Abstract Understanding how the brain’s macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial striatum (CPdm). We characterize changes in both the BOLD dynamics of individual cortical and subcortical brain areas, and patterns of inter-regional coupling (functional connectivity) between pairs of areas. Using a classification approach based on a large and diverse set of time-series properties, we found that CPdm neuromodulation alters BOLD dynamics within thalamic subregions that project back to dorsomedial striatum. In the cortex, the strongest changes in local dynamics were observed in unimodal regions, i.e., regions that process information from a single sensory modality, while changes in the local dynamics weakened along a putative cortical hierarchical gradient towards transmodal regions. In contrast, a decrease in functional connectivity was observed only for cortico-striatal connections after D1 excitation. Our results provide a comprehensive understanding of how targeted cellular-level manipulations affect local BOLD dynamics at the macroscale, including the role of a circuit’s structural characteristics and hierarchical cortical level in shaping those dynamics. These findings contribute to ongoing attempts to understand the influence of structure–function relationships in shaping inter-regional communication at subcortical and cortical levels.

Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions