Frequency-Specific Abnormalities Of Functional Homotopy In Alcohol Dependence: A Resting-State Functional Magnetic Resonance Imaging Study

Figures & data

Table 1 Demographics And Clinical Characteristics Of The Subjects

Variables	AD (n=24)	AND (n=30)	HC (n=35)	p-Value
Sex (number of men (%))	23 (96%)	30 (100%)	34 (97%)	0.562
Age (years)	49.8±9.8	50.4±8.5	47.4±9.8	0.411^a
Education (years)	8 (8, 11)	8 (8, 11)	8 (5, 11)	0.283^b
Years of drinking (years)	26.1±11.9	26.1±8.9	NA	0.995^c
Daily drinking (mL)	200 (150, 288)	300 (150, 413)	NA	0.017^d
AUDIT	23.2±6.4	23.4±6.0	NA	0.907^c
SADQ	19.5±7.0	19.7±7.9	NA	0.923^c
Mean FD	0.19 (0.12, 0.30)	0.14 (0.10, 0.21)	0.13 (0.09, 0.21)	0.095^b

Notes: Data are presented as mean±SD or median (P₂₅, P₇₅). ^aone-way ANOVA; ^bKruskal–Wallis H-test; ^ctwo-sample t-test; ^dMann–Whitney U-test.

Abbreviations: AD, alcohol dependence; AND, alcohol and nicotine co-dependence; HC, healthy control; NA, not applicable; AUDIT, alcohol use disorders identification test; SADQ, severity of alcohol dependence questionnaire.

Table 2 Differences In VMHC Between The AD, AND, And HC Groups In The Typical Frequency Band

Brain Area	BA	MNI	Peak	Voxel Size
				X, Y, Z
AD vs HC
AD<HC
Cerebellum posterior lobe	/	±30, −81, −33	−4.453	227
AD>HC
Middle frontal gyrus	10	±42, 54, 0	4.497	107
AND vs HC
AND>HC
Cerebellum 8	/	±18, −48, −57	3.872	16
Precuneus	7	±24, −63, −27	3.987	16
Middle frontal gyrus	6	±33, −6, −60	3.555	14
Superior frontal gyrus	6	±15, −15, 72	3.702	13

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; AD, alcohol dependence; AND, alcohol and nicotine co-dependence; HC, healthy control; BA, Brodmann’s area; MNI, Montreal Neurological Institute.

Figure 1 The main effect of group (addiction) on the typical frequency band (GRF correction, voxel-level p<0.01 and cluster-level p<0.05). The cool color indicates brain regions with decreased VMHC, and the warm color indicates brain regions with increased VMHC. The left side of the picture represents the left side of the brain.

Abbreviations: L, left; R, right; GRF, Gaussian random field; VMHC, voxel-mirrored homotopic connectivity.

Figure 2 (A) The VMHC differences between individuals with AD and HCs in the typical band (GRF correction, voxel-level p<0.01 and cluster-level p<0.05). (B) The VMHC differences between individuals with AND and HCs in the typical band (p<0.01, uncorrected). The hot color indicates that individuals with AD or AND had a significantly higher VMHC value compared to HCs, while the cool color indicates the opposite. The left side of the figure is the left side of the brain.

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; AD, alcohol dependence; AND, alcohol and nicotine co-dependence; HC, healthy control; L, left; R, right; GRF, Gaussian random field.

Table 3 Differences In VMHC In The Slow-5 And Slow-4 Frequency Bands Between Groups

Brain Area	BA	MNI	Peak	Voxel Size
				X, Y, Z
In slow-5 frequency band
AD<HC
Cerebellum posterior lobe	/	±30, −81, −33	−4.452	39
Inferior temporal gyrus	20	±54, −12, −24	−2.993	21
Parahippocampal gyrus	30	±12, −42, 0	−4.430	38
Caudate	/	±12, 9, 3	−4.604	20
Middle temporal gyrus	19, 39	±33, −69, 24	−3.878	20
Superior frontal gyrus	9	±15, 48, 33	−3.015	23
Superior frontal gyrus/middle frontal gyrus	6	±24, 0, 48	−3.488	39
AD>HC
Middle frontal gyrus	10	±42, 51, 0	4.580	59
AND>HC
Cerebellum posterior lobe	/	±15, −54, −57	3.130	20
Precuneus	7	±18, −66, 33	3.842	39
Supramarginal gyrus	40	±60, −48, 36	3.302	30
In slow-4 frequency band
AD<HC
Cerebellum posterior lobe	/	±24, −81, −21	−3.647	103
AD>HC
Middle frontal gyrus	10	±42, 54, 0	3.791	105
AND<HC
Fusiform gyrus	19	±21, −84, −21	−3.414	20
Superior frontal gyrus	8	±21, 15, 45	−3.587	49
AND>HC
Cerebellum 8	/	±18, −45, −57	4.000	26
Inferior parietal lobule	7	±33, −57, 48	3.595	35
Middle frontal gyrus	6	±33, −3, 60	4.114	29

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; AD, alcohol dependence; AND, alcohol and nicotine co-dependence; HC, healthy control; BA, Brodmann’s area; MNI, Montreal Neurological Institute.

Figure 3 Group comparison of the VMHC in the slow-5 and slow-4 frequency bands. (A) and (B) show the group differences in slow-5 frequency band (p<0.01, uncorrected). (C) and (D) show the group differences in the slow-4 frequency band. In (C) GRF correction was applied at a voxel level of p<0.01 and cluster-level p<0.05, while (D) was uncorrected with p<0.01. The cool color indicates brain regions with decreased VMHC, and the warm color indicates brain regions with increased VMHC in the comparison between individuals with AD (or AND) and HCs.

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; AD, alcohol dependence; AND, alcohol and nicotine co-dependence; HC, healthy control; L, left; R, right; FDR, false discovery rate.

Figure 4 Alterations of the FC between seeds that exhibited altered VMHC in group comparison (shown in Figure 2A) and whole brain voxels in the typical frequency band (GRF correction, voxel-level p<0.01 and cluster-level p<0.05). All seeds show a similar positive connectivity pattern in individuals with AD and HCs. The cool color indicates decreased seed-based FC in individuals with AD compared to HCs, while the warm color indicates increased seed-based FC.

Abbreviations: L, left; R, right; CPL, cerebellum posterior lobe; MFG, middle frontal gyrus; AD, alcohol dependence; HC, healthy control; FC, functional connectivity; ROI, regions of interest; VMHC, voxel-mirrored homotopic connectivity; GRF, Gaussian random field.

Figure 5 Alterations of the FC between seeds that exhibited altered VMHC in the group comparison (shown in Figure 3C) and whole brain voxels in the slow-4 band (GRF correction, voxel level p<0.01 and cluster-level p<0.05). All seeds show a similar positive connectivity pattern in individuals with AD and HCs. The cool color indicates decreased seed-based FC in individuals with AD compared to HCs, while the warm color indicates increased seed-based FC.

Abbreviations: L, left; R, right; CPL, cerebellum posterior lobe; MFG, middle frontal gyrus; AD, alcohol dependence; HC, healthy control; FC, functional connectivity; ROI, regions of interest; VMHC, voxel-mirrored homotopic connectivity; GRF, Gaussian random field.

Figure 6 Correlations between functional results (VMHC and FC) and clinical variables (AUDIT score and alcohol intake) in individuals with AD.

Abbreviations: CPL, cerebellum posterior Lobe; MFG, middle frontal gyrus; FC, functional connectivity; AUDIT, alcohol use disorders identification test; VMHC, voxel-mirrored homotopic connectivity; AD, alcohol dependence.