In this study, rsMRI technology was used to detect BA patients and HC controls, and the VMHC method was used to evaluate the changes in the functional connections between cerebral hemispheres. We have two major findings, first, it was mainly found that the VMHC values of these brain areas (bilateral basal ganglia/thalamus/ insula, cuneus/ calcarine/ lingual gyrus, PreCG, and PostCG) in BA patients were significantly lower than those in the normal controls. Second, functional connectivity was studied using VMHC abnormal brain regions as seed points, compared with the HC group. As far as we know, this is the first report that VMHC combined with seed-based rsFC method which has been used to study the changes of functional connectivity in the whole brain of BA patients. We believe that these findings will contribute to the development of an imaging biomarker for the diagnosis of BA, which is of great significance in improving the clinical efficacy and quality of life of patients with asthma.
Functional homotopy refers to the high similarity in endogenous spontaneous activities of neurons of the same origin in the left and right hemispheres of the brain, and it is related to brain stratification . The VMHC method measures interhemispheric coordination and is a rsMRI method used to study the functional connections between hemispheres, also, it is an important method to study brain information integration by measuring the correlation between cerebral hemisphere blood oxygen level-dependent time series and reflecting the information exchange and integration mode between cerebral hemispheres . At present, this method has been widely used to assess the functional connectivity of the cerebral hemisphere in various neuropsychiatric diseases. Meanwhile, asthma is considered to be a respiratory disease that seriously affects the central nervous system . Combined with our study, the VMHC values of eight brain regions, namely bilateral basal ganglia/thalamus/ insula, cuneus/calcarine/lingual gyrus, PreCG, and PostCG decreased in BA patients, suggesting that the functional connectivity in these brain regions is impaired in BA patients.
Both thalamus and basal ganglia are important to brain regions for the basal ganglia network , Xiaodan Yan et al. found that BOLD signal activation in the middle gyrus, occipital gyrus, lingual gyrus, and thalamus was reduced in a high-altitude group compared with those in normal altitude group, moreover, these high altitudes subjects had longer response time and lower response accuracy, they believe that this may be caused by the long-term hypoxia concentration and low pressure of high altitude people, and the function and development of the brain in the hypoxia environment will be affected, which will lead to the decline in cognitive ability . In this instance, we can explain the abnormality of the basal ganglia network of asthmatic patients, because asthmatics are characterized by blocked airflow and bronchospasm, and severe asthma attacks can lead to hypoxia . Besides, many studies have shown that the insula is an important brain region involved in the neuropathology of asthma, for example, according to the research of Rosenkranz et al, patients with stress-related diseases such as asthma, regions of the brain such as the insula may lead to inflammatory responses by affecting disease-specific emotions and incoming physiological signals . Also, Yuqun Zhang et al found that the FC value of the insular brain area of asthmatic patients decreased compared with that of normal patients, but after group cognitive behavior therapy treatment, the FC value of the insular subregion increased significantly . Additionally, the insula receives afferent information about the cord cortex of the thalamus, carries information related to respiration, and is closely related to the nerve center that processes emotions . Moreover, the insula is involved in the effective assessment of sensory stimuli, regulation of homeostasis responses, and visceral perception, moreover, the degree of insula activation can predict individual differences in the evaluation of stimulus intensity and visceral consciousness. All of these studies indicate that emotional stimulation and insular area are closely related to asthma. In brief, we found a decrease in VMHC in basal ganglia, thalamus and, the insular lobes, which may be used as a clinical indicator for evaluating BA patients.
Many pieces of evidence showed that asthma was a serious respiratory disease that can affect the nervous system [36, 7], furthermore, there has been functional MRI study with degree centrality (DC) that have confirmed that the sensorimotor network and visual network of asthmatic patients are abnormal . However, relevant studies on VMHC methods are still vacant. Brodmann Area (BA) 17/18/19 is the visual cortex, these brain regions as the main area of the visual network, its VMHC value is altered in asthmatic patients, the abnormal change in the visual brain network may imply that asthma can affect the spontaneous changes of the central nervous system. These important brain regions of the visual network play an important role in the body's visual function. Calcarine (BA19) as the visual contact area, which is responsible for visual processing, and forms visual joint cortex with BA18, and an rs-fMRI study on asthma confirmed that the FC value of BA19 on the left side of asthma patients was significantly lower than that of the normal control group . Besides, cuneus (BA17) mainly belongs to the primary visual center(V1), as the core of visual pathways , it is responsible for the preliminary processing of visual information, receiving information about the lateral geniculate body, and transmitting the information on other visual areas , and when the body is not paying attention, visual information will be difficult to transmit from V1 to other regions . Also, the lingual gyrus (BA18) from the secondary visual cortex (V2) is the visual contact area, which is mainly responsible for visual processing. Moreover, it receives the pre feedback connection between V1 and plays an important role in object shape vision and stereo vision [41, 42]. Thus, we demonstrated that the neural activity of the visual network between the two hemispheres of asthmatic patients changed synchronously, moreover, this change of visual brain network in BA patients may lead to abnormal visual function.
PreCG (BA4/6, M1) and PostCG (BA3, S1) belong to the motor and sensory centers respectively, they are also sensorimotor areas . In addition, the PostCG is the core component of the sensorimotor network , the motor center mainly controls the movement behavior of the body, while the sensory center has the basic somatosensory function, which is responsible for encoding touch and pain , also, receiving the sensory input from the limbs. Furthermore, Liu et al found that the sensorimotor network of asthmatic patients would change, and this change was related to the altered respiratory amplitude, in addition, Li used MRI to contrast the brain structure of asthma patients and normal controls, found that patients with asthma sensorimotor network is abnormal, they through the network abnormal airway obstruction and the degree of correlation analysis reflect the brain damage associated with asthma caused by respiratory damage, they believe that brain network potential parameters can be used as an understanding of the pathophysiology of asthma . Also, Zhang et al found the M1/S1 brain area abnormality in asthmatic patients, and the FC value of these two brain regions was lower in asthmatic patients than that of the normal control group . Therefore, we hypothesized that sensorimotor function might change in BA patients, and this change was associated with abnormalities in key brain areas of the sensorimotor network.
Our further seed-based rsFC analyses revealed that FC values of these brain regions (B- PreCG/PostCG, B- Cuneus/ Calcarine/ Lingual Gyrus, and R- Basal ganglia/Thalamus) were lower in BA patients, furthermore, the VMHC values corresponding to these brain regions in BA patients are also lower than those in normal subjects, which suggests that there are abnormal changes in resting-state functional connectivity between these brain regions in asthmatic patients and corresponding ataxia between cerebral hemispheres. Moreover, the inferior parietal lobule (ILP) is involved in the control of body perception, motor orientation, memory retrieval, language understanding, digital processing, and social cognition, this brain area is one of the main brain areas of the frontoparietal network, which plays an important role in attention and executive ability [46–48]. Kuo et a found that the FC value of the ILP brain region in untreated heroin addicts was significantly lower than that in normal patients, and they speculated that the IPL brain region might be a neural target for treatment and intervention . Besides, an MRI studied on asthma found that the degree centrality value of asthmatic patients in the IPL brain area was lower than that of normal controls, this study suggested that the IPL brain region can be used as one of the clinical indicators for the diagnosis of asthma . The supramarginal gyrus is involved in verbal divergent thinking, and this brain region is activated during divergent thinking tasks . The cingulate gyrus belongs to the limbic system, which is mainly involved in emotion formation, processing, learning, and memory , the interaction between the cingulate cortex and other brain networks may be very important to the body's consciousness . Furthermore, the caudate nucleus plays an important role in cognitive function , Zhang et al not only found the abnormality of FC value in asthma patients, but also found the change of FC values in caudate and cingulate brain regions , which were similar to our findings in BA patients. Hence, combined with our rsFC results, we speculate that asthma may involve changes in functional connectivity of multiple brain regions, which are closely related to the body's emotional, motor, cognitive and other functions, and this may mean that asthma patients are dysfunctional in the above abilities.