Identifying neural biomarkers and mechanisms of visual snow syndrome: advancing therapeutic targets for intervention

Visual snow syndrome (VSS) is a neurological condition that affects how people see the world. Those with VSS constantly experience visual disturbances, such as static-like vision, finding light painful or bothersome, floaters, and lingering afterimages. Further, patients with VSS often have concomitant migraine disorder and continuous tinnitus, which can be very difficult to manage. While visual snow can vary in severity, countless patients are profoundly impacted in their daily lives by the condition, with epidemiological studies showing that VSS affects around 2% of the population. VSS was only recognized as a medical condition ten years ago, and very little is known about what causes it and how best to treat it. In addition, the relationship of VSS with migraine, a frequent and highly disabling disease with which it shares biological similarities, is unclear. Comorbid migraine is linked to greater severity of VSS, with brain mechanisms such as cortical hyperexcitability and hyperresponsivity—particularly in visual regions—implicated in both conditions. Gaining deeper insight into the shared and distinct neural mechanisms of these disorders will enhance our knowledge and improve clinical recognition and differentiation between the two. In this fellowship I aim to better understand the mechanisms underlying VSS, and to identify brain biomarkers specific to VSS. This research will expand our understanding of the condition and lay the groundwork for developing targeted treatments for patients in the future. I will also explore how VSS differs from migraine, providing invaluable information for large groups of patients. My specific objectives are: To determine and quantify the neurotransmitters involved in VSS, and specifically to disentangle glutamate and GABA activity in the visual cortex. To study the brain mechanisms that determine VSS by measuring cortical excitability, inhibitory mechanisms, and excitation/inhibition balance within the visual system, and how these aspects influence visual processing and symptom generation in VSS. To differentiate the neurobiology of VSS from that of migraine, determining differences in habituation, visual processing, metabolic changes and cortical connectivity. To accomplish these goals, I will employ cutting-edge techniques that have never been applied to the study of this condition. In particular, I will use 7 Tesla magnetic resonance (MR) spectroscopy—the most powerful MR technology available for human research—to investigate changes in visual brain function and metabolism in patients with VSS, both at rest and during an active brain state. I will complement this approach with innovative methods for measuring brain activity, designed to stimulate and detect subtle changes in brain cortical nerve cells. Finally, I will employ drugs that modulate nerve cell signalling within these circuits, to establish a pharmacological model of VSS that enables direct and detailed investigation of the condition. In summary, this project will allow me to explore changes in brain function in patients with VSS, and, in the long term, to discover ways to improve outcomes for patients living with this disabling disorder. It will also deepen our knowledge of the neural mechanisms underlying abnormal sensory processing through a multidisciplinary approach, potentially influencing a wide range of disorders characterized by similar alterations.