Grant: Foundation Grant

Advanced Neuroimaging; Biomarkers; Cerebral Palsy; Clinical Trials; Developmental Neuroplasticity; Neuromodulation; Non-Invasive Brain Stimulation; Optimizing Outcomes; Perinatal Stroke

<html> <body> <p> <b>THE ALBERTA PERINATAL STROKE PROGRAM (APSP)</b> <br> <i>NEUROMODULATION TO OPTIMIZE OUTCOMES</i> <br> <br> <b>SCOPE</b> <br> Cerebral palsy (CP) causes most lifelong disability, affecting over 50000 Canadian children¹. Perinatal stroke is a leading cause of CP and, as a focal injury of defined timing, represents the ideal human model of developmental plasticity. Constructing the components of this model with modern technologies like neuroimaging and brain stimulation has revealed opportunities for non-invasive neuromodulation of plasticity to enhance function and life in children with disabilities previously considered untreatable.<br> <br> The fundamental concept and approach of the APSP is summarized in <b>Figure</b> <b>F1</b>. To realize this possibility, we have built an internationally recognized, population-based perinatal stroke cohort and translational clinical research program. Three primary research pillars - neuromodulation, neuroimaging, and outcomes - rest on foundations of applied technologies, discovery clinical neuroscience research and therapeutic trials. Our primary aim is to develop neuromodulatory interventions to reduce the lifelong burden of perinatal stroke on children and families.<br> <br> <b>THE CLINICAL QUESTION<i>: How does developmental plasticity determine outcome following perinatal stroke and how can this be modulated to improve function?</i></b> <br> <br> This primary question is addressed under 4 themes:<br> 1. Construct human <i>developmental plasticity models</i> to identify central modulation targets.<br> 2. Elucidate the fundamental <i>principles of motor learning</i> <i>modulation</i> in children.<br> 3. Define the <i>modulators of developmental plasticity</i> that determine outcome.<br> 4. Translate improved understandings of developmental plasticity into <i>clinical trials</i>.<br> <br> <b>TEAM</b> <br> The APSP consists of 11 specialized, integrated, and complimentary teams of &gt;50 dedicated scientists, clinicians, end-users, highly-qualified personnel and trainees. Major teams include non-invasive neuromodulation, neuroimaging, neurorobotics, neurophysiology, neuropsychology, trials, and translation. The APSP is also the core of an international perinatal stroke research network, maximizing collaboration and impact on a global scale. This proposal is ambitious but genuinely achievable with proven methodologies, expert teams, committed partners (&gt;$1M), and established infrastructure.<br> <br> <b>TRAINING</b> <br> The unique translational learning environment of the APSP will grow. A plethora of original, clinically-relevant, technology driven projects stimulates research training across the spectrum. Proven dedication to trainee success rests on structured elements including cross-cutting research and clinical experiences, teaching and communication, networking, peer support, and community connections. Mentorship infrastructure includes established systems and formal methodology while this project will advance three novel mentorship initiatives.<br> <br> <b>IMPACT</b> <br> Knowledge advanced by themes 1-3 will create new understandings of how plasticity in the developing brain determines outcome following early injury. Theme 4 will directly and immediately translate these findings to test and deliver new therapies to affected children. We aim to demonstrate how short-term modulation of developmental plasticity can generate clinically significant improvements in function and life success over decades. Demonstrating this process in perinatal stroke carries important implications for neuromodulation approaches across neurological diseases in children.</p> </body> </html>