Non-invasive brain stimulation (NIBS), particularly repetitive Transcranial Magnetic Stimulation (rTMS), has shown promise in human and veterinary medicine. While previous studies have demonstrated brain changes and behavioral improvements in healthy and patient dogs, the effects of rTMS on neurotransmitter levels remain underexplored. This study investigated the impact of accelerated high-frequency rTMS on cerebrospinal fluid (CSF) metabolites, focusing on dopaminergic (DOPAC, HVA) and serotonergic (5-HIAA) markers in healthy and anxious dogs. All procedures were approved by the institutional ethics committee and designed to minimize stress and ensure animal welfare. The study included 79 dogs, consisting of 59 healthy controls and 20 patient dogs diagnosed with an anxiety-related disorder. Using generalized linear mixed-effects models, results revealed a significant group effect (p’s < 0.05), with patient dogs consistently showing lower baseline levels of all three metabolites (DOPAC, HVA, and 5-HIAA) compared to healthy control dogs, underscoring a neurobiological basis for anxiety-related disorders in dogs. Furthermore, rTMS primarily influenced CSF metabolites after just one day of active stimulation, compared to sham or four days of stimulation (p’s < 0.05). This suggests that a shorter duration may have a more immediate impact, with prolonged treatment possibly leading to homeostatic adjustments in the brain. These results show that rTMS affects neurotransmitter pathways in a time-dependent manner and highlight the importance of baseline neurochemical differences when interpreting treatment outcomes. Although preliminary, this study provides valuable insights into the neurobiology of anxiety in dogs and highlights the potential of rTMS as a treatment approach in veterinary behavioral medicine.
Salden et al. (Wed,) studied this question.