases, especially during maintenance of smooth pursuit in the absence of a visual target. Furthermore, we suggest that parietal areas are related to the suppression of saccades during smooth pursuit.

On why left events are the right ones: Neural mechanisms underlying the left-hemifield advantage in rapid serial visual presentation

When simultaneous series of stimuli are rapidly presented left and right, containing two target stimuli T1 and T2, T2 is much better identified when presented in the left than in the right hemifield. Here, this effect was replicated, even when shifts of gaze were controlled, and was only partially compensated when T1 side provided the cue where to expect T2. Electrophysiological measurement revealed earlier latencies of T1- and T2-evoked N2pc peaks at the right than at the left visual cortex, and larger right-hemisphere T2-evoked N2pc amplitudes when T2 closely followed T1. These findings suggest that the right hemisphere was better able to single out the targets in time. Further, sustained contralateral slow shifts remained active after T1 for longer time at the right than at the left visual cortex, and developed more consistently at the right visual cortex when expecting T2 on the contralateral side. These findings might reflect better capacity of right-hemisphere visual working memory. These findings about the neurophysiological underpinnings of the large right-hemisphere advantage in this complex visual task might help elucidating the mechanisms responsible for the severe disturbance of hemineglect following damage to the right hemisphere.

Reduced neuronal activity in the V5 complex underlies smooth-pursuit deficit in schizophrenia: evidence from an fMRI study

Smooth-pursuit eye movements are the essential tool for a clear and stable visual perception of our environment by matching eye velocity to the velocity of moving objects. However, in about 50% of schizophrenic patients, this ability is disturbed. To reveal the cortical mechanisms that underlie this deficit, eye velocity-related neuronal activity was analyzed by functional magnetic resonance imaging (fMRI). Blocks of constant velocity ramps (10 degrees/s) were presented to 17 patients with schizophrenia and 16 matched controls while assessing smooth-pursuit velocity (SPV) during scanning sessions. Using random-effects analysis, the parametric modulation of brain hemodynamic responses related to SPV was compared between both groups. In schizophrenic patients, reduced SPV was significantly correlated with a focal decrease of the hemodynamic response in the V5 complex (t = 4.21, P(FWE-corrected) = 0.005). Our results provide direct evidence for reduced neuronal activity in V5 as one major factor underlying abnormal SPV in schizophrenia and suggest impaired motion perception. They confirm hypotheses about a V5 deficit derived from psychophysiological studies with schizophrenic patients in which deficient motion perception (especially velocity discrimination) was associated with impaired smooth-pursuit performance.

Visual search in patients with left visual hemineglect

In patients with hemi-spatial neglect eye movement patterns during visual search reflect not only inattention for the contralesional hemi-field, but interacting deficits of multiple visuo-spatial and cognitive functions, even in the ipsilesional hemi-field. Evidence for these deficits is presented from the literature and from saccadic scan-path analysis during feature and conjunction search in 10 healthy subjects and in 10 patients with manifest or recovered left visual neglect due to right-hemispheric stroke. Deficits include (1) a rightward shift of spatial representation, (2) deficient spatial working memory and failure of systematic search strategies, leading to multiple re-fixations, more after frontal lesions, and (3) a reduced spotlight of attention and a deficient pop-out effect of color, more after temporo-parietal lesions.

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search‐coil method, hand movements with an ultrasound‐emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye–hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye–hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.

Vergence deficits in patients with cerebellar lesions.

The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence (to ramp and sinusoidal targets). The aim of this study was to investigate whether circumscribed cerebellar lesions affect these dynamic vergence eye movements. Disconjugate fast and slow vergence, conjugate smooth pursuit and saccades were binocularly recorded by a scleral search coil system in 20 patients with acute cerebellar lesions (all ischemic strokes except for one) and 20 age-matched healthy controls. Patients showed impairment of slow vergence while fast vergence was unaffected. Slow vergence gain to sinusoidal targets was significantly reduced, both in convergence and divergence direction. Divergence but not convergence velocity to ramp targets was reduced. Conjugate smooth pursuit eye movements to sinusoidal and to step-ramp targets were impaired. Patients had saccadic hypometria. All defects were particularly expressed in patients with vermis lesions. In contrast to recent animal data fast vergence was not impaired in any of our patient subgroups. We conclude that (i) the human cerebellum, in particular the vermis, is involved in the processing of dynamic vergence eye movements and (ii) cerebellar lesions elicit dissociable effects on fast and slow vergence.

Cortical mechanisms of retinal and extraretinal smooth pursuit eye movements to different target velocities

Smooth pursuit eye movements (SPEM) are used to maintain focus upon moving targets. The generation of SPEM velocity is controlled by retinal information and extraretinal signals. Although there is a wealth of studies investigating retinal and extraretinal SPEM control, the main questions regarding the cortical mechanisms involved in the processing of SPEM to different stimulus velocities are still unresolved. We applied an innovative event-related fMRI-design by presenting target ramps at different velocities (5, 10, 15, 20 degrees/s) with both continuous target presentation and intervals of target blanking. The stimulus parameters were integrated into the statistical model and eye movements were registered to confirm SPEM performance. Our results clearly demonstrate that in humans the oculomotor network (V5, frontal and supplementary eye fields, lateral intraparietal area) is engaged in the processing of retinal and extraretinal SPEM velocity. Within this network neural activity increases with increasing target velocity. During extraretinal SPEM, additional engagement of the dorsolateral prefrontal cortex, angular gyrus, parahippocampal gyrus and superior temporal gyrus occurs. These regions encode cognitive functions such as memory, attention and monitoring. The activation of the inferior parietal cortex seems to be related to the interaction between velocity and blanking thereby underlining its relevance for task switching and sensorimotor transformation.

Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: An fMRI study.

Smooth pursuit eye movements (SPEM) are necessary to follow slowly moving targets while maintaining foveal fixation. In about 50% of schizophrenic patients SPEM velocity is reduced. In this study we were interested in identifying the cortical mechanisms associated with extraretinal processing of SPEM in schizophrenic patients. During condition A, patients and healthy subjects had to pursue a constantly visible target (10 degrees /s). During condition B the target was blanked out for 1000 ms while subjects were instructed to continue SPEM. Eye movement data were assessed during scanning sessions by a limbus tracker. During condition A, reduced SPEM velocity in patients was associated with reduced activation of the right ventral premotor cortex and increased activation of the left dorsolateral prefrontal cortex, the right thalamus and the Crus II of the left cerebellar hemisphere. During condition B, SPEM velocity was reduced to a similar extent in both groups. While in patients a decrease in activation was observed in the right cerebellar area VIIIA, the activation of the right anterior cingulate, the right superior temporal cortex, and the bilateral frontal eye fields was increased. The results implicate that schizophrenic patients employ different strategies during SPEM both with and without target blanking than healthy subjects. These strategies predominantly involve extraretinal mechanisms.