Accelerated high-frequency repetitive transcranial magnetic stimulation positively influences the behavior, monoaminergic system, and cerebral perfusion in anxious aggressive dogs: A case study

Abstract

Accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS) was proven to produce fast clinical effects in humans suffering from psychiatric illnesses. Although dogs also frequently present behavioral symptoms similar to mental illness, rTMS treatment was not yet investigated in this species. The aim of this study was to apply an aHF-rTMS treatment over the frontal cortex in an anxious aggressive dog. Because aHF-rTMS is used to treat anxiety and mood disorders in humans and shows changes in neuronal activity and on monoamine concentrations, it was hypothesized that the dog's behavior would improve after such a treatment. This improvement was expected to be accompanied by alterations in regional cerebral blood flow (rCBF) as well as in monoamine levels in cerebrospinal fluid (CSF) and serum. An aHF-rTMS protocol was applied twice (3 weeks separated) over the left frontal cortex (5 sessions, 20 Hz, 110% cortical motor threshold) in a 5-year-old neutered male Belgian Malinois dog showing anxious aggressive behavior. Each protocol was preceded and followed by a behavior assessment and a d,1 hexamethylpropylene amine oxime single-photon emission computed tomography scan. A Z-score for each volume of interest at each time point was obtained, whereby a |Z|-score > 3.09 (P-value of 0.001) indicated significant differences. Monoamines and their metabolites were quantified in CSF and serum using liquid chromatography coupled to electrochemical detection. An improvement of the dog's aggressive behavior was detected. At baseline, only a decreased rCBF of the left frontal cortex was noticeable (Z-score = −3.87). Twenty-four hours after the first protocol, the perfusion in the left frontal cortex was normalized and decreased in subcortical region (Z-score = −6.97). Three weeks after each stimulation protocol, no deviations in the rCBF were found. Parallel time-dependent changes of 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in serum and CSF were observed. This case study demonstrates that a single day aHF-rTMS treatment reduces a dog's anxious/aggressive behavior. This behavioral change was accompanied by immediate and long-lasting alterations in the rCBF and DOPAC concentration. This study confirms the interaction between the frontal cortex and the subcortical region in canine anxiety. Finally, DOPAC is put forward as a possible biomarker for the improvement of this behavior.