ERC FUNDED PROJECTS

How do we recognize that our limbs are part of our own body, and why do we feel that one’s self is located inside the body? These fundamental questions have been discussed in theology, philosophy and psychology for millennia. The aim of my ground-breaking research programme is to identify the neuronal mechanisms that produce the sense of ownership of the body, and the processes responsible for the feeling that the self is located inside the physical body. To solve these questions I will adopt an inter-disciplinary approach using state-of-the-art methods from the fields of imaging neuroscience, experimental psychology, computer science and robotics. My first hypothesis is that the mechanism for body ownership is the integration of information from different sensory modalities (vision, touch and muscle sense) in multi-sensory brain areas (ventral premotor and intraparietal cortex). My second hypothesis is that the sense of where you are located in the environment is mediated by allocentric spatial representations in medial temporal lobes. To test this, I will use perceptual illusions and virtual-reality techniques that allow me to manipulate body ownership and the perceived location of the self, in conjunction with non-invasive recordings of brain activity in healthy humans. Functional magnetic resonance imaging and electroencephalography will be used to identify the neuronal correlates of ownership and ‘in-body experiences’, while transcranial magnetic stimulation will be used to examine the causal relationship between neural activity and ownership. It is no overstatement to say that my pioneering work could define a new sub-field in cognitive neuroscience dealing with how the brain represents the self. These basic scientific discoveries will be used in new frontier applications. For example, the development of a prosthetic limb that feels just like a real limb, and a method of controlling humanoid robots by the illusion of ‘becoming the robot’.

909 850 €

Start date: 2008-12-01, End date: 2013-11-30

The vast majority of our knowledge about how the brain encodes information has been obtained from recordings of one or few neurons at a time or from global mapping methods such as fMRI. These approaches have left unexplored how neuronal activity is distributed in space and time within a cortical column and how hundreds of neurons interact to process sensory information. By taking advantage of the most recent advances in two-photon microscopy, the proposed project addresses two broad aims, with a particular focus on the function and development of primary visual cortex: 1) to understand how cortical neuronal networks encode visual information, and 2) to understand how they become specialised for sensory processing during postnatal development. For the first aim, we will use in vivo two-photon calcium imaging to record activity simultaneously from hundreds of neurons in visual cortex while showing different visual stimuli to anaesthetised mice. This approach enables us for the first time to characterise in detail how individual neurons and neuronal subsets interact within a large cortical network in response to artificial and natural stimuli. Genetically-encoded fluorescent proteins expressed in distinct cell-types will inform us how excitatory and inhibitory neurons interact to shape population responses during vision. For the second aim, the same approach will be used to describe the maturation of cortical network function after the onset of vision and to assess the role of visual experience in this process. We will additionally use Channelrhodopsin-2, a genetic tool for remote control of action potential firing, to examine the role of correlated neuronal activity on establishment of functional cortical circuits. Together, this work will bring us closer to unravelling how sensory coding emerges on the level of neuronal networks.

1 080 000 €

Start date: 2008-07-01, End date: 2013-06-30

Social neuroscientists study the neural mechanisms underlying our capacity to understand our own and other people’s feelings. Despite neuroscientists’ advances in plasticity research and empathy research, little is known about cortical and behavioural plasticity in emotion understanding and empathy. Clearly, in today’s world, acquiring the capacity to effectively enhance empathy and prosocial behaviour is of the utmost importance. In the present project, we will investigate the malleability of empathy via training. We will adopt a multimethod and interdisciplinary approach, combining techniques and paradigms from the fields of neuroscience, (bio-)psychology, and economics. Studies 1-3 will provide a cross-sectional look at structural and functional differences in the brains of individuals scoring high vs. low on empathy, of those with pathological deficits in empathy (psychopaths, alexithymics), and of individuals starting vs. finishing a three-year training program in Carl Rogers’ person-centred therapy, which aims to increase emotional capacity and empathy. Study 4 will examine brain plasticity using real-time fMRI: Participants will learn to self-regulate brain activity through the use of immediate feedback from emotion-related brain areas while practicing certain mental techniques. In Study 5, a small-scale longitudinal study, healthy individuals will receive extensive training by professional instructors in either empathy- or memory-enhancing techniques previously developed in the East and the West. We will measure training-related changes in brain structure and functioning, in hormone levels, and in behaviour. Evidence for emotional brain plasticity in adults and children would not only have important implications for the implementation of scientifically validated, effective training programs for schools and for economic and political organizations, but also for the treatment of the marked social deficits in autistic and psychopathic populations.

1 499 821 €

Start date: 2008-09-01, End date: 2014-08-31

The project aims at unraveling the molecular pathophysiology of recessive ataxias, a heterogeneous set of severely disabling neurodegenerative disorders due to loss of function of proteins involved either in mitochondrial/metabolic pathways or DNA repair. Friedreich ataxia, the most common form, is due to partial loss of function of frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Furthermore, the rare X-linked sideroblastic anemia with cerebellar ataxia is caused by mutation in ABCb7, an ATP-binding cassette transporter of the mitochondrial inner membrane necessary for cytosolic ISC export. ISC are versatile co-factors of proteins involved in electron transport, enzyme catalysis and regulation of gene expression. The synthesis and insertion of ISC into apoproteins involve complex machineries that are still poorly understood in the mammalian cell. The objectives of this proposal are: 1) to elucidate ISC biogenesis and metabolism in the mammalian cell, with an emphasis on the role of frataxin and ABCb7; 2) to better understand the molecular pathways that are involved in neuronal dysfunction due to defects in mitochondrial ISC metabolism. These objectives will be accomplished by a multidisciplinary approach combining molecular and biochemical approaches to study the ISC assembly machineries, bioinformatic and proteomic studies to identify new Fe-S proteins, the development and pathological analysis of animal and cellular models to dissect the molecular mechanisms, and transcriptomic analysis to uncover the common pathways among recessive ataxias. A specific focus of the proposal will be the involvement of DNA damage response pathways in neuronal dysfunction, as several DNA repair enzymes have recently been identified as Fe-S proteins and thus might be directly affected by frataxin and ABCb7 deficiency. This proposal should lead to the identification of different pathways for therapeutic intervention for these devastating disorders.

1 449 924 €

Start date: 2008-07-01, End date: 2013-06-30