Abstract
The neural circuit of the brain is organized as a hierarchy of functional units with wide-ranging connections that support the information flow and functional connectivity. Studies using magnetic resonance imaging (MRI) indicate a moderate coupling between structural and functional connectivity at the system level. However, how do connections of different directions (feedforward and feedback) and regions with different excitatory and inhibitory (E/I) neurons shape the hemodynamic activity and functional connectivity over the hierarchy are unknown. Here, we used functional MRI to detect optogenetic-evoked and resting-state activities over a somatosensory pathway in the mouse brain and compared with axonal projection and E/I distribution. With a highly sensitive ultrafast imaging, we identified extensive activation in regions up to the third order of axonal projections following optogenetic excitation of the ventral posteriomedial nucleus of the thalamus. The evoked response and functional connectivity correlated with feedforward projections but less with the feedback and weakened with the hierarchy. The hemodynamic signal exhibited regional and hierarchical differences, with slower and more variable responses in high-order areas and bipolar responses predominantly in the contralateral cortex. Importantly, the positive and negative parts of hemodynamics correlated with E/I neuronal densities, respectively. Furthermore, resting-state functional connectivity more associated with E/I distribution whereas stimulus-evoked effective connectivity followed structural wiring. These findings indicate that structure-function relationship is projection-, cell-type- and hierarchy-dependent. Hemodynamic transients could reflect E/I activity and the increased complexity of hierarchical processing.
Significance statement The neural circuit of the brain is organized as a hierarchy of functional units with complicated feedforward and feedback connections to selectively enhance (excitation) or suppress (inhibit) information from massive sensory inputs. How brain activity is shaped by the structural wiring and excitatory and inhibitory neurons are still unclear. We characterize how brain-wide hemodynamic responses reflect these structural constituents over the hierarchy of a somatosensory pathway. We find that functional activation and connectivity correlate with feedforward connection strengths and neuronal distributions. This association subsides with hierarchy due to slower and more variable hemodynamic responses, reflecting increased complexity of processing and neuronal compositions in high-order areas. Our findings indicate that hemodynamics follow the hierarchy of structural wiring and neuronal distribution.
Competing Interest Statement
The authors have declared no competing interest.