Disrupted interhemispheric functional connectivity in chronic insomnia disorder: a resting-state fMRI study

Figures & data

Figure 1 A flowchart of VMHC and the influenced connectivity patterns in CID patients. (A) The resting-state fMRI and T1-weighted data were preprocessed. (B and C) The time series of each voxel was extracted using a symmetrical hemisphere template in the MNI space. (D) Then, the VMHC was calculated. (E) The group mean of the VMHC was calculated to show the spatial distribution. (F) Group comparisons of the VMHC and (G) clinical associations in the CID patients were performed. (H) Finally, the network patterns (heterotopic connectivity) that were influenced by the altered VMHC in CID patients are shown.

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; CID, chronic insomnia disorder; fMRI, functional magnetic resonance imaging; HC, healthy control; MNI, Montreal Neurological Institute; T1WI, T1 weighted image.

Table 1 Comparison of the demographic and neuropsychological data of the CID and HC groups

Characteristic	Patients with CID	HC	P-value
	Mean (SD)	Mean (SD)
Gender (M/F)	19/10	20/10	0.926#
Age (y)	42.03 (11.37)	40.03 (11.23)	0.499
Education (y)	9.58 (2.97)	10.40 (3.97)	0.378
Duration of insomnia (y)	11.74 (9.38)	n/a (n/a)	n/a
STAI-s	28.17 (4.14)	26.50 (7.76)	0.309
STAI-t	32.17 (4.76)	28.76 (9.74)	0.095
BDI-II	6.03 (5.14)	4.90 (1.51)	0.262
PSQI	13.31 (2.48)	0.87 (1.04)	<0.0001
Mean head motion*	0.044 (0.025)	0.046 (0.039)	0.787

Notes:

# Chi-square tests;

* Head motions were evaluated according to the FD criteria described by Van Dijk et al.³¹

Abbreviations: CID, chronic insomnia disorder; HC, healthy controls; SD, standard deviation; M, male; F, female; y, years; STAI-s, State Trait Anxiety Inventory-state; STAI-t, State Trait Anxiety Inventory-trait; BDI, Beck Depression Inventory; PSQI, Pittsburgh Sleep Quality Index; n/a, not available; FD, framewise displacement.

Figure 2 VMHC spatial patterns at the group mean level of the CID and HC groups. The warm color tone indicates higher homotopic connectivity coefficients.

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; CID, chronic insomnia disorder; HC, healthy control; LH, left hemisphere; RH, right hemisphere.

Figure 3 Altered VMHC in the CID group compared with the HC group.

Notes: Blue-indigo color represents decreased VMHC in CID.
Abbreviations: VMHC, voxel-mirrored homotopic connectivity; CID, chronic insomnia disorder; HC, healthy control; L, left; LH, left hemisphere; MOG, middle occipital gyri; pMTG, posterior middle temporal gyrus; R, right; RH, right hemisphere.

Table 2 Differences in homotopic connectivity and heterotopic connectivity bet ween the CID patient and control groups (P<0.01, GRF-corrected for multiple comparisons at a cluster level of P<0.05)

Brain region	BA	Voxels size	Peak t-value	Peak coordinates in MNI space
				X	Y	Z
Differences in homotopic connectivity
MOG/pMTG	19	109	−4.776	±42	−75	15
Differences in heterotopic connectivity of the regions with altered VMHC
Right MOG/pMTG
Left MOG/pMTG	19,39	116	−4.552	−42	−78	18
Left precuneus/cuneus	7,19	99	−3.765	−15	−81	42
Left MOG/pMTG
Right cerebellum anterior lobe		172	−5.043	12	−51	−9
Left lingual gyrus	18,19	105	−3.877	−12	−72	−9
Left MOG	19	155	−4.083	−36	−78	9
Right middle occipital gyrus	19,18	145	−3.994	39	−69	12
Left precuneus/cuneus	19,7	166	−4.240	−21	−81	27
Left inferior parietal lobule	40	86	3.808	−60	−36	45

Notes: t: statistical value of peak voxels showing significant differences between the two groups (negative values: CID<HC; positive values: CID>HC). X, Y, Z are the coordinates of primary peak locations in the MNI space.

Abbreviations: CID, chronic insomnia disorder; GRF, Gaussian random field; BA, Brodmann’s area; MNI, Montreal Neurological Institute Coordinate System; MOG/pMTG, middle occipital gyrus/posterior middle temporal gyrus; HC, healthy controls.

Figure 4 Significant group differences in the connectivity patterns (heterotopic connectivity) of the seed regions, with decreased VMHC being observed in the right MOG/pMTG (A) and the left MOG/pMTG (B) (P<0.01, GRF-corrected at a cluster level of P<0.05).

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; MOG/pMTG, middle occipital gyrus/posterior middle temporal gyrus; GRF, Gaussian random field; LH, left hemisphere; RH, right hemisphere.

Figure 5 Significantly decreased VMHC values of the right or left MOG/pMTG in the ROC analysis, showing a moderate differentiating ability.

Abbreviations: VMHC, voxel-mirrored homotopic connectivity; MOG/pMTG, middle occipital gyrus/posterior middle temporal gyrus; ROC, receiver operator characteristic.

Figure 6 Correlations between the connectivity coefficients and the STAI-s and STAI-t scores in the CID patients.

Abbreviations: MOG, middle occipital gyrus; MOG/pMTG, middle occipital gyrus/posterior middle temporal gyrus; STAI-s, State Trait Anxiety Inventory-state; STAI-t, State Trait Anxiety Inventory-trait; CID, chronic insomnia disorder; zFC, z scores of functional connectivity; PCUN, precuneus; CAL, cerebellum anterior lobe; LG, lingual gyrus.

Table S1 ROC analysis for differentiating the patients from the healthy subjects

Brain regions	Area under the curve	Cutoff point	Sensitivity	Specificity
VMHC values in right or left MOG/pMTG	0.772	0.589a	66.7% (23/29)	79.3% (20/30)

Note:

a Using this cutoff point, the VMHC value of the right or left MOG/pMTG could correctly classify 23 of 29 patients and 20 of 30 healthy subjects, resulting in a sensitivity of 66.7% and a specificity of 79.3%, respectively.

Abbreviations: ROC, receiver operator characteristic; VMHC, voxel-mirrored homotopic connectivity; MOG/pMTG, middle occipital gyrus/posterior middle temporal gyrus.

Figure S1 TBSS results of the FA images between the controls and CID patients. Green represents the mean FA skeleton of all participants; red represents the regions with decreased FA in the CID patients (P<0.05, without correction for multiple comparisons).

Abbreviations: TBSS, tract-based spatial statistics; CID, chronic insomnia disorder; FA, fractional anisotropy.

Van DijkKRSabuncuMRBucknerRLThe influence of head motion on intrinsic functional connectivity MRINeuroImage201259143143821810475

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