Prefrontal Functional Connectivity During the Verbal Fluency Task in Patients With Major Depressive Disorder: A Functional Near-Infrared Spectroscopy Study

Abstract

Deviations in activation patterns and functional connectivity have been observed in patients with major depressive disorder (MDD) with prefrontal hemodynamics of patients compared with healthy individuals. The graph-theoretical approach provides useful network metrics for evaluating functional connectivity. The evaluation of functional connectivity during a cognitive task can be used to explain the neurocognitive mechanism underlying the cognitive impairments caused by depression. Overall, 31 patients with MDD and 43 healthy individuals completed a verbal fluency task (VFT) while wearing a head-mounted functional near-infrared spectroscopy (fNIRS) devices. Hemodynamics and functional connectivity across eight prefrontal subregions in the two groups were analyzed and compared. We observed a reduction in prefrontal activation and weaker overall and interhemispheric subregion-wise correlations in the patient group compared with corresponding values in the control group. Moreover, efficiency, the network measure related to the effectiveness of information transfer, showed a significant between-group difference [t (71.64) = 3.66, corrected p < 0.001] along with a strong negative correlation with depression severity (rho = -0.30, p = 0.009). The patterns of prefrontal functional connectivity differed significantly between the patient and control groups during the VFT. Network measures can quantitatively characterize the reduction in functional connectivity caused by depression. The efficiency of the functional network may play an important role in the understanding of depressive symptoms.

Keywords: efficiency; fNIRS; functional connectivity; major depressive disorder; verbal fluency task.

Figure 1

Labeling of the eight subregions mapped by 48 channels “R” indicates the right hemisphere, while “L” indicates the left hemisphere.

Figure 2

Activation maps of the two groups during the verbal fluency task.

Figure 3

Transient oxygenated hemoglobin concentration during the verbal fluency task. The green line represents the control group while the blue line represents the patient group. The shaded regions represent the standard errors of the mean.

Figure 4

(A) Correlation maps of the verbal fluency task for the two groups. The image shows the lower diagonal of the cross-correlation matrix. The rows and columns of the matrix represent the subgroup, while the cells of the matrix contain the color-coded correlation coefficient of the corresponding pair. The blue cells indicate a lower between-subgroup correlation, while higher between-subgroup correlations are indicated in magenta. (B) Subregion-based functional connectivity The line width indicates the strength of the correlation, as determined by the correlation coefficient (R) between each pair of subregions.

Figure 5

(A) Efficiency as a function of the threshold value. The green squares indicate efficiency in the control group while the blue squares indicate efficiency in the patient group. The error bar indicates the standard deviation. The magenta double asterisk indicates a significant difference at the level of 0.001, while red asterisks indicate a significant difference at the level of 0.05 (p-values were FDR-corrected). (B) Scatter plot of the efficiency at a threshold of 0.80 vs HAMD scores. The red line indicates the least-squares line. FDR, false discovery rate; HAMD, hamilton depression rating scale.