Disrupted Functional Brain Network Architecture in Sufferers with Boxing-Related Repeated Mild Traumatic Brain Injury: A Resting-State EEG Study.

BACKGROUND: Repetitive mild traumatic brain injury (rmTBI) often occurs in individuals engaged in contact sports, particularly boxing. This study aimed to elucidate the effects of rmTBI on phase-locking value (PLV)-based graph theory and functional network architecture in individuals with boxing-related injuries in five frequency bands by employing resting-state electroencephalography (EEG). METHODS: Twenty-fore professional boxers and 25 matched healthy controls were recruited to perform a resting-state task, and their noninvasive scalp EEG data were collected simultaneously. Based on the construction of PLV matrices for boxers and controls, phase synchronization and graph-theoretic characteristics were identified in each frequency band. The significance of the calculated functional brain networks between the two populations was analyzed using a network-based statistical (NBS) approach. RESULTS: Compared to controls, boxers exhibited an increasing trend in PLV synchronization and notable differences in the distribution of functional centers, especially in the gamma frequency band. Additionally, attenuated nodal network parameters and decreased small-world measures were observed in the theta, beta, and gamma bands, suggesting that the functional network efficiency and small-world characteristics were significantly weakened in boxers. NBS analysis revealed that boxers exhibited a significant increase in network connectivity strength compared to controls in the theta, beta, and gamma frequency bands. The functional connectivity of the significance subnetworks exhibited an asymmetric distribution between the bilateral hemispheres, indicating that the optimized organization of information integration and segregation for the resting-state networks was imbalanced and disarranged for boxers. CONCLUSIONS: This is the first study to investigate the underlying deficits in PLV-based graph-theoretic characteristics and NBS-based functional networks in patients with rmTBI from the perspective of whole-brain resting-state EEG. Joint analyses of distinctive graph-theoretic representations and asymmetrically hyperconnected subnetworks in specific frequency bands may serve as an effective method to assess the underlying deficiencies in resting-state network processing in patients with sports-related rmTBI.

Altered hemispheric asymmetry of attentional networks in patients with pituitary adenoma: an event-related potential study.

Background: Emerging evidence has been reported of attentional dysfunction in pituitary adenoma patients. However, the effect of pituitary adenomas on lateralized attention network efficiency remained to be clear. Thus, the present study aimed to investigate the impairment of lateralized attention networks in patients with pituitary adenoma. Methods: Eighteen pituitary adenoma patients (PA group) and 20 healthy controls (HCs) were included in this study. Both behavioral results and event-related potentials (ERPs) were acquired while subjects performed the Lateralized Attention Network Test (LANT). Results: Behavioral performances indicated the PA group had a slower reaction time and a similar error rate relative to the HCs group. Meanwhile, significantly increased executive control network efficiency suggested the dysfunction of inhibition control in PA patients. Regarding ERP results, there were no group differences in the alerting and orienting networks. The target-related P3 was significantly reduced in the PA group, suggesting an impairment of executive control function and attentional resources allocation. Moreover, the mean amplitude of P3 was significantly lateralized to the right hemisphere, and interacted with the visual field, exhibiting that the right hemisphere dominated the bilateral visual field, whereas the left hemisphere dominated the left visual field. In the specific high-conflict condition, the pattern of hemispheric asymmetry in the PA group was altered due to a mixed effect resulting from the compensatory recruitment of attentional resources in the left central parietal area and the destructive effects of hyperprolactinemia. Conclusion: These findings suggested that, in the lateralized condition, the decreased P3 in the right central parietal area and the diminished hemispheric asymmetry under high conflict load, may serve as the potential biomarkers of attentional dysfunction in patients with pituitary adenoma.

Neuropsychological Alterations of Prolactinomas' Cognitive Flexibility in Task Switching.

Prolactinomas have been reported to impair cognition in broad aspects. However, few studies investigated the influence of prolactinomas on cognitive flexibility never mentioning the underlying neural and electrophysiological mechanism. We recorded scalp electroencephalography (EEG) in a colour-shape switching task. Patients with prolactinomas showed longer reaction time in switch trials and larger switch costs relative to healthy controls (HCs). Compared to HCs who showed stronger frontal theta activity in switch trials, the generally weak frontal theta activity in patients implied that they could not afford the executive control to configure task sets. Meanwhile, machine-learning based classification revealed that patients manifested non-selective brain patterns in response to different task types (colour vs. shape task) and different task states (switch vs. repeat state), which collectively suggested the cognitive dysfunction in preparation for a changing environment. Compared to HCs who showed stronger frontoparietal synchronization in switch trials, this enhanced frontoparietal connectivity was disrupted among patients with severe prolactinomas. This finding implicated greater hyperprolactinemia was linked to a larger decrease in cognitive performance. Taken together, the present study highlighted frontal theta power, and frontoparietal connectivity at theta band as the electrophysiological markers of the impaired cognitive flexibility and task control in patients with prolactinomas.

Hyperprolactinemia Associated with Attentional Processing and Interference Control Impairments in Patients with Prolactinomas.

The cognitive impairment of pituitary adenomas (PAs) has received increasing attention. Hyperprolactinemia and tumor mass effect are the potential causes. The aim of this study was to identify possible cognitive impairment and to further explore the correlation between these indices and prolactin (PRL) levels, based on the control of tumor size. Twenty-seven patients with prolactinomas (patient group) and twenty-six matched health control group (HC group) were enrolled in this study. All participants performed the flanker task while we continuously recorded electroencephalography data. On the behavioral performance level, patients showed a significantly slower reaction time (RT) in both flanker types. Concerning the event-related potentials level, patients elicited reduced P2 and enhanced N2 amplitudes compared with the HC group, suggesting an impairment of attentional processing (P2) and conflict monitoring (N2). Moreover, the patient group also induced lower P3 amplitudes relative to the HC group in both types, indicating that there were deficits in attentional resource allocation ability. We also found a significant correlation between the P3 amplitudes and incongruent condition RTs, as well as the subsequent PRL levels in the patient group. In conclusion, this is an innovative study that reveals the impaired cognition abilities in prolactinomas, and also proposes the possible cognitive toxicity of oversecreted PRL levels, which provides evidence for further research on the cognitive decline in PAs.

Repeated Subconcussive Exposure Alters Low-Frequency Neural Oscillation in Memory Retrieval Processing.

Repeated subconcussive head impacts are frequently experienced by athletes involved in competitive sports, such as boxing. The objective of the present study was to investigate the changes in working memory performance and memory retrieval-related neural oscillations in boxing athletes who experienced repeated subconcussive head impacts. Twenty-one boxing athletes (boxing group) and 25 matched controls (control group) completed a modified visual working memory task, and their continuous scalp electroencephalography (EEG) data were collected simultaneously. The behavioral measures and retrieval-related low-frequency neural oscillations were analyzed at each working memory set size in both groups. Subjects in the boxing group showed a reduced mean accuracy, diminished capacity estimates, and slower reaction time at demanding set sizes, and a marginally increased intra-individual coefficient of variation (ICV) for overall set sizes. Additionally, decreased event-related frontal theta synchronization, parieto-occipital alpha desynchronization, and frontal low beta synchronization were observed in the boxing group, suggesting underlying working memory dysfunction for efficient neurocognitive resource employment, inhibition of distracting stimuli, and post-retrieval control in the boxing group. Moreover, a negative correlation was found between frontal beta synchronization and reaction time for most set sizes in both groups. The present study was the first to reveal the underlying working memory deficits caused by the cumulative effects of boxing-related subconcussive head impacts from the perspective of behavior and EEG time-frequency oscillations. Joint analysis of EEG low-frequency oscillations and the innovative task with multiple challenging load conditions may serve as a promising way to detect concealed deficiencies within working memory processing.

Altered Attention Network in Paratroopers Exposed to Repetitive Subconcussion: Evidence Based on Behavioral and Event-Related Potential Results.

Cognitive impairment caused by repetitive subconcussion has received increasing attention in recent years. Although the dysfunction of attention has been confirmed by neuropsychological research using scales, there is no event-related potentials (ERPs) research. The Attention Network Test (ANT) has been widely used to evaluate the three separate components of attention processing (alerting, orienting, and executive control). Twenty-seven paratroopers exposed to repetitive subconcussion (subconcussion group) and 25 matched healthy control participants (HCs group) were enrolled, and all of them performed the ANT test while continuous scalp electroencephalography data were recorded. On the behavioral performance level, the subconcussion group showed a slower task response, with an especially significant slower reaction time in alerting. Concerning ERP results, reduction amplitudes of cue-N1 in the alerting network were observed, indicating that this group was less able to make efficient use of cues and maintain an alerting state for incoming information. For the orienting network, no difference in N1 amplitude was observed between the two groups. Moreover, there was a reduced P3 amplitude in the executive control network in the subconcussion group compared with the HCs group, suggesting a dysfunction of attentional resource allocation and inhibition control in the former group. This study is, to our knowledge, the first analysis of the altered attention network caused by repetitive subconcussion from the perspectives of behavioral and neuropsychology levels. These preliminary results revealed the possible damage of the alerting and executive control networks and provided a reference for further research on subconcussion cognitive impairment.

DAXX inhibits cancer stemness and epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: DAXX is a transcription repressor that has been implicated in several types of cancers, but its role in the development of gastric cancer remains unknown. METHODS: We analysed the expression of DAXX in 83 pairs of gastric cancer samples, including neoplastic and adjacent tissues, and correlated the expression levels with clinical stages. We also investigated the molecular mechanisms by which DAXX downregulation promotes cancer growth using both in vitro and in vivo models. RESULTS: DAXX was downregulated in advanced gastric cancer samples. The expression of DAXX inversely correlates with that of cancer stem cell markers CD44 and Oct4 in gastric cancer lines. DAXX overexpression in gastric cancer cells inhibited migration, invasion and epithelial- mesenchymal transition (EMT). The inhibition of EMT was achieved through the repression of SNAI3, a key inducer of EMT, by recruiting HDAC-1 into the nucleus. Using a xenograft mouse model, we demonstrated that the MKN45 cells formed smaller tumours when DAXX was overexpressed. Wild-type AGS cells were not able to form tumours in nude mice, but in contrast, formed visible tumours when DAXX was silenced in the cells. CONCLUSION: We for the first time demonstrated that DAXX functions as a tumour suppressor in gastric cancer by inhibiting stem cell growth and EMT.

CLIC4 abrogation promotes epithelial-mesenchymal transition in gastric cancer.

Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

Runx1 promotes satellite cell proliferation during ischemia - Induced muscle regeneration.

RUNX1 is a transcription factor that is not expressed in uninjured muscles, but can be detected in denervated muscles, suggesting a role of RUNX1 in muscle's response to injury. However, the role of RUNX1 in muscle's response to ischemia has not been reported. Our study showed that Runx1 is up regulated in skeletal muscle during ischemia reperfusion induced injury. Over-expression of Runx1 in C2C12 cells inhibits myogenic differentiation, but promotes proliferation of myoblasts. Consistent with these findings, we found that Runx1 expression was decreased in differentiated satellite cells. Our results indicate that Runx1 regulates muscle regeneration by promoting proliferation of satellite cells.