In the present study, we illustrated alterations in the FC of the SC_thalamus with whole-brain voxels in PTN patients using rs-fMRI. Compared with HCs, FC between the SC_thalamus and the posterior central gyrus, middle frontal gyrus, and right supramarginal gyrus altered in PTN patients. In addition, correlations existed between FC and the course of PTN. These results indicated that functional brain connectivity altered in the pathological condition of PTN in the resting state. Previous rs-fMRI studies have found an altered local activity in the thalamus of PTN patients [13], which is consistent with our findings. Our results expanded the central mechanism underlying the pathogenesis of PTN.
The thalamus is an established brain region for nociceptive transmission. Nociceptors in the head and face are relayed to the thalamus via the trigeminal thalamus system by conduction. After passing through the ventral posterior medial nucleus of the thalamus, nociceptors are projected to the cerebral cortex. When the connection between them is impaired, pain symptoms are the consequences of the specific functional connection between the ventral posterior medial nucleus of the thalamus and the nociceptive centers of the brain [26, 27]. In this study, we calculated FC between the SC_thalamus and the whole brain according to the changes in BOLD signals in rs-fMRI images, thus reflecting the collaboration of functional activities between brain regions. A decrease/increased in the FC indicated the inhibited/activated functional collaboration of neurons between brain regions.
An increased FC was observed in the middle frontal gyrus with the SC_thalamus in PTN patients. The middle frontal gyrus in the prefrontal cortex is responsible for modulating pain perception [28, 29], and its activity is associated with pain stimulation and regulation, negative emotion perception, and cognitive appraisal [30]. In a task-state fMRI study, varying degrees of enhancement in frontal lobe brain activity pain after pain stimulation in the face are observed in PTN patients [31]. Here, an increased FC between the SC_thalamus (ROI) and middle frontal gyrus indicated a close functional connection of the SC_thalamus with frontal lobe neurons, further confirming the crucial and coordinated roles of SC_thalamus and frontal lobe have in the nociceptive transduction pathway. This alteration may be explained by the transient spontaneous pain in PTN patients with activated conduction fibers, enhanced nociceptive transmission, and abnormal changes in the FC of pain-associated brain regions.
FC of the SC_thalamus with postcentral gyrus increased in PTN patients, and it was positively correlated with the course of PTN. The postcentral gyrus is the primary sensory cortex that localizes pain and recognizes pain intensity [32, 33]. Nociceptors in the head and face in PTN patients are projected via the thalamus to the postcentral gyrus [34]. The increased FC in the SC_thalamus and postcentral gyrus of PTN patients probably was caused by the enhanced functional synergy of the thalamic retroventral nucleus with the postcentral gyrus conduction pathway in response to the prolonged trigeminal neuralgia stimulation. Previous data have shown an enhanced neural spontaneous activity in the thalamus and posterior central gyrus of PTN patients detected by resting-state functional nuclear magnetic resonance [35], consistently supporting our findings. We also found a positive correlation between FC of the SC_thalamus and postcentral gyrus and the course of PTN, indicating that chronic pain of PTN gradually altered the functional synergism between the SC_thalamus and postcentral gyrus.
FC of the SC_thalamus with the right supramarginal gyrus decreased in PTN patients, which was negatively correlated with the course of PTN. The supramarginal gyrus surrounds the terminal portion of the ascending ramus of lateral sulcus, and forms the inferior parietal lobule [36]. The role of the supramarginal gyrus greatly varies in the left and right hemispheres, with the right supramarginal gyrus dominant in emotion [37]. Because of recurrent attacks of trigeminal neuralgia, PTN patients suffered from a decreased FC of the right supramarginal gyrus to minimize the emotional cognition of pain. Pain stimulation can reduce the FC between the left amygdala and right supramarginal gyrus [38], which is consistent with our findings. The FC of the SC_thalamus and right supramarginal gyrus was negatively correlated with the course of PTN, indicating that PTN-induced persistent chronic pain gradually attenuated the functional synergy between the SC_thalamus and right supramarginal gyrus and impaired the ability of the right supramarginal gyrus in the emotional regulation of pain sensation.
LIMITATIONS
Three limitations existed in the present study. First, clinical application of rs-fMRI was limited by a long scanning time and high requirements for the participants. Second, a sample size in our study challenged the reliability of our conclusion. Third, we excluded left-handed PTN patients, and whether our findings were applicable to them remains unclear. In the future, a multi-center, large-scale study is needed to further validate our findings.