Understanding the functional organization of brain networks requires clearly dissecting the contributions of both long-range and local circuits to information processing. This chapter describes a methodological framework that combines functional MRI (fMRI) with optogenetic focal silencing to systematically determine the relative contributions of different circuits to fMRI responses at both whole-brain and laminar levels. Using cerebral blood volume (CBV)–weighted fMRI together with optogenetic activation of local GABAergic neurons within the mouse somatosensory network, sensory-driven input circuits were effectively separated from downstream output circuits. Selective suppression of excitatory outputs allowed us to characterize the specific roles of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC), and intracortical (IC) circuits in shaping somatosensory processing. Furthermore, laminar-specific fMRI analyses differentiated TC and CC input layers, revealing circuit-dependent processing mechanisms that could not be resolved through conventional brain-wide analyses. These findings provide a strategy for investigating brain-wide network organization with circuit-level specificity, potentially offering insights into functional reorganization associated with neuroplasticity, disease, and learning. By complementing traditional electrophysiological and microscopic methods, this integrative approach significantly advances our understanding of functional connectivity and information flow within the brain.