Functional Magnetic Resonance Imaging of cortical layers to measure directionality of information flow in brain networks for pain

• Applicant: Dr. Peter Koopmans
• Subject Area: Human Cognitive and Systems Neuroscience ; Experimental and Theoretical Network Neuroscience ; Medical Physics, Biomedical Technology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 310872863

In my ongoing 5 year Emmy Nöther project I am developing functional Magnetic Resonance Imaging (fMRI) of cortical layers. This technique holds the key to unveiling the directionality of long-range information flow through the brain, as the cortical laminar structure is characterised by a division into feedforward and feedback processing layers. Long-range connectivity is absolutely critical for understanding human cognition, and is considered to be the linchpin setting apart the human brain from animals. The ability to measure directionality in those connections will allow us to separate bottom-up signalling from modulatory, top-down processing, which is of particular importance in those brain areas that are characteristically not part of a strict hierarchy, and may even reverse direction depending on the specific cognitive process (e.g. bottom-up painful stimulation versus top-down modulation through placebo-based pain suppression). My Emmy Nöther project has a two-pronged approach to establish fMRI for cortical layers: 1. Optimise measurement of cortical laminar signals. We develop fMRI methodology to improve its intrinsic specificity to better separate signals from the different cortical laminae. 2. Develop analysis tools to characterise laminar signals. Even when the laminar features are successfully captured in the fMRI data, standard fMRI analysis techniques cannot exploit their directional nature. We therefore develop new analysis tools to infer directional connectivity in layer fMRI datasets. While we have translated many of our aims in established pipelines and proofs-of-concept there remain two large hurdles currently preventing layer fMRI approaches to be adopted by mainstream cognitive neuroscience. (1) The low intrinsic specificity of fMRI’s most sensitive methods can prevent separation of the laminar signals. (2) More-specific fMRI methods suffer from a poor sensitivity and efficiency resulting in long data acquisition times which are impractical in many cognitive tasks (examples include (ethical) issues with prolonged painful stimulation or adaptation/learning effects in tasks). In this application for a sixth year of funding, we aim to scale these hurdles. Specifically, we will translate the very recently developed arterial blood contrast (ABC) fMRI data acquisition method to the realm of cortical laminar fMRI, leveraging our pipelines and techniques already established in the main Emmy Nöther project. We anticipate that this exciting new ABC fMRI method will greatly benefit layer fMRI as it promises superiority in both specificity and efficiency at the same time.

• DFG Programme: Independent Junior Research Groups