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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Personalised rehabilitation of stroke patients evaluated with multimodal quantitative tools

Alternative title: Personlig rehabilitering av hjerneslag pasienter evaluert med multimodale kvantitative metoder

Awarded: NOK 12.0 mill.

In this project we aim to understand the relationship between the parameters determining neuroplastic changes after stroke so that we can we can best promote functional outcome. Armed with such knowledge, we hope to be able to tailor rehabilitation of stroke patients to achieve a higher level of neurological restoration than is currently possible. Towards this goal, we will apply a range of advanced clinical imaging, rehabilitation, and analytical tools to quantify the size of brain lesions and assess the surviving functional neural network connections in the brain of stroke patients. We will correlate such changes over time to different biomarkers, and train the surviving neural networks to maximize restoration of motor functions. Finally, we will apply mathematical and computational methods to model and predict how stroke rehabilitation can rewire the neural network connections to best facilitate restoration of lost motor function in individual patients. We have now completed several pilots in which we tested and optimised new protocols for advanced neuroimaging, neurological assessment, and relevant data analyses and continue with the recruitment of patients and healthy volunteers to the study.

Intrinsic neuroplasticity after stroke can be adaptive or maladaptive, which suggests that any attempt to harness it that fails to fully comprehend or suitably engage fundamental underlying mechanisms, may inadvertently exacerbate lesion-induced deficits rather than contribute towards functional restoration. The factors that determine whether the neuroplastic response to an ischemic event is adaptive or maladaptive depends, in part, on how the brain insult initiates and regulates the surviving neuronal transcriptional response to the injury. Understanding the relationship between these parameters can secure an adaptive rather than maladaptive neuroplastic change to the injury. Armed with such knowledge, rehabilitation of stroke patients could be tailored to achieve a higher level of neurological restoration than is currently possible. However, there are major gaps in our knowledge regarding the exact mechanisms regulating such responses. For example, no studies have studies stratified their data according to neurologic deficit, age, lesion volume or loss of neural network. Furthermore, the limitation of the widely applied NIHSS, mRS and the FMA scale is that these neurologic scores say nothing about how stroke induces changes in brain structure and network function, nor do they explain how targeted rehabilitation rewires the brain network (connectome), a process that is essential for improving neurologic function. This is a fundamental problem in stroke rehabilitation today. Our goal is to improve rehabilitation of stroke patients to restore motor function to a level that is not possible with current knowledge. We aim to accomplish this by brain mapping stroke patients to quantify the surviving neural connections and training relevant networks to engage and strengthen existing synaptic connections and establish new ones that can facilitate gain of motor function in a patient specific manner.

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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering