Functional-Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function due to its ability to noninvasively tag ‘active’ brain regions. Nevertheless, until now fMRI only detected neural activity indirectly, by relying on slow hemodynamic couplings whose relationships with underlying neural activity were not fully known. DIRECT-fMRI aimed to develop and apply novel MR methodologies for directly mapping neural activity and gaining insights into its nature, without relying on hemodynamics or neurovascular couplings, thereby generating novel means for studying global circuitry in vivo.
The objectives of the project were to (1) develop novel means for mapping neural activity in the brain without relying on blood oxygenation level dynamics, which is the current state-of-the-art; and (2) to demonstrate the methods’ applicability in rodents behaving in the scanner, thus bridging Cognitive and Systems Neuroscience approaches.
Along this project, we were able to establish the “µFMRI” methodology, as foretold, using diffusion weighted signals and, through orthogonal validation (such as optical microscopy in living brain slices), to show that it arises from swelling of cells and not only from vascular responses. We successfully established functional magnetic resonance spectroscopy in mice and tested the method in-vivo, to probe the dynamics of the neurotransmitters involved. Finally we managed to apply these methods to awake-behaving mice and, in the latest phase and continuation of the project, we used them to interrogate the visual system modulations upon restricted sensorial input. As unforeseen side projects, we have also developed deeper understanding of the diffusion weighted MR signals in tissues, and successfully applied some of these novel concepts to study stroke; we are currently applying them to Alzheimer and Parkison’s animal models in subsequent projects.
DIRECT-fMRI will thus benefit society by providing means for detecting and understanding neural activity in subjects with disrupted vasculature; in addition, it provides crucial basic knowledge on the neurophysiology of brain activity, and the development of rodent behavior in the magnet is revolutionary in terms of understanding the neural correlates of behavior.
