Kinetic models for synaptic vesicle release

Verhage, M. [Promotor]Cornelisse, L.N. [Copromotor

Stationary and Recurrent Properties of Atrial Fibrillation Conduction Patterns in Goat

Introduction. Electrical mapping of the atria is used to assess the substrate of atrial fibrillation (AF). Targeted ablation of the AF substrate assumes spatiotemporal stationarity. In this study we analyzed long AF recordings of AF using high-density contact mapping.Methods. In 12 goats with stable AF 10 successive 60s files were recorded, within a single AF episode. AF cycle length, fractionation index (FI), lateral dissociation, conduction velocity, breakthroughs and preferentiality of conduction (Prefi were assessed to construct AF-property maps. The Pearson correlation coefficient (PCC) between AF-property maps of consecutive recordings was calculated. Recurrence plots and recurrence quantification analysis were used to identify recurrent patterns.Results Spatiotemporal stationarity for the 6 properties were high, PCC ranged from 0.66 +/- 0.11 for Pref to 0.98 +/- 0.01 for FI. The PCC is not affected by the time delay between files. Yet, highly dynamic patterns were found. Recurrence plots revealed few (1.6 +/- 0.7) recurrent patterns in individual animals.Conclusions AF properties were stationary in stable AF. This cannot be attributed to stable recurrent conduction patterns. during This suggests that spatial properties of the atrium determine AF properties

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network

A framework for focal and connectomic mapping of transiently disrupted brain function

The distributed nature of the neural substrate, and the difficulty of establishing necessity from correlative data, combine to render the mapping of brain function a far harder task than it seems. Methods capable of combining connective anatomical information with focal disruption of function are needed to disambiguate local from global neural dependence, and critical from merely coincidental activity. Here we present a comprehensive framework for focal and connective spatial inference based on sparse disruptive data, and demonstrate its application in the context of transient direct electrical stimulation of the human medial frontal wall during the pre-surgical evaluation of patients with focal epilepsy. Our framework formalizes voxel-wise mass-univariate inference on sparsely sampled data within the statistical parametric mapping framework, encompassing the analysis of distributed maps defined by any criterion of connectivity. Applied to the medial frontal wall, this transient dysconnectome approach reveals marked discrepancies between local and distributed associations of major categories of motor and sensory behaviour, revealing differentiation by remote connectivity to which purely local analysis is blind. Our framework enables disruptive mapping of the human brain based on sparsely sampled data with minimal spatial assumptions, good statistical efficiency, flexible model formulation, and explicit comparison of local and distributed effects

A rightward shift in the visuospatial attention vector with healthy aging

The study of lateralised visuospatial attention bias in non-clinical samples has revealed a systematic group-level leftward bias (pseudoneglect), possibly as a consequence of right hemisphere dominance for visuospatial attention. Pseudoneglect appears to be modulated by age, with a reduced or even reversed bias typically present in elderly participants. It has been suggested that this shift in bias may arise due to disproportionate aging of the right hemisphere and/or an increase in complementary functional recruitment of the left hemisphere for visuospatial processing. In this study, we report rightward shifts in subjective midpoint judgement relative to healthy young participants whilst elderly participants performed a computerized version of the landmark task (in which they had to judge whether a transection mark appeared closer to the right or left end of a line) on three different line lengths. This manipulation of stimulus properties led to a similar behavioural pattern in both the young and the elderly: a rightward shift in subjective midpoint with decreasing line length, which even resulted in a systematic rightward bias in elderly participants for the shortest line length (1.98° of visual angle). Overall performance precision for the task was lower in the elderly participants regardless of line length, suggesting reduced landmark task discrimination sensitivity with healthy aging. This rightward shift in the attentional vector with healthy aging is likely to result from a reduction in right hemisphere resources/dominance for attentional processing in elderly participants. The significant rightward bias in the elderly for short lines may even suggest a reversal of hemisphere dominance in favour of the left hemisphere/right visual field under specific conditions