Inference of direct and multistep effective connectivities from functional connectivity of the brain and of relationships to cortical geometry.
BACKGROUND
The problem of inferring effective brain connectivity from functional connectivity is under active investigation, and connectivity via multistep paths is poorly understood.


METHODS
A method is presented to calculate the direct effective connection matrix (deCM), which embodies direct connection strengths between brain regions, from functional CMs (fCMs) by minimizing the difference between an experimental fCM and one calculated via neural field theory from an ansatz deCM based on an experimental anatomical CM.


RESULTS
The best match between fCMs occurs close to a critical point, consistent with independent published stability estimates. Residual mismatch between fCMs is identified to be largely due to interhemispheric connections that are poorly estimated in an initial ansatz deCM due to experimental limitations; improved ansatzes substantially reduce the mismatch and enable interhemispheric connections to be estimated. Various levels of significant multistep connections are then imaged via the neural field theory (NFT) result that these correspond to powers of the deCM; these are shown to be predictable from geometric distances between regions.


METHODS
This method gives insight into direct and multistep effective connectivity from fCMs and relating to physiology and brain geometry. This contrasts with other methods, which progressively adjust connections without an overarching physiologically based framework to deal with multistep or poorly estimated connections.


CONCLUSIONS
deCMs can be usefully estimated using this method and the results enable multistep connections to be investigated systematically.
School of Physics, The University of Sydney, Sydney, New South Wales 2006, Australia; Center of Excellence for Integrative Brain Function, The University of Sydney, New South Wales 2006, Australia. Electronic address: grishma.pandejee@sydney.edu.au.
Grishma
G
Mehta-Pandejee
School of Physics, The University of Sydney, Sydney, New South Wales 2006, Australia; Center of Excellence for Integrative Brain Function, The University of Sydney, New South Wales 2006, Australia.
P A
PA
Robinson
School of Physics, The University of Sydney, Sydney, New South Wales 2006, Australia; Center of Excellence for Integrative Brain Function, The University of Sydney, New South Wales 2006, Australia; School of Information Technology and Electrical Engineering, University of Queensland, St Lucia, Queensland 4072, Australia.
James A
JA
Henderson
School of Physics, The University of Sydney, Sydney, New South Wales 2006, Australia; Center of Excellence for Integrative Brain Function, The University of Sydney, New South Wales 2006, Australia; Sir Peter Mansfield Imaging Center, University of Nottingham, Nottingham NG7 2RD, United Kingdom.
K M
KM
Aquino
Center of Excellence for Integrative Brain Function, The University of Sydney, New South Wales 2006, Australia; Design Lab, University of Sydney, Sydney, New South Wales 2006, Australia.
Somwrita
S
Sarkar
D000328:Adult; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D003198:Computer Simulation; D063132:Connectome / Q000379:methods*; D006801:Humans; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology; D009434:Neural Pathways / Q000033:anatomy & histology* / Q000502:physiology*
Anatomical connectivity; Cortical geometry; Effective connectivity; Functional connectivity; Global mode removal; Multistep connections; Neural field theory; Norm-minimization