The human brain is one of the largest and most complex biological networks known to exist. It consists of a large number of interacting circuits, which play a crucial role determining the computations it can perform and, thus, in enabling our cognitive abilities. The architecture of these circuits in humans, and therefore the computational basis of human cognition, remains largely unknown. The project focused on the multiscale imaging of human cortical microcircuits and on how these circuits contribute to computation and cognition. A structural and functional assessment of microcircuitry in the human brain only recently came within the realm of possibilities, thanks to the development of, first, optical tissue clearing and light sheet microscopy and, second, magnetic resonance imaging (MRI) at ultra-high field-strengths (UHF) of 7T and above. In-vivo functional imaging of human cortical activity, spatially resolved for cortical columns and layers, was also recently shown to be feasible with UHF fMRI. When UHF structural and functional MR imaging are combined, this has the exciting potential of imaging the connections and activity of different components within the cortical microcircuit.
The project concluded with the achievement of several imaging platforms, methodologies and data sets which achieved human cortical architecture and connectivity imaging and made large strides towards understanding human cortical computations. An ex vivo human brain MRI platform was developed with a suite of UHF imaging hardware and software for human brain tissue, which have led to new standards of quality and resolution of mesoscale ex vivo human brain tissue MRI scans for the investigation of cortical layer structure and white matter connections. A tissue clearing and light sheet fluorescence microscopy platform for human brain tissue was developed, which can image very large human brain tissue samples at microscopic resolution. These have created new standards of quality and field-of-view of ex vivo microscale human brain tissue microscopy for the investigation of cortical cytoarchitecture and microcircuitry. An in vivo MR imaging platform for white matter microstructure and high-resolution gray matter fMRI was created, including head coils tailored to high-resolution fMRI of the human visual cortex, methods for in vivo analysis of structural human brain connectivity and its functionally relevant microstructure (such as axonal diameters, density and myelination) with MRI, and an open-source analysis tool for analysis of human brain connectivity and microstructure with MRI.
Achieving the aims significantly advance our measurement of cortical architecture and understanding of how cortical microcircuits compute, provides important new reference data for graph analytical characterizations of the human connectome and generative models of human cortical dynamics, and informs modelling studies human cortical processing in health or after brain damage.
