Ongoing projects

Using chemogenetics to re-adjust the output of the basal forebrain after cholinergic neuron depletion; 01/10/2021 - 30/09/2025

Abstract

Dementia due to the ageing world population is amongst the most defining public health concerns of this century. According to the world-health-organization, the incidence rate of neurodegenerative diseases such as Alzheimer's Disease (AD) is expected to rise exponentially in the coming decades. In addition to the decline in quality of life for the patients, the economic and societal burden of these conditions is huge. The recent failure of numerous clinical trials in AD calls for ideas in the direction of novel treatment strategies. To this end, the importance of targeted reduced systems such as animal models remains irreplaceable. In this project we will pursue a novel hypothesis that depletion of cholinergic neurons in the basal forebrain results to long-lasting changes in the GABAergic output of this neuromodulatory system and contributes to disease progression. We will first combine resting state fMRI with calcium imaging to associate both whole-brain BOLD-signal and functional connectivity with their direct underlying neuronal correlates in a rat model of cholinergic depletion and then use designer receptors activated exclusively by designer drugs (DREADDs) in the basal forebrain in order to re-adjust the output to the cerebral cortex and hippocampus. Last but not least we will evaluate the behavioral improvements caused by this manipulation.

Researcher(s)

Research team(s)

Network Analysis in Neocortex during Passive and Active Learning (neuronsXnets). 01/09/2021 - 31/08/2025

Abstract

How does the brain perform the complicated computations that allow us to learn about and interact with the environment? The rapid advances in new optical imaging, the powerful statistical analysis/machine-learning techniques, and the availability of computational resources, provide a unique opportunity to decipher this fundamental question. NeuronsXnets forms an international, multidisciplinary and intersectoral collaboration network involving leading groups in neuroscience, neuromorphic computing, data science, systems, optical tools/imaging, and hospitals. It takes advantage of this unique environment to improve the understanding of neural circuit function and integrate its findings in deep learning architectures and in neuromorphic circuits, aiming to develop a new generation of computing technologies based on the organizing principles of the biological nervous system, optimized for higher levels of cognition. NeuronsXnets will perform knowledge transfer through hands-on training and research activities during 196 secondments, courses, 4 international workshops, and seminars, to train a new generation of highly skilled systems neuroscientists and computer scientists/engineers. All partners, especially the SMEs, will benefit from the cross-fertilization, by integrating the findings and systems they have developed in their existing solutions or in new systems, capitalizing on the research results that will be achieved, and creating a long-term link between business, research, higher education & hospitals. Through open access to the developed tools and collected data, NeuronsXnets can make significant impact on the scientific community. We are committed to educate and mentor young students and raise the public knowledge about the fascinating field of neuroscience. We will strive for research excellence, to develop innovative systems, and pursue entrepreneurial objectives, leading to a new era of collaborative research in neuroscience & bio-inspired technologies.

Researcher(s)

Research team(s)

Understanding therapeutic efficacy of calorie restriction in Alzheimer's disease: dynamic rsfMRI and vascular reactivity as biomarkers in an AD rat model 01/01/2021 - 31/12/2023

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with Aβ -peptide plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, researchers have been testing the hypothesis that caloric restriction (CR) regimens can protect against cognitive decline. The exact mechanisms through which CR promotes health and lifespan are still not fully understood. Nevertheless, numerous studies were designed to unravel the responses to CR. There is increasing evidence that synaptic defects affect synaptic transmission mechanisms. These synaptic transmission deficits may influence the functional connectivity (FC) in the brain, by impairing communication between brain regions. FC can be measured using resting state functional MRI (rsfMRI), and is defined as the temporal correlation between low frequency fluctuations in the BOLD fMRI signal in distinct brain areas. RsfMRI has identified default mode and task positive network disruptions as promising biomarkers for AD. Recently, the rsfMRI field has seen a shift from 'static' BOLD signal analysis to more time-resolved dynamic analysis. Dynamic rsfMRI is a state-of-the-art approach, which has revealed new insights into the macro-scale organization of functional networks. While CR is already known to influence memory performance, tauopathy and Aβ plaque formation, AD patients also have cerebral amyloid angiopathy (CAA), which influences vascular reactivity and therefore neurovascular coupling. It is of interest to identify these early markers of pathology progression using non-invasive imaging, as well as monitor the effect of CR on CAA, cerebral blood flow (CBF) and vascular reactivity using arterial spin labeling. In contrast to the BOLD signal which depends on the local cerebral metabolic rate of oxygen, CBF and cerebral blood volume, pCASL provides an absolute measure that only reflects CBF and hence enables to further disentangle the BOLD response and associated FC analysis. An alternative to dietary CR are nutrients that mimic these beneficial effects on brain aging (CR mimetics). These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. In this project, we will combine dynamic rsfMRI, pCASL and behavioral tests in a TgF344-AD rat model, which recapitulates the major hallmarks of AD. We postulate the hypotheses that early decreases in (dynamic) FC and CBF may be potential prognostic biomarkers of the long-term outcome (memory and neuropsychiatric deficits) in this AD rat model; that FC and CBF at the time point when behavioural deficits occur, may be predictive biomarkers of the therapy (i.e. CR); that CR alleviates both memory and neurovascular deficits in this AD rat model; and that CR mimetics provide a therapeutic alternative with the same effects on memory and vascular reactivity.

Researcher(s)

Research team(s)

Upgrade of 9.4T Bruker BioSpec MRI imaging system to Avance NEO hardware architecture. 01/05/2020 - 30/04/2024

Abstract

Upgrade of the hardware of existing equipment (9.4T MRI system from Bruker) to perform state of the art MRI investigations in the brain of small animals such as mice, rats and birds. This hardware upgrade will enable implementation of all new Bruker software packages.

Researcher(s)

Research team(s)

Improved classification of Alzheimer's disease assessed from the slowly propagating waves of BOLD intensity, the Quasi-Periodic patterns, observed in dynamic resting-state fMRI in a AD rat model at rest and upon sensory stimulation. 01/01/2020 - 31/12/2023

Abstract

The rsfMRI field has seen a shift from 'static' blood-oxygen level dependent (BOLD) signal analysis to time-resolved dynamic analysis. Dynamic rsfMRI (drsfMRI) is a state-of-the-art approach, which has revealed many new insights into the macro-scale organization of functional networks and could already identify short-lasting large scale spatiotemporal patterns of BOLD activity, the 'Quasi-Periodic Patterns' (QPPs) in humans and rats. The QPPs describe recurring spatiotemporal neural events that display anti-correlation between two major brain networks (DMN and TPN), and therefore represent likely contributors to their functional organisation. Therefore, we reason that QPPs could provide new insights into AD network dysfunction and improve disease diagnosis. We postulate the hypothesis that QPPs would help understand the aberrant DMN and TPN Functional Connectivity (FC) observed in Alzheimer's disease, and might serve as a more sensitive biomarker than conventional rsfMRI measures, improving AD classification both in an early pre-plaque stage as late post-plaque stage. In this project, we will use state-of-the-art MRI to investigate: a) how QPPs in a rat model for AD (TgF344), differs from control animals, b) the vascular contribution to QPPs, c) how these QPPs might interact with sensory stimulation processing, d) how the QPPs acquired at rest or sensory stimulation contribute to the DMN and DMN-TPN FC, and how they improve AD classification.

Researcher(s)

Research team(s)

Neurobiological predictors and social enhancers of vocal learning. 01/10/2019 - 30/09/2023

Abstract

Cultural transmission of vocal behaviours such as human speech or bird song, are greatly influenced by how adults interact with each other and with their young. Even though these behavioural observations are well established, surprisingly, the neurobiological mechanisms via which social enhancement potentiates learning are still poorly understood. Recently, we discovered that future song learning accuracy can be predicted very early in the song learning process based on the structural properties of the auditory areas of the zebra finch brain. Building further on this recent discovery, we aim to (1) identify the neurobiological basis of this prediction; (2) uncover the functional neural circuit that selectively responds to social factors inherent to song learning; and (3) unravel the functional and structural connectivity between the prediction site and remote brain areas. To reach these aims, we will use advanced magnetic resonance imaging (MRI) tools that enable to repeatedly quantify the structural architecture and connectivity of the zebra finch brain along the process of vocal learning. We will validate these insights by advanced histology. Moreover, this will be the first study to employ awake functional MRI in juvenile zebra finches to repeatedly probe brain activation patterns in response to specific stimuli presented by a video. To establish brain-behaviour relationship, we will evaluate the MRI outcome relative to several behavioural measures in the same bird.

Researcher(s)

Research team(s)

Novel Biomaterial-based Device for the Treatment of Progressive MS - An Integrated Pan- European Approach (PMSMatTrain). 01/05/2019 - 30/04/2023

Abstract

PMSMatTrain is focusing on gaining a comprehensive understanding of the progressive (late degenerative phase) of multiple sclerosis (PMS) from basics to translation, fully supported by 8 beneficiaries (6 research institutions, 2 SMEs). Recruited ESRs will receive compulsory discipline-specific, generic and complementary transferable skills training. PMSMatTrain's Joint Research Education and Training programme (JRTP) will provide early stage researchers with high quality research and transferable skills training in intellectual property, leadership skills, innovation, regulatory affairs, entrepreneurship, gender policy, and medical device evaluation, which will ensure that they are immediately employable in industry. The consortium will develop a multi-modal hyaluronan-based medical device designed to release small molecular weight anti-inflammatory molecules (APRIL and sPIF) followed by remyelination and neuroprotective drugs (ibudilast and miconazole). PMSMatTrain will for the first time utilise these functionalised multi-modal biomimetic hyaluronan scaffolds as a tool to investigate cross-talk between signals arising due to chronic neuroinflammation and those leading to demyelination and axonal loss, while identifying molecular mechanisms that facilitate remyelination and neuroprotection in PMS. This approach could yield the first cortex-proximal and directed biomaterials-based disease-modifying therapy for PMS. These scaffolds will be tested in state of the art MS patient induced stem cell-derived oligodendrocyte cultures and organotypic cultures to investigate MS pathophysiology. In vivo responses will be characterised using field-leading MRI and mass spectrophotometry protocols. PMSMatTrain will also generate a clinically-relevant in silico model of drug elusion and dispersal within the CNS. Our industry partners will develop the end-device by providing standardised manufacturing protocols for scaled-up production and commercialisation of the cGMP product.

Researcher(s)

Research team(s)

How the interplay between basal forebrain neuronal populations determines brain state and how this is changed in Alzheimer's disease. 01/10/2018 - 30/09/2022

Abstract

During the last decades, the achievement of a better and improved quality of life has resulted in increased life expectancy. This is mainly due to progress in translational research and development of new therapeutic approaches. The downside is that age is one of the major risk factors for dementias and neurodegenerative disorders such as Alzheimer's disease (AD), characterized by a marked decline of cognitive functions (e.g. short- and long-term memory loss) and dysregulation of higher cortical functions (e.g. impaired judgement and thinking). The pathological condition of these diseases is disabling enough to compromise the activity of everyday life. Lengthening the life span has little value if the quality of life cannot be ensured. Unfortunately, the pathogenesis of AD is still far from being understood and this could be the reason why none of the currently available pharmacological therapies for this disease are satisfactory. Current treatments are purely symptomatic and do not act on the onset and progression of the pathology. It is well known that Basal Forebrain (BF) cholinergic neurons are prone to degeneration during aging as well as in dementias like AD. Furthermore, "the cholinergic hypothesis of geriatric cognitive dysfunction" is also supported by the significant correlation between the level of cholinergic depletion and the degree of cognitive deficits. Acetylcholine is a neuromodulator broadly investigated for its role in learning and memory, but it is not the only player in AD. In fact, in the BF, intermingled with cholinergic neurons, there are also two non-cholinergic neuronal types: GABAergic and glutamatergic neurons. It has been discovered that dysfunctions at the level of glutamatergic and GABAergic systems are involved as well in AD. Until recently, neuroscientists have limited the research of AD to the study of a single neuronal type (mainly BF cholinergic neurons), overlooking the possible role of non-cholinergic neuronal populations (GABAergic and glutamatergic). However, it is of the utmost importance to uncover the interaction between BF cholinergic and non-cholinergic neurons to develop novel strategies for the treatment of AD. The proposed research project aims to investigate the interaction between the three distinct BF populations and to elucidate how the BF cholinergic neuronal activity influences the other two BF neuronal types both in healthy and in pathological conditions. To date, it is still far from being understood how the neural state of the cholinergic neurons influences the GABAergic and glutamatergic neurons in the BF and how these, in turn, adjust cholinergic neuromodulation. We suggest to study the activity of BF neuronal populations and their interactions during spontaneous activity and determine the relationship of the activity of these three neuronal populations with whole brain functional connectivity. Then we will target and stimulate the BF cholinergic neurons using optogenetics to understand how it influences network interactions and to identify the optimal conditions of stimulation in an AD animal model that can induce network states as observed during spontaneous activity in healthy animals. To achieve these goals, we propose a methodological approach that is both innovative and multimodal because it combines cutting edge techniques such as fMRI tools, optogenetics and fiber-optic calcium recording. The results of this study will provide an increased and better understanding of BF neural circuitry, thus opening new future perspectives for the treatment of cognitive disorders.

Researcher(s)

Research team(s)

Past projects

Cholinergic and noradrenergic neuromodulation of memory and mood. 01/04/2020 - 31/03/2021

Abstract

The current therapies of Alzheimer's disease (AD) are insufficient and novel treatments are necessary. Cholinergic and noradrenergic neurotransmitter systems are involved in memory and mood modulation. An add-on effect of increased noradrenergic signalling in addition to the standard therapy of increased cholinergic signalling has been proposed for AD patients. However, the interaction between the two systems is not well understood. In this proposal, we will evaluate the effects of activating via DREADDs 1) cholinergic neurons in medial septum, which project to hippocampus, 2) noradrenergic neurons in locus coeruleus, which project to medial septum and hippocampus, and 3) cholinergic and noradrenergic neurons. We will evaluate the effect of these different modulations on behaviour (memory and mood) and whole-brain functional connectivity and cerebral blood flow in a promising rat model for Alzheimer's disease. Finally, we will assess whether early deficits in functional connectivity and cerebral blood flow can predict long-term behavioural outcome in (untreated) AD rats and whether deficits in these parameters can predict the responsiveness to the treatment (one of the three possible modulations).

Researcher(s)

Research team(s)

Improved classification of Alzheimer's disease: differentiation of slow propagating waves of BOLD intensity of dynamic rsfMRI in AD mice models in pre-plaque and post-plaque stages. 01/01/2019 - 31/12/2020

Abstract

There is increasing evidence that in neurodegenerative diseases (ND) synaptic defects affect synaptic transmission mechanisms. These synaptic transmission deficits may influence the functional connectivity (FC) in the brain, by impairing communication between brain regions. FC can be measured using resting state functional MRI (rsfMRI), and is defined as the temporal correlation between low frequency fluctuations in the blood-oxygen-level-dependent (BOLD) fMRI signal in distinct brain areas. Thus rsfMRI enables a nuanced appreciation of the system-scale network structure of the brain. It was reported that various topological properties of resting state functional networks correlate with higher cognitive functions and are susceptible to various pathological disruptions. Patients with Alzheimer's disease (AD) display aberrant brain function. RsfMRI has identified default mode (DMN) and task positive (TPN) network disruptions as promising biomarkers for AD. Recently, the rsfMRI field has seen a shift from 'static' BOLD signal analysis to more time-resolved dynamic analysis. Dynamic rsfMRI (drsfMRI) is a state-of-the-art approach, which has revealed many new insights into the macro-scale organization of functional networks and could already identify short-lasting large scale patterns of spatiotemporal BOLD activity, the 'Quasi- Periodic Patterns' (QPPs) in human and rats. Just recently, we observed the existence of QPPs of a set of large-scale Quasi-Periodic patterns in healthy anesthetized mice, similar as to what has been observed in other species, and which highly resemble known mouse resting state networks. The latter hints at a neuronal origin and a contribution to brain functional connectivity. We further illustrated how global signal regression affects the spatiotemporal dynamics, suggesting a potential role for its effect in conventional rsfMRI studies. Patterns could be observed reliably at the single subject level, marking promise in the advance towards more reliable rsfMRI research. Finally, the QPPs of neural activity, describe recurring spatiotemporal events that display DMN with TPN anti-correlation. QPPs therefore represent likely contributors to the DMN's and TPN's functional organisation. Therefore, we reason that QPPs could provide new insights into AD network dysfunction and improve disease diagnosis. We postulate the hypothesis that QPPs would help understand the aberrant DMN and TPN FC observed in Alzheimer's disease, and might serve as a more sensitive biomarker than conventional rsfMRI measures, improving AD classification both in an early pre-plaque stage as late post-plaque stage. In this project, we will use state-of-the-art MRI to investigate: a) how QPPs in a mouse models for AD (Tg2576), differs from control animals, b) how these QPPs might interact with sensory stimulation processing, c) how the QPP acquired at rest or sensory stimulation contribute to the DMN and DMN-TPN FC, and how they improve AD classification.

Researcher(s)

Research team(s)

Cholinergic and noradrenergic modulation of memory and mood. 01/10/2018 - 30/09/2021

Abstract

The current therapies of Alzheimer's disease (AD) are insufficient and novel treatments are necessary. Cholinergic and noradrenergic neurotransmitter systems are involved in memory and mood modulation. An add-on effect of increased noradrenergic signalling in addition to the standard therapy of increased cholinergic signalling has been proposed for AD patients. However, the interaction between the two systems is not well understood. In this proposal, we will evaluate the effects of activating via DREADDs 1) cholinergic neurons in medial septum, which project to hippocampus, 2) noradrenergic neurons in locus coeruleus, which project to medial septum and hippocampus, and 3) cholinergic and noradrenergic neurons. We will evaluate the effect of these different modulations on behaviour (memory and mood) and different brain network properties in a promising AD rat model and in healthy rats. We will look at functional connectivity in the brain, oscillations in local field potentials in hippocampus (which reflect local hippocampal network properties), and whole-brain activity state related to sharp-wave ripples, a neuronal event that occurs within hippocampus and that is associated with memory. Finally, we will assess whether early deficits in functional connectivity and cerebral blood flow can predict long-term behavioural outcome in (untreated) AD rats and whether deficits in these parameters can predict the responsiveness to the treatment (one of the three possible modulations).

Researcher(s)

Research team(s)

Does melanopsin mediate seasonal neuroplasticity in starlings ? 01/10/2018 - 31/03/2021

Abstract

Light is an important environmental factor driving many functions in animal physiology. There are two systems for detecting light in animals i) The classical visual system for image formation (IF) and ii) The Non-image-forming (NIF) visual circuit. NIF in mammals is mediated by melanopsin containing intrinsically photoreceptive retinal ganglionic cells and innervates brain regions regulating sleep, circadian functions, cognition etc. We hypothesize that the NIF circuit mediates the light's influence in neuroplasticity of seasonal songbirds. To test this, we use European starling's which shows extensive neuroplasticity in response to seasons, in vivo MRI and molecular biology techniques.

Researcher(s)

Research team(s)

The role of non-cholinergic neurons in cholinergic neuromodulation. 01/10/2018 - 31/10/2019

Abstract

During the last decades, the achievement of a better and improved quality of life has resulted in increased life expectancy. This is mainly due to progress in translational research and development of new therapeutic approaches. The downside is that age is one of the major risk factors for dementias and neurodegenerative disorders such as Alzheimer's disease (AD), characterized by a marked decline of cognitive functions (e.g. short- and long-term memory loss) and dysregulation of higher cortical functions (e.g. impaired judgement and thinking). The pathological condition of these diseases is disabling enough to compromise the activity of everyday life. Lengthening the life span has little value if the quality of life cannot be ensured. Unfortunately, the pathogenesis of AD is still far from being understood and this could be the reason why none of the currently available pharmacological therapies for this disease are satisfactory. Current treatments are purely symptomatic and do not act on the onset and progression of the pathology. It is well known that Basal Forebrain (BF) cholinergic neurons are prone to degeneration during aging as well as in dementias like AD. Furthermore, "the cholinergic hypothesis of geriatric cognitive dysfunction" is also supported by the significant correlation between the level of cholinergic depletion and the degree of cognitive deficits. Acetylcholine is a neuromodulator broadly investigated for its role in learning and memory, but it is not the only player in AD. In fact, in the BF, intermingled with cholinergic neurons, there are also two non-cholinergic neuronal types: GABAergic and glutamatergic neurons. It has been discovered that dysfunctions at the level of glutamatergic and GABAergic systems are involved as well in AD. Until recently, neuroscientists have limited the research of AD to the study of a single neuronal type (mainly BF cholinergic neurons), overlooking the possible role of non-cholinergic neuronal populations (GABAergic and glutamatergic). However, it is of the utmost importance to uncover the interaction between BF cholinergic and non-cholinergic neurons to develop novel strategies for the treatment of AD. The proposed research project aims to investigate the interaction between the three distinct BF populations and to elucidate how the BF cholinergic neuronal activity influences the other two BF neuronal types both in healthy and in pathological conditions. To date, it is still far from being understood how the neural state of the cholinergic neurons influences the GABAergic and glutamatergic neurons in the BF and how these, in turn, adjust cholinergic neuromodulation. We suggest to study the activity of BF neuronal populations and their interactions during spontaneous activity and determine the relationship of the activity of these three neuronal populations with whole brain functional connectivity. Then we will target and stimulate the BF cholinergic neurons using optogenetics to understand how it influences network interactions and to identify the optimal conditions of stimulation in an AD animal model that can induce network states as observed during spontaneous activity in healthy animals. To achieve these goals, we propose a methodological approach that is both innovative and multimodal because it combines cutting edge techniques such as fMRI tools, optogenetics and fiber-optic calcium recording. The results of this study will provide an increased and better understanding of BF neural circuitry, thus opening new future perspectives for the treatment of cognitive disorders.

Researcher(s)

Research team(s)

Melanopsin mediated photoreception: A common regulator of both seasonal neuroplasticity and cerebral vasculature function. 01/04/2018 - 31/03/2019

Abstract

Light is one of the most important environmental factors driving many important functions in animal physiology including reproduction and neuroplasticity. It has also been shown to regulate vasculature development, its arrangement and function. In this context, Melanopsin, an opsin molecule found in ganglionic cell layer of retina (in mammals) has been shown to regulate the NON IMAGE FORMING (NIF) circuit in mammalian brain, mediating the effect of light on many physiologies including sleep, cognition and mood. Recently, melanopsin have been found in blood vessels of aorta influencing the light mediated vasodilation and also have been shown to regulate the formation of retinal blood vasculature. Light (or photoperiod) is known to influence neuroplasticity regulating it seasonally in seasonal birds (specially the song control system). Our own findings show that melanopsin is present in starling brain regions which displays seasonal neuroplasticity, which also corresponds to the mammalian like NIF network. Interestingly, we recently found melanopsin in the blood vessel linings in avian (European starlings) telencephalon. Thus, we hypothesized that melanopsin may be the common regulator of seasonal vasculature function (including both angiogenesis and blood flow). In this proposal, we will use ex vivo molecular techniques to map the expression of melanopsin in a seasonal avian model, the European starlings. We will also develop in vivo imaging methods (MRI) to map and track vasculature function in a seasonal context. As neuroplasticity and vasculature development have a causal relationship with both influenced by light, a common regulator will have evolutionary significance. Knowledge of seasonal cycle of neuroplasticity/vasculature will also help to understand mechanisms that could promote brain repair in pathological conditions such as brain trauma or neurodegenerative diseases.

Researcher(s)

  • Promotor: Majumdar Gaurav

Research team(s)

The 'Non image' forming photoreception in seasonal birds: A possible role in Seasonal neuroplasticity. 01/02/2018 - 30/09/2018

Abstract

Light is an important environmental factor driving important functions in animal physiology through the vision forming circuit or by non-image forming (NIF) brain circuit. NIF in mammals starts with melanopsin (OPN4) containing intrinsically photoreceptive retinal ganglionic cells (ipRGCs), that innervate brain regions regulating sleep, circadian functions, cognition etc. NIF has high sensitivity to blue light wavelength, which activates the melanopsin. Also, light through photoperiodic differences in seasons induces neuroplasticity in song bird's song control system (SCS), which may be hormone independent. We hypothesize that NIF processes underlie this neuroplasticity based on its influence in multiple brain regions not involved in visual system. To test this, we use European starling's, which show extensive SCS neuroplasticity in response to seasons. We want to first demonstrate that a NIF circuit exists in birds using in vivo MRI imaging along with molecular biology techniques with the contribution of eyes and brain in it. Then we propose to modulate the neuroplasticity by directly activating NIF through melanopsin by using blue light. Our results will for the first time link light and neuroplasticity. Melanopsin is also involved in disorders like Alzheimer's, seasonal affective disorder (SAD) and Light at night (LAN) related problems in cities. Thus, light, melanopsin and its influence on neuroplasticity may pave a way for further understanding of neurobiological disorders.

Researcher(s)

Research team(s)

Seasonal neuroplasticity of visual and auditory system integration: an in vivo MRI study in starling. 01/04/2017 - 31/03/2018

Abstract

Previous studies from our team have demonstrated that seasonal plasticity in the songbird brain extends the song control system (SCS) covering sensory systems such as the visual and the auditory system. In this project we want to investigate whether seasonal neuroplastic changes in these circuits imply also functional changes that steer behavioral differences in favor of reproduction. This would revolutionize the concept of seasonal plasticity which was until recently well described only for the SCS with a clear behavioral read out, i.e. changes in song performance. Since visual inputs, linked to mate attraction, change over the seasons, it is our objective to study seasonal changes in visual system processing. This will be done in both male and female starling using functional magnetic resonance imaging (fMRI). We hypothesize that structural and functional changes in the sensory systems are specific for particular stimulus categories such as sexually relevant stimuli. To investigate this hypothesis, we will perform visual fMRI with visual reproductive relevant stimuli over the seasons.

Researcher(s)

Research team(s)

Multimodal Imaging of cholinergic neuromodulation during specific memory phases in the rodent brain. 01/01/2017 - 31/12/2020

Abstract

Advances in translational research and widespread distribution of therapeutic means have led to dramatic increases in global life expectancy over the past decades. However, at the same time longevity imposes a great impact on the quality of life of the ageing population. Numerous neurological diseases such as various types of dementia (e.g. Alzheimer's) rise exponentially with age inflicting great economic and social burden to the societies. To this end, basic brain research continues to be a major component in providing the necessary insights for the reversal of these trends. Memory and learning are inextricably related to most dementias but our understanding of the underlying mechanisms remains rudimentary. Further, the amount of certain brain chemicals (neurotransmitters), in particular one called acetylcholine, is also reduced. This project will use a combination of state-of-the-art magnetic resonance and calcium imaging in order to a) uncover the relationship between learning and specific pathways of cholinergic transmission by using DREADDs (specifically designed receptors that can be introduced in specific cells and modulate their activity), b) understand the dynamics of this relationship during ageing, and c) test if application of this approach in rodent models of Alzheimer's disease that loose cholinergic cells can ameliorate the effects and improve memory. If successful, this project will provide the basis for developing new therapeutic approaches in the future.

Researcher(s)

Research team(s)

Unraveling the effect of thyroid hormones on seasonal neuroplasticity in the song control system of adult songbirds. 01/10/2016 - 30/09/2019

Abstract

Prior studies mainly focused on the effect of T on SCS plasticity. However, it has been shown that steroid-independent photostimulation can also induce SCS plasticity, but its mechanism remains unclear [9-11]. One of the proposed alternatives is the mediating effect of THs, as THs play an important role in the regulation of seasonal reproduction and are associated with neurogenesis. Surprisingly, the effect of THs on SCS plasticity has only been studied partially [24]. In addition, it is unknown whether THs mediate SCS plasticity in a direct or an indirect manner. To this end we designed a series of experiments divided into 3 work packages (WP).

Researcher(s)

Research team(s)

Seasonal neuroplasticity of visual and auditory system integration: an in vivo MRI study in starling. 01/10/2016 - 30/09/2019

Abstract

This project onderzoeken we of seizoenale neuroplastische veranderingen in sensorische netwerken van seizoenale zangvogels gepaard gaan met functionle veranderingen die leiden tot gedragswijzigingen die reproductie in de hand werken. Het onderzoek maakt gebruik van multisensory fMRI.

Researcher(s)

Research team(s)

Neuro-image guided investigation of the critical role of aromatase inhibitors on brain function 01/04/2016 - 31/03/2017

Abstract

The hormone estrogen has neuroprotective function in the brain. Thus synthesis of estrogen in the brain and ovaries is important for healthy brain functioning. The cythorome P450 aromatase, a key enzyme in the biosynthetic pathway of estrogen, catalyzes the conversion of androgens to estrogen in neurons and activated astrocytes. Aromatase inhibitors are commonly used to treat women with invasive estrogen receptor positive breast cancer. In these patients, however, diminished estrogen levels have been linked with cognitive decline and an increased risk for developing Alzheimer's disease. How aromatase inhibition relates to cognitive dysfunction and AD needs to be investigated. The association between aromatase activity, estrogen level and cognitive performance is complicated and is not completely understood. The aim of this study is to assess how aromatase inhibitors affect the functional and structural network organization of the brain via resting state functional magnetic resonance imaging (MRI) and diffusion tensor imaging. Both of these MRI techniques provide significant information into brain function in disease and health and into the effects of interventions in functional and structural networks.

Researcher(s)

  • Promotor: Kara Firat

Research team(s)

An immunofluorescence toolbox for the assessment of synaptic pathology. 01/04/2016 - 28/02/2017

Abstract

Within the lab, many ongoing projects use Resting state functional MRI to study the brain's functional network architecture during development, health and disease. These longitudinal in vivo studies often require ex vivo confirmation of the observed phenomena. As such, within this project we wish to implement an immunofluorescence analysis pipeline to asses synaptic and neuronal pathology in mice, rats and zebra finches. We will set up a pipeline to determine: (i) the amount of structurally intact synapses, (ii) the GABA/GLU ratio, (iii) the amount and ratio of GABAergic and glutamatergic synapses and (iv), the amount of serotonergic, noradrenergic, dopaminergic and cholinergic neurons.

Researcher(s)

  • Promotor: Praet Jelle

Research team(s)

Do thyroid hormones play a role in photoperiod induced neuroplasticity and neurogenesis in seasonal songbirds? (M. GAURAV, Indië). 01/03/2016 - 31/08/2017

Abstract

This project investigates the role of hypothalamus-pituitary-thyroid hormons in the photoperiodicity induced neuroplasticity in seasonal songbirds and the interaction with hypothalamic-pituitary-gonadal axis hormones.

Researcher(s)

Research team(s)

The influence of soluble amyloid β on resting state functional connectivity in the absence or presence of amyloid β plaques. 01/01/2016 - 28/02/2017

Abstract

Alzheimer's disease (AD) is a devastating neurological disorder and the most common type of dementia in the elderly population. It is mainly characterised by the appearance of small protein aggregates inside the brain, commonly known as amyloid beta (Aβ) plaques. These Aβ plaques form when soluble Aβ peptides oligomerize, a process which was found to occur more frequently when high concentrations of soluble Aβ are present. During preliminary studies in transgenic AD mice, we have observed that the strength of functional connectivity (FC) between brain regions initially increases. During the period of intense Aβ plaque formation however, FC decreases. These results postulated a dynamic rewiring of the brains' connections to adapt to high concentrations of soluble Aβ and Aβ plaque formation. In this project, we wish untangle the influence of soluble Aβ on resting state functional connectivity in the presence or absence of Aβ plaques. We will make use of the Tet-Off APP mouse model which allows inducible over-expression of the amyloid precursor protein by means of doxycycline treatment. We will use Rs fMRI to longitudinally follow up changes in FC between different brain regions due to this controlled over-expression of amyloid precursor protein. The results of this research will allow a better understanding of how the brain adapts to progressive amyloidosis and how both clinicians and researchers should interpret AD Rs fMRI data.

Researcher(s)

  • Promotor: Praet Jelle

Research team(s)

Ultrafast Functional Ultrasound (fUS) Imaging for highly resolved targetted mapping of functional connectivity in the awake mouse brain (FUSIMICE). 01/12/2015 - 30/11/2018

Abstract

In this project, a new imaging methodology (functional Ultra Sound) is developed, tested and compared with resting state functional Magnetic Resonance Imaging to study the functional connectivity between different brain circuits.

Researcher(s)

Research team(s)

Spatial neglect in rodents: a model for studying neuroplasticity at the network level. 01/10/2015 - 30/09/2019

Abstract

Diseases that afflict the brain, such as stroke, are associated with high morbidity for patients and their families and incur a tremendous burden to individuals and the society. Spatial neglect is a frequent consequence of brain damage, manifesting attentional deficits in perceiving and responding to stimuli in the contralesional field. Neglect affects roughly one third of stroke victims and greatly interferes with all daily activities, being one of the most disabling neurological syndromes. Despite partial recovery in the first months after stroke, yet poorly understood, one third of these patients remain severely disabled and require specific treatment. Although a number of treatments exist for human patients none is extremely successful, as we do not understand sufficiently the neural mechanisms underlying the disorder with multiple questions remaining to be addressed. To tackle some of these complicated issues, we propose to use a multimodal approach that combines functional magnetic resonance imaging, electrophysiology and stimulation of neuromodulatory nuclei in a rat model of spatial neglect. These state-of-the-art techniques will be applied after temporary and chronic focal lesions of central nodes of the neglect network in rats causing neglect like deficits that simulate the disorder in humans. Our proposal will significantly advance the understanding of the neural processes involved in neglect and specifically the role of functional connectivity at the neural circuit level. Furthermore, we will evaluate a novel and highly promising rehabilitation method that utilizes the role of neuromodulation in attentional processes by optogenetic stimulation of the cholinergic nucleus basalis of Meynert. If successful, this would provide a tremendous impact both in basic and clinical research and provide the basis for novel rehabilitative approaches in humans (e.g. by deep brain stimulation).

Researcher(s)

Research team(s)

The role of the extracellular matrix proteases MMP-9 and uPA in the development of posttraumatic epilepsy following traumatic brain injury. 01/10/2015 - 30/09/2017

Abstract

We propose a novel hypothesis for the development of PTE with a central role for ECM modulating components MMP-9 and uPA. TBI results in blood-brain barrier disruption, hyperexcitability and primary damage triggering repair mechanisms such as modulation of the ECM by proteases MMP-9 and uPA. These alterations in ECM proteases MMP-9 and uPA, followed by brain inflammation, induce abnormal synaptic remodeling and epileptogenesis, ultimately leading to PTE.

Researcher(s)

Research team(s)

Sleep deprivation, soluble Amyloid ɴand the glymphatic system. A neurotoxic triad during Alzheimer's Disease? 01/10/2015 - 07/03/2017

Abstract

Alzheimer's disease (AD) is a devastating neurological disorder and the most common type of dementia in the elderly population. It is mainly characterised by the appearance of small protein aggregates inside the brain, commonly known as amyloid beta (Aß) plaques. These Aß plaques form when the soluble Aß peptides oligomerize, a process which was found to occur more frequently when high concentrations of soluble Aß are present. Very recently, a system responsible for the clearance of normal metabolic waste products and thus also the soluble Aß protein was identified inside the brain. This system, termed the glymphatic system (GS), was shown much more active during sleep compared to awake. As such, during sleep the GS clears waste products from the brain which formed during normal daytime activities. In this research project, we wish to investigate in more detail the relationship between sleep (and more specifically sleep disturbances), the GS, soluble Aß and the formation of Aß plaques. As sleep disturbances were seen to coincide with Aß plaque formation, we wish to elucidate which one of the 2 occurs first and, how this influences the GS. This is of particular interest to the general population as modern lifestyle considers sleep as a necessary evil with many people working during the night and even more sleeping too little too few, which could possibly result in sleep debt and thus an increased risk of developing AD.

Researcher(s)

Research team(s)

WildCog: Evolution and local adaptation of cognitive abilities and brain structure in the wild. 01/09/2015 - 31/08/2018

Abstract

Cognition plays a critical role in how organisms interact with their social and ecological environment, and while the mechanisms underlying cognitive processes are becoming clearer, we still know little about the evolution of cognitive traits in natural populations. Cognitive abilities of organisms implicitly lie at the core of many fields since they determine in part how organisms compete with each other and acquire mates, how they find food and avoid being eaten, how they flexibly adjust to new contexts, and how they navigate landscapes. Many different cognitive capacities have been characterized and show within and across species variation, yet the extent to which this variation results from ecological imperatives faced by each species or population remains to be determined. Furthermore, despite progress in the neurophysiology of cognition in model organisms, we still have little understanding of the neural structure underlying cognitive traits important in wild organisms as well as how natural selection influences neural structure. Our goal is to examine the evolution of cognitive traits in a wild bird species by measuring multiple cognitive abilities, neural structure via MRI, and fitness to provide new insights into variation and the evolution of cognition. We will study 8 populations of great tits that lie along two ecological gradients (altitude, urbanization) that should favor different cognitive traits. Success in this ambitious project requires us to design new cognitive tests and a new touchscreen test system, new analytic methods (automated video analysis), explore brain structure in a non-model organism using MRI, and measure ecology and fitness of wild birds. To do this, we have assembled an interdisciplinary research group including specialties in brain imaging, animal cognition, computer sciences/ analytics, and evolutionary biology. This combination of expertise gives us the tools to succeed since each researcher has the appropriate skills to execute their portion of the study while contributing new methods and knowledge. In each case, there is considerable potential for novel contributions within each field as well as important advances for the interdisciplinary efforts linking evolution, cognition, and neurosciences. Combining data on fitness, cognition, and brain physiology on the same individuals in wild populations of birds will give us an unprecedented understanding of how selection operates on and shapes variation in cognition.

Researcher(s)

Research team(s)

Processes of integration in multi-stable visual motion perception. 15/07/2015 - 14/07/2016

Abstract

Perceptual multi-stability is established when the brain fails to reach a single interpretation of the input from the external world. In the visual modality, a number of ambiguous visual patterns have been described such as the Necker cube, motion plaids, and binocular rivalry. Multi-stable stimuli can provide unique insights into visual processing, as changes in perception are decoupled from changes in the stimulus. Understanding of how multi-stable perception occurs might help one to understand visual perception in general. In order to explore this question, we developed a novel pseudo-plaid stimulus composed of numerous small apertures simulating neural receptive fields. Importantly, this stimulus allows parametric manipulation of the underlying features driving perception and can help us understand the nature of motion integration processes. In this project, we have already used this stimulus in psychophysics experiments with human subjects. Currently the same stimulus is being used in electrophysiological measurements from non-human primate visual cortex. Our findings suggest that stimulus intersections can strongly bias motion perception towards a coherent integrated pattern. Preliminary results from early visual stages (area V1) demonstrate that neurons respond irrespective of perception based on the local stimulus features. On the contrary, neurons at higher visual stages (area MT) modulate their activities in parallel with perception (consistent with human psychophysics) indicating that integration of contextual motion information has taken place.

Researcher(s)

Research team(s)

A system for simultaneous acquisition of MRI and intracranial electrophysiology: a ground-breaking multimodal approach to study brain networks and their components. 01/06/2015 - 31/12/2017

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)

Biomedical Microscopic Imaging and in-vivo Bio-Imaging (EGAMI). 01/01/2015 - 31/12/2020

Abstract

EGAMI stands for Expert Group Antwerp Molecular Imaging. Moreover, EGAMI is the mirror word of 'image'. EGAMI clusters the internationally recognized expertise in the profession of fundamental and biomedical imaging at the University of Antwerp: the Bio-Imaging Lab, the Molecular Imaging Center Antwerp (MICA), Radiology, the Laboratory for Cell Biology and Histology, and the Vision Lab (for post-processing of medical images). EGAMI's mission is providing an integrated research platform that comprises all aspects of multimodality translational medical imaging. Multimodality refers to the integration of information from the various imaging techniques. Within EGAMI, there is pre-clinical and clinical expertise and infrastructure for magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). EGAMI executes projects ranging from applied biomedical (imaging) and fundamental research to imaging methodologies. Die applied biomedical research focusses on the research fields neuro(bio)logy (i.e. development and validation of biomarkers (as well as therapy evaluation) for diseases like Alzheimer's, schizophrenia, multiple sclerosis etc.) and oncology (i.e. biomarkers for improved patient stratification and therapy monitoring). Since the pre-clinical biomedical research within EGAMI makes use of miniaturized versions of imaging equipment for humans (scanners) is it inherently translational, in other words initial findings acquired in animal experiments can be translated into clinical applications for improved diagnosis and treatment of patients ('from bench to bedside'). Beside the application of imaging in the biomedical research, EGAMI also conducts projects that aim to achieve an improvement and optimization of the imaging methodology. The expertise of the MICA (e.g. the development of new radiotracers) and of the Vision Lab (e.g. the development of image reconstruction, segmentation, and analysis algorithms) offers here the strategic platform to assemble intellectual property rights.

Researcher(s)

Research team(s)

In vivo MR imaging of small laboratory animals. 01/01/2015 - 31/12/2019

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)

Neuro Image-guided decoding of mechanisms involved in healthy, accelerated and pathological aging. 01/01/2015 - 31/12/2018

Abstract

The overall goal of project is to contribute new information that will greatly increase our understanding about underlying mechanisms of hypothalamus-driven normal, accelerated and pathological aging of the brain, with the focus on structural alterations and subsequent alterations of specific functional networks such as the default mode network (DMN) and its anticorrelated networks. Our results will provide fundamental knowledge for age dependent intrinsic network structural changes as a reference for pathological aging studies where altered DMN activity needs to be reliably differentiated from that observed in healthy aging.

Researcher(s)

Research team(s)

Amyloid β and sleep problems, a neurotoxic pas de deux during aging? 01/01/2015 - 31/12/2018

Abstract

The goal of this project is to investigate in more detail the link between sleep disturbances, amyloid pathology, the glymphatic system and aging. For this we will make use of state of the art MRI, EEG, immunohistochemistry, MALDI, PCR and ELISA. The combination of these in vivo and ex vivo techniques will offer us the possibility to elucidate this link, and to determine whether the glymphatic system might be an attractive target for future AD therapy development.

Researcher(s)

Research team(s)

Characterization of early functional network alterations in olfactory system and its association with default mode network in the course of Alzheimer's disease. 01/01/2015 - 31/12/2016

Abstract

Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly with no effective treatment. Olfactory deficits are commonly observed in people with AD and can be an early biomarker to detect the disease. Neuroimaging tools such as resting state magnetic resonance imaging may detect subtle changes in brain functional networks within olfactory system during the disease progression. Understanding how brain networks are connected with each other during the disease progression is a key factor in decoding the molecular mechanisms of AD, early diagnosis and slowing the progression of the disease. The overall goal of this project is to investigate patterns of functional connectivity alterations in the olfactory brain structures in a mouse model of AD. This knowledge may provide a great opportunities for early diagnosis of AD and development of new treatment strategies.

Researcher(s)

  • Promotor: Kara Firat

Research team(s)

The impact of reproductive axis hormones on changes in brain functional networks during healthy, accelerated and pathological aging (i.e. Alzheimer's disease). 01/11/2014 - 31/10/2018

Abstract

Aging has profound effects on many cellular processes that predispose to neurodegeneration, impairment in cognitive function, as well as changes in brain functional networks (e.g. default mode network (DMN) and its anticorrelated networks) and synaptic alterations. However, the key mechanisms orchestrating brain aging remain largely unknown. The hypothalamus, a key region of the hypothalamic–pituitary–gonadal axis (HPG-axis), is crucial for the neuroendocrine interaction between the central nervous system and various peripheral functions, but seems also involved in age-related neurodegeneration. This knowledge drives a new paradigm shift suggesting that the aging process is driven by the integration of immune and hormonal responses, with the hypothalamus having a leading role. A broad literature also suggests the involvement of menopause and age-related testosterone decline-induced alterations in HPG axis hormone levels in the etiology of Alzheimer's disease (AD), which is the most common form of dementia in elderly population. The overall goal of this preclinical project is to investigate patterns of functional alterations in the DMN and its anticorrelated networks using rsfMRI across from normal aging to accelerated and pathological aging (i.e, AD), and to explore whether differences in functional connectivity are associated with differences in HPG axis hormones and hypothalamic inflammation. The first aim of the study is to observe the short and long term effect of luteinizing hormone (LH) and estrogen hormone treatment, on the DMN and its anticorrelated networks. We hypothesize that loss of estrogenic support after ovariectomy will have significant effect on these networks, and these effect can be reversed after hormone therapy. The second aim of the project is to gain more insight into how the alterations of the GnRH-HPG axis receptor signalling alter functional networks of the brain during pathological aging (i.e. AD). The third aim is to examine the capacity of a GnRH agonist, leuprolide acetate, which decreases the release of LH, and amyloid load to modulate DMN and its anticorrelated networks, in the brain of Tg2576 carrying Swedish APP mutation.

Researcher(s)

Research team(s)

Untangling Alzheimer's disease: the relationship between neuropathology and neurocognitive-behavioral deficits, and its therapeutic significance. 01/10/2014 - 30/09/2017

Abstract

Alzheimer's disease (AD) is a progressive brain disease that causes cognitive alterations, memory loss and behavioral changes. Neuropathological hallmarks of AD include brain atrophy, and the presence of two different types of protein aggregations: tangles composed of hyperphosphorylated Tau and plaques consisting of amyloid. The neurodegenerative process in AD is initially characterized by synaptic damage accompanied by neuronal loss. Moreover, synaptic loss is one of the strongest correlates to the cognitive impairment in patients with AD. The mechanisms underlying synaptic and cognitive deficits in AD remain poorly understood. To gain further insights into these mechanisms, we will examine how the brain changes in mutant Tau mice and how Tau is involved in cognitive and behavioral processes and related brain areas. Recent studies have suggested that targeting Tau is therapeutically promising. This will be done by compounds that dephosphorylate Tau. The different compounds will be evaluated by correlating behavioral with electrophysiological outputs, and state of the art in situ visualization techniques.

Researcher(s)

Research team(s)

Image-guided decoding of mechanisms involved in healthy, accelerated and pathological aging. 01/10/2014 - 30/09/2017

Abstract

Aging has profound effects on many cellular processes that predispose to neurodegeneration, impairment in cognitive function, as well as changes in brain functional connectivity networks (e.g. default mode network) and synaptic alterations. However, the key mechanisms orchestrating brain aging remain largely unknown. More and more findings in rodents and humans have established that inflammatory processes in the hypothalamus can contribute to neurodegeneration upon aging via reproductive (HPG) axis. However, the exact mechanisms by which (i) Inflammatory signalling in the hypothalamus contributes to the occurrence of age-related functional connectivity and synaptic alterations, and (ii) hypothalamic HPG signalling modulates age-related neurodegeneration and cognitive changes are not well understood and need further investigation. The main goals of this project are to investigate: (i) how deregulation of the HPG axis impacts brain networks that display aging decline, (ii) how hypothalamic inflammation is steering deregulation of HPG axis in healthy aging, accelerated aging and pathological aging, and (iii) how hypothalamic inflammatory responses become activated upon healthy, accelerated and pathological aging, with specific focus on cellular, connectional architecture of functional networks. This project will contribute new information that will greatly increase our understanding about underlying mechanisms of hypothalamus-driven systematic aging of the brain.

Researcher(s)

Research team(s)

Unraveling the effect of thyroid hormones on seasonal neuroplasticity in the song control system of adult songbirds. 01/10/2014 - 30/09/2016

Abstract

Prior studies mainly focused on the effect of T on SCS plasticity. However, it has been shown that steroid-independent photostimulation can also induce SCS plasticity, but its mechanism remains unclear [9-11]. One of the proposed alternatives is the mediating effect of THs, as THs play an important role in the regulation of seasonal reproduction and are associated with neurogenesis. Surprisingly, the effect of THs on SCS plasticity has only been studied partially [24]. In addition, it is unknown whether THs mediate SCS plasticity in a direct or an indirect manner. To this end we designed a series of experiments divided into 3 work packages (WP).

Researcher(s)

Research team(s)

Study on the neural substrate of speech development using fMRI in the zebra finch model. 01/10/2014 - 30/09/2016

Abstract

Zebra finches are widely used models to study vocal learning. Like human babies learn how to speak, zebra finch juveniles learn how to sing during a specific sensitive period. The aim of this project is to investigate the neural mechanisms behind this sensitive period by analyzing song production and perception using song recordings and in vivo functional MRI during auditory stimulation with various songs including songs with different social context. The same group of birds is studied at several time points during and after song learning to monitor changes occurring in the brain. Sensory-motor learning is investigated in males, that learn how to sing from an adult tutor, and sensory learning in females, that do not sing but to whom song is crucial for mate choice. In addition, the effect of social environment during the sensitive period for vocal learning will be investigated. Ultimately, this study can reveal the time window and spatial coordinates of crucial events in the brain during song development and thereby initiates the investigation of the underlying neural and molecular mechanisms of song development as a model for human vocal development.

Researcher(s)

Research team(s)

Studying deficits in the neurovascular coupling in a mouse model of Alzheimer's disease: an in vivo MRI approach. 01/02/2014 - 31/12/2014

Abstract

The neurovascular coupling, essential for normal brain function, is compromised already in an early stage of Alzheimer's Disease. In the present project we want to study the hemodynamic coupling to neuronal activity changes using functional magnetic resonance imaging. We believe that accurate early identification of these pathological processes would be a significant benefit for the development of new treatment strategies.

Researcher(s)

  • Promotor: Blockx Ines

Research team(s)

Can sleep disturbances lead to functional connectivity changes in mice brain? 01/02/2014 - 31/12/2014

Abstract

An undeniable link has been shown between sleep deprivation and Aβ plaque formation in Alzheimer's disease. Nonetheless, the chicken-egg question still remains. With this project we wish to initiate a new research line in which we will study the effect of sleep deprivation on functional connectivity in mice brain using magnetic resonance imaging. As such, this project will form the basis for future research to answer this chicken-egg question.

Researcher(s)

  • Promotor: Praet Jelle

Research team(s)

Studying the interaction between synaptic loss, neuroinflammation and amyloid pathology in mouse models of Alzheimer's disease 01/01/2014 - 31/12/2017

Abstract

Alzheimer's disease (AD) is the most common form of dementia, with a high prevalence in the elderly population. Amyloid pathology and inflammatory cascades, which show toxic effects at the synapses, have been implied as possible driving forces behind AD. Gaining a deeper insight in these early events is crucial for a better understanding of the mechanisms that drive AD progression. In this project we focus on the interaction between synaptic deficits, amyloidosis and inflammation using resting-state functional Magnetic Resonance Imaging in a mouse model of amyloidosis..

Researcher(s)

Research team(s)

Defining fMRI resting state network alterations and perfusion deficits in a mouse model of Alzheimer's Disease. 01/01/2014 - 31/10/2016

Abstract

The primary goal of this project is to comprehensively determine the relationship between intrinsic functional network connectivity changes and altered CBF in a mouse model of AD. Our hypothesis is that the early pathological processes in AD that lead to synaptic deficits could be reflected by aberrant functional connectivity measured by rsfMRI. Additionally, perfusion measurements using ASL, will reveal a better understanding of perfusion deficits in AD.

Researcher(s)

  • Promotor: Blockx Ines

Research team(s)

Targeting the HPG-axis to modulate synaptic dysfunction and its keyplayers in Alzheimer's disease. 01/01/2014 - 31/12/2015

Abstract

This project represents a formal research agreement between UA and on the other hand SAO. UA provides SAO research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Functional imaging and analysis of tumors (FIAT). 01/01/2014 - 31/12/2015

Abstract

The FIAT consortium will make concrete improvements to quantitative functional imaging of tumours, which will be incorporated in clinical and preclinical application packages, clinical software modules, image analyses and ultimately routine clinical procedures.

Researcher(s)

Research team(s)

Study on the Neural Substrates of Auditory Social Cues during Vocal Learning using fMRI in the Zebra Finch Model. 13/11/2013 - 31/10/2015

Abstract

Zebra finches are widely used models to study vocal learning. Like human babies learn how to speak, zebra finch juveniles learn how to sing during a specific sensitive period. This project aims at elucidating the link between social context and vocal learning by studying the perception of auditory social cues during and after vocal learning in zebra finches. Using functional MRI, the neural substrates of such song perception are investigated as well as how these are modulated by social environment.

Researcher(s)

  • Promotor: Van Ruijssevelt Lisbeth

Research team(s)

Molecular Imaging of Brain Pathophysiology (BrainPath). 01/10/2013 - 30/09/2017

Abstract

BRAINPATH aims to build upon current developments in molecular imaging by creating an academic-industrial training and mobility network for the next revolution of imaging technology. Molecular in vivo imaging is a fertile area which combines expertise, state-of-art equipment and many disciplines and inter-sector work environments. Our goal is to better understand brain diseases and develop new preclinical imaging strategies. We believe optical imaging in particular represents a technology that has the potential to exploit further our knowledge in this area.

Researcher(s)

Research team(s)

Effects of brain-derived estrogens on behaviourally relevant auditory perception and song learning (memory) in the adult songbird brain. 01/10/2013 - 22/08/2016

Abstract

In this project we are interested what hormonal interactions are needed (fast neuronal and/or slow gonadal) to create the permissive circumstances for neuroplastic changes seen in seasonal breeders. We want to examine if starlings have a more 'juvenile' pattern of connectivity when they are capable of learning new songs and when they can discriminate auditory vocal signals better. We will do this by using real-time, non-invasive, in vivo imaging tools that allow the follow-up of anatomical and functional changes of the songbird brain. The study of the reactivation of juvenile-like plasticity may potentially lead to a recovery of function in a variety of neurodevelopmental disorders.

Researcher(s)

Research team(s)

Unravelling the complex interplay of Aβ, inflammation and synaptic defects in mouse models of Alzheimer's disease. 01/10/2013 - 31/12/2013

Abstract

Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss and cognitive and behavior changes. AD pathology consists of an increased formation of amyloid plaques, tau-fibrils, inflammation and neurodegeneration in the brain. Amyloidosis and inflammation, both early events, have gained interest as potential causes of AD, which puts the focus of many studies on these events. Soluble amyloid beta oligomers (sAβ) and inflammation lead to synaptic defects at an early stage, affecting synaptic transmission mechanisms (e.g. long term potentiation) necessary for learning and memory. This eventually results in cognitive defects arising in late stage AD. However, treatment studies targeting amyloidosis and inflammation have led to inconsistent results. A plausible explanation is that many studies have been focusing on amyloid plaques, while sAβ, occurring even earlier, is more likely to be the culprit behind the AD symptoms. Furthermore, amyloidosis and inflammation seem to be closely related, since tackling inflammation pre-and post-plaque stage show different effects on pathology i.e. amelioration and aggravation respectively. The synaptic defects caused by sAβ and inflammation may result in altered brain functional connectivity (FC), which can be measured in vivo using resting state functional MRI (rsfMRI) and which is defined as the temporal correlation of the low frequency fluctuations (LFF) in the Blood-Oxygenation-Level-Dependent (BOLD) signal of spatially distinct areas. Our hypothesis is that amyloidosis, inflammation and synaptic defects are closely related and influence each other starting from early stages in AD. They represent interesting targets for drug development but much is unknown about these events. We believe that unravelling this complex interplay in mouse models will be useful for studies in animals and AD patients. Furthermore, we believe that the synaptic defects in AD could be reflected as alterations in FC. This could mean that rsfMRI may represent an in vivo method to follow up synaptic integrity in different stages of disease and to monitor the effect of manipulations.

Researcher(s)

Research team(s)

Research and applications in biological image and signal processing. 01/04/2013 - 30/03/2017

Abstract

The objective of the project is to develop a magnetic immunodiagnostic method for MRI - based assessment of brain tumors. Scientific problem: The role of different mechanisms in the progression of carcinogenesis process in brain tumors has not been fully identified. Hypothetic framework: We propose to explore three specifics mechanism of carcinogenesis: self-renewal process, cellular growth and proliferation and angiogenesis of the tumor; all of them, through the expression of molecular biomarkers (CD133, EGF-R and VEGF-R), its interactions and the role of these mechanisms in the carcinogenesis process. All of these mechanisms separately can be explored with single target, and has been explored since few decades ago, that is why we propose a multivariate approach, using multitarget contrast enhanced MRI techniques. We propose to use magnetic resonance approach to the molecular characterization of the disease, using both classic relaxation and magnetic transfer technique.

Researcher(s)

Research team(s)

Unraveling the interaction between testosterone and thyroid hormones and their impact on seasonal changes in the songbird brain. 01/01/2013 - 31/12/2016

Abstract

We will follow the seasonal plasticity in SCS nuclei of male starlings with appropriate MRI tools and investigate the expression of receptors and enzymes that are essential in T and TH function in the SCS. Combining data from control birds and birds where T and TH availability has been manipulated will allow us to identify their individual impact as well as unravel their interactions.

Researcher(s)

Research team(s)

Longitudinal developmental changes in brain metabolism of the neonatal transgenic 'Huntington's Disease' rats, s tudied with MRspectroscopy, at rest and with a challenge. 01/01/2013 - 31/12/2015

Abstract

The aim of the project is to study the bioenergetics defects in HD pathogenesis using proton and phosphor magnetic resonance spectroscopy (1H MRS/31P MRS). More specifically, we want to study the longitudinal developmental changes in brain metabolism of the neonatal HD rat at different conditions: rest, during stimulation, and recovery. The work will shed new light on fundamental mechanisms of bioenergetics defects in HD pathogenesis, which may help provide useful biomarkers for disease onset that can be used to assess the effects of potential therapeutic agents for the disorder.

Researcher(s)

Research team(s)

Hormones and neuroplasticity: image guided discoveries of molecular mechanisms in neuroplasticity (PLASTOSCINE). 01/10/2012 - 31/12/2017

Abstract

In this project we want to tackle the question of how brain plasticity is regulated at the molecular level in two songbird models with different song learning and neuroplasticity characteristics, with the help of recently developed tools in brain imaging and epigenetics. Our hypothesis is that hormone and environment (light) induced effects contribute to brain plasticity at least in part through epigenetic programming.

Researcher(s)

Research team(s)

Diffusion Kurtosis Magnetic Resonance Imaging in Neurodevelopment and Neurodegeneration. 01/10/2012 - 31/03/2016

Abstract

This project represents a formal research agreement between UA and on the other hand Janssen Pharmaceutica. UA provides Janssen Pharmaceutica research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Study on the neural substrate of speech development using fMRI in the zebra finch model. 01/10/2012 - 30/09/2014

Abstract

Zebra finches are widely used models to study vocal learning. Like human babies learn how to speak, zebra finch juveniles learn how to sing during a specific sensitive period. The aim of this project is to investigate the neural mechanisms behind this sensitive period by analyzing song production and perception using song recordings and in vivo functional MRI during auditory stimulation with various songs including songs with different social context. The same group of birds is studied at several time points during and after song learning to monitor changes occurring in the brain. Sensory-motor learning is investigated in males, that learn how to sing from an adult tutor, and sensory learning in females, that do not sing but to whom song is crucial for mate choice. In addition, the effect of social environment during the sensitive period for vocal learning will be investigated. Ultimately, this study can reveal the time window and spatial coordinates of crucial events in the brain during song development and thereby initiates the investigation of the underlying neural and molecular mechanisms of song development as a model for human vocal development.

Researcher(s)

Research team(s)

Optimized workflow for in vivo small animal diffusion weighted MRI studies of white matter diseases: from acquisition to quantification. 01/07/2012 - 30/06/2016

Abstract

While the number of applications of diffusion MRI has exploded in recent years, obtaining reliable and quantitative diffusion information remains a challenging task. In this project, we aim to develop diffusion weighted MRI (DWI) sequences and processing routines to obtain reliable diffusion measures within an acceptable acquisition time and at high spatial resolution to reduce partial volume effects. This would be of particular interest for in vivo pre-clinical research in small animals as mice in which the needed signal to noise ratio for reliable diffusion measures sets constraints on the spatial resolution and measure time. We will develop a diffusion –acquisition & reconstruction -workflow that reconstructs a high resolution isotropic DWI data from a set of multi-slice 2D diffusion weighted images -acquired with a 7 or 9.4 T Bruker MR scanner -with a high in-plane resolution and a lower through-plane resolution and in which the stacks of slices are differently orientated. The new reconstruction method needs to model both the different orientations of the MR images as the different orientations of the applied diffusion weighted gradients. For this super resolution at these high magnetic field, sampling the DWI with conventional fast echo planar imaging sequences will be (1) too sensitive to orientation dependent eddy current image distortions – which prevents the multi angle acquisitions and (2) suffers from local loss of signal due to B0-inhomogeneities. Therefore, we aim to develop the method based on DW-Fast Spin echo acquisition in which the images don't show B0-inhomogeneities problems and moreover can be acquired at different angles. First, we will optimize the DWI with Fast Spin Echo sampling and reconstruction. Based on this sequence, further developments will be performed to set the optimal acquisition scheme to get to super-resolution DWI: being the best combination of the set of orientations of the multi-slice stacks combined with the different directions of the DW gradients. Hereto, we can define different development steps which each will deal with specific MR acquisition and/or processing challenges : motion artifacts, multi-shot acquisition, minimization of eddy current effects, phase-wrapping, T2-modulation over k-space, denoising. The MR-sequences will be developed and implemented – in ParaVision software- on the Bruker MR scanners from the Bio-Imaging lab. The reconstruction algorithms will be developed in Matlab at the Vision lab. This new development can only be realized based on the experiences and close collaboration of both research labs.

Researcher(s)

Research team(s)

Imaging of Neuroinflammation in Neurodegenerative Diseases (INMIND). 01/03/2012 - 28/02/2018

Abstract

The goal of this project (INMiND) is to carry out collaborative research on molecular mechanisms that link neuroinflammation with neurodegeneration in order to identify novel biological targets for activated microglia, which may serve for both diagnostic and therapeutic purposes, and to translate this knowledge into the clinic.

Researcher(s)

Research team(s)

Multimar: Multidisciplinary magnetic resonance. 01/01/2012 - 31/12/2016

Abstract

MULTIMAR or Multidisciplinary Magnetic Resonance comprises a network of 10 Flemish and 9 'international' research groups active in multidisciplinary and complementary research with a focus on methodologies that emanate from the phenomenon of magnetic resonance. These groups form a network organized around electron magnetic resonance (EMR, Prof. Van Doorslaer UA coordinator), nuclear magnetic resonance (NMR, Dr. N. Van Nuland, coordinator), and (pre-clinical) biomedical magnetic resonance (Prof. U. Himmelreich, coordinator). Further strengthening of the collaborations in magnetic resonance research in Flanders is supported by various regional large scale facilities for spectroscopy and imaging. The 'international' partners possess the expertise, equipment and research interests, which are complementary to at least two Flemish partners so that scientific interaction and exchange is instigated beyond the disciplinary borders.

Researcher(s)

Research team(s)

Modulation of neuroinflammation during de- and re-myelination processes: an in-vivo study. 01/01/2012 - 31/12/2015

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Speeded up processing and reconstruction of magnetic resonance images (SUPERMRI). 01/01/2012 - 31/12/2013

Abstract

The SuperMRI project aims at - speeding up the acquisition process by developing new imaging sequences and sparse sampling strategies - reducing the computation time of iterative reconstruction algorithms by developing fast and generic forward and backward projectors through parallelization and distribution of the algorithms, in combination with suitable hardware architecture (GPU or FPGA). - Significantly improving the image quality by developing novel reconstruction algorithms for MRI, related to compressive sensing and discrete tomography. - developing fast tomographic image processing algorithms that exploit the available k-space data, with focus on segmentation and motion compensation.

Researcher(s)

Research team(s)

Non-invasive bio-imaging of trypanosomes in rats. A novel model for in vivo monitoring of a chronic Trypanosoma brucei infection in rats, by means of bioluminiscent and magnetic resonance imaging, in order to study treatment failure and relapse. 01/01/2012 - 31/12/2013

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Functional identification of innate immune responses following stem cell implantation in the central nervous system of mice. 01/10/2011 - 10/04/2013

Abstract

In this PhD project we aim to completely characterize the migration behaviour, fate and physiology of different stem cell types following administration in the 'experimental autoimmune encephalomyelitis' (EAE) mouse model for Multiple Sclerosis. A combination of in vivo (BLI and MRI) and post-mortem (histology) imaging modalities will be used to reveal different cell characteristics and compare these characteristics between the different cell types included in this study. These results will enable us to effectively modify stem cell populations in order to enhance possible therapeutic effects (e.g. enhanced migration towards target sites and increased survival of grafted stem cells).

Researcher(s)

Research team(s)

Learning and brain plasticity: a three levels approach. 01/01/2011 - 31/12/2014

Abstract

In some species of songbirds, the brain displays a pronounced seasonal rewiring which is associated with seasonal behavioural changes in vocal communication (singing only in spring). Both humans and songbirds learn their vocal communication and depend on speech- or song input during critical/sensitive periods in life in order to do so. For some bird species, like the zebra finch, this sensitive period is limited to a certain period after hatching (age-limited learner), in others, like the canary, this sensitive period is re-opened seasonally (open-ended learner). Longitudinal studies which obtain information both on structure and activity of the brain in living birds (using neuro-imaging) and at the same time their behaviour (singing/learning) create the unique opportunity to detect relevant moments of behaviourally related neuronal circuit changes enabling not only cause-and-effect relationship- but also target definition for subsequent gene expression studies. This information will contribute in unravelling the molecular mechanisms of neural circuitry rewiring and speech learning processes both with relevance for regenerative medicine in general and for children who, because of a history of deafness, missed out on the input they needed to learn their language properly in particular.

Researcher(s)

Research team(s)

Temporal analysis in the macaque and the songbird auditory system using fMRI. 01/01/2011 - 15/01/2012

Abstract

The aim of this project is to study how different amplitude modulation rates are processed in the ascending auditory cortex of macaques and songbirds and to determine if this processing is lateralised. To answer these questions, functional Magnetic Resonance Imaging (fMRI) will be used. The work will shed new light on fundamental mechanisms of auditory temporal analysis of general relevance to the analysis of ethological sounds in different species.

Researcher(s)

  • Promotor: Poirier Colline

Research team(s)

Functional plasticity of auditory and visual systems of songbirds in a seasonal context. 01/10/2010 - 30/09/2013

Abstract

Songbirds exhibit seasonal plasticity in a broad variety of behavioral and morphological traits associated with reproduction. Changes in song production are well described while changes in song perception are not. In the present project, we will study the seasonal functional variation in auditory processing of the European starling (Sturnus vulgaris) using functional magnetic resonance imaging. We will test if the neural substrates of song perception will differ according to the function and the social value of the songs and if seasonal changes of these neural substrates will be observed only for the songs whose function and social value change seasonally. Because we suspect steroids to be involved in the seasonal changes we measure, the neural substrates of song perception will also be investigated after administering steroids. We expect at least some of the seasonal changes to be reproduced by steroid hormones, providing a causal link between steroids and perceptual sensory plasticity. An anatomical seasonal plasticity in the visual system's optic chiasm has also been identified in starlings. The exact ultrastructural explanation/mechanism behind this remarkable change however remains unknown. In a second part of this project we will study the exact mechanisms responsible for seasonal anatomical variation in the optic chiasm.

Researcher(s)

Research team(s)

Resting state fMRI in small animals: a new angle for assessing neuroplasticity ? 01/10/2010 - 30/09/2011

Abstract

This project has a double purpose. The first objective is implementation and optimization of 'resting state fRMI' in control rats as a proof of principle. Most of the research is done in humans and only a few studies on animals are reported. It will be a challenge to develop a scanning and analysis protocol with optimal parameters for scanning, anesthesia and data-processing. Subsequently the implementation and optimization will be extended to songbirds. The second objective is to understand the accordance of low frequent fluctuations measured during resting state in different brain regions and the anatomical and functional connectivity of these regions (as observed with DTI en MEMRI).

Researcher(s)

Research team(s)

Biomedical Microscopic Imaging and in-vivo Bio-Imaging (EGAMI). 01/02/2010 - 31/12/2014

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)

Imagine Trypanosomes: a novel model for in vivo monitoring of Trypanosoma brucei infections by means of bioluminescence and magnetic resonance imaging. 01/01/2010 - 31/12/2013

Abstract

The overall objective of the project is to develop an in vivo BLI/MRI model for experimental studies on human African trypanosomiasis that allows high resolution localisation of parasites and associated inflammatory reactions during tissue invasion.

Researcher(s)

Research team(s)

Innovative Medical Imaging for Neurological Disorders (iMIND). 01/01/2010 - 31/12/2011

Abstract

This project represents a formal research agreement between UA and on the other hand IBBT. UA provides IBBT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Evaluation of a recent developed in vivo MRI technique - Diffusion Kurtosis representation - by means of transgene rat models for polyglutamine disorders. 01/01/2010 - 31/12/2011

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Temporal analysis in the macaque and the songbird auditory system using fMRI. 01/10/2009 - 15/01/2012

Abstract

The aim of this project is to study how different amplitude modulation rates are processed in the ascending auditory cortex of macaques and songbirds and to determine if this processing is lateralised. To answer these questions, functional Magnetic Resonance Imaging (fMRI) will be used. The work will shed new light on fundamental mechanisms of auditory temporal analysis of general relevance to the analysis of ethological sounds in different species.

Researcher(s)

Research team(s)

The influence of neuronal plasticity on the olfaction in the transgenic rat model for Huntington disease investigated with in vivo MRI. 01/02/2009 - 30/09/2010

Abstract

In vivo MRI will be used to study the role of neurogenesis in the loss of olfaction in a transgenic rat model of Huntington's disease. Therefore we will use 1) in situ labeling of neuronal stem cells and 2) manganese enhanced MRI, two revolutionary in vivo MRI methods.

Researcher(s)

  • Promotor: Van Camp Nadja

Research team(s)

Defining the interdependence of the brain's vascular dysfunction and the prescence of cerebral amyloid deposits by using new tools in Alzheimer research. 01/01/2009 - 31/12/2011

Abstract

Work within this project aims to investigate the progression of the neurodegenerative processes involved in Alzheimer's disease (AD). Using in vivo magnetic resonance imaging (MRI) tools across different mouse models, we will concentrate on defining parameters which can indicate defects in cerebral autoregulation, the loss of cholinergic active neurons and the accumulation of the amyloid plaques. This project encloses a longitudinal study and will result in the exploration and discovery of in vivo biomarkers for the early detection of AD. This would be the first attempt being extensive in that way to follow up MR detectable changes in a longitudinal manner across different mouse models for AD.

Researcher(s)

  • Promotor: Vanhoutte Greetje

Research team(s)

Functional imaging (MRI) of starlings brains to unravel the neural basis of vocal communication in songbirds as a model for human communication. 01/01/2009 - 31/12/2010

Abstract

Our project aims at understanding brain-behaviour interactions, with a special emphasis on the role of social factors on these interactions and as possible inducers of brain plasticity. This will be made possible by a whole brain approach, based on a rapidly expanding technique: small animal fMRI, applied to an original animal model: the European starling.

Researcher(s)

  • Promotor: Poirier Colline

Research team(s)

Capacity building biomedical imaging: MRI equipment for small laboratory animals. 19/12/2008 - 01/05/2015

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)

The causal links between brain plasticity, motor activity and motivation: an in vivo neuro MRI study in songbirds. 01/10/2008 - 30/09/2010

Abstract

The main goal of this project is to shed light on the causal relationship between steroid hormones (testosterone), brain plasticity (of the song control system and other relevant regions), motor behavior (song) and (sexual) motivation by making use of the newest possibilities offered by MR-imaging. All experiments will be conducted with the starling (Sturnus vulgaris) as model species. Three hypotheses will be tested: 1. Testosterone acts directly on the song control system and is the cause of its growth and higher song production, 2. Testosterone does not act directly on the song control system but on other regions in the brain who are involved in sexually motivated behavior, 3. The higher (motor) activity (song) induces brain plasticity.

Researcher(s)

Research team(s)

Development of combined magnetic resonance imaging and bioluminescence imaging to study stem cell migration and survival in mouse brain after neurotrauma. 01/10/2008 - 30/09/2009

Abstract

In this study, we aim to investigate whether genetic modification of exogenous stem cells with chemokine receptors enhances their migration towards lesions in brain tissue. Magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) technology will be used and validated to visualize migration and survival of grafted stem cells in vivo.

Researcher(s)

Research team(s)

Nanoparticles for therapy and diagnosis of Alzheimer disease. (NAD) 01/09/2008 - 31/08/2013

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

Researcher(s)

Research team(s)

In situ labeling of endogenous neuronal stem cells and the visualization of their recruitment and incorporation in the mouse brain with in vivo microMRI. 01/01/2008 - 31/12/2009

Abstract

In healthy adult mice the major location with the production of neural precursor cells is 'the subventricular zone (SVZ' located near the later ventricles of the brain. From this region, the neural precursor cells migrate towards the olfactory bulb where they differentiate into new interneurons. This migration occurs in healthy animals along a specific pathway, the Rostral Migration Stream (RMS). In vivo examination of this normal migration is the first step towards possible manipulation of endogenous neural precursor cells for therapeutic purposes. For the in situ labeling of the precursor cells with a superparamagnetic contrast agent, we will evaluate and compare two new labeling techniques: 1)Direct injection of superparamagnetic iron oxide particles (SPIO's) into the lateral ventricle so that the SVZ cells after uptake of the SPIO's will be visible with in vivo MRI. 2)Viral introduction of a MRI reportergen into the SVZ cells by which the cells will produce a superparamagnetic contrast agent and can be visualized by MRI. The successful design of a cellular imaging study with in vivo MRI depends on series of methodological evaluations and optimizations. The evaluation of both labeling techniques will be based on: 1) toxicity and effect on the cell proliferation and migration of the contrast agent and the reportergen, 2) the identification of the cell types by which the contrast agent is taken up/produced, 3) the visualization of the neuronal migration with in vivo MRI and 4) the visualization of incorporated new neurons in the olfactory bulb. The validation of the MRI studies will be done by immunohistochemistry.

Researcher(s)

Research team(s)

Functional mapping of auditory responses in the zebra finch brain using spin-echo fMRI. 01/01/2008 - 31/12/2009

Abstract

The aim of this project is to develop SE fMRI on the zebra finch brain. By measuring neural responses to different auditory stimuli, this technique should allow us to map the auditory responses in the whole brain and should provide significant insights about auditory selectivity and lateralisation of the zebra finch brain.

Researcher(s)

  • Promotor: Poirier Colline

Research team(s)

In-vivo visualisation and quantification of endogenous neuronal stem cell recruitment in the songbird brain using imaging methods (BLI and MRI). 01/12/2007 - 31/12/2012

Abstract

This project aims at visualising and quantifying endogenous neuronal stem cell recruitment in the brain of living songbirds using Bioluminescent Imaging (BLI) with the reporter gene luciferase and Magnetic Resonance Imaging (MRI) using either the reporter gene Ferritine or MRI contrast agents that are internalised by the neuronal progenitor cells in the subventricular zone. The developed tools will then be used to study the underlying mechanisms of seasonal changes in neuronal recruitment.

Researcher(s)

Research team(s)

Exploring neuronal networks in transgenic rat models of polyglutamine disorders using micropet and magnetic resonance imaging. 01/10/2007 - 31/10/2009

Abstract

To gain insight in the effect of neurodegeneration on the functioning of neuronal networks in HD and SCA17 by the application of complementary in vivo imaging techniques that (1) specifically provide information at the molecular level ¿ receptors and metabolism ¿ using ¿PET imaging; that (2) are able to measure axonal transport rates and neuronal connections using MEMRI; and that (3) allow to study the downstream effects within a neuronal network after systemic administration of a a- /antagonist using phMRI.

Researcher(s)

Research team(s)

Non invasive quantitative molecular imaging with applications for studying cellular processes in oncology and neurology. 01/01/2007 - 31/12/2011

Abstract

This project represents a formal research agreement between UA and on the other hand the Federal Public Service. UA provides the Federal Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Magnetic Resonance in the materials, chemical and biomedical sciences. 01/01/2007 - 31/12/2011

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel.

Researcher(s)

Research team(s)

European project on the characterisation of transgenic rat models for neurodegenerative and psychiatric diseases: automated home cage analyses, live imaging and treatment. (RATstream) 01/01/2007 - 30/06/2010

Abstract

The RATstream' consortium will concentrate on the comprehensive phenotypical characterization of rat models of neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease (PD) and spinocerebellar ataxia type 17 (SCA17). Ultimately, the project will deliver a procedure for low cost automated drug screening along with a set of data describing the phenotype for each of the models. To achieve this goal, automated home cage systems for behavioural and physiological phenotyping will be developed by two SMEs and validated independently by two academic partners and individual data will be incorporated into an integrated database developed by a third SME. In a joint effort the groups will develop a comprehensive set of behavioural and physiological phenotyping procedures including PET and DTI technologies to systematically detect neuropsychiatric correlates of neuronal dysfunction and disease progression in rat models of HD, PD, and SCA17. The resulting set of biomarkers will lead to a valid set of minimised experiments and markers best suited to provide read-out parameters in pre-clinical studies applying novel substances delaying or preventing neurodegeneration.

Researcher(s)

Research team(s)

Optimization of the image quality of fast Magnetic Resonance Diffusion Tenor Imaging through adapted acquisition and image processing. 01/01/2007 - 31/12/2008

Abstract

The framework of this project fits in the need to develop an optimized and fast DTI sequence suited to perform quantitative studies at high magnetic field strengths and enabling the follow up of the progression of diseases or possible therapies. To accomplish this, developments will be made both at the site of image acquisition and image post processing.

Researcher(s)

Research team(s)

Magnetic resonance criteria for early diagnosis and therapeutic monitoring of Huntington Disease based on Diffusion Tensor Imaging (DTI). 01/01/2007 - 31/12/2008

Abstract

The framework of this project fits in the need for early diagnosing and therapeutical monitoring of the pathogenesis of Huntington's Disease. To accomplish this, we set up a longitudinal study involving the use of transgenic rat models which will be submitted to an innovative imaging tool based on diffusion of water within the brain structures.

Researcher(s)

  • Promotor: Vanhoutte Greetje

Research team(s)

Auditive perception and processing by song birds and crocodiles: ethological and functional MRI approach. 01/01/2007 - 31/12/2007

Abstract

Researcher(s)

Research team(s)

Development of reporter gene imaging for MRI and BLI assessment of migration and survival of transplanted mesenchymal and neural stem cells after traumatic brain injury in mice. 01/10/2006 - 30/09/2010

Abstract

Stem cell transplantation after neurotrauma is a promising field of research in current biomedical research. However, to date, little is known about successful migration and survival of transplanted stem cell populations on site of trauma. This project aims to develop genetically modified adult and embryonic stem cell populations which can be assessed by MRI and BLI after transplantation in traumatised mouse brain.

Researcher(s)

Research team(s)

Study of interactions between anatomical plasticity and electrophysiological activity in the song control circuit of adult songbirds. 01/10/2006 - 30/09/2009

Abstract

Researcher(s)

Research team(s)

The causal links between brain plasticity, motor activity and motivation: an in vivo neuro MRI study in songbirds. 01/10/2006 - 30/09/2008

Abstract

Researcher(s)

Research team(s)

In vivo imaging study into the neural substrate of songprocessing and memory in songbirds. 01/10/2006 - 30/09/2008

Abstract

Songbirds (i.e. Passeriformes) share with humans the capacity of vocal imitation. Like human speech is, is birdsong a complex natural learned behavior that requires memorization of the song of an adult tutor. The acquisition and production of songs is controlled by a circuit of brain regions, the song control system (SCS). Also the auditory system, responsible for perception and processing of auditory information, is critical for song learning. Song learning inquires hearing, listening and memorizing songs, intrinsically suggesting an active role of the auditory system. Although the auditory pathways are far less explored than the vocal pathways, phenomena's like habituation and hierarchical organization were determined in the auditory system. More evidence for a functional connection between the two circuits is the indication that parts of the auditory system (and not of the SCS!) act as the neural substrate for song recognition memory (i.e. the so called tutor template). In clinical research, the neural substrate for speech and language is examined with in-vivo functional MRI in order to localize the auditory and speech induced activations in the human brain. The successful implementation of this method in songbirds (Van Meir et al., 2004) allows us to visualize the auditory brain activity in the auditory and/or vocal circuit in anaesthetized animals. This will allow us to detect for brain activity during exposure to different auditory stimulations (for example conspecific and birds' own song, manipulated song, multi tones,') within the same individual and even before and after song learning (tutoring birds). Thanks to the combination with experimental animal research, underlying cellular and molecular mechanisms of cognition can be investigated. The purpose of the project is to determine the neural substrate that is necessary for auditory recognition in songbirds. Is this region related to the conventional song circuit? When we analyze with fMRI the neuronal activation in zebra finches with exposure to learned song and other acoustic stimuli in relation to the degree of song learning, the neural substrate in songbirds that is involved with auditory recognition can be investigated.

Researcher(s)

Research team(s)

The relevance of the integrity of the blood-brain barrier in Parkinson's Disease. 01/03/2006 - 31/12/2007

Abstract

Neurodegenerative disorders such as Parkinson's Disease, are often associated with neuroinflammation. How neuroinflammation affects the integrity of the blood-brain barrier and in which way this contributes or this is attributed to neurodegeneration is still unknown. In vivo multimodal imaging, applying MRI and microPET allow to investigate this triangle of pathological processes in vivo and during the course of the pathology.

Researcher(s)

  • Promotor: Van Camp Nadja

Research team(s)

Influence of physiological and gross morphological properties of the song control nuclei outside the singing season on hormone induced songbehaviour in songbirds. 01/03/2006 - 31/12/2007

Abstract

The song control nuclei in the brain of songbirds are an excellent model to study brainplasticity. Manganese-enhanced and diffusion-weighted MRI allow us to image volumes, activity, cellular density and connectivity of these areas in a repeated fashion. During this project we investigate whether the physiological and gross-morphological features of the song control nuclei outside the period of song-production determine the song activity later on and to which degree they influence the impact of hormones on the song behaviour.

Researcher(s)

  • Promotor: Van Meir Vincent

Research team(s)

In situ labeling of endogenous neuronal stem cells and the visualization of their recruitment and incorporation in the mouse brain with in vivo microMRI. 01/01/2006 - 31/12/2007

Abstract

In healthy adult mice the major location with the production of neural precursor cells is 'the subventricular zone (SVZ' located near the later ventricles of the brain. From this region, the neural precursor cells migrate towards the olfactory bulb where they differentiate into new interneurons. This migration occurs in healthy animals along a specific pathway, the Rostral Migration Stream (RMS). In vivo examination of this normal migration is the first step towards possible manipulation of endogenous neural precursor cells for therapeutic purposes. For the in situ labeling of the precursor cells with a superparamagnetic contrast agent, we will evaluate and compare two new labeling techniques: 1) Direct injection of superparamagnetic iron oxide particles (SPIO's) into the lateral ventricle so that the SVZ cells after uptake of the SPIO's will be visible with in vivo MRI. 2) Viral introduction of a MRI reportergen into the SVZ cells by which the cells will produce a superparamagnetic contrast agent and can be visualized by MRI. The successful design of a cellular imaging study with in vivo MRI depends on series of methodological evaluations and optimizations. The evaluation of both labeling techniques will be based on: 1) toxicity and effect on the cell proliferation and migration of the contrast agent and the reportergen, 2) the identification of the cell types by which the contrast agent is taken up/produced, 3) the visualization of the neuronal migration with in vivo MRI and 4) the visualization of incorporated new neurons in the olfactory bulb. The validation of the MRI studies will be done by immunohistochemistry.

Researcher(s)

Research team(s)

Improvement of the image quality for fast Diffusion Tensor Imaging. 01/01/2006 - 31/12/2007

Abstract

Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is a recently developed technique who permits to study the architecture of white brainmatter (WM) in vivo and in an non-invasive way. DT-MRI is based on the Brownian movement of H2O-molecules in biological tissue and makes it possible to determine the anisotropic diffusion of these molecules . This anisotropic diffusion can be related to aligned microstructures, like WM brain fibres, which has a great value in biomedical applications. Since a large amount of data is needed for this technique, it is desirable to use fast imaging sequences. However, these kind of sequences introduce specific artefacts in the images which degrade the quality of the DT-measurements. For this reason, several strategies will be used to upgrade this quality. The present acquisition standard for fast DTI, Echo Planar Imaging (EPI), is prone to severe susceptibility artefacts which introduce geometric distortions in the images. These artefacts are more explicit when working at higher field strengths (here: 7 Tesla and 9.4 Tesla). By using an adapted EPI-sequence, it is possible to measure the local susceptibility artefacts and to correct for distortions. Another strategy that will be used is to combine DTI with Fast Spin Echo (FSE). This technique should be less sensitive to susceptibility artefacts. A recent approach, in which multiple receivers are used (Parallel Imaging) will be used to reduce artefacts in DT-MRI.

Researcher(s)

Research team(s)

Catecholaminergic modulation of auditory processing in songbirds as assessed by functional magnetic resonance imaging (fMRI): a window into cognitive processing in non-mammalian vertebrates. 01/01/2006 - 31/12/2006

Abstract

The main question that will be studied during the proposed experiments is the analysis of the role played by the catecholaminergic innervation of the auditory and song control areas in the control of auditory processing in songbirds. Special attention will be given first to norepinephrine (NE), the catecholamine that is most likely associated with the modulation of sound processing. Future studies should also consider the potential role of dopamine.

Researcher(s)

Research team(s)

Diagnostic Molecular Imaging : A network of excellence for identification of new molecular imaging markers for diagnostic purposes. (DIMI) 01/04/2005 - 30/09/2010

Abstract

Researcher(s)

Research team(s)

A novel Approach of Neuroplasticity: in-vivo MRI of the songbird brain. 01/01/2005 - 31/12/2008

Abstract

Songbirds share with humans the capacity to produce learned vocalizations (song) and the neural substrate for song learning and production displays a remarkable seasonal plasticity. It is our aim to study these neuroplastic features, using in-vivo MRI and functional MRI of songbirds and experimentally manipulated songbirds, in order to unravel the pattern of neuroplasticity in relation to seasonal changes in song perception, learning and song production in songbirds.

Researcher(s)

Research team(s)

NMR for in vivo imaging and spectroscopy on small animals; 9.4 T magnet. 01/12/2004 - 30/11/2007

Abstract

Researcher(s)

Research team(s)

MRI equipment for small and big laboratory animals. 01/12/2004 - 30/11/2007

Abstract

Researcher(s)

Research team(s)

In vivo imaging study into the neural substrate of songprocessing and memory in songbirds. 01/10/2004 - 30/09/2006

Abstract

Songbirds (i.e. Passeriformes) share with humans the capacity of vocal imitation. Like human speech is, is birdsong a complex natural learned behavior that requires memorization of the song of an adult tutor. The acquisition and production of songs is controlled by a circuit of brain regions, the song control system (SCS). Also the auditory system, responsible for perception and processing of auditory information, is critical for song learning. Song learning inquires hearing, listening and memorizing songs, intrinsically suggesting an active role of the auditory system. Although the auditory pathways are far less explored than the vocal pathways, phenomena's like habituation and hierarchical organization were determined in the auditory system. More evidence for a functional connection between the two circuits is the indication that parts of the auditory system (and not of the SCS!) act as the neural substrate for song recognition memory (i.e. the so called tutor template). In clinical research, the neural substrate for speech and language is examined with in-vivo functional MRI in order to localize the auditory and speech induced activations in the human brain. The successful implementation of this method in songbirds (Van Meir et al., 2004) allows us to visualize the auditory brain activity in the auditory and/or vocal circuit in anaesthetized animals. This will allow us to detect for brain activity during exposure to different auditory stimulations (for example conspecific and birds' own song, manipulated song, multi tones,') within the same individual and even before and after song learning (tutoring birds). Thanks to the combination with experimental animal research, underlying cellular and molecular mechanisms of cognition can be investigated. The purpose of the project is to determine the neural substrate that is necessary for auditory recognition in songbirds. Is this region related to the conventional song circuit? When we analyze with fMRI the neuronal activation in zebra finches with exposure to learned song and other acoustic stimuli in relation to the degree of song learning, the neural substrate in songbirds that is involved with auditory recognition can be investigated.

Researcher(s)

Research team(s)

European Molecular Imaging Laboratories (EMIL). 01/07/2004 - 30/06/2009

Abstract

Researcher(s)

Research team(s)

European Molecular Imaging Labs (EMIL). 01/01/2004 - 30/06/2009

Abstract

Researcher(s)

Research team(s)

Development and non-invasive monitoring of new animal models based on local, somatic transgenesis for a better diagnosis and therapy of neurodegenerative diseases. 01/01/2004 - 31/12/2008

Abstract

The project involves the development of an alternative for the development of transgenic animal models, with focus on neurodegenerative diseases. The basis principle is the use of lenti viral vectors for systematic suppression of different genes by RNA inhibition. Non invasive bio-imaging methods such as in-vivo micro PET, micro SPECT, micro CT , micro MRI and bioluminescence will be developed and implemented on small animals Besides transduction of adult differentiated cells, also the potential of stem cell migration will be tackled in the developed models.

Researcher(s)

Research team(s)

Corrections of EPI distorsions, necessarily for accurate high field functional Magnetic Resonance Imaging. 01/05/2003 - 30/04/2005

Abstract

): The use of Echo Planar Imaging (EPI) as a rapid Magnetic Resonance Imaging (MRI) technique, b1Jth in human as animal brain research, is susceptible to geometric distortions. In the frame of this project, new developments -both on the level of MR image acquisition and MR image processing will be made to correct for these EPI-distorsions. The developped correction technique will be implemented and validated in functional MRI (fMRI) studies perfonned in rats and songbirds.

Researcher(s)

Research team(s)

Calamity fund: adjustment repair costs of magnet. 01/04/2003 - 31/12/2003

Abstract

Researcher(s)

Research team(s)

In vivo magnetic resonance imaging study into the neural substrate of songprocessing and memory in songbirds. 01/01/2003 - 31/12/2004

Abstract

Researcher(s)

Research team(s)

Advanced NMR applications in the material-, chemical and biomedical sciences. 01/01/2002 - 31/12/2006

Abstract

Researcher(s)

Research team(s)

Sexual selection-research as a model system for studying the relationship between hormones, brain and behaviour. 01/01/2002 - 31/12/2005

Abstract

Researcher(s)

Research team(s)

Research in the field of "Bio-Imaging". 01/10/2001 - 31/08/2010

Abstract

Researcher(s)

Research team(s)

ZAPBOF-interdisciplinary project "Bio-Imaging": first support. 01/10/2001 - 30/09/2004

Abstract

Researcher(s)

Research team(s)

An integrated computer modelling and experimental study of the operations and function of the cerebellum. 01/01/2000 - 31/12/2003

Abstract

Notwithstanding the simple and regular anatomical organisation of the cerebellum, its function and activity remains unclear. This project aims at better understanding the function and activity of the cerebellum applying computer simulations and experiments in both men and animals. To that end morphological and electrophysiological techniques will be used on rats and functional magnetic resonance imaging will be performed on rat and men.

Researcher(s)

Research team(s)