Neural effects of oxytocin and mimicry in frontotemporal dementia: A randomized crossover study

Abstract

Objective: To determine whether intranasal oxytocin, alone or in combination with instructed mimicry of facial expressions, would augment neural activity in patients with frontotemporal dementia (FTD) in brain regions associated with empathy, emotion processing, and the simulation network, as indexed by blood oxygen-level dependent (BOLD) signal during fMRI.

Methods: In a placebo-controlled, randomized crossover design, 28 patients with FTD received 72 IU intranasal oxytocin or placebo and then completed an 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.

Clinicaltrialsgov identifier: NCT01937013.

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.

© 2020 American Academy of Neurology.

Figures

Figure 1. Main effect of oxytocin on blood oxygen level–dependent (BOLD) signal during facial expression processing

(A) Regions showing increased BOLD signal after oxytocin treatment compared to placebo and regions showing greater BOLD signal during placebo treatment compared to oxytocin. Whole-brain analyses were conducted at p < 0.001, corrected to family-wise error p < 0.05. (B) Example distributions of mean percent BOLD signal change during oxytocin and placebo treatments across conditions and expressions in clusters showing a main effect of treatment with opposing activation patterns. IFG = inferior frontal gyrus; PMC = premotor cortex.

Figure 2. Interaction of treatment and condition on blood oxygen level–dependent (BOLD) signal during facial expression processing

(A) Regions showing increased BOLD signal after oxytocin compared to placebo treatment during imitate compared to view and regions showing greater BOLD signal during placebo treatment compared to oxytocin for imitate in comparison to view. Whole-brain analyses were conducted at p < 0.001, corrected to family-wise error p < 0.05. (B) Example distributions of mean percent BOLD signal change (beta weights) during imitate and view conditions on oxytocin and placebo treatments across expressions in clusters identified in the treatment × condition interaction showing different activation patterns. Bars indicate where significant differences exist. IFG = inferior frontal gyrus; PMC = premotor cortex.

Figure 3

(A) Regions showing increased BOLD signal in healthy controls during imitate vs patients with frontotemporal dementia (FTD) during imitate or controls during view and regions showing greater BOLD signal in patients with FTD during imitate vs controls during imitate or patients during view. Whole-brain analyses were conducted at p < 0.001, corrected to family-wise error p < 0.05. (B) Example distributions of mean percent BOLD signal change (β weights) during imitate and view conditions in controls and patients across expressions in clusters identified in the group × condition interaction showing different activation patterns. Bars indicate where significant differences exist. IFG = inferior frontal gyrus; IPL = inferior parietal lobule; PMC = premotor cortex.