Interhemispheric Functional Connectivity Alterations in Diabetic Optic Neuropathy: A Resting-State Functional Magnetic Resonance Imaging Study

Figures & data

Figure 1 Example of diabetes optic neuropathy seen on fluorescence fundus angiography (A) and fundus camera (B).

Figure 2 Relationship between magnetic resonance imaging and DON. Diabetes may cause DON. Once DON occurs, it may affect the function of vision and lead to abnormal nerve activity in areas of the brain that are related to visual discrimination.

Abbreviation: DON, diabetes optic neuropathy.

Table 1 VMHC Method Applied in Ophthalmological and Neurogenic Diseases in the Literature

Author, Year	Disease	Brain Areas		(Refs.)
		UDs>NCs	UDs<NCs
Hou et al, 2017	Early blindness		MTG, MFG, ITG	[^Citation17]
Shi et al, 2019	Corneal ulcer		LING/CAL, PreCG/PoCG, MFG	[^Citation18]
Ye et al, 2018	Unilateral acute open globe injury		CAL, Ling, Cun, MOG	[^Citation19]
Zhang et al, 2018	Comitant exotropia	STG, MFG	PreCG, IPL, SPL	[^Citation20]
Shao et al, 2018	Left eye monocular blindness	Insula, MFG	Cun/CAL/LING	[^Citation47]
Shao et al, 2018	Right eye monocular blindness		Cun/CAL/LING, M1/S1, SPL	[^Citation47]
Dong et al, 2019	Acute eye pain		LING/CAL, PreCG/PosCG, MFG	[^Citation48]
Wang et al, 2020	Diabetic nephropathy retinopathy		BMTG, BMOG, BMFG	[^Citation21]

Abbreviations: UD, unusual disease; NC, normal controls; MTG, middle temporal gyrus; MFG, medial frontal gyrus; ITG, inferior temporal gyrus; LING, lingual; CAL, calcarine; PreCG, Precentral; PosCG, postcentral gyrus; Cun, Cuneus; MOG, Middle Occipital Gyrus; IPL, inferior parietal lobule; SPL, superior parietal lobule; M1, primary motor cortex; S1, primary somatosensory cortex; BMTG, bilateral middle temporal gyrus; BMOG, bilateral middle occipital gyrus; BMFG, bilateral medial frontal gyrus.

Table 2 Conditions of Participants Included in the Study

Condition	DON	HCs	t	P-value*
Male/female	12/16	12/16	N/A	>0.99
Age (years)	58.85±5.72	57.56±5.83	0.471	0.954
Weight (kg)	65.32±7.76	62.52±9.14	0.214	0.874
Handedness	28R	28R	N/A	>0.99
Duration of DON (days)	48.42±5.84	N/A	N/A	N/A
Best-corrected Va-left eye	0.40±0.28	1.05±0.20	−4.032	0.022
Best-corrected Va-right eye	0.25±0.12	1.05±0.15	−3.643	0.017

Notes: *P <0.05 Independent t-tests comparing two groups.

Abbreviations: DON, diabetic optic neuropathy; HCs, healthy controls; N/A, not applicable.

Table 3 Brain Areas with Significantly Different VMHC Values Between HCs and DON

Brain Areas	MNI Coordinates
	X	Y	Z	BA	Peak Voxels	T value
HCs>DON
RTI	48	−6	−33	21	49	4
LTI	−48	−6	−33	21	49	4
RCM	3	−18	39	24	34	4.9
LCM	−3	−18	39	24	34	4.9
RSM	6	−9	57	24	49	4.1
LSM	−6	−9	57	24	49	4.1

Abbreviations: HCs, healthy controls; DON, diabetic optic neuropathy; RTI, right temporal inf; LTI, left temporal inf; RCM, right cingulum mid; LCM, left cingulum mid; RSM, right supp motor; LSM, left supp motor.

Figure 3 Spontaneous brain activity in patients with diabetes optic neuropathy (DONs) versus healthy controls (HCs). (A and B) Significant activity differences were observed in the right temporal inferior area, left temporal inferior area, right cingulum mid area, left cingulum mid area, right supp motor area, and left supp motor area. Red or yellow denote higher voxel mirrored homotopic connectivity(VMHC) values. P<0.01 for multiple comparisons using Gaussian random field theory (z>2.3; P<0.01; cluster >40 voxels, AlphaSim corrected). (C) Mean values of altered VMHC values between the two groups.

Abbreviations: TI, temporal inf; CM, cingulum mid; SM, supp motor; VMHC, voxel mirrored homotopic connectivity; HCs, healthy controls; DON, diabetes optic neuropathy.

Table 4 Conversion Between the Five-Level Classification Method and Snellen and Log MAR

Five-Level Classification	Snellen	Snellen	Log MAR
3.0	5/500	0.01	2
4.0	5/50	0.1	1
4.1	5/40	0.12	0.9
4.2	5/32	0.15	0.8
4.3	5/25	0.2	0.7
4.4	5/20	0.25	0.6
4.5	5/16	0.3	0.5
4.6	5/13	0.4	0.4
4.7	5/10	0.5	0.3
4.8	5/8	0.6	0.2
4.9	5/6	0.8	0.1
5.0	5/5	1.0	0.0
5.1	5/4	1.2	−0.1
5.2	5/3	1.5	−0.2
5.3	5/2.5	2.0	−0.3

Figure 4 The VMHC results of brain activity in the DON group. (A)The mean VMHC value of the mid cingulum showed a negative correlation with the left best-corrected VA (r=0.7913, P<0.0001). (B)The best-corrected VA of the right eye negatively correlated with VMHC signal values of the supp motor area (r=0.4080, P=0.0003).

Abbreviations: VMHC, voxel mirrored homotopic connectivity; DON, diabetes optic neuropathy; HC, healthy control; VA, visual acuity.

Figure 5 ROC curve analysis of mean VMHC values for altered brain regions.

Notes: The area under the ROC curve for VMHC values: RTI/LTI (0.858), RCM/LCM (0.835), and RSM/LSM (0.813).
Abbreviations: ROC, receiver operating characteristic; VMHC, voxel-mirrored homotopic connectivity; RTI, right temporal inferior; LTI, left temporal inferior; RCM, right cingulum mid; LCM, left cingulum mid; RSM, right supp motor; LSM, left supp motor.

Figure 6 The voxel mirrored homotopic connectivity (VMHC) results of brain activity in the DON group. Compared with the healthy controls (HCs), the VMHC of the following regions in the DON group were decreased to various extents: 1, right cingulum mid area (t=4.9); 2, left cingulum mid area (t=4.9); 3, right supp motor area (t=4.1); 4, left supp motor area (t=4.1); 5, right temporal inferior area (t=4); 6, left temporal inferior area (t=4). The sizes of the spots denote the degree of quantitative changes.

Table 5 Brain Regions Alternation and Its Potential Impact

Brain Regions	Experimental Result	Brain Function	Anticipated Results
Temporal inf	DONs<HCs	Object vision^Citation29	Deficit in visual discrimination or recognition
Cingulum mid	DONs<HCs	Eye movement^Citation49	Reflects visual impairment
Supp motor	DONs<HCs	Saccadic and pursuit eye movements^Citation39	Deficits in saccade sequences generation

Abbreviations: HCs, healthy controls; DON, diabetes optic neuropathy; HCs, healthy controls; DON, diabetes optic neuropathy.

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