Neuroscience and Brain Disorders
16:05 - 17:25 | Meeting Room 102 (Level 1)
Chair: Prof. Ruben J. Cauchi
Dr Rebecca Cacciottolo
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery
A key pathological hallmark of neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) is the accumulation of protein aggregates in neurons, though the underlying mechanisms driving their formation and their exact role in disease progression remain unclear. Understanding the causes and consequences of protein aggregation is critical to uncovering potential therapeutic targets.
Our research focuses on investigating the cellular mechanisms underlying aggregation in ALS, using a fruit fly model to explore how disruptions in key pathways contribute to this process. Specifically, we are studying the impact of a major ALS genetic risk factor, which encodes a protein involved in intracellular trafficking, on aggregation dynamics. Our findings reveal the presence of ubiquitin-positive inclusions, as well as an increase in the concentration of factors linked to vesicle trafficking and transport. These results suggest that impaired protein recycling and intracellular transport may play a central role in aggregation formation and neurodegeneration in ALS.
By identifying these critical points of failure, our work provides new insights into how cellular dysfunction promotes aggregation and exacerbates disease pathology. This research lays the foundation for future studies aimed at restoring cellular homeostasis and mitigating the toxic effects of aggregates in ALS. Understanding these processes is essential to developing interventions that could slow or halt disease progression, offering hope for improved outcomes in patients suffering from this devastating condition.
Dr Paul Herrera
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterised by the degeneration of motor neurons, ultimately leading to muscle weakness, paralysis, and respiratory failure. Genetic susceptibility to ALS is elevated in genetically isolated populations, such as Malta, where reduced genetic diversity increases the prevalence of rare, potentially pathogenic variants. Building on several years of whole-genome sequencing data from a Maltese ALS case-control cohort, we developed a robust variant-filtering pipeline to identify rare genetic contributors to disease risk. Variants were prioritised based on patient specificity, protein-coding impact, and low allele frequency in European reference populations (<1.5%), enriching for candidates likely to disrupt gene function. Recurrently observed variants were subsequently analysed to identify genes and molecular pathways with potential relevance to ALS pathogenesis.
Using this approach, we identified a Golgi-associated candidate gene harbouring shared missense variants in three unrelated ALS patients. The encoded protein belongs to the golgin family and is implicated in Golgi organisation and vesicle trafficking – cellular processes previously linked to ALS. To assess functional relevance in vivo, we generated Drosophila models with either whole-body knockdown or complete deletion of the gene orthologue. Motor function was evaluated using established flight and climbing assays. In both models, no significant differences were observed between experimental and control flies, suggesting no overt neuromuscular phenotype under baseline conditions. However, further functional studies may help elucidate whether the interplay of other factors, including environmental stressors, could increase the penetrance of this potential genetic contributor to ALS susceptibility.
Ms Sylvana Tabone
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery
Motor neuron disease (MND) is increasingly considered a non-cell autonomous disease because its progression is influenced not only by the affected motor neurons themselves but also by the dysfunction of surrounding non-neuronal cells, such as glia. This study focuses on a novel risk gene involved in vesicle trafficking – a pathway known to be central to motor neuron function. Using Drosophila melanogaster as a model organism, we functionally characterised this gene by performing tissue-specific disruption. Our preliminary results demonstrate that the gene is essential for motor system integrity, but its requirements vary significantly across tissues. While motor neuron-specific disruption resulted in a gradual, age-related functional decline, which is indicative of a role in long-term neuronal maintenance, glial-specific disruption produced a far more severe phenotype, including developmental lethality and acute locomotor impairment. These findings suggest that the gene is critical for the glial-mediated support of motor circuits. Ultimately, this work validates a novel MND genetic risk factor and reinforces the non-cell autonomous hypothesis, suggesting that glial dysfunction may be a primary driver rather than a secondary consequence of motor neuron degeneration.
Dr Nowell Zammit
Centre for Molecular Medicine and Biobanking
While the discovery of synapses consolidated much of the foundation behind modern neuroscience, it also raised fundamental questions regarding the mechanisms by which neurons communicate. Findings from our laboratory have shown that during working memory (WM), neurons exploit their complex electrophysiological dynamics to synchronise and/or desynchronise from one another flexibly. Leveraging temporal summation, neurons calibrate the timing of their peaks with one another to selectively amplify or attenuate their impact on downstream neuronal targets. Similarly, during WM, neural inhibition in the form of beta rhythmic activity is disengaged by modifying its phase interaction with fast gamma frequencies, which code sensory information. Recently, we conducted human closed-loop experiments to test this mechanism causally. We found that the delivery of sensory information during specific phases of inhibitory beta rhythms modulates subsequent memory by interfering with retained stimulus representations. In the current experiments presented herein, we move on to characterise the ‘when’ behind these inhibitory interactions. Our findings indicate that neural synchronisation and thus connectivity in general, is not engaged continuously, but rather occurs discretely during specific instances when neural ensembles switch to brief high-power bursts. Bursts induce synaptic weight changes, leaving enduring ‘synaptic impressions’ that reduce reliance on persistent activity, decreasing metabolic costs and interference. As a result, we would suggest that WM control hinges on transient, burst-driven windows in which inhibition can be effectively channelled at critical moments, where quite literally, ‘tomorrow might be too late, it’s now or never, as the transfer cannot wait’.
Prof. Chris Porter
Department of 福利在线免费 Systems, Faculty of 福利在线免费 and Communication Technology
Funded by the UM’s Research Excellence Fund, the BrainWeb project investigated the feasibility of a low-cost, effective, and user-friendly brain-computer interface (BCI) solution to provide individuals with severe motor impairments - such as those with advanced amyotrophic lateral sclerosis (ALS) or stroke-related disabilities - with unrestricted access to the Internet. The project focused on enabling essential activities, including communication, education, employment, entertainment, and other forms of digital participation that are central to autonomy and quality of life.
In alignment with national and international priorities in assistive technology research, the project also explored interdisciplinary collaboration across neuroscience, engineering, and human-computer interaction. Throughout the project, BrainWeb delivered a working solution that was also demonstrated locally and internationally. Boggle, an open-source BCI web browser, the main deliverable arising from the project, also received an award at an HCI conference in Italy for the best interactive experience.
This presentation offers a post-project overview of the BrainWeb initiative, summarising its key technical and research deliverables, reflecting on the challenges encountered, and highlighting lessons learned. The talk concludes with recommendations for future research and development in accessible, affordable BCI technologies.
Prof. Mireille M. Sant
Department of Media, Communications and Technology Law, Faculty of Laws
Rapid advances in neuroimaging and neurotechnology are expanding the capacity to collect, analyse, and deploy neurodata, raising significant ethical and legal questions concerning privacy, autonomy, and human dignity. This ongoing research examines how Europe’s existing legal framework facilitates, constrains, or redirects ethically responsible brain research and neurotechnology innovation, and whether these developments may require additional rights or protections, such as those proposed under the banner of ‘NeuroRights’.
The research focuses on the European Union’s regulatory landscape, including the EU Charter of Fundamental Rights, the General Data Protection Regulation (GDPR), the European Health Data Space (EHDS), and the Artificial Intelligence Act (AI Act). Particular attention is given to how neurodata are categorised and assessed as sensitive or high-risk, the significance of purpose and context in data processing, and the role of safeguards such as data protection impact assessments. A key concern is the distinction between fundamental research and commercial or consumer applications of neurotechnology.
Drawing on emerging comparative case studies, including national mental health legislation and constitutional developments beyond Europe, the research highlights how protective legal measures may produce unintended consequences, potentially limiting participation in research or creating regulatory uncertainty. Preliminary findings suggest that rather than a legal vacuum, existing frameworks already offer substantial protections. The research explores how reinterpreting and operationalising existing rights, alongside clearer guidance and proportionate safeguards, may better protect cognitive liberty while supporting ethically robust and innovative brain research.
Dr Claude J. Bajada
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery
Glioblastomas are aggressive, high-grade gliomas characterised by rapid infiltration of neighbouring tissue and a poor prognosis, with a median survival of approximately 14.6 months. A primary challenge in treating these tumours is their diffuse invasion along white matter pathways, which traditional linear growth models often fail to predict accurately. This presentation introduces recent advancements in the Brain Research through Imaging Analysis for Neuro-oncology (BRIAN) project, which aims to improve predictive modelling of tumour propagation.
Utilising diffusion MRI, we employ diffusion orientation distribution functions (dODFs) rather than standard tensor models to capture complex neural architecture. By applying probabilistic tractography algorithms (iFOD2), we simulate tumour spread from seed points, modelling both spherical proliferation and tract-constrained invasion. While the early phases of this project established proof-of-concept feasibility in single subjects, current work has scaled up. We have estimated growth parameters on a training set of 20 individuals and are currently applying these predictive models to a cohort of 66 unseen participants.
The objective is to accurately predict 'tumour failure locations,' areas likely to be involved in future propagation but invisible on standard structural imaging. By simulating how a tumour traverses healthy brain architecture, this approach aims to refine surgical planning. This allows clinicians to target resection margins that account for likely infiltration paths, potentially reducing recurrence and improving patient outcomes.
Prof. Ian Thornton
Department of Cognitive Science, Faculty of Media and Knowledge Sciences
Classic visual search tasks have taught us much about the role of attention during exploration of the environment. In the last decade, typical single-target search tasks have been extended by incorporating concepts from the animal foraging literature, in particular, the use of multiple targets per trial (e.g., Kristjánsson, Jóhannesson, & Thornton, 2014). The Multi-Item Localisation (MILO) task is related to modern foraging tasks in sharing multiple targets, but incorporates one other important innovation: targets must be selected in a specific sequential order (Thornton & Horowitz, 2004; 2020). The use of a sequence (e.g., numbers 1–8), makes it possible to explore within-trial temporal context. That is, at any moment within a trial we know exactly where you’ve been and where you are going next in the sequence. This makes it possible to use simple manipulations to explore both retrospective and prospective aspects of search behaviour. In the current talk, I will report data from two recent projects. The first demonstrates that past targets can be effectively ignored, even in the absence of a direct, spatially-localised selection action. The second shows how the MILO task can be used with complex, higher-level stimuli – facial expressions – to explore categorical boundaries in natural sequences.