In our study, FCS analysis revealed that sFCS in the bilateral precuneus and cuneus was decreased in patients with PPPD, and no significant alterations was observed in global FCS and lFCS in PPPD patients, the results indicated that FCS changes was mainly occurred in the cuneus and precuneus. Results of seed-based FC analysis on regions with reduced FCS showed that reduced sFCS was mainly caused by the weakened FC in the right precuneus and cuneus. Moreover, FCS/FC changes were negatively correlated with clinical symptom scores, and the lower the FCS/FC values, the more severe the patients' symptoms.
Our previous study performed local brain functional analysis in PPPD patients, and found that the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in the right precuneus were significantly decreased, indicating that the spontaneous functional activity in this area was altered . In the current study, results of FCS further confirmed the dysfunction of the precuneus, and the areas with reduced FCS were more extensive than areas with abnormal ALFF and ReHo, indicating that precuneus dysfunction in PPPD patients may be more obvious compared with the results from our previous study. Margulies et al performed FC analysis of the precuneus using resting-state functional MRI, and found three subregions within the precuneus, including anterior sensorimotor, central cognitive, and posterior visual regions . In our study, the altered FCS in the precuneus was mainly located in the posterior visual region, which is mainly involved in the integration of vestibular and visual information. For patients with PPPD, the reduced sFCS in the precuneus may lead to abnormal integration of vestibular and visual information, causing abnormal spatial perception, and resulting in dizziness in PPPD patients. In addition, the higher the FCS values, the greater the connection strength of the node to other nodes. The precuneus is the important network node within the default mode network (DMN) . It is speculated that the dysfunction of the precuneus may lead to abnormal function of DMN, which cannot effectively evaluate the information from internal and external environment, and cannot achieve a clear spatial perception . If abnormality in the DMN persists during rest state, persistent dizziness and unsteadiness may occur in patients with PPPD.
In our study, the reduced sFCS of the right precuneus in PPPD patients was mainly located at the junction of the parietooccipital and calcarine sulci, which mainly include the cortex around the calcarine sulcus, posterior cingulate cortex, and retrosplenial cortex. The cortex around the calcarine sulcus is mainly located in the visual association cortex, which is involved in visual information processing and the integration of vision and other information . Functional abnormalities in this area may lead to abnormalities in visual information processing and integration of visual and vestibular information, resulting in abnormal spatial perception, causing symptoms such as dizziness and unsteadiness in patients with PPPD. Functional abnormalities in this area may be related to the aggravation of dizziness and unsteadiness that triggered by complex visual stimuli. When patients are exposed to visual stimuli or complex visual environments, the complex visual information is conveyed which exacerbates the deficits in visual information processing and integration, and aggravate the symptoms (dizziness and unsteadiness) of PPPD patients.
Studies have shown that the posterior cingulate cortex plays an important role in emotion regulation, spatial attention, memory, and navigation [17-20]. The abnormal function of the posterior cingulate cortex in patients with PPPD may cause abnormalities in the functions of spatial attention and navigation in PPPD patients, leading to abnormal spatial perception when patients expose to complex visual environment, and resulting in the occurrence of dizziness. The posterior cingulate cortex is also an important part of the limbic system and involved in emotion regulation. The abnormal function of this area may also lead to emotion regulation abnormalities in PPPD patients, which may be associated with the different levels of anxiety and depression in PPPD patients.
Studies have shown that the retrosplenial cortex directly participates in the coordination and transformation between the egocentric and allocentric spatial reference frames, that enables us to orient ourselves in the environment [21-26]. Patients with retrosplenial cortex lesions are unable to identify landmarks, but are unable to use this information to derive navigational information orientate themselves [27,28]. The abnormal function of the retrosplenial cortex in patients with PPPD may cause deficits in the coordination of egocentric and allocentric spatial reference frames, leading to abnormal spatial perception and spatial disorientation, resulting in dizziness in patients with PPPD.
Seed-based FC analysis was further conducted to explore FC changes in regions with reduced FCS, and decreased FC was found in the same regions showing reduced FCS, the results indicated that decreased FCS was caused by the decreased FC in the precuneus and cuneus, which further confirmed the local functional abnormality of the precuneus and cuneus. It is worth noting that in seed-based FC analysis, although most of the ROIs showed decreased FC with precuneus and cuneus, but some ROIs showed altered FC with other regions. ROI3, ROI7, ROI12 showed weaker FC with the cerebellum, ROI3, ROI12 showed weaker FC with precentral gyrus and postcentral gyrus. The results indicated that functional abnormalities in precuneus and cuneus in patients with PPPD can cause abnormal sensorimotor integration, and weakened ability to control body movement and posture through integrating visual and vestibular information, thereby causing unsteadiness in patients with PPPD.
In addition, Kaoru et al.  showed that various sensory information including visual, vestibular or proprioceptive sensations is routed to the central cortex, and integrated by posterior parietal cortex and temporoparietal cortex to create an internal estimate model of body, then sensory information is further transfered to premotor and supplementary motor areas for movement encoding, which can produce voluntary movements and maintain body balance. This transformation of sensory information can also be called dorsal stream. In patients with PPPD, altered functional activity of the precuneus and cuneus cause abnormal information exchange in cuneus-precuneus, precuneus- premotor area/precentral gyrus. We speculate that the dorsal stream, i.e. cuneus-precuneus- premotor area is abnormal, causing symptoms such as dizziness and instability in PPPD patients.