The Bio-imaging lab hosts several PhD students. For example The following PhD projects are currently running in the lab:
- Dissecting the functional integrity of direct and indirect pathways of the dopaminergic system in Huntington's Disease - Funded by BOF
Huntington's disease (HD) is a rare, autosomal dominant inherited neurodegenerative disorder caused by an expanded polyglutamine sequence in the huntingtin gene (HTT) encoding for mutant huntingtin (mHTT). HD neuropathology is characterized by basal ganglia neurodegeneration, leading to progressive motor, psychiatric, and cognitive impairments, and ultimately death. While the pathogenic mechanisms by which mHTT causes selective dysfunction of the medium-size spiny neurons (MSNs) in the basal ganglia remain uncertain, we have extensive (pre)clinical evidence on the progressive loss of both D1 receptors (D1R) and D2 receptors (D2R), involved in direct and indirect dopaminergic pathways, respectively. Although MSN degeneration occurs roughly in equal proportions for D1R and D2R, the indirect dopaminergic pathway is affected first, resulting in the occurrence of the involuntary movements (hyperkinesia) characteristic of HD. As of today, there is a substantial knowledge gap in understanding the relationship between dopaminergic receptor density and the functional signalling of both direct and indirect dopaminergic pathways. In this project, a multimodal approach will be applied consisting of advanced non-invasive functional magnetic resonance imaging (fMRI), electrophysiology, behaviour, and post-mortem techniques in HD mouse models, with specific modulation of the direct or indirect dopamine pathway. The outcome will increase our understanding of the functional integrity of both dopaminergic pathways of the basal ganglia in HD.
- Mapping functional and structural brain plasticity following traumatic spinal cord injury using in vivo brain imaging methods
Traumatic spinal cord injury (SCI) is a devastating condition characterized by long-term motor and sensory neurological deficits. The functional loss in patients with SCI is mostly dictated by the precise anatomical location, with the cervical region accounting for nearly 50% of all patients, with contusion injuries being the most frequent.Following SCI, the entire central nervous system experiences increased neuroplasticity levels over several months as the spinal cord attempts to stabilize itself, meaning that most of the recovery occurs within the first year after their SCI. Emerging therapeutic strategies focused on neuromodulator approaches (including epidural or transcranial stimulation, opto- or chemogenetics, and brainmachine interface)to restore function after SCI are in development. The idea behind these approaches is to stimulate specific spared pathways between the brain and spinal cord to facilitate activitydependent plasticity, thus, ultimately, improving functional recovery.However, our understanding of cerebral neuroplasticity following SCI is still extremely limited. In the era of precision medicine, the ability to visualize and quantify the spatiotemporal changes occurring in the brain following SCI represents an extremely powerful approach toward patient-specific neuromodulation. The goal of this project is to develop non-invasive in vivo brain imaging approaches to visualize functional and structural plasticity occurring in the brain following SCI. Using a clinically relevant cervical contusion rat model of SCI, we will apply state-of-the-art MRI and PET neuroimaging methods in a unique longitudinal multimodal approach to study functional (resting state and stimulus-based fMRI), structural (diffusion MRI), and molecular (SV2A PET imaging)connectivity. In addition, we will study the association between these imaging biomarkers with a battery of motor outcomes, providing an extremely powerful paradigm for the interpretation of cerebral plasticity occurring during disease progression.Once determined, we will modulate the neuronal activity of the identified pathways using DREADDS (Designer Receptors Exclusively Activated by Designer Drugs) that activate engineered receptor complexes expressed in selected neuronal populations. This approach will allow us to determine whether the stimulation of identified cerebral pathways has the potential to steer adaptive neuroplasticity toward the improvement of functional outcomes and determine whether this process can be visualized non-invasively using brain imaging
- Establishing a multimodal preclinical imaging platform for the in vivo assessment of spinal cord injury outcome and therapeutic response - Funded by WFL
Spinal cord injury (SCI) is a devastating condition characterized by long-term motor and sensory neurological deficits, severely affecting the life of patients and their families. Although emerging therapeutic strategies focused on functional recovery are being explored, their development and translation to clinical use are severely limited by the lack of functional, objective, and non-invasive imaging biomarkers. Without quantifiable prognostic biomarkers, the clinical heterogeneity between SCI patients limits healthcare workers' qualitative measure of the potential future functional recovery. Using clinically relevant rat models, we propose a multimodal neuroimaging approach focused on synaptic and white matter markers to determine the prognostic and predictive outcome of (non)traumatic SCI. Longitudinal imaging with positron emission tomography (PET, for synaptic marker) and magnetic resonance imaging (MRI, for inflammation and white matter integrity) will be used for the establishment of a multimodal imaging platform to define lesions affecting the spinal cord to ultimately provide meaningful information related to lesion severity, functional outcome, and predictive value in a therapeutic context. Our platform will facilitate the interpretation of therapeutic results in preclinical studies, supporting the identification of most responsive treatment approaches and thus lowering the risks and costs for pharmaceutical companies' interest in the clinical translation of SCI.
- Unraveling the effect of thyroid hormones on seasonal neuroplasticity in the song control system of adult songbirds - Funded by FWO
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. 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. In addition, it is unknown whether THs mediate SCS plasticity in a direct or an indirect manner.
- Neurobiological predictors and social enhancers of vocal learning - Funded by BOF
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.
- 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 - 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 - Funded by FWO
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.