The brain is an extremely complex network of neuronal circuits, and the neurons’ axons are its communication cables. Axons transmit signals with different conduction velocities (CV) according to their microstructure, including their diameter and a surrounding insulating layer - the myelin sheath. Neurodegenerative diseases may cause either demyelination (e.g., multiple sclerosis) or axon degeneration (e.g., amyotrophic lateral sclerosis or Alzheimer) triggering widespread functional challenges. An understanding of how the structural connectivity of the brain can be related to brain function is key to deciphering neurodegenerative disease mechanisms and comprehending human behaviour.
To date, magnetic resonance imaging (MRI) is the only technique that provides non-invasive in-vivo information about the structural connectivity between the different human brain regions. Previous MRI studies focus on the amount of myelin present, regardless of how tightly the myelin is wrapped around the axon. However, the loosening of myelin layers is believed to precede demyelination in neurodegenerative diseases.
This project aims to develop a novel MRI-based myelin integrity measure and to use it as a correlate of CV. This implies the biophysical modelling and its validation with post-mortem and in vivo animal models before methods can be applied to humans. This novel framework may enable a much more detailed and non-invasive study of the brain tissue and provide accurate estimates of CV which can serve as an early biomarker of pathology.
Image: Electron microscopy image of demyelinated axons (left) and unaltered axons (right). The demyelination can be observed as the myelin - black structure around the white circular structure, the axons – disappears. Image from [1].
[1] Lin X, Njenga MK, Johnson AJ, Pavelko KD, David CS, Pease LR, Rodriguez M. Transgenic expression of Theiler's murine encephalomyelitis virus genes in H-2(b) mice inhibits resistance to virus-induced demyelination. J Virol. 2002 Aug;76(15):7799-811. doi: 10.1128/jvi.76.15.7799-7811.2002. PMID: 12097592; PMCID: PMC136370.