Chemogenetic sensory fMRI reveals behaviorally relevant bidirectional changes in primate somatosensory network

Concurrent genetic neuromodulation and functional magnetic resonance imaging (fMRI) in primates has provided a valuable opportunity to assess the modified brain-wide operation in the resting state. However, its application to link the network operation with behavior still remains challenging. Here, we combined chemogenetic silencing of the primary somatosensory cortex (SI) with tactile fMRI and related behaviors in macaques. Focal chemogenetic silencing of functionally identified SI hand region impaired grasping behavior. The same silencing also attenuated hand stimulation-evoked fMRI signal at both the local silencing site and the anatomically and/or functionally connected downstream grasping network, suggesting altered network operation underlying the induced behavioral impairment. Furthermore, the hand region silencing unexpectedly disinhibited foot representation with accompanying behavioral hypersensitization. These results demonstrate that focal chemogenetic silencing with sensory fMRI in macaques unveils bidirectional network changes to generate multifaceted behavioral impairments, thereby opening a pivotal window toward elucidating the causal network operation underpinning higher brain functions in primates. •FMRI-guided chemogenetic silencing of macaque SI hand region induced grasping deficit•Sensory-evoked BOLD response decreased at local and remote areas in grasping network•Hand region silencing enhanced foot representation with behavioral hypersensitization•Chemogenetic fMRI revealed behaviorally relevant bidirectional network modulation Hirabayashi et al. demonstrate that chemogenetic silencing of macaque SI hand representation impairs grasping and enhances sensitivity to foot stimulation. These behavioral effects co-occur with decreased fMRI activation in the grasping-related network and enhanced foot representation. This study reveals how local inactivation affects the network operation within and across areas.