ERC FUNDED PROJECTS

All of us know of individuals who remain cognitively sharp at an advanced age. Identifying novel factors which associate with inter-individual variability in -and can be considered protective for- cognitive decline is a promising area in ageing research. Considering its strong implication in neuroprotective function, COGNAP predicts that variability in circadian rhythmicity explains a significant part of the age-related changes in human cognition. Circadian rhythms -one of the most fundamental processes of living organisms- are present throughout the nervous system and act on cognitive brain function. Circadian rhythms shape the temporal organization of sleep and wakefulness to achieve human diurnality, characterized by a consolidated bout of sleep during night-time and a continuous period of wakefulness during the day. Of prime importance is that the temporal organization of sleep and wakefulness evolves throughout the adult lifespan, leading to higher sleep-wake fragmentation with ageing. The increasing occurrence of daytime napping is the most visible manifestation of this fragmentation. Contrary to the common belief, napping stands as a health risk factor in seniors in epidemiological data. I posit that chronic napping in older people primarily reflects circadian disruption. Based on my preliminary findings, I predict that this disruption will lead to lower cognitive fitness. I further hypothesise that a re-stabilization of circadian sleep-wake organization through a nap prevention intervention will reduce age-related cognitive decline. Characterizing the link between cognitive ageing and the temporal distribution of sleep and wakefulness will not only bring ground-breaking advances at the scientific level, but is also timely in the ageing society. Cognitive decline, as well as inadequately timed sleep, represent dominant determinants of the health span of our fast ageing population and easy implementable intervention programs are urgently needed.

1 499 125 €

Start date: 2018-01-01, End date: 2022-12-31

Adaptive behaviour is typically attributed to an executive-control system that allows people to regulate impulsive actions and to fulfil long-term goals instead. Failures to regulate impulsive actions have been associated with a variety of clinical and behavioural disorders. Therefore, establishing a good understanding of impulse-control mechanisms and how to improve them could be hugely beneficial for both individuals and society at large. Yet many fundamental questions remain unanswered. This stems from a narrow focus on reactive inhibitory control and well-practiced actions. To make significant progress, we need to develop new models that integrate different aspects of impulsive action and executive control. The proposed research program aims to answer five fundamental questions. (1) Can novel impulsive actions arise during task-preparation stages?; (2) What is the role of negative emotions in the origin and control of impulsive actions?; (3) How does learning modulate impulsive behaviour?; (4) When are impulsive actions (dys)functional?; and (5) How is variation in state impulsivity associated with trait impulsivity? To answer these questions, we will use carefully designed behavioural paradigms, cognitive neuroscience techniques (TMS & EEG), physiological measures (e.g. facial EMG), and mathematical modelling of decision-making to specify the origin and control of impulsive actions. Our ultimate goal is to transform the impulsive action field by replacing the currently dominant ‘inhibitory control’ models of impulsive action with detailed multifaceted models that can explain impulsivity and control across time and space. Developing a new behavioural model of impulsive action will also contribute to a better understanding of the causes of individual differences in impulsivity and the many disorders associated with impulse-control deficits.

1 998 438 €

Start date: 2018-06-01, End date: 2023-05-31

Alzheimer's Disease (AD) is a major health problem in aging societies. Remarkable progress in the study of the rare genetic forms of the disease has lead to the identification of several key players like APP and the secretases, but the molecular basis of sporadic AD remains largely unresolved. The convergence of several factors (multicausality) has to be considered. miRNAs are crucially involved in normal brain functioning and integrity. Evidence obtained from analyzing a limited number of brains indicates that miRNA expression is affected in sporadic AD. We propose the hypothesis that such changes can affect normal functioning of neurons increasing their susceptibility to AD. We will document in 3 brain regions in >100 sporadic AD patients and in >100 controls alterations in miRNA expression and explore whether similar alterations can be detected in cerebrospinal fluid. This part of the study will firmly establish which miRNAs are altered in AD. We will then investigate the functional relevance of those miRNAs by gain and loss of function experiments in brains of zebra fish and mice. We will determine the target genes of the miRNA with genetic and proteomic approaches, and establish the functional networks controlled by those miRNA. We anticipate that this will lead to complete novel insights in the role of miRNAs in AD and in maintenance of brain integrity. Our work is likely to have diagnostic relevance for AD and will identify novel drug targets for the disease.

2 500 000 €

Start date: 2011-05-01, End date: 2016-04-30

Understanding nanostructures down to the atomic level is the key to optimise the design of advanced materials with revolutionary novel properties. This requires characterisation methods enabling one to quantify atomic structures with high precision. The strong interaction of accelerated electrons with matter makes that transmission electron microscopy is one of the most powerful techniques for this purpose. However, beam damage, induced by the high energy electrons, strongly hampers a detailed interpretation. To overcome this problem, I will usher electron microscopy in a new era of non-destructive picometer metrology. This is an extremely challenging goal in modern technology because of the increasing complexity of nanostructures and the role of light elements such as lithium or hydrogen. Non-destructive picometer metrology will allow us to answer the question: what is the position, composition and bonding of every single atom in a nanomaterial even for light elements? There has been significant progress with electron microscopy to study beam-hard materials. Yet, major problems exist for radiation-sensitive nanostructures because of the lack of physics-based models, detailed statistical analyses, and optimal design of experiments in a self-consistent computational framework. In this project, novel data-driven methods will be combined with the latest experimental capabilities to locate and identify atoms, to detect light elements, to determine the three-dimensional ordering, and to measure the oxidation state from single low-dose recordings. The required electron dose is envisaged to be four orders of magnitude lower than what is nowadays used. In this manner, beam damage will be drastically reduced or even be ruled out completely. The results of my programme will enable precise characterisation of nanostructures in their native state; a prerequisite for understanding their properties. Clearly this is important for the design of a broad range of nanomaterials.

1 998 750 €

Start date: 2018-05-01, End date: 2023-04-30