Altered Resting-State Functional Connectivity of Striatal-Thalamic Circuit in Bipolar Disorder

<div><p>Bipolar disorder is characterized by internally affective fluctuations. The abnormality of inherently mental state can be assessed using resting-state fMRI data without producing task-induced biases. In this study, we hypothesized that the resting-state connectivity related to the frontal, striatal, and thalamic regions, which were associated with mood regulations and cognitive functions, can be altered for bipolar disorder. We used the Pearson's correlation coefficients to estimate functional connectivity followed by the hierarchical modular analysis to categorize the resting-state functional regions of interest (ROIs). The selected functional connectivities associated with the striatal-thalamic circuit and default mode network (DMN) were compared between bipolar patients and healthy controls. Significantly decreased connectivity in the striatal-thalamic circuit and between the striatal regions and the middle and posterior cingulate cortex was observed in the bipolar patients. We also observed that the bipolar patients exhibited significantly increased connectivity between the thalamic regions and the parahippocampus. No significant changes of connectivity related to the frontal regions in the DMN were observed. The changed resting-state connectivity related to the striatal-thalamic circuit might be an inherent basis for the altered emotional and cognitive processing in the bipolar patients.</p></div

Clinical correlations between the altered functional connectivity and the clinical rating scales.

<p>Clinical correlations between the altered functional connectivity and the clinical rating scales.</p

The mean functional connectivity across all participants.

<p>(a) The mean 90 90 correlation matrix across all participants. The anatomical locations of 90 ROIs are listed in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096422#pone.0096422.s001" target="_blank">Table S1</a>. The warm colors represent the positive correlations whereas the cool colors represent the negative correlations between ROIs. (b) The modular structure of brain functional connectivity across all participants. This modular pattern is obtained by reordering regions in the mean correlation matrix according to maximizing the strength of connectivity close to the main diagonal of the matrix. Module 6 consisted of 3 striatal regions and 8 thalamus subregions forming the striatal-thalamic circuit. Module 3 consisted of 9 medial frontal regions, 1 temporal region, 7 parietal regions, 1 posterior cingulate cortex and 1 occipital region forming the DMN. The details of the modular structure are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096422#pone.0096422.s002" target="_blank">Table S2</a>.</p

Demographic and clinical details.

<p>HAMD: Hamilton Depression Rating Scale, 17 items; YMARS: Young Mania Rating Scale;</p>†<p>Continuous variables are expressed as mean ± standard deviation (SD);</p>a<p>Pearson Chi-Square test;</p>b<p>Two-tailed two-sample <i>t</i>-test.</p

Significantly changed connectivity related to the striatal-thalamic circuit in bipolar patients.

<p>Significantly changed connectivity related to the striatal-thalamic circuit in bipolar patients.</p

Anatomical regions exhibiting significant differences of cortical shape complexity between remitting and non-remitting depressed patients.

<p>The regions showing significant differences were the sulcal pits of the orbital part of left middle frontal gyrus (Frontal_Mid_Orb_L), the gyral saddle areas of the triangular part of left inferior frontal gyrus (Frontal_Inf_Tri_L), the gyral nodes of left hippocampus (Hippocampus_L), and the sulcal pits of right hippocampus (Hippocampus_R) as shown in (A) posterior, (B) anterior, (C) superior, (D) inferior (E) right-lateral, (F) left-lateral, (G) left-medial, and (H) right-medial views.</p

Comparison of cortical shape complexities estimated by mean curvedness between non-remitting and remitting MDD patients in contrast with healthy controls.

<p>MDD: major depressive disorder; HC: healthy controls.</p>a<p>Anatomical regions are listed as the labels in the Anatomical Automatic Labeling (AAL) atlas; Frontal_Mid_R: right middle frontal gyrus; Frontal_Inf_Tri_L: left inferior frontal gyrus, triangular part; Frontal_Inf_Orb_R: right inferior frontal gyrus, orbital part; Rectus_L: left gyrus rectus; Cingulum_Ant_R: right anterior cingulate and paracingulate gyri; Calcarine_R: right calcarine fissure and surrounding cortex; Thalamus_R: right thalamus; Heschl_L: left Heschl gyrus; Frontal_Mid_L: left middle frontal gyrus; Hippocampus_R: right hippocampus.</p>b<p>Ss: sulcal saddle; Gs: gyral saddle; Sp: sulcal pit; Gn: gyral node.</p>c<p>Curvedness values are given as mean (standard deviation).</p

Demographic information and clinical parameters.

<p>MDD: major depressive disorder; HC: healthy controls; HAMD-17: Hamilton Depression Rating Scale, 17 items; YMRS: Young Mania Rating Scale; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin norepinephrine reuptake inhibitor; SARI: serotonin antagonist reuptake inhibitor; NDRI: norepinephrine dopamine reuptake inhibitor; TCA: tricyclic antidepressant.</p>a<p>Continuous variables are expressed as mean±standard deviation (SD).</p

Anatomical regions exhibiting significant differences of cortical shape complexity between non-remitting depressed patients and healthy controls.

<p>The curvedness values significantly differed between non-remitting patients and healthy controls in the the right middle frontal gyrus (Frontal_Mid_R), the orbital part of right inferior frontal gyrus (Frontal_Inf_Orb_R), the left gyrus rectus (Rectus_L), and the right calcarine fissure and surrounding cortex (Calcarine_R) in the sucal pits. Significant differences also existed in the gyral saddle parts of the right thalamus (Thalamus_R) and the left Heschl gyrus (Heschl_L) and the gyral nodes of the right anterior cingulate and paracingulate gyri (Cingulum_Ant_R). In the triangular part of left inferior frontal gyrus (Frontal_Inf_Tri_L), we also discovered significant differences in the gyral saddle and sulcal saddle areas, respectively. All areas exhibiting significant differences were shown in (A) posterior, (B) anterior, (C) superior, (D) inferior (E) right-lateral, (F) left-lateral, (G) left-medial, and (H) right-medial views.</p