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Integrated Article


Master of Science




Finger, Elizabeth


Oxytocin (OXT) is a promising treatment candidate for improving empathy deficits in Frontotemporal Dementia (FTD). However, given the heterogeneous nature of FTD, OXT may not exert therapeutic effects uniformly across the patient population. It was predicted that individual patterns of atrophy would predict variable behavioural responses to OXT, indexed by accuracy on a facial expression recognition task. Linear regression results indicated that structural volumes cannot predict treatment response, but age is a significant predictor, with younger patients showing greater expression recognition accuracy following treatment with OXT. Further, in a seed-based functional connectivity analysis, the insula demonstrated increased coupling with the cingulate gyrus and decreased coupling with the basal forebrain and occipital gyrus. For the amygdala seed region, widespread decoupling with occipitotemporal regions was observed. These findings provide evidence for differential age effects of OXT and OXT modulation of functional connectivity between brain regions supporting social cognition.

Summary for Lay Audience

Frontotemporal Dementia (FTD) is a neurodegenerative dementia for which there is currently no approved treatment. FTD is marked by changes in social behaviour including loss of empathy. Empathy describes the ability to understand and share how others are feeling and subsequently responding appropriately. Empathy deficits hinder patients’ abilities to maintain relationships with peers, coworkers and even loved ones. Further, the burden of caring for patients with FTD often falls on a spouse or family member, causing these caregivers significant distress. Therefore, the lack of available treatments for FTD is a critical unmet need.

Oxytocin (OXT), is a hormone that holds potential as a treatment for empathy deficits in FTD. OXT molecules attach to oxytocin receptors (OXTRs) to exert their effects. OXTRs are found in several regions throughout the brain but many are located in regions involved in emotion processing. OXT may therefore serve as a symptomatic treatment for patients with FTD because brain regions that are rich in OXTR support social behaviours. However, FTD is marked by variable patterns of deterioration, or atrophy, in brain tissue from patient to patient. Further, several affected brain regions work together to support social behaviours and the communication between these structures, called functional connectivity (FC), is also variably disrupted across patients. Therefore, the present study sought to determine whether the pattern or extent of atrophy in brain structures important in conducting social behaviours can predict how well a patient will respond to treatment with OXT. The study also sought to determine whether FC between these structures does indeed change following administration of OXT. Treatment response was measured through patients’ ability to accurately identify emotions in facial expressions as this ability is important for informing empathic responses.

Results indicated that integrity of brain tissue does not predict treatment response however, age was identified as a significant predictor, where younger patients present greater benefit from treatment with OXT. Further, FC between structures that may subserve empathy did change following OXT. These findings provide evidence for age-differential effects of OXT and modulation of FC between brain regions supporting social cognition.

Available for download on Saturday, May 31, 2025

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