The differential influence of fixation and directed visual attention on reaction times of goal-directed saccades and especially on the occurrence of express saccades was investigated. In all the experiments the subjects were instructed first to keep their direction of gaze at the center of a translucent screen with or without a central fixation point. When a new stimulus appeared, the subjects had to look at it as soon as possible. In some control experiments the subjects had to direct their gaze to the screen center and simultaneously direct their attention to a peripheral light spot before the target for the saccade appeared. Many express saccades occurred when either active fixation of a central fixation point or attention directed to a peripheral visual target (regardless of its position) was interrupted 200 ms before the target for the saccade appeared. Express saccades were almost completely abolished in the presence of fixation and/or directed visual attention at the moment in which the saccade target appeared. We conclude that express saccades occur if visual attention has already been released at the moment when the target for the saccade appears. This disengagement needs some time which adds to the reaction time.

We investigated the quantitative relationship between saccadic activity (as reflected in frequency of occurrence and amplitude of saccades) and blood oxygenation level dependent (BOLD) changes in the cerebral cortex using functional magnetic resonance imaging (fMRI). Furthermore, we investigated quantitative changes in cortical activity associated with qualitative changes in the saccade task for comparable levels of saccadic activity. All experiments required the simultaneous acquisition of eye movement and fMRI data. For this purpose we used a new high-resolution limbus-tracking technique for recording eye movements in the magnetic resonance tomograph. In the first two experimental series we varied both frequency and amplitude of saccade stimuli (target jumps). In the third series we varied task difficulty; subjects performed either pro-saccades or anti-saccades. The brain volume investigated comprised the frontal and supplementary eye fields, parietal as well as striate cortex, and the motion sensitive area of the parieto-occipital cortex. All these regions showed saccade-related BOLD responses. The responses in these regions were highly correlated with saccade frequency, indicating that repeated processing of saccades is integrated over time in the BOLD response. In contrast, there was no comparable BOLD change with variation of saccade amplitude. This finding speaks for a topological rather than activity-dependent coding of saccade amplitudes in most cortical regions. In the experiments comparing pro- vs anti-saccades we found higher BOLD activation in the "anti" task than in the "pro" task. A comparison of saccade parameters revealed that saccade frequency and cumulative amplitude were comparable between the two tasks, whereas reaction times were longer in the "anti" task than the pro task. The latter finding is taken to indicate a more demanding cortical processing in the "anti" task than the "pro" task, which could explain the observed difference in BOLD activation. We hold that a quantitative analysis of saccade parameters (especially saccade frequency and latency) is important for the interpretation of the BOLD changes observed with visual stimuli in fMRI.

Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.

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