Alterations of the default mode network and cognitive impairments in patients with chronic obstructive pulmonary disease

Figures & data

Table 1 Demographic characteristics of participants

Variables	Control group (n=30)	Mild COPD (n=29)	Moderate COPD (n=30)	Severe COPD (n=24)	F/χ^2-value	P-value
Age (years)	57.43±8.66	59.38±8.27	60.90±10.63	63.42±9.53	1.96	0.12a
Sex (M/F)	(21/9)	(13/16)	(16/14)	(17/7)	7.01	0.07b
Education (years)	9.20±2.29	9.86±2.66	9.60±2.06	9.25±2.80	0.46	0.71a
BMI (kg/m^2)	23.9±3.02	24.20±4.40	23.25±4.20	22.16±3.41	1.48	0.22a
Smoking history (Y/N)	(19/11)	(12/17)	(15/15)	(16/8)	4.63	0.20b
Smoking index (packs/year)	22.79±6.91	21.08±9.06	24.27±7.04	25.00±5.05	0.84	0.47a
FEV1 (%)	106.62±22.86	85.47±4.17*	66.23±8.21*,#	38.18±7.39*,#,+	132.87	0.001a
Blood gas analysisc
PH	7.40±0.01	7.40±0.02	7.40±0.01	7.40±0.02	0.104	0.958a
PaO2 (mmHg)	115.65±8.92	101.27±8.64*	76.90±5.79*,#	66.97±3.75*,#,+	163.19	0.001a
SaO2 (%)	38.88±2.73	38.81±3.99	39.19±2.54	40.05±4.21+	5.15	0.003a
PaCO2 (mmHg)	98.22±0.51	97.09±0.79*	94.59±0.97*,#	92.04±1.38*,#,+	120.29	0.001a

Notes: Data are presented as the mean ± standard deviation, except where indicated otherwise.

a ANOVA;

b Chi-square test;

c Control group (n=15), mild COPD (n=16), moderate COPD (n=22), severe COPD (n=17).

* P<0.05 versus control group;

# P<0.05 versus mild COPD;

+ P<0.05 versus moderate COPD.

Abbreviations: ANOVA, analysis of variance; BMI, body mass index; F, female; FEV₁, forced expiratory volume in 1 second; M, male; N, no; PaCO₂, arterial partial pressure of carbon dioxide; PaO₂, arterial partial pressure of oxygen; PH, power of hydrogen; SaO₂, oxygen saturation; Y, yes.

Table 2 Cognitive function test scores of participants

Variables (score)	Control group	Mild COPD	Moderate COPD	Severe COPD	F-value	P-value
MoCA	26.17±1.29	24.34±2.39*	22.20±3.44*,#	21.75±2.83*,#	17.44	0.001
Visuospatial executive	4.53±0.57	4.03±0.86	3.40±1.04*	3.12±0.99*,#	14.43	0.001
Naming function	3.00±0.00	2.90±0.31	2.77±0.50	2.83±0.38	2.38	0.07
Attention	5.40±0.56	5.24±0.69	4.73±0.91*	4.88±0.74*	5.19	0.002
Verbal	1.90±0.48	1.79±0.82	1.60±0.62	1.46±0.78	2.26	0.08
Abstraction	1.80±0.41	1.45±0.78	1.33±0.76*	1.46±0.59	2.83	0.04
Delay recall	3.33±0.96	2.90±1.24	2.40±1.25*	2.58±0.83*	4.10	0.008
Orientation	5.97±0.18	5.90±0.41	5.77±0.43	5.46±0.59*,#	7.51	0.001

Notes: Data are presented as the mean ± standard deviation, except where indicated otherwise.

* P<0.05, versus control group;

# P<0.05, versus mild COPD.

Abbreviation: MoCA, Montreal Cognitive Assessment.

Table 3 The post hoc multiple comparisons of FC values of DMN among four groups

Brain region	Voxel	Z-value	P-value	MNI coordinates			Brodmann area
				X	Y	Z
The FC values decreased gradually
Control group > mild COPD
L-inferior temporal gyrus	45	3.62	0.001	−42	−9	−42	20
R-hippocampus	16	4.07	0.001	24	−6	−21	–
R-middle occipital gyrus	23	3.35	0.001	30	−90	15	18
R-fusiform gyrus	16	2.91	0.001	33	−36	−24	37
Control group > moderate COPD
L-middle temporal gyrus	20	3.41	0.001	−54	0	−30	21
Control group > severe COPD
R-medial orbitofrontal cortex	293	4.78	0.001	3	51	−12	11
R-middle orbitofrontal cortex	68	3.82	0.001	24	66	−9	11
R-supper medial frontal gyrus	16	3.32	0.001	6	51	36	9
R-opercular part of inferior frontal gyrus	16	3.14	0.001	51	24	36	44
L-anterior cingulate cortex	293	4.53	0.001	−3	45	3	10
L-posterior cingulate cortex	111	4.54	0.001	−3	−48	27	30
R-middle cingulum cortex	37	3.46	0.001	3	−15	39	23
L-middle temporal gyrus	35	3.35	0.001	−66	−15	−9	21
L-inferior temporal gyrus	240	4.20	0.001	−48	−21	−30	20
L-hippocampus	240	4.72	0.001	−15	−9	−21	–
L-precuneus gyrus	50	3.68	0.001	−3	−45	57	5
R-rectus gyrus	293	4.29	0.001	6	39	−18	11
R-posterior central gyrus	87	3.85	0.001	39	−24	54	4
Mild COPD > moderate COPD
None
Mild COPD > severe COPD
L-medial orbitofrontal cortex	95	3.60	0.001	6	42	−12	11
R-middle frontal gyrus	16	3.23	0.001	33	24	39	46
L-superior frontal gyrus	32	3.19	0.001	−21	24	42	0
L-opercularis frontalis inferioris gyrus	33	2.91	0.001	−42	15	33	44
L-anterior cingulate cortex	95	3.71	0.001	−3	45	3	10
L-posterior cingulate cortex	120	4.32	0.001	−3	−45	27	26
L-precuneus gyrus	120	3.68	0.001	−6	−54	21	23
L-inferior parietal gyrus	41	3.54	0.001	−51	−27	39	2
L-posterior central gyrus	41	3.56	0.001	−54	−18	42	3
Moderate COPD > severe COPD
R-medial orbitofrontal cortex	51	4.40	0.001	6	45	−12	11
L-superior frontal gyrus	19	3.41	0.001	−24	15	48	8
L-anterior cingulate cortex	26	4.02	0.001	−6	30	24	32
R-inferior temporal gyrus	12	3.97	0.001	48	−33	−24	20
R-superior parietal gyrus	24	3.73	0.001	15	−54	63	5
R-rectus gyrus	51	4.00	0.001	3	36	−15	11
L-precuneus gyrus	12	3.95	0.001	−9	−48	63	5
L-fusiform gyrus	17	4.37	0.001	−24	−39	−15	30
R-fusiform gyrus	34	4.25	0.001	30	−9	−33	36
L-cuneus gyrus	11	3.77	0.001	0	−81	30	18
The FC values increased gradually
Severe COPD > moderate COPD
R-rolandic operculum	10	4.34	0.001	42	0	15	48
Severe COPD > mild COPD
None
Severe COPD > control group
R-rolandic operculum	15	4.45	0.001	42	−3	15	48
Moderate COPD > mild COPD
R-orbit inferior frontal gyrus	16	3.91	0.001	30	33	−15	47
R-supramarginal gyrus	17	3.60	0.001	63	−33	42	40
R-parahippocampus	10	4.15	0.001	27	−12	−36	–
Moderate COPD > control group
L-triangle of inferior frontal gyrus	18	3.96	0.001	−42	39	9	45
R-middle frontal gyrus	13	3.81	0.001	27	9	48	6
L-supramarginal gyrus	39	4.08	0.001	−57	−39	30	48
L-inferior parietal gyrus	11	3.94	0.001	−48	−39	42	40
L-lingual gyrus	23	4.17	0.001	−15	−78	−51	18
Mild COPD > control group
None

Abbreviations: DMN, default mode network; FC, functional connectivity; L, left; MNI, Montreal Neurological Institute; R, right.

Figure 1 The cross-sectional MRI images of brain activation regions (yellow areas) related to DMN (the left posterior cingulate cortex as the seed) among four groups.

Notes: (A) Control subjects; (B) mild COPD group; (C) moderate COPD group; (D) severe COPD group.
Abbreviations: DMN, default mode network; MRI, magnetic resonance imaging.

Table 4 Brain regions in DMN that have significantly different FC

Brain region	Voxel	Z-value	P-value	MNI coordinates			Brodmann area
				X	Y	Z
L-hippocampus	10	4.18	0.001	−15	−9	−21	–
L-anterior cingulate cortex	10	4.11	0.001	−3	−48	27	30
R-medial orbitofrontal cortex	54	4.08	0.001	3	51	−12	11
L-posterior cingulate cortex	54	3.90	0.001	−3	45	3	10
R-parahippocampus	12	4.01	0.001	27	−12	−36	36
L-supramarginal cortex	15	3.45	0.001	−60	−39	30	48

Abbreviations: DMN, default mode network; FC, functional connectivity; L, left; MNI, Montreal Neurological Institute; R, right.

Figure 2 Brain regions of DMN that had significantly different FC values among the four groups.

Notes: (A) Horizontal axial; (B) coronal; (C) sagittal; (D) the three-dimensional brain map of significant group effect (red areas). The statistic t-score bar is shown in the maps.
Abbreviations: DMN, default mode network; FC, functional connectivity; L, left; R, right.

Figure 3 Comparisons of FC values of brain regions in DMN among the four groups.

Notes: For L-ACC, R-MOFC, and L-HP, severe COPD patients had significantly lower FC than the other three groups (P<0.01), and mild COPD patients had a lower FC of L-HP compared with the control group (P<0.05). Whereas, for L-SMG, both moderate and severe COPD patients had significantly different FC values when compared with the mild COPD patients and the control group (all P<0.05). For L-PCC, severe COPD patients had significantly lower FC values than mild COPD patients and the control group (P<0.01). For R-PHP, severe COPD patients had significantly lower FC values than moderate COPD patients and the control group (P<0.01), and mild COPD patients had significantly different FC values compared with moderate COPD patients and the control group (P<0.01). **P<0.01; *P<0.05.
Abbreviations: DMN, default mode network; FC, functional connectivity; L-ACC, left anterior cingulated cortex; L-HP, left hippocampus; L-SMG, left supra marginal gyrus; L-PCC, left posterior cingulate cortex; R-MOFC, right medial orbitofrontal cortex; R-PHP, right parahippocampus.