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. 2023 Mar 15;18(3):e0282087.
doi: 10.1371/journal.pone.0282087. eCollection 2023.

Network analysis reveals abnormal functional brain circuitry in anxious dogs

Yangfeng Xu  1   2 , Emma Christiaen  3 , Sara De Witte  1 , Qinyuan Chen  1 , Kathelijne Peremans  2 , Jimmy H Saunders  2 , Christian Vanhove  3 , Chris Baeken  1   4   5
Affiliations

Network analysis reveals abnormal functional brain circuitry in anxious dogs

Yangfeng Xu et al. PLoS One. .

Erratum in

Abstract

Anxiety is a common disease within human psychiatric disorders and has also been described as a frequently neuropsychiatric problem in dogs. Human neuroimaging studies showed abnormal functional brain networks might be involved in anxiety. In this study, we expected similar changes in network topology are also present in dogs. We performed resting-state functional MRI on 25 healthy dogs and 13 patients. The generic Canine Behavioral Assessment & Research Questionnaire was used to evaluate anxiety symptoms. We constructed functional brain networks and used graph theory to compare the differences between two groups. No significant differences in global network topology were found. However, focusing on the anxiety circuit, global efficiency and local efficiency were significantly higher, and characteristic path length was significantly lower in the amygdala in patients. We detected higher connectivity between amygdala-hippocampus, amygdala-mesencephalon, amygdala-thalamus, frontal lobe-hippocampus, frontal lobe-thalamus, and hippocampus-thalamus, all part of the anxiety circuit. Moreover, correlations between network metrics and anxiety symptoms were significant. Altered network measures in the amygdala were correlated with stranger-directed fear and excitability; altered degree in the hippocampus was related to attachment/attention seeking, trainability, and touch sensitivity; abnormal frontal lobe function was related to chasing and familiar dog aggression; attachment/attention seeking was correlated with functional connectivity between amygdala-hippocampus and amygdala-thalamus; familiar dog aggression was related to global network topology change. These findings may shed light on the aberrant topological organization of functional brain networks underlying anxiety in dogs.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Anxiety symptoms of dogs.
Fig 2
Fig 2
A. Regions of interest (ROIs) overlaid on a T1 template. Only the right ROIs are visualized. The left ROIs are identical. B. Pipeline of the data analysis: 1) the mean time series of predefined ROIs are extracted from the preprocessed rs-fMRI images, 2) the Pearson correlation coefficient is calculated between the time series of each pair of ROIs, 3) for each rs-fMRI scan, a 30 x 30 correlation matrix is obtained, 4) the weakest connections are removed, 5) a functional network or graph, in which the nodes correspond with the ROIs and the edges with the correlation coefficients, is constructed based on the correlation matrix, and 6) global and nodal network metrics are calculated to quantify the network.
Fig 3
Fig 3. Formulas to calculate the network measures.
Fig 4
Fig 4
A. Global network metrics visualized as a boxplot with median and interquartile range. B. Nodal network metrics.
Fig 5
Fig 5. Connections of the anxiety circuit that differ significantly between the patient group and control group.
Connections that are significantly higher in the patient group are indicated in yellow, connections that are significantly lower are indicated in blue. Abbreviations: AMG, amygdala; FL, frontal lobe; HC, hippocampus; MES, mesencephalon and THL, thalamus.
Fig 6
Fig 6. Correlations of global network metrics, nodal degree, global efficiency and clustering coefficient, and connection strength with anxiety symptoms.
Data are visualized as a scatter plot with regression line and 95% confidence interval.
See this image and copyright information in PMC

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