RS-fMRI is non-invasive measure of neuronal function when patients are at rest [28, 29]. FC is widely used in RS-fMRI studies. FC refers to the temporal correlation between spatially remote neurophysiological events [30]. FC analyses can offer high spatial resolution and high spatial specificity relative to where the corresponding changes in neurophysiological signals take place [31]. We investigated FC in extra-visual resting-state networks in pituitary adenoma patients with vision restoration using a seed-based approach with a priori defined ROIs. Our data revealed a mixture of increases and decreases in FC in the brain network.
Our data showed that the decreased FC with right A1 in the right middle temporal gyrus (MT). The results may imply that there was coexist neural connection between the right A1 and MT, and the FC decreased when vision restoration. The middle temporal complex (MT/MST) is area specialized for the procession of motion vision [32, 33, 34, 35]. Recent studies also show that the visual motion area MT+/V5 responds to auditory motion [36, 37]. In sighted individuals, MT/MST responds to motion perception in the visual modality, but not to sound [35]. In contrast, MT/MST of congenitally blind individuals responds to auditory and tactile motion [38]. So blindness can cause a multi-modal response in MT/MST. In early blind individuals who got partial visual restoration in adulthood, auditory motion responses within the MT/V5 area. So Saenz et al.[36]concluded that auditory and visual responses coexist after vision restoration. Jiang et al. [10] showed auditory motion responses increased in the MT area and decreased in the right planum temporale in sight-recovery subjects. So authors proposed that the cortical plasticity that caused by early blindness is permanent and can persist even after visual restoration. The neuroplasticity may have an adaptive or maladaptive effect on restoration of the deprived sense [9]. Strelnikov, et al. [39] showed that synergy between the auditory and visual areas play a key role on the cross-modal plasticity. Alink, et al.[40]show that auditory motion complex and the visual motion area hMT/V5 + are involved in the generation of cross-modal dynamic capture illusion and the audiovisual integration occurs in early motion areas. Our results may imply that coexisting neural connection between the right A1 and MT + decreased after vision restoration. To the best of our knowledge, we do not find a possible reason for the decreased FC of the right A1 and MT+, more fMRI studies are needed in the future.
It is widely accepted that the occipital cortex of blind human is involved in language processing [13]. Braille reading in blind individuals triggers a large scale network of brain cortex, including posterior and medial occipital areas, fusiform gyrus, area hMT+, inferior temporal gyrus, inferior frontal, prefrontal, intraparietal sulcus, and somatosensory motor areas [41]. In congenitally blind subjects, the increased connectivity between visual cortex and Broca's area might relate to the role of the occipital cortex in semantic processing. [13, 42]. Deen, et al.[42]proposed that there is co-activation between the Broca's area and most of the occipital cortex. Ricciardi, et al. (2007) [38]showed that the increased FC between Broca's area and hMT + might be relate to the role of tactile flow processing in Braille reading. There are two explanations about the mechanisms of cross-modal plasticity in the occipital cortex. One is that the cross-modal plasticity arise through enhancing of existing bottom-up sensory connections from sensory areas, and sensory thalamic input during development can reorganize cortical function. The other is that cross-modal plasticity in blind adults is activated by top-down feedback from higher-order polymodal and amodal cortices. [43, 13].Our results may imply that FC between Broca and left middle temporal gyrus decreased after visual restoration. However, the mechanism resulting in functional alteration in Broca after vision restoration is still to be elucidated, more fMRI studies are needed in the future.
Our data show that the decreased FC with right A1 was identified in left insula lobule, left postcentral gyrus and increased FC with right A1 in the right paracentral lobule. Increased FC with Broca was identified in left insula lobule and right thalamus. The left insula lobule, left postcentral gyrus, right paracentral lobule, right thalamus are subareas of the multisensory system [44]. The multisensory system at the cortical locations consist of the frontal lobe, temporal lobe, parietal lobe and insular. The multisensory system at the subcortical locations involve the superior colliculus and basal ganglia [44, 45]. Insular lesions can result in a multisensory deficiency [46]. The anterior insular has connections with the orbital- frontal lobe, thalamus and limbic lobe. The posterior insular has connections with the frontal, temporal, parietal lobe and thalamus[47, 48]. The thalamus play a crucial role in multisensory integration processes [49]. It has been accepted that early sensory experience plays an important role in shaping the development of the neural circuitry underlying multisensory processes. In lid-sutured monkeys, studies showed that visual and multisensory areas lose responsiveness to visual stimulation [50, 51, 52]. In dark-reared cats, studies showed that multisensory neurons at cortical and subcortical sites cannot integrate cross-modal inputs [53, 54].In individuals with congenital dense bilateral cataracts, studies have revealed that their ability to integrate more complex cross-modal stimuli (e.g. speech input) is impaired [55, 56], despite a gain in reaction times for simple cross-modal stimuli (e.g. simultaneously presented light flashes and noise bursts) as compared to their unimodal counterparts [57]. Some studies have proposed that superior temporal areas (particularly, the superior temporal sulcus) was critical sites for multisensory audio-visual integration [58, 59]. Calvert, et al.[58]have showed that multisensory audio-visual integration was within extrastriate visual areas. When brain receives streams of information from multiple sensory modalities, visual information was more frequently preferentially processed than the other sensory modalities. Multisensory information competes for preferential access to consciousness. In terms of multisensory competition, neural representations in the dominant sensory modality may suppress neural representations in the dominated modalities. Weissman, et al.[60]reported that enhanced prestimulus activity in the prefrontal cortex and decreased prestimulus activity in the DMN predicted better task performance. Some connectivity study about the visual and auditory activity showed that the sensory systems have dynamic interaction with the prefrontal cortex, the sensorimotor cortex, and the DMN during multisensory competition. The mechanism of multisensory competition is still unclear. One theory is the top-down control from the prefrontal cortex to dominate the outcome of multisensory competition. The other is the bottom-up processing in the sensory systems decide result of the winner. Huang, et al. [61]revealed that visual dominance originated from top-down control, while auditory dominance originated from altered sensory processing in the auditory cortex. Our data show that the functional connection between right A1 and left insula lobule and left postcentral gyrus decreased and between right A1 and right paracentral lobule increased. The functional connection between Broca and left Insula lobule and right thalamus increased. The study indicates that the visual restoration lead to different multisensory interactions within the cortical and subcortical regions, but the mechanism is not clear.
The DMN involves the PCC, medial prefrontal cortex and lateral parietal cortex. The DMN activates in the resting condition and de-activates in the task condition. This network plays a role in the detection and monitoring of environmental events and internal mentation[62, 63, 64]. Our data show that FC between DMN and right brodmann area 17 and left cuneus increased. When the DMN detect the decreased visual cortical activity, the decreased deactivation in DMN may likely occur. The strong DMN activity is related with reduced visual cortical excitability [65]. Our previous data show that the FC decreased in visual cortex after vision recovery (the results not presented in the paper), and this study reveal that decreased FC with right A1 and Broca in the right middle temporal gyrus. So it may be justified to propose that decreased visual cortex activity in some way incur decreased DMN deactivation (stronger activity). It was also assumed the compensatory mechanism arised as feedback connection by Top-down influences of DMN. However, the mechanism resulting in functional alteration in DMN after vision restoration is still to be elucidated. We also found a decrease in the FC between the DMN and the cerebellum (right declive). The cerebellum has an interaction with the frontal eye fields [66, 67] and take part in the control of eye movement [68, 69]. Our data propose that the vision improvement lead to the decreased function of the cerebellum with DMN.
The ECN gets activated when fMRI tasks include executive functions. It involves the dorsolateral prefrontal cortex and posterior parietal cortex[70, 71, 72]. This network activates when a task needs cognitive control and working memory[27]. Our data show that decreased FC with ECN was identified in right posterior cingulate, right angular and right precuneus after visual restoration. The posterior cingulate /precuneus is a very important part of DMN. The angular gyrus(AG) plays role in language and semantic processing [73, 74] or spatial attention and orienting [75]. The AG was identified as an important parietal node of the DMN [76, 77, 78], and was reported with task-related deactivations [79]. So this result may indicate that there is contrary activity of the DMN and CEN after vision recovery. Consistent with our result, some study show that the DMN and CEN have antagonistic activity in resting state.[72]. Chen, et al. [80]found that the ECN has inhibitory control on DMN. Bauer, et al[81]showed that the ECN negatively regulates the DMN. Whitfield-Gabrieli, et al.[82]reported that the anticorrelations between DMN and ECN is associated with cognition hyperactivity such as complex working memory.
The SN constitutes the dorsal anterior cingulate cortex, bilateral insula and presupplementary motor area. This network has a key role in regulating the dynamic changes in other networks. The SN has function in the commencement of control of cognition processes [83, 84, 85]. Our data show that increased FC with SN was identified in right fusiform gyrus, left lingual gyrus/BA 19 and right brodmann area 19. The results indicate that the vision restoration lead to enhanced FC of vision cortex with SN. There is anatomical connection between the visual cortex and the SN [86]. The SN was found to involve in top-down attentional control [87, 88]. Our previous data show that the FC decreased within visual cortex after vision recovery (the results not presented in the paper). This study reveal that decreased FC with right A1, Broca and SN in the right middle temporal gyrus. So decreased visual stimulation may result in the enhanced FC between the visual system and the SN. Our data show that decreased FC with SN in right hippocampus, right corpus callosum and right precuneus. The hippocampus is critical for learning, memory and cognition. The hippocampal region has been considered part of the DMN [77, 89]. The precuneus was key node of DMN. Our data show that FC between DMN and right brodmann area 17 and left cuneus increased. Studies reported that the SN drives the DMN during both resting state and tasks in healthy younger population [90, 91]. So the increased activity of DMN may lead to decreased influence of SN on DMN itself. Taken together, it is reasonable to posit that when decreased FC within visual cortex is detected, higher than normal SN and DMN activity is initiated to achieve the compensatory mechanism as feedback connection by top-down influences, then the correspondingly decreased SN activity on DMN occur in the brain network.
Our data show that decreased FC with DMN, ECN and SN was simultaneously identified in the right precuneus. Precuneus is an area with high metabolic rates compared to other networks during rest. Precuneus is widely accepted as the importance structure in the DMN as it assists in various behavioural functions[92, 93, 94]. Many studies showed that the precuneus play the vital role in autobiographical memory retrieval, emotional stimulus processing and reward outcome monitoring.[95, 96, 97]. Some studies showed that the SN play a role in the dynamic switching of antagonistic activity between the DMN and CEN in cognitively normal young brains [98, 99, 91].Multiple experiments have shown that DMN, SN, and CEN is respectively associated with mindfulness [100, 101, 102], and also interact with each other [100, 103]. During the active state of meditation, between-network connectivity of DMN, CEN and SN are increased [104, 105]. Our results imply that precuneus may involve in three networks and relate to between-network connectivity of DMN, CEN and SN after visual restoration, but the mechanism is not clear.