Background-The presence of focal fibrillation waves during atrial fibrillation (AF) can, besides ectopic activity, also be explained by asynchronous activation of the atrial endo-and epicardial layer and transmurally propagating fibrillation waves. To provide direct proof of endo-epicardial asynchrony, we performed simultaneous high-resolution mapping of the right atrial endo-and epicardial wall during AF in humans. Method and Results-Intraoperative mapping of the endo-and epicardial right atrial wall was performed during (induced) AF in 10 patients with AF (paroxysmal: n=3; persistent: n=4; and longstanding persistent: n=3) and 4 patients without a history of AF. A clamp made of 2 rectangular 8×16 electrode arrays (interelectrode distance 2 mm) was inserted into the incision in the right atrial appendage. Recordings of 10 seconds of AF were analyzed to determine the incidence of asynchronous endo-epicardial activation times (≥15 ms) of opposite electrodes. Asynchronous endo-epicardial activation ranged between 0.9 and 55.9% without preference for either side. Focal waves appeared equally frequent at endocardium and epicardium (11% versus 13%; P=0.18). Using strict criteria for breakthrough (presence of an opposite wave within 4 mm and ≤14 ms before the origin of the focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. Conclusions-We provided the first evidence for asynchronous activation of the endo-epicardial wall during AF in humans.Endo-epicardial asynchrony may play a major role in the pathophysiology of AF and may offer an explanation why in some patients therapy fails. (Circ Arrhythm Electrophysiol. 2016;9:e003648.

CVICerebral visual impairment RTF Reaction time to fixation GFA Gaze fixation area SRT Saccade reaction times AIM The aim of this study was to compare visually guided ocular motor behaviour in children with visual processing and ⁄ or motor deficits with an age-matched comparison group and an adult group.METHOD Visual stimuli were shown to 28 children with visual processing and ⁄ or motor deficits (11 females, 17 males; mean age 7y 5mo, SD 2y 9mo, range 2-14y;) and an age-matched comparison group of 213 typically developing children (115 females, 98 males; mean age 5y 8mo, SD 3y 5mo, range 0-12y). The adult group consisted of nine females and two males with (mean age of 24y 4mo, SD 4y 8mo). Individuals who had a likely diagnosis of cerebral visual impairment (CVI), an opticopathy with unknown location, nystagmus, glaucoma, or a cataract were included in the study. Exclusion criteria were a visual acuity below 0.2, a developmental age under 1 year, and the presence of brain tumours, autism, and anxiety disorders. Orientating eye movements to large cartoons were quantified using the reaction time to fixation (RTF) and gaze fixation area (GFA). A Mann-Whitney U test was used to compare the differences between groups and Bonferroni post-hoc testing was used to analyse age dependence of RTF and GFA values within the comparison group.RESULTS Individuals with CVI showed significantly prolonged RTF values; those with congenital nystagmus showed significantly increased GFA values. In the comparison group, RTF was significantly longer in children under the age of 2 years than in children aged 4 years and older (290 and 200ms respectively; p<0.001). No developmental change was found for GFA values. INTERPRETATIONIncreased RTF values in individuals with CVI relate to visual processing deficits.The data suggest that visually guided ocular motor responses mature during the first 3 years of life.Early human development involves the maturation of complex interactions between cortical networks that are specialized for target selection (visual system), motor preparation (premotor system), and generation of eye movements (ocular motor system).1,2 Recently, two areas have been described that act as attention networks: a dorsal frontoparietal network and a ventral frontoparietal network.3 It is proposed that the dorsal stream enables the selection of goal-driven (voluntary) attention, whereas the ventral stream detects stimulus-driven (reflexive) attention.3 Activation in the dorsal premotor region, the frontal eye field, and the superior parietal cortex was shown during voluntary or reflexive shifts of attention. This suggests not only involvement of multiple brain areas but also dynamic interaction between the cortical attention networks.

Introduction Intra‐atrial conduction abnormalities are associated with the development of atrial fibrillation (AF) and cause morphological changes of the unipolar atrial electrogram (U‐AEGM). This study examined the impact of different atrial programmed electrical stimulation (APES) protocols on U‐AEGM morphology to identify the most optimal APES protocol provoking conduction abnormalities. Methods APES techniques (14 protocols) were applied in 30 patients referred for an electrophysiology study, consisting of fixed rate, extra, and decremental stimuli at different frequencies. U‐AEGM morphologies including width, amplitude, and fractionation for patients without (control group) and with a history of AF (AF group) were examined during APES. In addition, sinus rhythm (SR) U‐AEGMs preceding different APES protocols were compared to evaluate the morphology stability over time. Results U‐AEGM morphologies during SR before the APES protocols were comparable (all P > .396). Atrial refractoriness was longer in the AF group compared to the control group (298 ± 48 vs 255 ± 33 ms; P ≤ .020), but did not differ between AF patients with and without amiodarone therapy (278 ± 48 vs 311 ± 40 ms; P ≥ .126). Compared to the initial SR morphology, U‐AEGM width, amplitude, and fractionation changed significantly during the 14 different APES protocols, particularly in the AF group. In both groups, U‐AEGM changes in morphology were most pronounced during fixed‐rate stimulation with extra stimuli (8S1‐S2 = 400‐250 ms). Conclusion APES results in significant changes in U‐AEGM morphology, including width, amplitude, and fractionation. The impact of APES differed between APES sequence and between patients with and without AF. These findings suggest that APES could be useful to identify AF‐related conduction abnormalities in the individual patient.

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