Clinical studies in PRISM1 (Psychiatric Ratings using Intermediate Stratified Markers) indicated that social dysfunction is transdiagnostically associated with default mode network dysconnectivity. Low social functioning groups exhibit decreased DTI fractional anisotropy in backbone structures of the DMN such as forceps minor, the interhemispheric connection of the orbitofrontal cortices (OFC). This study aims to back-translate these data by understanding the role of parvalbumin interneurons (PV+) in OFC.We studied the effect PV+ interneuron activation on social behaviors in mice by using an automated behavioral setup. We introduced an excitatory DREADD to PV+ interneurons in a PV-Cre mouse line. For activating hM3Dq receptors, Clozapine-N-oxide (CNO) was injected acutely. Functional ultrasound (fUS) imaging was conducted to observe the effect of this manipulation on cerebral blood volume (CBV) changes and DMN connectivity.CNO administration induced activation of PV+ interneurons and impairment of social behaviors in the hM3Dq group, demonstrated by different social parameters. Whole brain fUS imaging results showed CBV changes in several brain areas as well as region-specific connectivity changes.In conclusion, we have shown that activation of PV+ interneurons in the OFC altered the DMN connectivity pattern, and subsequently led to impairment of social behaviors. PRISM clinical findings have successfully been back-translated to a preclinical model.