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.

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.

Omega-3 polyunsaturated fatty acid attenuates traumatic brain injury-induced neuronal apoptosis by inducing autophagy through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

BACKGROUND: Enhancing autophagy after traumatic brain injury (TBI) may decrease the expression of neuronal apoptosis-related molecules. Autophagy-mediated neuronal survival is regulated by the sirtuin family of proteins (SIRT). Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA supplementation attenuated neuronal apoptosis by modulating the neuroinflammatory response through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury (TBI). However, no studies have elucidated if the neuroprotective effects of ω-3 PUFAs against TBI-induced neuronal apoptosis are modulated by SIRT1-mediated deacetylation of the autophagy pathway. METHODS: The Feeney DM TBI model was adopted to induce TBI rats. Modified neurological severity scores, the rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect Beclin-1 nuclear translocation and autophagy pathway activation. The impact of SIRT1 deacetylase activity on Beclin-1 acetylation and the interaction between cytoplasmic Beclin-1 and Bcl-2 were assessed to evaluate the neuroprotective effects of ω-3 PUFAs and to determine if these effects were dependent on SIRT1-mediated deacetylation of the autophagy pathway in order to gain further insight into the mechanisms underlying the development of neuroprotection after TBI. RESULTS: ω-3 PUFA supplementation protected neurons against TBI-induced neuronal apoptosis via enhancement of the autophagy pathway. We also found that treatment with ω-3 PUFA significantly increased the NAD+/NADH ratio and SIRT1 activity following TBI. In addition, ω-3 PUFA supplementation increased Beclin-1 deacetylation and its nuclear export and induced direct interactions between cytoplasmic Beclin-1 and Bcl-2 by increasing SIRT1 activity following TBI. These events led to the inhibition of neuronal apoptosis and to neuroprotective effects through enhancing autophagy after TBI, possibly due to elevated SIRT1. CONCLUSIONS: ω-3 PUFA supplementation attenuated TBI-induced neuronal apoptosis by inducing the autophagy pathway through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

Omega-3 polyunsaturated fatty acid attenuates the inflammatory response by modulating microglia polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway following experimental traumatic brain injury.

BACKGROUND: Microglial polarization and the subsequent neuroinflammatory response are contributing factors for traumatic brain injury (TBI)-induced secondary injury. High mobile group box 1 (HMGB1) mediates the activation of the NF-κB pathway, and it is considered to be pivotal in the late neuroinflammatory response. Activation of the HMGB1/NF-κB pathway is closely related to HMGB1 acetylation, which is regulated by the sirtuin (SIRT) family of proteins. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA inhibited TBI-induced microglial activation and the subsequent neuroinflammatory response by regulating the HMGB1/NF-κB signaling pathway. However, no studies have elucidated if ω-3 PUFA affects the HMGB1/NF-κB pathway in a HMGB1 deacetylation of dependent SIRT1 manner, thus regulating microglial polarization and the subsequent neuroinflammatory response. METHODS: The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and HMGB1, were used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1/NF-κB signaling pathway activation to evaluate the effects of ω-3 PUFA supplementation. The impact of SIRT1 deacetylase activity on HMGB1 acetylation and the interaction between HMGB1 and SIRT1 were assessed to evaluate anti-inflammation effects of ω-3 PUFAs, and also, whether these effects were dependent on a SIRT1-HMGB1/NF-κB axis to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. RESULTS: The results of our study showed that ω-3 PUFA supplementation promoted a shift from the M1 microglial phenotype to the M2 microglial phenotype and inhibited microglial activation, thus reducing TBI-induced inflammatory factors. In addition, ω-3 PUFA-mediated downregulation of HMGB1 acetylation and its extracellular secretion was found to be likely due to increased SIRT1 activity. We also found that treatment with ω-3 PUFA inhibited HMGB1 acetylation and induced direct interactions between SIRT1 and HMGB1 by elevating SIRT1 activity following TBI. These events lead to inhibition of HMGB1 nucleocytoplasmic translocation/extracellular secretion and alleviated HMGB1-mediated activation of the NF-κB pathway following TBI-induced microglial activation, thus inhibiting the subsequent inflammatory response. CONCLUSIONS: The results of this study suggest that ω-3 PUFA supplementation attenuates the inflammatory response by modulating microglial polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury.

KLF16 suppresses human glioma cell proliferation and tumourigenicity by targeting TFAM.

BACKGROUND: This study aims to via unveiling the novel mechanisms of KLF16 in regulating expression of genes involved in glioma. METHODS: KLF16 or KLF16-siRNA was transfected to U87MG cells by lentivirus. Colony formation assay was applied for detecting cell proliferation. MTT assay was adopted to assess cell viability. TUNEL assay was selected to evaluate cell apoptosis. Flow cytometry was used to determine cell cycle. Real-time PCR was performed to test mRNA expression. Western blot was used to detect protein level. Luciferase assay was applied to confirm the regulatory relationship between KLF16 and Mitochondrial transcription factor A (TFAM). Chromatin immunoprecipitation was adopted to test the protein binding site. The nude mouse transplantation tumour experiment was selected to test cancer cell proliferation in vivo. RESULTS: KLF16 was decreased in glioma cells and tissues. KLF16 obviously restrained U87MG cell proliferation both in vivo and in vitro. KLF16 transfection reduced mRNA and protein levels related to cell proliferation. KLF16 targeted a putative binding site near the transcription start sites (TSSs) of TFAM gene, thus suppressing glioma cell proliferation. KLF16-siRNA exhibited the opposite impact. KLF16 presented significant negative correlation with TFAM level in glioma patients. CONCLUSIONS: KLF16 is a key regulator of glioma cell proliferation by directly targeting TFAM.

Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury.

BACKGROUND: Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. METHODS: The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. RESULTS: It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1ß, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological functions after TBI. We further demonstrated that ω-3 PUFA supplementation inhibited HMGB1 nuclear translocation and secretion and decreased expression of HMGB1 in neurons and microglia in the lesioned areas. Moreover, ω-3 PUFA supplementation inhibited microglial activation and the subsequent inflammatory response by regulating HMGB1 and the TLR4/NF-κB signaling pathway. CONCLUSIONS: The results of this study suggest that microglial activation and the subsequent neuroinflammatory response as well as the related HMGB1/TLR4/NF-κB signaling pathway play essential roles in secondary injury after TBI. Furthermore, ω-3 PUFA supplementation inhibited TBI-induced microglial activation and the subsequent inflammatory response by regulating HMGB1 nuclear translocation and secretion and also HMGB1-mediated activation of the TLR4/NF-κB signaling pathway, leading to neuroprotective effects.

Performance of remote target pointing hand movements in a 3D environment.

In this study, we investigated and modeled the performance of target pointing hand movements in a hand free, touchless 3D environment. The targets had different positions, sizes and distances. Performance measurements included total movement time and movement trajectories. The total movement time consisted of a "primary submovement time" and a "secondary submovement time". Results indicated that the total movement time for targets with depth in the upper part of the spherical framework (3.10s) was shorter than for targets without depth (3.79s). The time for targets without depth in the lower part of the spherical framework (2.94s) was shorter than for targets with depth (3.57s). Within a 3D perspective display, the perception of distance and size depends on its depth position. Our results confirmed the adequacy of the 3D information in the display by showing the longest total movement time was observed for the reach of the "forward" target (3.94s). Fitts' model explained the total movement time (for targets without depth r(2)=.72; for targets with depth r(2)=.72). This study showed that participants navigated the 3D space naturally and could move the cursor using both sequential a axis moving strategy and a straight line moving strategy. Real-life applications of the proposed method include interface design for 3D perspective displays and hand movements in 3D environments.