Hemodynamic transient and functional connectivity follow structural connectivity and cell type over the brain hierarchy

Abstract

The neural circuit of the brain is organized as a hierarchy of functional units with wide-ranging connections that support 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 in relation to axonal projection and E/I distribution. Using 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 more than feedback projections and weakened with the hierarchy. The hemodynamic response exhibited regional and hierarchical differences, with slower and more variable responses in high-order areas and bipolar response predominantly in the contralateral cortex. Importantly, the positive and negative parts of the hemodynamic response correlated with E/I neuronal densities, respectively. Furthermore, resting-state functional connectivity was more associated with E/I distribution whereas stimulus-evoked effective connectivity followed structural wiring. These findings indicate that the structure-function relationship is projection-, cell-type- and hierarchy-dependent. Hemodynamic transients could reflect E/I activity and the increased complexity of hierarchical processing.

Evolution of aberrant brain-wide spatiotemporal dynamics of resting-state networks in a Huntington’s disease mouse model

“…Deficits in neuronal synchrony in the motor cortex during non-motion, measured with Ca 2+ imaging, as well as electrophysiological alterations, were also reported at this age in the zQ175 mice, explaining a potential compensatory mechanism of motor network synchrony during motion 56,57 transmodal regions on the other end, which underly multi-input integration, such as the DMN constituents, a major hub for incorporating cortical information [59][60][61][62] . This gradient cortical hierarchy was also found in mice, with similarities observed in both functional and long-range axonal properties 61,63,64 . The transmodal DMLN regions play a central part in multimodal input, hence, they are highly adaptive to different types of information, therefore playing a crucial role in normal sensory processing and integration 62,63 .…”