Disrupted Resting-State Functional Connectivity and Effective Connectivity of the Nucleus Accumbens in Chronic Low Back Pain: A Cross-Sectional Study

Figures & data

Table 1 Demographic and Clinical Data of Patients

Item	Control (n = 34)	cLBP (n = 34)	P
Age (years)	38.2 ± 12.8	40.1 ± 9.6	0.49
Sex (male/female)	5/29	5/29	1^a
VAS scores	NA	6.7 ± 1.2	NA
Present pain intensity scores	NA	1.9 ± 1.6	NA
Pain duration (years)	NA	8.3 ± 7.1	NA
MoCA scores	27.1 ± 1.5	26.7 ± 1.8	0.31
HAMD scores	2.26 ± 3.16	4.76 ± 6.55	0.049
HAMA scores	1.44 ± 2.72	3.65 ± 7.63	0.12

Note: ^aChi-squared test.

Abbreviations: cLBP, chronic low back pain; VAS, Visual Analog Scale; MoCA, Montreal Cognitive Assessment; HAMD, Hamilton’s Depression Scale; HAMA, Hamilton Anxiety Scale; NA, not applicable.

Table 2 Resting-State Functional Connectivity of the Nucleus Accumbens

Comparison	Seed	Region	MNI Coordinates			Cluster Size	Z Value
			X	Y	Z
Control>cLBP	L_NAc	L_SMG	−64	−34	26	1505	4.54
		R_Pre	8	−12	46	918	3.82
		L_cerebellum	−12	−38	−32	136	3.88*
		Brainstem	6	−34	−48	60	3.56*
		R_Ins	32	16	6	86	3.64*
Control<cLBP	L_NAc	L_SFC	−12	26	56	1445	4.19
		L_MTG	−64	−14	−10	1091	4.08
		L_AnG	−44	−56	28	858	3.87
		R_MTG	64	−8	−26	798	3.67
		OFC	4	50	−20	682	4.24
	R_NAc	L_SFC	−12	56	34	1203	4.1
		OFC	0	44	−14	648	4.01
		L_AnG	−56	−68	24	542	3.84

Note: *Small volume corrected.

Abbreviations: cLBP, chronic low back pain; MNI, Montreal Neurologic Institute; NAc, nucleus accumbens; SMG, supramarginal gyrus; Pre, precentral gyrus; Ins, insula; SFC, superior frontal cortex; MTG, middle temporal gyrus; AnG, angular gyrus; OFC, orbital frontal cortex; L, left; R, right.

Figure 1 Group-differences of the resting-state functional connectivity of the left NAc. Higher (blue) and lower (red) resting-state functional connectivity was found in the patients with cLBP compared to the HC.

Abbreviations: cLBP, chronic low back pain; HC, healthy controls; NAc, nucleus accumbens; Cer, cerebellum; SMG, supramarginal gyrus; Ins, insula; OFC, orbital frontal cortex; MTG, middle temporal gyrus; AnG, angular gyrus; SFC, superior frontal cortex; L, left; R, right.

Figure 2 Group-differences of the resting-state functional connectivity of the right NAc. Higher (blue) and lower (red) resting-state functional connectivity was found in the patients with cLBP compared to the HC.

Abbreviations: cLBP, chronic low back pain; HC, healthy controls; NAc, nucleus accumbens; OFC, orbital frontal cortex; AnG, angular gyrus; SFC, superior frontal cortex; L, left.

Table 3 Resting-State Functional Connectivity of the Nucleus Accumbens Subregions

Comparison	Seed	Region	MNI Coordinates			Cluster Size	Z Value
			X	Y	Z
Control>cLBP	L_shell	L_SMG	−58	−26	18	1709	5.07
		L_cerebellum	−16	−40	−22	130	3.8*
		R_SMG	58	−26	40	498	3.9
		R_SFC	18	−10	72	2257	4.27
		R_Pins	40	−10	10	94	3.99*
Control<cLBP	L_core	L_MTG	−66	−28	−20	1021	4.23
		L_TMP	−48	14	−38	514	5.52
		L_AnG	−46	−62	26	858	3.62
		R_MTG	58	−2	−30	763	4.45
		L_SFC	−8	54	36	579	3.54
		R_thalamus Proper	6	−4	−4	47	3.65*
	L_shell	OFC	6	50	−20	688	3.84
		L_SFC	−12	60	30	628	4.43
	R_shell	L_AnG	−52	−68	28	864	4.32
		L_SFC	−10	58	32	844	4.08

Note: *Small volume corrected.

Abbreviations: cLBP, chronic low back pain; MNI, Montreal Neurologic Institute; SMG, supramarginal gyrus; SFC, superior frontal cortex; Pins, posterior insula; MTG, middle temporal gyrus; TMP, temporal pole; AnG, angular gyrus; OFC, orbital frontal cortex; L, left; R, right.

Table 4 The Effective Connectivity of the Nucleus Accumbens

Group	Item	From SFC	From LNAc	From RNAc	From LCer
HC	To SFC	0	−0.044	−0.053	−0.043
	To LNAc	−0.069	0	0.164*	−0.191*
	To RNAc	−0.178*	−0.121	0	−0.22**
	To LCer	0.07*	0.085	0.134*	0
cLBP	To SFC	0	−0.018	0.015	−0.177*
	To LNAc	−0.04	0	0.074	−0.305*
	To RNAc	−0.029	−0.004	0	−0.431**^Δ
	To LCer	0.054	0.047	0.093*	0

Notes: There are source regions in rows and target regions in columns. *Significant differences within group (p<0.05); **significant differences within group (p < 0.001); ^ΔSignificant differences between groups (p<0.05).

Abbreviations: HC, healthy controls; cLBP, chronic low back pain; SFC, superior frontal cortex; NAc, nucleus accumbens; Cer, cerebellum; L, left; R, right.

Figure 3 Effective connectivity of the NAc. (A) Locations of brain regions used in the dynamic causal modelling. (B) Five models used in the DCM analysis. (C) Results from Bayesian model selection; the single-group level t-test showed that the fully connected model was the best model for the two groups.

Abbreviations: HC, healthy controls; cLBP, chronic low back pain; SFC, superior frontal cortex; NAc, nucleus accumbens; Cer, cerebellum; FFX, fixed effects; L, left; R, right.

Figure 4 The winning model and the connectivity parameters for the two groups. The solid lines represent connectivity values greater than 0.1 Hz, the dotted lines represent the connectivity values below 0.1 Hz, and their thickness reflects the size of the value. The red round represents the significant group differences between cLBP and HC.

Abbreviations: HC, healthy controls; cLBP, chronic low back pain; SFC, superior frontal cortex; NAc, nucleus accumbens; Cer, cerebellum; L, left; R, right.

Figure 5 Results of the correlation analysis. There was a significant negative correlation between the rsFC values of the left NAc-SFC and HAMD scores (r = −0.402, p = 0.018), a significant positively correlation between the rsFC values of the left NAc-OFC and the present pain intensity scores (r = 0.406, p = 0.017) in patients group.

Abbreviations: NAc, nucleus accumbens; SFC, superior frontal cortex; OFC, orbital frontal cortex; HAMD, Hamilton’s Depression Scale.

Data Sharing Statement

The data of the 68 participants are in-house dataset and are available from the corresponding author upon reasonable request.