Data_Sheet_1_Decreased integration of default-mode network during a working memory task in schizophrenia with severe attention deficits.pdf

BackgroundWorking memory (WM) and attention deficits are both important features of schizophrenia. WM is closely related to attention, for it acted as an important characteristic in activating and manipulating WM. However, the knowledge of neural mechanisms underlying the relationship between WM and attention deficits in schizophrenia is poorly investigated.MethodsGraph theory was used to examine the network topology at the whole-brain and large-scale network levels among 125 schizophrenia patients with different severity of attention deficits (65 mild attention deficits; 46 moderate attention deficits; and 14 severe attention deficits) and 53 healthy controls (HCs) during an N-back WM task. These analyses were repeated in the same participants during the resting state.ResultsIn the WM task, there were omnibus differences in small-worldness and normalized clustering coefficient at a whole-brain level and normalized characterized path length of the default-mode network (DMN) among all groups. Post hoc analysis further indicated that all patient groups showed increased small-worldness and normalized clustering coefficient of the whole brain compared with HCs, and schizophrenia with severe attention deficits showed increased normalized characterized path length of the DMN compared with schizophrenia with mild attention deficits and HCs. However, these observations were not persisted under the resting state. Further correlation analyses indicated that the increased normalized characterized path length of the DMN was correlated with more severe attentional deficits and poorer accuracy of the WM task.ConclusionOur research demonstrated that, compared with the schizophrenia patients with less attention deficits, disrupted integration of the DMN may more particularly underlie the WM deficits in schizophrenia patients with severe attention deficits.</p

Statistical maps showing VMHC differences in different brain regions between studied groups.

<p>Red denotes VMHC differences in the ANOVA analyses and the yellow/red color bar indicates the <i>F</i> value from the ANOVA analyses. Blue denotes lower VMHC and the green/blue color bars indicate the <i>T</i> value from post hoc analysis between compared groups. Of note, the two-sample t-test results within a mask showed significant group differences in the ANOVA analysis. VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.</p

Significant differences in seed-based resting-state FC between groups.

<p>FC = functional connectivity; MNI = Montreal Neurological Institute; TRD = treatment-resistant depression; TSD = treatment-sensitive depression; HS = healthy subjects; R = right; L = left.</p

Receiver operating characteristic (ROC) curves by using the mean VMHC value in the calcarine cortex.

<p>A. Separating TRD from TSD; B. Separating TRD from HS; C. Separating TSD from HS. VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.</p

Statistical maps showing seed-based FC differences between subject groups (seed: the left calcarine cortex).

<p>Red denotes FC differences in the ANOVA analyses and the color bar indicate the <i>F</i> value from the ANOVA analyses. Blue denotes lower FC and the color bars indicate the <i>T</i> value from post hoc analysis between each pair of groups. Of note, the two-sample <i>t</i>-test results within a mask showed significant group differences in the ANOVA analysis. FC = functional connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.</p

Bar plots representing the mean (and standard error) VMHC value of the calcarine cortex.

<p>Significant differences found between the TRD group and the TSD group or the HS group (TRD vs TSD: <i>p</i><0.001; TRD vs HS: <i>p</i><0.01). VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.</p

Decreased Interhemispheric Coordination in Treatment-Resistant Depression: A Resting-State fMRI Study

<div><p>Background</p><p>Previous studies have demonstrated that patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) differed at neural level. However, it remains unclear if these two subtypes of depression differ in the interhemispheric coordination. This study was undertaken for two purposes: (1) to explore the differences in interhemispheric coordination between these two subtypes by using the voxel-mirrored homotopic connectivity (VMHC) method; and (2) to determine if the difference of interhemispheric coordination can be used as a biomarker(s) to differentiate TRD from both TSD and healthy subjects (HS).</p><p>Methods</p><p>Twenty-three patients with TRD, 22 with TSD, and 19 HS participated in the study. Data of these participants were analyzed with the VMHC and seed-based functional connectivity (FC) approaches.</p><p>Results</p><p>Compared to the TSD group, the TRD group showed significantly lower VMHC values in the calcarine cortex, fusiform gyrus, hippocampus, superior temporal gyrus, middle cingulum, and precentral gyrus. Lower VMHC values were also observed in the TRD group in the calcarine cortex relative to the HS group. However, the TSD group had no significant change in VMHC value in any brain region compared to the HS group. Receiver operating characteristic curves (ROC) analysis revealed that the VMHC values in the calcarine cortex had discriminatory function distinguishing patients with TRD from patients with TSD as well as those participants in the HS group.</p><p>Conclusions</p><p>Lower VMHC values of patients with TRD relative to those with TSD and those in the HS group in the calcarine cortex appeared to be a unique feature for patients with TRD and it may be used as an imaging biomarker to separate patients with TRD from those with TSD or HS.</p></div

Significant differences in VMHC values between groups.

<p>VMHC = voxel-mirrored homotopic connectivity.</p><p>TRD = treatment-resistant depression.</p><p>TSD = treatment-sensitive depression.</p><p>HS = healthy subjects.</p

Characteristics of patients with TRD or TSD and HS.

a<p>The <i>P</i> value for gender distribution in the three groups was obtained by chi-square test.</p>b<p>The <i>P</i> values were obtained by one-way analysis of variance tests.</p>c<p>The <i>P</i> values were obtained by two sample <i>t</i>-test.</p><p>TRD = treatment-resistant depression.</p><p>TSD = treatment-sensitive depression.</p><p>HS = healthy subjects.</p><p>HRSD = Hamilton Rating Scale for Depression.</p

ROC analysis for differentiating different studied groups.

a.<p>By this cut-off point, the VMHC value of calcarine could correctly classify 17 of 23 patients with TRD and 18 of 22 patients with TSD, resulted in a sensitivity of 73.91% and a specificity of 81.82%. The means of other cut-off points were similar. VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.</p