The human dog: the effects of accelerated HF-rTMS on functional connectivity and the serotonergic system. A translational canine model. (De humane hond)

This project proposal concerns the use of the dog as a natural animal model for research on the

effects of a treatment used in human psychiatry that modulates the brain function in regions that

are deficient in human depression and anxiety disorders. The problem with these diseases is that

treatment outcome with classical modalities is suboptimal. Alternative treatments involve noninvasive

stimulation of brain regions implicated in depression and anxiety. Focal repetitive

transcranial magnetic stimulation (rTMS) can influence brain cell functioning with minimal side

effects and is approved for use in depression. Major knowledge gaps remain regarding its working

mechanism. Limitations of research in humans emphasize the need for an adequate natural animal

model to further unravel its action mechanisms. The advantage of using the dog as a natural animal

model is multifold. The dog develops natural behavioral disorders that resemble human disease

with similar brain dysfunction, they have a larger brain that allow focal activation of specific brain

regions as opposed to rats and mice, different potential targets can be investigated in the individual

dog and the dog itself, as a patient, may benefit. In this proposal we will extend current research in

normal dogs and anxiety disordered dogs, focussing on the effect on brain metabolism and the

serotonergic system with imaging and biological markers. Both show deficits that are associated

with mood and behavioural disorders.