In this study, compared with HC group, DC, ALFF and DC-FA coefficients in VC1 were significantly lower in T2DM group, while FA had no significant change. The DC in VC1 was positively correlated with Trial 4 and Total trial 1–5 in CVLT. The positive correlation between DC-FA coefficients in VC1 and Total perseverative responses % of WCST was also observed.
Decreased DC and ALFF in VC1 were shown in T2DM group. Function abnormalities in VN have been observed in previous studies, but VN has not been subdivided for comparison (Huang et al., 2019; Huang et al., 2020). This present study further divide the VN into different regions (VC1, VC2, and VC3) using data-driven ICA method which is able to separate signals from noise effectively and detect differences between individuals with high sensitivity (Lu et al., 2020). At the same time, two neuronal indicators derived from BOLD signal were selected to reflect neuron function decrements since DC and ALFF reflect the neuronal own activity and its relationship with the surrounding neurons respectively (Hu et al., 2019). The abnormal neuronal function mainly concentrated in VC1, while there was no significant change in VC2 and VC3. VC1 (the primary visual cortex) is located in BA 17 including inferior talus gyrus in occipital cortex which receive visual input from the lateral geniculate nucleus, perform initial integration, and then transmit information to other areas of the visual cortex for complex processing (Engel et al., 1997; Tootell et al., 1998; Yu et al., 2020; Qi et al., 2021). VC2 and VC3 (visual joint cortex) play important roles in visual image, visual color and visual perception mainly located in BA 18 and BA 19 including outside the occipital cortex (Roland and Gulyas, 1995; Schiffino and Holland, 2016). The dysfunction of the primary visual cortex (VC1) may be a potential image biomarker of cognitive impairment and provide a new insight into the mechanism of T2DM in the early stage of cognitive change (pre MCI stage).
FA in T2DM group had no significant change compared with HC group, while DC-FA coefficients in VC1 exhibited lower. Different from our results, previous studies found that lower FA in visual regions such as fusiform gyrus, precuneus, cuneus (Wessels et al., 2006; Franc et al., 2011; Ma et al., 2022). This discrepancy could be explained by the different selection strategies of the subjects. Specifically, this study selected T2DM patients without retinopathy (an early stages of type 2 diabetes) whereas previous studies focused on DR patients who may be at a more severe stage leading to structural changes (Zilliox et al., 2016). As for functional-structural coupling coefficients, similar to our findings, network studies found that functional-structural coupling coefficients in T2DM was lower than HC group (Wang et al., 2019). The difference is that the previous studies calculated indicators of the whole network, while we take the specific functional network (VN) into consideration to explore the relationship between cerebral function and structure. Additionally, there have been some studies exploring FA and neuronal activity in both gray matter and white matter providing consolidate support to calculate the functional-structural coupling coefficients in VN combining DC, ALFF and FA (Seitz et al., 2018; Ji et al., 2019; Avila-Villanueva et al., 2020; Baxi et al., 2020). No significant structural changes were found in T2DM patients in the pre-MCI stage, but neuronal abnormalities and functional-structural decoupling had occurred in this stage, which may suggest that cerebral structure and function are closely related (Wang et al., 2014). In the future research, it is necessary to further explore the detailed mechanism about the relationship between structure and function in T2DM patients through the functional-structural coupling.
There were positive correlations between functional indicator, functional-structural coupling properties and T2DM patients’ neuropsychological results, especially in memory and executive function. According to previous studies, it is inconsistent about the relationship between abnormal DC and cognitive impairment in T2DM patients. Some studies suggested that altered DC in multiple brain regions were not associated with neuropsychological tests` scores in T2DM patients (Liu et al., 2018; Li et al., 2020b), while Xia et al. found that memory scores were positively correlated with reduced DC in the left medial prefrontal cortex associated with visual processing (Xia et al., 2020), corresponding to our correlation analysis results in VC1. A hypothesis to explain this difference is that the cognitive status of T2DM patients in different researches are miscellaneous. Although functional-structural coupling has been identified to be closely related to cognitive impairment in some cognitive associated disorders such as Alzheimer's disease and multiple sclerosis (Dai et al., 2019; Koubiyr et al., 2021), few studies have reported the relationship between functional-structural coupling coefficients and cognitive deficits in T2DM patients. This study explored this correlation and found that the higher the DC-FA coefficients were, the higher the executive function related scores were. Taken together, these findings indicate that DC and DC-FA coefficients in VN may be potential imaging biomarkers for revealing early cognitive deficits of different dimensions in T2DM.
This study has some limitations. The cross-sectional design limited our ability to demonstrate how functional–structural coupling coefficients dynamically reorganize in T2DM at the early stage of cognitive deficits. Future longitudinal studies are needed. There remain many clinical factors, such as diabetes medication, that have the potential effects on this study results. However, it is rather difficult to avoid these factors because the treatments have to be administrated to prevent the deterioration of the diseases.