Supplemental Table 1. Neuropsychological assessment scores at baseline and at day 7 and day 30 follow-up in participants.
Patients
(n=17) Pscontrol
Controls
(n=18) Pcontrol Pbetween-group
Corsi block test 0.006*# 0.606
Baseline 47.12 (6.99) 48.61 (8.92) 0.587
Day 7 follow-up 39.35 (6.75) 49.94 (8.15) <0.001
Day 30 follow-up 43.41 (6.67) 49.17 (7.88) 0.026
Digit span forward test 0.168 0.904
Baseline 7.35 (1.06) 7.22 (1.06) 0.717
Day 7 follow-up 6.76 (1.20) 7.39 (1.09) 0.117
Day 30 follow-up 6.94 (1.43) 7.33 (1.19) 0.384
Digit span backward test 0.533 0.918
Baseline 4.59 (1.06) 4.72 (1.02) 0.706
Day 7 follow-up 4.29 (1.05) 4.67 (1.19) 0.333
Day 30 follow-up 4.47 (0.87) 4.83 (1.10) 0.289
Digit symbol test <0.0001*# 0.813
Baseline 29.12 (5.48) 28.83 (4.95) 0.873
Day 7 follow-up 16.12 (5.00) 28.44 (5.31) <0.0001
Day 30 follow-up 25.12 (5.00) 29.28 (5.21) 0.022
Verbal fluency test 0.149 0.53
Baseline 35.35 (5.90) 34.94 (5.47) 0.833
Day 7 follow-up 33.06 (5.51) 36.83 (7.32) 0.095
Day 30 follow-up 35.12 (5.51) 36.94 (7.41) 0.416
Trail-making test A† <0.0001*# 0.061
Baseline 47.53 (10.58) 50.56 (10.08) 0.392
Day 7 follow-up 63.59 (9.04) 49.33 (10.64) <0.001
Day 30 follow-up 54.71 (9.22) 50.11 (8.93) 0.144
Pegboard (favoured
hand)† 0.03 0.144
Baseline 90.65 (22.27) 93.78 (19.67) 0.662
Day 7 follow-up 106.76 (15.98) 90.89 (17.76) 0.009
Day 30 follow-up 98.76 (13.83) 93.33 (15.01) 0.274
Paired association learning 0.002*# 0.633
Baseline 18.53 (2.03) 18.22 (1.90) .647
Day 7 follow-up 16.12 (1.69) 18.72 (1.99) <0.001
Day 30 follow-up 17.06 (1.64) 18.56 (1.89) 0.018
Data are presented as mean ± SD. P values were derived from repeated measures ANOVA or paired t-tests within groups or two-sample t-tests between-groups. Ppatientsy represents p values within the surgery group; Pcontrol represents p values within the controls. * Post hoc comparisons showed significant differences between the baseline and day 7 follow-up conditions; # Post hoc comparisons showed significant differences between the day 7 follow-up and day 30 follow-up
conditions.† The lower the scores are, the better the performance.
Supplemental Table 2. Intrinsic connectivity networks in the DLPFC within the healthy controls and patients before and after surgery.
Cluster size (voxel)
MNI (x, y, z) T-value
Control: positive FC network
Lt.DLPFC/APFC/IFG 1333 (-51, 33, 18) 28.99
Rt.DLPFC/APFC/IFG 357 (48, 39, 3) 11.32
Lt.PaCiG 68 (-3, 24, 42) 8.38
Rt.FP 26 (27, 36, -18) 5.68
Lt.IPS 862 (-54, -39, 42) 13.40
Lt.ITG 341 (-51, -60, -12) 11.27
Control: negative FC network
Rt.medPFC 60 (6, 57, 12) -5.25
Rt.AG 170 (48, -54, 24) -9.43
Rt.PCC/PCu 533 (3, -72, 27) -8.65
Lt.MTG (pole) 87 (-63, -6, -24) -6.53
Rt.MTG (pole) 113 (60, -9, -18) -9.92
Pre: positive FC network
Lt.DLPFC/APFC/IFG 1262 (-48, 39, 12) 21.86
Rt.DLPFC/APFC/IFG 687 (45, 39, 15) 11.72
Lt.PaCiG 89 (-6, 24, 39) 7.00
Lt.IPS 585 (-42, -54, 48) 12.16
Rt.IPS 173 (48, -45, 51) 6.96
Lt.ITG 167 (-60, -60, -15) 8.55
Rt.ITG 41 (63, -51, -21) 6.21
Pre: negative FC network
Rt.medPFC 80 (6, 60, 3) -7.29
Rt.PCC 152 (3, -51, 27) -7.55
Post 7d: positive FC network
Lt.DLPFC/APFC/IFG 1205 (-48, 42, 18) 17.02
Rt.DLPFC/APFC/IFG 545 (45, 21, 30) 10.4
Lt.PaCiG 58 (-3, 33, 39) 7.58
Lt.IPS 525 (-42, -51, 42) 9.17
Lt.ITG 105 (-57, -51, -12) 6.54
Rt.ITG 37 (51, -45, -21) 5.68
Post 7d: negative FC network
Rt.SFG 38 (12, 24, 60) -6.80
Post 30d: positive FC network
Lt.DLPFC/APFC/IFG 1371 (-48, 33, 18) 28.62
Rt.DLPFC/APFC/IFG 745 (48, 45, -6) 10.45
Bi.PaCiG 24 (0, 30, 36) 4.66
Lt.IPS 724 (-45, -48, 39) 11.92
Rt.IPS 130 (42, -45, 45) 8.78
Lt.ITG 266 (-60, -45, -21) 8.31
Rt.ITG 151 (54, -42, -21) 8.70
Post 30d: negative FC network
Rt.medPFC 154 (3, 54, 6) -6.57
Lt.PCu/PCC 282 (-9, -57, 24) -8.26
Rt.TP 83 (54, 3, -33) -6.52
Lt.MTG (pole) 41 (-60, -6, -18) -5.70
The results were thresholded based on an uncorrected voxel-wise height threshold of P < 0.001 combined with an FDR-corrected cluster-wise threshold of P < 0.05. Abbreviations: MNI, Montreal Neurological Institute; X, Y, Z, coordinates of primary peak locations in the MNI space;
Control, healthy controls; FC, functional connectivity; Pre, preoperation; Post 7d, day 7 follow-up after the operation; Post 30d, day 30 follow-up after the operation; DLPFC, dorsolateral prefrontal cortex; APFC,anterior prefrontal cortex; IFG, inferior frontal gyrus; PaCiG, paracingulate gyrus;
FP, frontal pole; IPS, intraparietal sulcus; ITG, inferior temporal gyrus; medPFC, medial prefrontal cortex; AG, angular gyrus; PCC, posterior cingulate cortex; PCu, precuneus; SFG, superior frontal gyrus; MTG,middle temporal gyrus; TP,temporal pole; Lt, left; Rt, right.
Supplemental Table 3. DLPFC-functional connectivity changes between the patients over time and the healthy controls.
Anatomical regions Cluster size
(voxel) MNI (x, y, z) T-value
Pre vs. control
Rt.DLPFC 30 (36, 24, 27) 4.31
Rt.AG 29 (48, -57, 24) 4.97
Post 7d vs. control
Rt.DLPFC 81 (36, 27, 27) 5.29
Rt.AG 35 (48, -57, 27) 4.97
PCC 27 (0, -51, 36) 3.46#
Post 30d vs. control
Rt.DLPFC 30 (36, 24, 27) 3.85
Rt.AG 29 (48, -57, 24) 3.85
Post 7d vs. pre
Lt. SPL 42 (-54, -36, 54) -6.83
The results were thresholded based on an uncorrected voxel-wise height threshold of P < 0.001 combined with an FDR-corrected cluster-wise threshold of P < 0.05. Abbreviations: MNI, Montreal Neurological Institute; X, Y, Z, coordinates of primary peak locations in the MNI space;
Control, healthy controls; Pre, preoperation; Post 7d, day 7 follow-up after the operation; Post 30d, day 30 follow-up after the operation; DLPFC, dorsolateral prefrontal cortex; AG, angular gyrus; PCC, posterior cingulate cortex; SPL,superior parietal lobule; Lt, left; Rt, right. #P < 0.005 uncorrected.
Supplemental Table 4. Association between executive function, left DLPFC connectivity and cytokines in patients on day 7 after cardiac surgery.
Verbal Fluency Test
Paired associate verbal learning
Digit span forward
Digit span backward
Digit symbol
Trail making test
Pegboard favored hand
PCC Rt.AG Rt.DLPFC Lt.SPL TNF-α IL-6
Corsi Block -0.221 (0.394)
-0.037 (0.889)
0.219 (0.398)
0.258 (0.317)
-0.075 (0.774)
0.102 (0.697)
0.297 (0.248)
0.252 (0.330)
0.222 (0.391)
0.072 (0.783)
-0.137 (0.601)
0.181 (0.486)
-0.097 (0.710) Verbal Fluency
Test
-0.008 (0.977)
-0.036 (0.892)
-0.166 (0.525)
-0.225 (0.385)
0.370 (0.144)
0.046 (0.862)
0.120 (0.647)
-0.010 (0.971)
-0.325 (0.203)
0.050 (0.849)
-0.088 (0.738)
0.368 (0.146) Paired associate
verbal learning
-0.097 (0.712)
-0.198 (0.447)
-0.193 (0.459)
-0.042 (0.873)
-0.415 (0.098)
0.085 (0.747)
-0.127 (0.626)
0.099 (0.707)
-0.001 (0.997)
0.072 (0.783)
-0.193 (0.458) Digit span
forward
0.108 (0.697)
-0.006 (0.983)
0.088 (0.736)
0.049 (0.852)
-0.006 (0.981)
0.089 (0.733)
0.023 (0.929)
-0.166 (0.524)
0.089 (0.735)
0.227 (0.382) Digit span
backward
-0.091 (0.729)
0.047 (0.859)
0.094 (0.720)
0.151 (0.562)
-0.039 (0.883)
-0.037 (0.888)
-0.046 (0.862)
0.305 (0.233)
0.073 (0.780)
Digit symbol -0.125
(0.633)
-0.180 (0.489)
-0.092 (0.725)
-0.206 (0.429)
0.764 (< 0.001)*
0.569 (0.017)*
0.238 (0.358)
0.114 (0.662) Trail making
test
0.110 (0.674)
0.777 (< 0.001)*
0.788 (< 0.001)*
-0.157 (0.546)
-0.232 (0.370)
0.685 (0.002)*
0.672 (0.003)*
Pegboard favored hand
0.127 (0.628)
0.246 (0.341)
-0.153 (0.559)
-0.591 (0.012)*
0.016 (0.952)
0.193 (0.457)
PCC 0.707
(0.001)*
-0.090 (0.732)
-0.243 (0.348)
0.741 (0.001)*
0.381 (0.131)
Rt.AG -0.190
(0.465)
-0.414 (0.099)
0.570 (0.017)*
0.410 (0.102)
Rt.DLPFC 0.321
(0.210)
0.361 (0.154)
-0.207 (0.426)
Lt.SPL 0.015
(0.956)
-0.026 (0.921)
TNF-α 0.407
(0.105) Data are presented as r (P value); *P < 0.05. Abbreviations: DLPFC, dorsolateral prefrontal cortex; AG, angular gyrus; PCC, posterior cingulate cortex; SPL, superior parietal lobule; Lt, left; Rt, right.
Supplemental Table 5. Prediction of executive function by
left
DLPFC connectivity on day 7 after cardiac surgery.Digit symbol Trail-making test Pegboard (favoured
hand) Rt.AG 2.31 (-25.79, 30.41) 36.84 (3.63, 70.04) * 5.22 (-128.3, 138.7) PCC 0.13 (-13.65, 13.91) 18.25 (0.33, 36.17) * -0.83 (-66.20, 64.54) Rt.DLPFC 25.66 (10.25, 41.06) ** -5.02 (-48.25, 38.22) -32.33 (-142.7, 78.04) Lt.SPL 14.22 (0.3233, 28.12) * 3.63 (-27.56, 34.82) -68.28 (-133.8, -2.74) * Data are presented as ß (95% CI); *P < 0.05; **P < 0.01. Abbreviations: DLPFC, dorsolateral prefrontal cortex; AG, angular gyrus; PCC, posterior cingulate cortex; SPL, superior parietal lobe;
Lt, left; Rt, right.
Supplemental Table 6. Prediction of executive function by cytokines on day 7 after cardiac surgery.
Digit symbol Trail-making test Pegboard (favoured
hand) TNF-α 1.5 (-0.16, 3.16) 2.41 (0.91, 3.91) ** 0.59 (-6.606, 7.788) IL-6 1.29 (-0.65, 3.24) 2.46 (0.69, 4.23) * 2.83 (-4.91, 10.57) Data are presented as ß (95% CI); *P < 0.05; **P < 0.01.