To the best of our knowledge, we are the first to evaluate functional network brain-activity changes associated with AMD using the DC method (Figure 5). This method has been used to study optic neuritis , congenital comitant strabismus , high myopia  and other diseases, and has made good progress, toward the prospect of clinical application.(Figure 6).
The lingual gyrus is located in the visual joint cortex of the occipital lobe, where it is mainly responsible for vision processing . Studies have shown that glutamate andγ-aminobutyrate (GABA) in the occipital cortex are involved in the process of vision development , and local brain function activity of our visual system represented by fMRI decreased with increases in GABA level . Another study used resting-state cortical entropy to express the activity of cerebral cortex after hypopsia, and found that the loss of central vision was associated with increased resting-state cortical entropy . Studies have found that the activity of the lingual gyrus increases with the development of vision [32, 33]. In the present study, DC values of the lingual gyrus in patients with AMD decreased to a certain level in comparison with that of healthy people, suggesting that the activity of the lingual gyrus decreased; nevertheless, it retained a high DC value, which may suggest that the lingual gyrus is very active in brain visual processing. When AMD patients have poor vision, it may maintain a high level of activity to slow the development of vision loss.
The fusiform gyrus lies in the mid-bottom of the visual joint cortex, responsible for face recognition and object secondary classification recognition, which can produce face-like recognition of visual images that are unreal faces . Previously, researchers studied the relationships between the fusiform gyrus and autism , epilepsy , chronic schizophrenia , and found that blood flow in the fusiform gyrus increased with visual stimulation, and that the fusiform gyrus is closely related to vision . The DC value of the fusiform gyrus increased in our study, possibly as a result of compensatory increase of facial classification and recognition in patients with AMD.
The inferior temporal gyrus is part of the temporal lobe that is mainly responsible for speech processing, memory processing, visual perception and integration functions . Grotheer et al. found that the inferior temporal gyrus is selective to visual stimuli, suggesting a function involved in information processing . Previous studies showed that patients without language disorders and language advantages showed declines in language and visual memory after partial resection of the inferior temporal gyrus [41-44]. Similarly, we recorded low DC values in the inferior temporal gyrus in patients with AMD, although with an increasing trend compared with the HCs. We speculate that the visual processing ability of the inferior temporal gyrus in patients with AMD has a compensatory effect on vision loss.
The subcallosal gyrus is part of limbic system and is mainly responsible for the regulation of emotion . Subcallosal gyrus dysfunction is related to depression , schizophrenia , Alzheimer’s disease , and others. In our study, we adopted the Ham-D/A to evaluate potential emotional changes of patients. We found that scores of depression and anxiety both positively correlated with the DC values of the subcallosal gyrus in patients with AMD; therefore we suspect that loss of vision caused by the disease triggers mood swings, leading to the occurrence of mental diseases.
The middle frontal gyrus is located between the suprafrontal sulcus and the subfrontal sulcus, and is related to memory processing and attention control . The frontal orbital area is located around the intersection of the papillary muscle of the optic nerve and the precentral gyrus, while the precentral gyrus is closely related to eye movement and visual attention . Reseachers reported that, under normal conditions, the middle frontal gyrus can change attention control from exogenous to endogenous . Gohel et al. reported that the functional activity of the middle frontal gyrus increased in patients with glioma, suggesting that the resting-state fMRI of the middle frontal gyrus can be added to the non-invasive mode list, and can be used in the context of glioma to assess the hemispheric advantage of language and to guide the selection of treatment options . Similarly, a study indicated that the increase in the DC value may be represent a compensatory activation of visual connection in the middle frontal gyrus.
The insular gyrus is anatomically closely connected with the frontal lobe, the parietal lobe and the temporal lobe , and is mainly responsible for dealing with sensory experiences produced by convergence information. The insula includes the anterior insular gyrus and the posterior insular gyrus . A previous study found that the insular promoted emotional changes and formation of subjective feelings by integrating sensory information of internal and external sensations; therefore, it is considered to be the center of the significant network . In our study, compared with HCs, the insular lobes showed increased DC values, and this may be a functional compensation for the reduction of integrated internal and external senses, thereby avoiding the separation of senses (Table 3).
Our study has some limitations. First, we did not include sufficient samples, which may give rise to unintended errors. Second, the visual impairment caused by AMD may have influence on patient psychology. Before the study, the neuropsychological status of the patients was not evaluated; emotional states might have an impact on the experimental results. Third, the influences of sound and light and other physical factors were not ruled out during MRI examinations. In future studies, we will expand the sample size, assess psychological changes of patients with AMD in advance, and control the influence of physical factors, so as to further study the neuropathological mechanism of patients with AMD.