OBJECTIVE: Reduced empathy is one of the hallmark and untreatable symptoms of frontotemporal dementia (FTD). The objective of this study was to determine whether intranasal oxytocin, alone or in combination with instructed mimicry of facial expressions, would augment neural activity in patients with FTD in brain regions associated with empathy, emotion processing and the simulation network, as indexed by blood-oxygen-level dependent (BOLD) signal during functional magnetic resonance imaging (fMRI).

METHODS: In a placebo-controlled, randomized cross-over design, 28 patients with FTD received 72 IU of intranasal oxytocin or placebo and then completed a fMRI facial expression mimicry task.

RESULTS: Oxytocin alone, and in combination with instructed mimicry, increased activity in regions of the simulation network and in limbic regions associated with emotional expression processing.

CONCLUSIONS: The findings demonstrate latent capacity to augment neural activity in affected limbic and other frontal and temporal regions during social cognition in patients with FTD, and support the promise and need for further investigation of these interventions as therapeutics in FTD.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a single dose of 72 IU intranasal oxytocin augments BOLD signal in patients with FTD during viewing of emotional facial expressions.

Supplementary Material includes 12 pages, Tables e-1 to e-9.