Multimodal associations of human brain plasticity investigated with simultaneous PET/MR

Background: Neuronal plasticity is the brains ability to continuously adapt to experiences and learning of new skills. Although this affects multiple characteristics of the brain such as structure, function and metabolism, direct interactions between these aspects are largely missing. Using recent advancements in neuroimaging we aim to identify novel relationships of how neuronal plasticity is related across these characteristics. Hypotheses: Compared to a control group, specific training of a cognitive task will result in alterations regarding structure (gray matter volume and white matter neuronal pathways), function (neuronal activation and connectivity) as well as glucose metabolism. Furthermore, these alterations of multiple imaging modalities are related across each other. Project design: 40 healthy subjects will undergo two simultaneous PET/MR measurements at baseline and after 4 weeks. During the measurements a cognitively challenging task will be performed and the training group (20 subjects) will practice during the 4-week period. Methods: Structural and functional magnetic resonance imaging (MRI) will be acquired simultaneously with positron emission tomography (PET). A novel PET measurement protocol enables the assessment of glucose metabolism during task-performance. Effects of neuroplasticity will be investigated for brain structure (gray and white matter), task-specific neuronal activation and glucose metabolism as well as entire brain networks. Multimodal associations will be assessed to identify relationships of neuroplasticity between metabolism, structure and function. Innovation and implications: We combine simultaneous PET/MR and novel task-specific PET imaging to study brain metabolism, structure and function in a single measurement session. This provides optimal sensitivity for assessment of multimodal neuroplasticity associations. Knowledge how cognitive training affects multiple characteristics of the brain will also increase our understanding of disorders like depression, dementia and brain injuries, since these are diagnosed with cognitive evaluations. Considering the vast usage of the applied imaging procedures in diagnosis and therapy monitoring, the thorough investigation of multimodal associations offers great benefit for the interpretability of neuroimaging in clinical routine. 1

The brain has the essential ability to adapt to an ever-changing environment, which is known as neuroplasticity. Learning of novel skills represents one example of such neuroplastic adaptations, however, the underlying physiological mechanisms are not yet fully understood. To investigate these neuroplastic mechanisms in more detail, 41 healthy volunteers were included in this study while learning a complex cognitive task, which required rapid visual processing and motor coordination. Each participant completed two measurements with simultaneous acquisition of functional positron emission tomography (fPET) and functional magnetic resonance brain imaging (fMRI) data. We focused on two essential aspects of brain function. First, glucose metabolism was assessed with fPET since the brain consumes a vast amount of energy by using glucose together with oxygen as main sources of energy. Second, connections between brain regions were assessed with fMRI, as it is known that brain function relies on efficient interaction and communication between brain regions and networks. In an initial pilot study, the measurement protocol was optimized to enable robust identification of changes in glucose metabolism with a novel approach. Next, application of this technique showed that first-time performance of a cognitive task leads to a considerable increase in the association between glucose metabolism and connectivity. This indicates that the energy metabolism indeed supports the interaction between brain regions, which for the current task was specific to networks of visual processing and attention. Finally, we investigated effects of learning as the training group of 21 volunteers practiced the cognitive task on a regular basis within a four-week learning period between the two measurements. The study showed an adapted interaction of brain networks involved in salience and visual processing after learning. Specifically, general adaptations were dependent on glucose metabolism, which have previously been related to strengthened synaptic links between nerve cells. On the other hand, adaptations during task execution itself were dependent on the functional interaction between brain networks, indicating an efficient neuronal representation of the task. Interestingly, the combination of these two adaptive mechanisms was associated with individual task performance and learning progress. In sum, the methodological advancements obtained in this project enabled the identification of neuroplastic mechanisms in the human brain as induced by learning a novel skill. We specifically demonstrate that interregional communication in the brain is tightly coupled to the underlying energy demands and that learning induces complex adaptations to both of these aspects. Considering that numerous neurological and psychiatric disorders are characterized by altered energy metabolism and interactions between brain regions, the findings may on the long run aid for a better understanding of cognitive deficits in these disorders.