Title Promoter Affiliations Abstract "New avenues to facilitate neuroplasticity in the healthy brain: The effect of transcranial direct current stimulation on motor learning and the impact of acute physical exercise on brain derived neurotrophic factor up-regulation" "Nici Wenderoth" "Research Group for Rehabilitation in Internal Disorders, Movement Control & Neuroplasticity Research Group, Research Group for Neurorehabilitation (eNRGy)" "The brain is a fascinating organ that controls every single movement of the human body. More importantly, it has the ability to change and adapt to its own environment. This ability is known as neuroplasticity and it is the key to learning and memory. Therefore, the idea behind this doctoral project is to take advantage of this human plastic brain and manipulate the environment by using innovative non-invasive brain stimulation techniques to boost neuroplasticity in the healthy brain.There are different non-invasive brain stimulation techniques, however, in this dissertation we focus on two of them exclusively: transcranial direct current stimulation (tDCS) and physical exercise. We investigated each of these techniques to explore and learn more about them individually with the purpose of designing an innovative protocol to combine them.The first technique we investigated was tDCS. TDCS is a simple technique that has been shown to effectively stimulate the brain as measured by imaging techniques as well as by neurophysiological and behavioral measurements. In the present work, we found that the effect of tDCS is task-specific and that the behavioral response to this technique is highly variable, with only 43% of subjects showing the expected benefits. These results thus highlight that the effect of tDCS is specific not only to the task being acquired, but also to the individual receiving the stimulation. Notably, we observed an overall small to moderate effect of tDCS on motor learning, which based on our findings, could result, at least partly, from the large inter-subject variability. Importantly, however, our data was acquired in young healthy subjects while it is likely that effectiveness of tDCS would generally be higher in neurological patients, providing an optimistic view on the implementation of this technique in patient’s populations.The second technique used in this project was physical exercise. Exercise is not only easy to perform and cost-effective but has also additional secondary beneficial effects such as improvements in metabolic and cardiovascular risk profiles. Moreover, exercise could have a positive effect on the brain by activating brain derived neurotrophic factor (BDNF) related processes. We confirmed that intense exercise can increase BDNF levels. Further, it is important to mention that our findings show a slightly higher BDNF serum concentration after the high intensity interval training protocol (HIT) than after the continuous high intensity exercise protocol (CON). Thus, we argue that the HIT protocol could be a potential intervention to promote neuroplasticity and in turn brain health.To conclude, tDCS and exercise are both promising methods to enhance neuroplasticity. However, the effectiveness of these interventions on neuroplasticity in healthy humans has proven challenging with only few studies reporting a beneficial effect of exercise on cognition and with small to moderate effect sizes found in our and many other tDCS studies. We therefore propose that combining both interventions might boost neuroplasticity in a manner that exceeds their sum. Ultimately, these findings may contribute indirectly to the improvement and design of new motor rehabilitation approaches in patients with brain damage or neurological conditions." "The obese brain: the relationship between brain structure, neurocognitive functioning and motor coordination in obese children" "Frederik Deconinck" "Department of Movement and Sports Sciences" "This proposal will be carried out in the Motor Control research group led by Prof. M. Lenoir. In this group the main focus is on motor competence in children and adolescents (typically developing, DCD, gifted children, athletes) with about 10 ongoing PhD projects. The group is internationally recognized as one of the pioneers to focus on the mechanisms of lower motor competence in obese (OB) children and has a long-standing research collaboration with the Zeepreventorium, De Haan. The relation between OB and gross and fine motor skill by means of behavioral tests was extensively documented during the PhDs of E. D’Hondt (2011) and I. Gentier (2014). This project builds further on the finding that childhood obesity is not only associated with lower gross motor competence, but also with fine motor skill execution. More specifically, Gentier et al (2014) foundevidence for suboptimal control processes in obese children (e.g. decision making, integration of feedback in ongoing action). The combination with brain imaging expertise is the next logical step in unraveling these mechanisms.Therefore we will collaborate with Prof. K. Caeyenberhgs, who has gained much experience with a variety of state-of-the-art medical imaging techniques (e.g. DTI, MTI) in young children with Traumatic Brain Injury. To learn more about the latest technological developments of structural MRI with specific emphasis on brain white brain matter microstructure, she went to the lab of Prof. D. Jones (CUBRIC, Cardiff; a stay abroad is planned to this lab). With respect to all these MRIexperiences, Caeyenberghs has an existing collaboration with the Radiology Department (UZ Ghent), Prof. E. Achten (neuroradiologist), GIFMI and there is a partnership with the MRP of the Institute for Neuroscience.-" "Unravelling European Governmental Venture Capital Funds: investment patterns, innovation and brain drain." "Steven Vanhaverbeke, Ann Gaeremynck, Liesbeth Bruynseels" "Department of Management, Strategy and Innovation (main work address Leuven), Accounting Research Group (main work address Leuven)" "In my research I will focus on Corporate Governance and the Board of Directors. More information on the specific topic and a summary will follow soon." "Can non-invasive brain stimulation combined with oxytocin-based pharmacotherapy enhance brain function in autism? Investigating the neural and behavioral effects of two promising intervention approaches" "Kaat Alaerts" "Research Group for Neurorehabilitation (eNRGy)" "The last decade, neuroscience research provided increasing insights in how different brain regions work together to constitute the neural networks that underlie human social behavior. Targeting these networks to improve or restore social function would be of high relevance for neuropsychiatric conditions that have specific implications in social and communicative domains, such as autism spectrum disorders. At present, neuro-modulating approaches mainly rely on behavioral therapies. The current research project will explore novel avenues for enhancing neuro-modulation of the social networks in the autistic brain. Initial promising results have emerged for intranasal administration of the social neuropeptide oxytocin for promoting social functioning. Also strong therapeutic potential is anticipated for applying noninvasive excitatory brain stimulation over key brain loci in the autistic brain. A specific interest this project lies in assessing whether these novel intervention approaches can enhance the neural communications or connectivity within social brain networks. In normal development, the neural circuits that underlie human social behavior are not fixed, but constantly change from interactions with our surroundings. This project will define whether plastic neural changes can be specifically enhanced from neuropeptide treatments and/or non-invasive brain stimulation." "Can non-invasive brain stimulation combined with oxytocin-based pharmacotherapy enhance brain function in autism? Investigating the neural and behavioral effects of two promising intervention approaches." "Kaat Alaerts" "Research Group for Neurorehabilitation (eNRGy)" "The last decade, neuroscience research provided increasing insights in how different brain regions work together to constitute the neural networks that underlie human social behavior. Targeting these networks to improve or restore social function would be of high relevance for neuropsychiatric conditions that have specific implications in social and communicative domains, such as autism spectrum disorders. At present, neuro-modulating approaches mainly rely on behavioral therapies. The current research project will explore novel avenues for enhancing neuro-modulation of the social networks in the autistic brain. Initial promising results have emerged for intranasal administration of the social neuropeptide oxytocin for promoting social functioning. Also strong therapeutic potential is anticipated for applying noninvasive excitatory brain stimulation over key brain loci in the autistic brain. A specific interest this project lies in assessing whether these novel intervention approaches can enhance the neural communications or connectivity within social brain networks. In normal development, the neural circuits that underlie human social behavior are not fixed, but constantly change from interactions with our surroundings. This project will define whether plastic neural changes can be specifically enhanced from neuropeptide treatments and/or non-invasive brain stimulation." "Cause-effect relationships between brain networks and inter-limb coordination in older adults and the effect of oscillating transcranial brain stimulation on training-induced neuroplastic changes and motor performance." "Raf MEESEN" "Rehabilitation Research Center, Catholic University of Leuven, TU Dortmund University" "Healthy aging is a societal challenge with a huge economic impact. Therefore, it is of utmost importance to gain knowledge on agerelated neurodegenerative changes that limit active participation in society. Age-related structural and functional declines in the brain have an important impact on motor coordination between limbs (""inter-limb coordination""). Since most of our daily activities are characterized by inter-limb movements, such as tying shoelaces or driving a vehicle, research towards a better understanding of the underlying neural mechanisms of impaired coordination is highly relevant. While previous literature combining brain imaging and interlimb tasks have yield correlational evidence between brain dynamics and motor coordination in older adults, this project will use noninvasive brain stimulation to interfere with ongoing brain function in order to assess cause-effect relationships between brain function and behavior. Furthermore, in the last part of this project we will use the knowledge gained in the first part to develop a specific brain stimulation protocol as an intervention to improve inter-limb coordination in older adults. More specifically, we will investigate whether stimulation-supported training yields better performance effects than training alone. In sum, this project is logically built up from the search for neural mechanisms underlying impaired coordination in older adults, towards a goal-oriented intervention program to improve motor skills." "Ageing and brain plasticity. Training-induced alterations in spectral power of the brain and motor coordination" "Andreas Daffertshofer, Stephan Swinnen" "Movement Control & Neuroplasticity Research Group" "Declines in sensorimotor and cognitive function are well-known consequences of ageing. Improving our understanding of what ageing entails at cellular up to systemic levels is hence timely and urgent. And, finding strategies to decelerate or even reverse the pervasive effects of aging can have a major societal impact. The aim of this thesis was to investigate changes in spectral dynamics of the brain associated with bimanual task difficulty, motor learning and ageing. We provided a concise literature review of the electro- and magneto-encephalographic (EEG/MEG) studies on bimanual coordination. This review revealed converging evidence for (1) stronger suppression of spectral power during motor execution of bimanual compared to unimanual movements, (2) the involvement of supplementary motor area (SMA), premotor cortex, sensorimotor cortices (M1/S1), anterior cingulate cortex and cerebellum during anti-phase compared to in-phase movements, and for (3) increases of inter-hemispheric connectivity in the beta band for bimanual compared to unimanual movements. The review also revealed gaps in the literature, which motivated two experimental studies.One of these gaps was related to the study of continuous non-isofrequency rotational movements. Therefore, we investigated how the brain copes with task difficulty in non-isofrequency bimanual movements. Beta (15-30 Hz) power in the non-dominant (right) hemisphere was modulated with task difficulty, presumably reflecting stronger control of the right M1/S1 over the non-dominant (left) hand. By using realistic head models, we were able to estimate neural activity in the cortex, and assessed functional connectivity in terms of beta-band synchronisation, in a bilateral network including M1/S1, dorsal premotor cortex and the precuneus. Beta synchronisation increased with increasing task demand. Further confirmation of the increases in beta synchronisation as a coping mechanism of the brain to deal with task difficulty was found in the positive correlation between the connectivity of the network and the performance error.Another gap identified in the literature review concerned the neural correlates of motor learning without online feedback across extended practice. Importantly, age-related alterations in learning strategies had not been studied in the context of EEG/MEG spectral dynamics across different frequency bands and motor task variations. We therefore investigated learning strategies supported by spectral dynamics in the theta (4-8 Hz), alpha (8-12 Hz) and beta bands, and how these differed between young and older adults. Importantly, we found different spectral dynamics over different brain regions underlying the retrieval of motor memories. Additionally, training-induced changes in the last compared to the first session were observed over the prefrontal cortex (PFC) in the theta band, and over M1/S1 in the alpha and beta bands. Finally, age-related effects were mainly found in the beta band covering parietal, central and medial PFC. All these findings were accompanied by a reduced learning gain in the older compared to the young adults.In this thesis, we provided an overview of the EEG/MEG literature on bimanual coordination which may serve as a starting point to any scientist new to the subject. We highlighted the role of the beta power and long-range synchronisation in the execution of different precision movements beyond the well-known role in the initiation of movement and sustainment of muscle contractions. We provided a comprehensive view of learning-related spectral changes by investigating theta, alpha and beta bands which usually are studied individually. Finally, at a time when life expectancy is constantly increasing thanks to medical improvements, ageing-related functional changes in the brain ought to be understood. We hope that the present work contributed to this understanding by detailing learning- and age-related modulations in frequency-specific dynamics in the cortex." "Aging and brain plasticity: alterations in brain structure, function and connectivity in relation to complex motor behavior." "Stephan Swinnen" "Movement Control & Neuroplasticity Research Group" "Here, we aim to advance our understanding of age-related changes in the brain and their consequences for movement control. Our basic premise is that alterations in motor functioning are constrained by functional, structural, and connectivity changes in the normally aging brain. To address this challenge, we will use an array of techniques including (a) behavioral paradigms to study complex motor tasks requiring cognitive control (b) state-of-the-art magnetic resonance imaging (MRI) techniques to study brain function, structure, and connectivity, and (c) transcranial magnetic stimulation (TMS) techniques to study the status of inhibitory networks. Even though overall brain structure and function will be assessed, our focus is on the integrity of the corpus callosum (CC) because it is a central structure in the organization of complex brain functions that regulates the interactions between both hemispheres. Age-related changes in the CC parallel overall changes in the brain which are characterized by an anterior-posterior gradient in degeneration. Complex bimanual coordination tasks are studied for this purpose because they are sensitive to changes in the structural integrity of the CC and also because they shed light on cognitive control functions, such as motor response switching and (multiple) task management." "Extracellular vesicle (EV) transport across the brain barriers: from mechanistic and biological insights towards strategies for delivery of therapeutics to the brain." "Kris Gevaert, An Hendrix, Roosmarijn Vandenbroucke, Kevin Braeckmans" "Department of Biomolecular Medicine, Department of Human Structure and Repair, Department of Biomedical molecular biology, Department of Pharmaceutics" "Extracellular vesicles (EVs) are nanosized membrane vesicles released by a broad range of cells. We study the mechanism by which EVs cross the central nervous system (CNS) barriers using innovative EV-loading technologies and surface proteome analysis. Next, we use this knowledge to develop novel brain targeting strategies for drug delivery." "Radiation effects on human brain development, modeled in human brain organoids" "Sarah Baatout" "Department of Biotechnology" "Exposure of pregnant women to ionizing radiation (IR) can profoundly impact the fetal brain development, leading to microcephaly. To date, the mechanisms of radiation-induced neurodevelopmental disorders remain insufficiently known. To fill this gap and to better resemble aspects of the human brain developmental physiology to study mechanisms of IR-induced microcephaly, here we use human brain organoids."