Topological Organization of Metabolic Brain Networks in Pre-Chemotherapy Cancer with Depression: A Resting-State PET Study

<div><p>This study aimed to investigate the metabolic brain network and its relationship with depression symptoms using ¹⁸F-fluorodeoxyglucose positron emission tomography data in 78 pre-chemotherapy cancer patients with depression and 80 matched healthy subjects. Functional and structural imbalance or disruption of brain networks frequently occur following chemotherapy in cancer patients. However, few studies have focused on the topological organization of the metabolic brain network in cancer with depression, especially those without chemotherapy. The nodal and global parameters of the metabolic brain network were computed for cancer patients and healthy subjects. Significant decreases in metabolism were found in the frontal and temporal gyri in cancer patients compared with healthy subjects. Negative correlations between depression and metabolism were found predominantly in the inferior frontal and cuneus regions, whereas positive correlations were observed in several regions, primarily including the insula, hippocampus, amygdala, and middle temporal gyri. Furthermore, a higher clustering efficiency, longer path length, and fewer hubs were found in cancer patients compared with healthy subjects. The topological organization of the whole-brain metabolic networks may be disrupted in cancer. Finally, the present findings may provide a new avenue for exploring the neurobiological mechanism, which plays a key role in lessening the depression effects in pre-chemotherapy cancer patients.</p></div

Network hubs in metabolic brain network.

<p>(A) Axial, B) coronal, and (C) sagittal. Metabolic correlation networks and hubs overlaid on the ICBM152 brain template. Hubs only in NC subjects are colored in yellow, hubs only in cancer patients are colored in green; hubs in both groups are colored in red, and nonhub regions are colored in blue. The size of the spheres is proportional to the betweenness value of nodes.</p

Differences in glucose metabolism between cancer patients and NC subjects.

<p>Blue represents hypo-metabolism in cancer patients compared with NC subjects. The results were calculated and displayed using the xjView (a viewing program for SPM, <a href="http://www.alivelearn.net/xjview8/" target="_blank">http://www.alivelearn.net/xjview8/</a>).</p

The significant difference connectivity map of resting-state brain metabolism networks between cancer and NC groups.

<p>(A) Axial, (B) coronal, and (C) sagittal. Connectivity increases (red lines) and decreases (blue lines) in cancer patients compared with NC subjects. Yellow spheres represent network regions, and the size is proportional to the number of times these regions are involved in a significant difference in connectivity (<i>P</i> < 0.01, uncorrected). Lines represent resting-state connectivity between regions, and the weight of the line indicates the strength of the difference in <i>Z</i> values.</p

Demographic and clinical characteristics of the subjects.

<p>Demographic and clinical characteristics of the subjects.</p

Brain regions displaying aberrant relationships between depression and metabolism in cancer patients.

<p>The regions were mapped onto the cortical surfaces and visualized using the BrainNet Viewer (<a href="http://www.nitrc.org/projects/bnv" target="_blank">http://www.nitrc.org/projects/bnv</a>). Scatter plots with a curve-fitting line showing the metabolism values as a function of the depression state at minimum sparsity (S = 24%) in cancer patients. Abbreviation: IFGtriang.L = left Inferior frontal gyrus (triangular part); ROL.L = left Rolandic operculum; INS.L = left Insula; HIP.L = left Hippocampus; HIP.R = right Hippocampus; PHG.R = right Para-hippocampal; AMYG.L = left Amygdala; AMYG.R = right Amygdala; CUN.L = left Cuneus; TPOmid.L = left middle temporal gyrus. BDI-II, Beck Depression Inventory-II.</p

Brain regions showing abnormal nodal betweenness centralities in the metabolic brain network of cancer patients.

<p>Red nodes have significantly higher betweenness centralities, and the blue nodes have significantly lower betweenness centralities, in cancer patients. The size of the node is the absolute value of the differentials between cancer patients and NC subjects. L, left hemisphere; R, right hemisphere.</p