Sebastian Sten

Sebastian's PhD focused on describing the Neurovascular copuling and how the neurons control the vasoactive resoponse. Sebastian defended his thesis 2020 and a summary of his work is found below.

The brain is critically dependent on the continuous supply of oxygen and glucose, which is carried and delivered by blood. When a brain region is activated, metabolism of these substrates increases rapidly, but is quickly offset by a substantially higher increase in blood flow to that region, resulting in a brief oversupply of these substrates. This phenomenon is referred to as functional hyperemia, and forms the foundation of functional neuroimaging techniques such as functional Magnetic Resonance Imaging (fMRI), which captures a Blood Oxygen Level-Dependent (BOLD) signal. fMRI exploits these BOLD signals to infer brain activity, an approach that has revolutionized the research of brain function over the last 30 years. Due to the indirect nature of this measure, a deeper understanding of the connection between brain activity and hemodynamic changes — a neurovascular coupling (NVC) — is essential in order to fully interpret such functional imaging data. NVC connects the synaptic activity of neurons with local changes in cerebral blood flow, cerebral blood volume, and cerebral metabolism of oxygen, through a complex signaling network, consisting of multiple different brain cells which release a myriad of distinct vasoactive messengers with specific vascular targets. To aid with this complexity, mathematical modeling can provide vital help using methods and tools from the field of Systems Biology. Previous models of the NVC exist, conventionally describing quasi-phenomenological steps translating neuronal activity into hemodynamic changes. However, no mechanistic mathematical model that describe the known intracellular mechanisms or hypotheses underlying the NVC, and which can account for a wide variety of NVC related measurements, currently exists. Therefore, in this thesis, we apply a Systems Biology approach to develop such intracellular mechanisms based models using in vivo experimental data consisting of different NVC related measures in rodents, primates, and humans.

This new model-based understanding opens the door for a more integrative approach to the analysis of neuroimaging data, with potential applications in both basic science and in the clinic.

You can read Sebastians PhD thesis here.