Elsevier

Journal of Veterinary Behavior

Volume 33, September–October 2019, Pages 108-113
Journal of Veterinary Behavior

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

https://doi.org/10.1016/j.jveb.2019.07.004Get rights and content

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.

Section snippets

Case presentation

A 5-year-old neutered male white-coated Malinois dog (32 kg) was presented with anxious aggressive behavior.

History and presenting signs

The patient is, together with its 16 siblings, the accidental offspring between its half-brother and its mother. Neither parent showed behavioral problems. The owner purchased the dog at the age of 8 weeks. During the first year of its life, the dog received behavioral training and showed no signs of abnormal behavior. At the age of 1 year, the dog started to show aggression combined with anxious behavior in several situations (e.g., when meeting unfamiliar people or when separated from the

Physical evaluation

After thorough clinical examination, no clinical abnormalities were found. The dog's blood analysis showed no deviations from the norm. A 3 tesla magnetic resonance imaging showed no visible structural abnormalities in the dog's brain, whereas a functional d,1 hexamethylpropylene amine oxime single-photon emission computed tomography ([99mTc]HMPAO-SPECT) showed a decreased left frontal perfusion (when compared with a control group). The control group consisted of 16 healthy dogs ranging from 1

Behavioral evaluation

The dog's behavior was assessed using the validated canine behavioral questionnaire completed by the owner (Hsu and Serpell, 2003, Duffy and Serpell, 2012), providing information concerning the dog's behavior and temperament in 13 scales (Table 1). This questionnaire contains 101 questions grouped into seven sections: training and obedience, aggression, fear and anxiety, separation-related behavior, excitability, attachment and attention seeking, and miscellaneous. The responses to the

Diagnosis

Based on the dog's history, the physical examination, the MRI images, the 99Tc-HMPAO SPECT scan, and the questionnaires, the dog was diagnosed with anxious aggressive behavior specifically toward nonfamiliar people and animals.

Neuronavigation protocol

Neuronavigation is a technique whereby three-dimensional information about neurological structures enclosed by the skull or the vertebral column is provided. This study focuses on the noninvasive stimulation of the left frontal cortex. Therefore, the left frontal cortex had to be externally located with neuronavigation. To obtain this information, a tomographical data set (MRI) had to be acquired. The neuronavigation and external localization was performed as described by Dockx et al. (2017).

[99mTc]HMPAO-SPECT scan

Follow-up

The owner noticed behavioral changes two to three weeks after the first stimulation session. The most prominent reported change was a reduction of the fixation onto persons, dogs, or objects. Even more, a reduction in aggressive behavior toward unfamiliar dogs, humans, and objects was noticed several weeks after the second aHF-rTMS protocol was administered. The owner reported that the dog did no longer show the urge to approach the person or target it had seen. This was in sharp contrast to

Discussion

This study showed that an aHF-rTMS treatment applied over the left frontal cortex induced not only changes in the cerebral perfusion at the simulation site but also at remote locations as well. These changes lasted at least 3 weeks and were accompanied by improvement of the dog's behavior. Even more, simultaneous changes of DOPAC concentrations in CSF and serum were observed.

The patient had, at baseline, a hypoperfused left frontal cortex and showed anxious aggressive behavior toward people and

Acknowledgments

This research was funded by Ghent university special research fund (BOF 394 01J05715) and was supported by the Ghent university multidisciplinary research partnership “The integrative neuroscience of behavioral control.” The authors would like to thank Mrs. Ria Berckmans (Centre for Neurosciences, Vrije Universiteit Brussel) for her excellent technical assistance during the analysis of the serum and CSF samples.

The authors thank the division of veterinary nuclear medicine (department of medical

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