Mood symptoms, cognitive function, and changes of brain hemodynamics in patients with COVID-19: A functional near-infrared spectroscopy study

Figure 1 Channel arrangement and regions of interest for functional near-infrared spectroscopy measurement. The left and right dorsolateral prefrontal cortex (channels 6, 11, 14, 17-18, 20, 25, 31-34, 39, 42, 45, green label), left and right frontopolar area (channels 9, 15-16, 19, 21-23, 27-30, 33, 35-37, 41, 43, 48, purple label), left and right Broca’s area (channels 2-3, 5, 7-8, 13, 44, 46, 49, 50-51, 53, yellow label), left and right premotor and supplementary motor cortex (channels 1, 4, 10, 40, 47, 52, red label), left and right frontal eye fields (channels 12, 24, 26, 38, blue label).

Figure 2 Four types of connectivity. Nodes refer to channels of different regions of interest (ROIs) by different colors, and the black lines between two channel pairs represent a connection. To better explain the four connectivity types, no correlation threshold was set, so all connections (whether significant or not) between each channel pairs were drawn. A: Short-I connectivity for the intrahemispheric connectivity with each ROI; B: Short-II connectivity for the intrahemishperic connectivity between different ROIs; C: Long-I connectivity for the interhemispheric connectivity between symmetrical ROIs; D: Long-II connectivity for the interhemispheric connectivity between asymmetrical ROIs.

Figure 3 Group comparison of functional connectivity network. A-D: Group-averaged functional connectivity (FC) matrix in the uninfected group (A) and infected group (B) and statistical t-value matrix (C) and statistical t-value (false discovery rate) matrix (D) shown in Figure 3 channels were rearranged according to six regions of interest (Broca-left (L), dorsolateral prefrontal cortex-L [DLPFC-L], frontopolar area-L [FPA-L], FPA-R, DLPFC-R, Broca-R). In the group-averaged FC matrix, each pixel in the FC matrix maps had the Pearson correlation coefficient r value of the channel pairs, and the warm and cool colors indicated a positive and negative correlation, respectively. In Figure 3C, the two-sample t-test for the uninfected group and infected group was performed (without false discovery rate correction), and P-values were at 0.05 threshold, so any channel pairs’ t-value corresponding to the P-value greater than 0.05 were defined as 0. Figure 3D shows the false discovery rate correction result, and t-values of channel pairs not preserved after false discovery rate correction were defined as 0.

Figure 4 Group comparison of connection edge number. A-D: The four types (Short-I, Short-II, Long-I, Long-II) of connection edge numbers of each subject in the uninfected group (blue star) and infected group (red circle) at different thresholds (0.4-0.9). The blue and red lines represent the group mean in the uninfected group and infected group at each threshold, respectively.

Figure 5 Group comparison of graph analysis indicators. A-C: The global efficiency (A), local efficiency of the dorsolateral prefrontal cortex (DLPFC) (B), and degree centrality of the DLPFC (C) of each subject in the uninfected group (blue star) and infected group (red circle) at different thresholds. The blue and red lines represent the group mean in two different groups at each threshold, respectively.

Figure 6 Scatter maps showing the correlations between the scores of Patient Health Questionnaire-9 and network measures and correlations between the scores of General Anxiety Disorder-7 and network measures. The black dotted line indicates the Linear fitting trend. A: Correlation between Patient Health Questionnaire-9 (PHQ-9) and global efficiency; B: Correlation between PHQ-9 and local efficiency of dorsolateral prefrontal cortex; C: Correlation between PHQ-9 and Short-II (intrahemispheric connectivity between different regions of interest); D: Correlation between General Anxiety Disorder-7 (GAD-7) and global efficiency; E: Correlation between GAD-7 and local efficiency of dorsolateral prefrontal cortex; F: Correlation between GAD-7 and Short-II. All correlations were calculated at 0.5 threshold.

Figure 7 Blood oxygen waveform graphs during the task. A: Waveform graph for the uninfected group; B: Waveform graph for the infected group; C: Average blood oxygen waveform graph between two groups. HbO: Oxygenated hemoglobin; HbR: Deoxygenated hemoglobin.

Figure 8 Activation of oxygenated hemoglobin based on S integral value. A: Activation of oxygenated hemoglobin (HbO) based on S IV (the size of neural activity during the task) in the healthy group when P < 0.05 is in the range of -3 to 6; B: Activation of HbO based on S IV in the brain of the coronavirus disease 2019 (COVID-19) group when the P value of the COVID-19 group was < 0.05; C: The position corresponding to the significant difference of HbO S IV in brain activation during verbal fluency test tasks between the healthy group and the COVID-19 group.