The neural and physiological mechanisms of Animal-Assisted Interventions (AAI): A systematic review and integrated framework

Background Animal-Assisted Interventions (AAIs) have demonstrated therapeutic benefits across various clinical populations, yet the underlying neurobiological mechanisms remain poorly understood. Prior research examined peripheral biomarkers but lacked integration with central nervous system processes. This preregistered systematic review aims to describe, evaluate, and synthesize evidence on the neural and physiological mechanisms underlying the effects of AAI. Methods Following PRISMA guidelines, we systematically searched ProQuest, PubMed, PsycINFO, and Scopus through November 2025 using three concept groups: animal interventions, neurological measures, and physiological measures. Inclusion criteria required empirical studies that measured neurological or physiological outcomes from structured AAIs using live animals. Thirty-four studies were obtained after screening (seven neuroimaging and twenty-seven biomarker studies). Results Neuroimaging findings indicated increased functional connectivity within emotion regulation (prefrontal–amygdala) and reward circuits (caudate, striatum), associated with symptom improvement in ADHD, PTSD, and internet gaming disorder. Salivary cortisol concentrations decreased in 64.3% of studies, and salivary oxytocin concentrations increased in 60%. Autonomic outcomes were inconsistent, likely due to methodological heterogeneity. Conclusions AAIs modulate fronto-limbic circuitry and HPA-axis activity through enhanced prefrontal-amygdala connectivity, reward circuit activation, cortisol reduction, and an increase in oxytocin. These mechanisms collectively contribute to symptom reduction in mood and stress-related disorders. Future research requires larger RCTs with integrated multimodal assessments to establish causal pathways.