The effect of target detection on memory retrieval.

Attention and memory are fundamental cognitive processes that closely interact. In the attentional boost effect (ABE), the stimuli that co-occur with targets are remembered better than those that co-occur with distractors in target detection tasks performed during memory encoding. In target detection tasks performed during retrieval, the stimuli that co-occur with targets are recognized as 'old' more easily than the stimuli that co-occur with distractors. This study mainly explored the internal mechanism of the effect of target detection on recognition. In Experiment 1, the full attention (FA; where participants performed only the memory task) condition was used to compare with divided attention (DA; where participants performed target detection while performing memory retrieval) condition to explore the impact of target detection and distraction inhibition on recognition. In Experiment 2, the proportion of old and new words in the retrieval stage was adjusted to 1:1 to eliminate the possible reaction tendency caused by the high proportion of old words. In Experiment 3, the presentation time of words was extended to 1.5 s and 3 s to eliminate the possible impact of rapid processing. The results indicated that the effect of target detection on recognition was attributed to both target detection and distraction rejection and is not affected by the ratio of old and new words and the word presentation time. The effect of target detection on recognition may be owing to temporal yoking of the dual tasks, which is different from the effect of target detection on memory encoding.

Assessment of impaired consciousness using EEG-based connectivity features and convolutional neural networks.

Growing electroencephalogram (EEG) studies have linked the abnormities of functional brain networks with disorders of consciousness (DOC). However, due to network data's high-dimensional and non-Euclidean properties, it is difficult to exploit the brain connectivity information that can effectively detect the consciousness levels of DOC patients via deep learning. To take maximum advantage of network information in assessing impaired consciousness, we utilized the functional connectivity with convolutional neural network (CNN) and employed three rearrangement schemes to improve the evaluation performance of brain networks. In addition, the gradient-weighted class activation mapping (Grad-CAM) was adopted to visualize the classification contributions of connections among different areas. We demonstrated that the classification performance was significantly enhanced by applying network rearrangement techniques compared to those obtained by the original connectivity matrix (with an accuracy of 75.0%). The highest classification accuracy (87.2%) was achieved by rearranging the alpha network based on the anatomical regions. The inter-region connections (i.e., frontal-parietal and frontal-occipital connectivity) played dominant roles in the classification of patients with different consciousness states. The effectiveness of functional connectivity in revealing individual differences in brain activity was further validated by the correlation between behavioral performance and connections among specific regions. These findings suggest that our proposed assessment model could detect the residual consciousness of patients.

Aberrant temporal correlations of ongoing oscillations in disorders of consciousness on multiple time scales.

Changes in neural oscillation amplitude across states of consciousness has been widely reported, but little is known about the link between temporal dynamics of these oscillations on different time scales and consciousness levels. To address this question, we analyzed amplitude fluctuation of the oscillations extracted from spontaneous resting-state EEG recorded from the patients with disorders of consciousness (DOC) and healthy controls. Detrended fluctuation analysis (DFA) and measures of life-time and waiting-time were employed to characterize the temporal structure of EEG oscillations on long time scales (1-20 s) and short time scales (< 1 s), in groups with different consciousness states: patients in minimally conscious state (MCS), patients with unresponsive wakefulness syndrome (UWS) and healthy subjects. Results revealed increased DFA exponents that implies higher long-range temporal correlations (LRTC), especially in the central brain area in alpha and beta bands. On short time scales, declined bursts of oscillations were also observed. All the metrics exhibited lower individual variability in the UWS or MCS group, which may be attributed to the reduced spatial variability of oscillation dynamics. In addition, the temporal dynamics of EEG oscillations showed significant correlations with the behavioral responsiveness of patients. In summary, our findings shows that loss of consciousness is accompanied by alternation of temporal structure in neural oscillations on multiple time scales, and thus may help uncover the mechanism of underlying neuronal correlates of consciousness. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09852-9.

Disrupted Control Architecture of Brain Network in Disorder of Consciousness.

The human brain controls various cognitive functions via the functional coordination of multiple brain regions in an efficient and robust way. However, the relationship between consciousness state and the control mode of brain networks is poorly explored. Using multi-channel EEG, the present study aimed to characterize the abnormal control architecture of functional brain networks in the patients with disorders of consciousness (DOC). Resting state EEG data were collected from 40 DOC patients with different consciousness levels and 24 healthy subjects. Functional brain networks were constructed in five different EEG frequency bands and the broadband in the source level. Subsequently, a control architecture framework based on the minimum dominating set was applied to investigate the of control mode of functional brain networks for the subjects with different conscious states. Results showed that regardless of the consciousness levels, the functional networks of human brain operate in a distributed and overlapping control architecture different from that of random networks. Compared to the healthy controls, the patients have a higher control cost manifested by more minimum dominating nodes and increased degree of distributed control, especially in the alpha band. The ability to withstand network attack for the control architecture is positive correlated with the consciousness levels. The distributed of control increased correlation levels with Coma Recovery Scale-Revised score and improved separation between unresponsive wakefulness syndrome and minimal consciousness state. These findings may benefit our understanding of consciousness and provide potential biomarkers for the assessment of consciousness levels.

Quality of life and related factors in adult patients with epilepsy in China.

OBJECTIVE: The objective of this work was to study the quality of life (QOL) of adult patients with epilepsy in northern China. METHODS: Three hundred three adult patients with epilepsy were identified using a strict procedure of diagnosis at the outpatient clinic of the epilepsy center, and then their QOL was evaluated with the Chinese version of the Quality of Life in Epilepsy Inventory-89. RESULTS: QOLIE-89 total score and many of the subscale scores were decreased. The greatest decreases were observed in the Seizure Worry and Medication Effects subscale scores. QOLIE-89 total scores of married patients (57.1±15.3) were lower than those of unmarried patients (70.9±15.7) (P<0.001). Correlation analysis revealed that QOLIE-89 total score was negatively correlated with age, course of disease, seizure severity, antiepileptic drug, type of seizure, and seizure frequency (r=-0.334, -0.281, -0.424, -0.117, -0.145, and -0.274 respectively, P<0.01), and was positively correlated with educational level and economic status (r=0.245 and 0.328 respectively, P<0.01). Multiregression analysis revealed that five factors entered the regression equation: age (ß=-0.545, P=0.001), course of disease (ß=-0.311, P=0.001), seizure severity (ß=-10.014, P=0.001), educational level (ß=3.274, P=0.002), and economic status (ß=6.431, P=0.001). CONCLUSION: Quality of life of adult patients with epilepsy decreases with older age, more difficult course of disease, and higher seizure frequency. Higher educational level and economic status are protective factors in the QOL of adult patients.

Altered inter-frequency dynamics of brain networks in disorder of consciousness.

OBJECTIVE: Growing evidence have linked disorders of consciousness (DOC) with the changes in frequency-specific functional networks. However, the alteration of inter-frequency dynamics in brain networks remain largely unknown. In this study, we investigated the network integration and segregation across frequency bands in a multiplex network framework. APPROACH: Resting-state EEG data were recorded and analysed from 19 patients in minimally conscious state, 35 patients in unresponsive wakefulness syndrome (UWS) and 23 healthy controls. Frequency-based multiplex (cross-frequency) networks were reconstructed by integrating the five frequency-specific networks. Multiplex graph metrics, named multiplex participation coefficient and multiplex clustering coefficient, were employed to assess the network topology of subjects with different levels of consciousness. MAIN RESULTS: Results revealed DOC networks, compared to those of healthy controls, may work at a less optimal point (closer to complete disorder) with increased integration and decreased segregation considering inter-frequency dynamics. Both metrics show increased spatial and temporal variability with the consciousness levels. Moreover, significant correlation can be found between the alteration of cross-frequency networks in DOC patients and their behavioural performance at both local and global scales. SIGNIFICANCE: These findings may contribute to the development of EEG network study and benefit our understanding of the processes of consciousness and their pathophysiology for DOC.

Characterization of network switching in disorder of consciousness at multiple time scales.

OBJECTIVE: Recent works have shown that flexible information processing is closely related to the reconfiguration of human brain networks underlying brain functions. However, the role of network switching for consciousness is poorly explored and whether such transition can indicate the behavioral performance of patients with disorders of consciousness (DOC) remains unknown. Here, we investigate the relationship between the switching of brain networks (states) over time and the consciousness levels. APPROACH: By applying multilayer network methods, we calculated time-resolved functional connectivity from source-level EEG data in different frequency bands. At various time scales, we explored how the human brain changes its community structure and traverses across defined network states (integrated and segregated states) in subjects with different consciousness levels. MAIN RESULTS: Network switching in the human brain is decreased with increasing time scale opposite to that in random systems. Transitions of community assignment (denoted by flexibility) are negatively correlated with the consciousness levels (particularly in the alpha band) at short time scales. At long time scales, the opposite trend is found. Compared to healthy controls, patients show a new balance between dynamic segregation and integration, with decreased proportion and mean duration of segregated state (contrary to those of integrated state) at small scales. SIGNIFICANCE: These findings may contribute to the development of EEG-based network analysis and shed new light on the pathological mechanisms of neurological disorders like DOC.

Optical Depolarization of DCX-Expressing Cells Promoted Cognitive Recovery and Maturation of Newborn Neurons via the Wnt/ß-Catenin Pathway.

Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI). C57BL/6 mice underwent lateral fluid percussion TBI. TBI mice were transfected with a lentivirus carrying the DCX-ChR2-EGFP gene. We observed that not only immature neurons but also type-2b intermediate progenitor (IPs) and neuroblasts expressed DCX-EGFP, indicating that DCX-expressing newborn cells could provide a long time window for electrical activity regulation. Quantitative results showed that the number of EGFP-expressing cells began to rise at 3 days after TBI and peaked at 9 days after TBI. By optical depolarization of DCX-EGFP-expressing cells between 3 and 12 days, we observed significantly improved cognitive deficits after TBI with enhanced survival and maturation of newborn cells in the dentate gyrus. We also investigated the role of optical depolarization in neural stem cells transfected with a lentivirus carrying the ChR2-DCX-EGFP gene in vitro. By administrating verapamil to block L-type calcium channels, we verified that the up-regulation of MAP2, NeuN, Neurog2, NeuroD1 and GluR2 in newborn cells was mediated by ChR2-elicted depolarization. By using ß-catenin inhibitor Dkk1, we demonstrated that optical depolarization of DCX-EGFP-expressing cells facilitated survival and maturation probably through the Wnt/ß-catenin signaling cascade.

[Effects of ethyl pyruvate on splenocyte proliferation and apoptosis in burn rats with delayed resuscitation].

OBJECTIVE: To investigate the effects of ethyl pyruvate (EP) on splenocyte proliferation and apoptosis in burn rats with delayed resuscitation, and its potential underlying mechanism. METHODS: Seventy two male Wistar rats were randomly divided into sham-scalded control group (n=24), scald group (n=24), and scald with EP treatment group (n=24). Animals were sacrificed on days 1, 3, and 5 postburn, and spleen samples were collected to determine splenocyte proliferation and apoptosis. RESULTS: Splenic lymphocyte proliferation response to T cell mitogen, concanavalin A (Con A), as significantly depressed from 1 to 5 days after burn injury (all P<0.05). Meanwhile, burn injury resulted in a marked increase in splenic CD3(+)CD4(+)T lymphocyte apoptosis in comparison with that in sham-scalded controls on day 1 postburn (P<0.05). Treatment with EP after burns resulted in a dramatic restoration of lymphocyte proliferation response and reduction of splenic CD3(+)CD4(+)T lymphocyte apoptosis compared with scald group (P<0.05). CONCLUSION: Administration of EP can markedly improve the splenocyte proliferation response and inhibit splenic CD3(+)CD4(+)T lymphocyte apoptosis in thermally injured rats.

[Effects of ethyl pyruvate on cell-mediated immune function in rats with delayed resuscitation after burn injury].

OBJECTIVE: To investigate the effects of ethyl pyruvate (EP) on cell-mediated immune function in rats with delayed resuscitation after burn injury, and its potential regulatory mechanism. METHODS: Wistar rats were subjected to 30% full-thickness scald injury with delayed resuscitation. One hundred and three male rats were randomly divided into normal controls (n=7), sham scald group (n=32), scald group (n=32) in which 40 ml/kg normal saline was infused peritoneally 6 hours after scald, and EP treatment group (n=32) in which 40 mg/kg EP was injected peritoneally 6 hours after scald. Animals were sacrificed on postburn day 1, 3, 5, and 7, and spleen was collected to determine splenocyte proliferation, IL-2 production and cell-surface IL-2 receptor (IL-2R) expression. RESULTS: Splenic lymphocyte proliferation responses to T cell mitogen, concanavalin A (Con A), were depressed from 1 to 7 days after scald injury (all P<0.05). Meanwhile, in comparison with sham scald group, burn injury resulted in a significant decrease in splenic production of IL-2 on postburn day 1, 3, as well as 5, and a marked suppression of IL-2R expression on days 1 and 3 postburn (all P<0.05). Treatment with EP after burn injury showed a dramatic restoration of lymphocyte proliferation rate and increased production of IL-2 at various time points (all P<0.05). However, treatment with EP did not affect IL-2R expression compared with scalded rats (all P>0.05). CONCLUSION: Treatment with EP could markedly elevate splenic T lymphocyte proliferation response and increase production of IL-2 following burn injury, thereby improving cell-mediated immunity in thermally injured rats with delayed resuscitation.

[High mobility group box-1 protein activates Janus kinase-signal transducer and activator of transcription pathway in rat peritoneal macrophages].

OBJECTIVE: To investigate the potential signal transduction mechanism in high mobility group box-1 protein (HMGB1)-induced inflammatory response in rat peritoneal macrophages. METHODS: Peritoneal macrophages obtained from male Wistar rats were incubated for 3 days before they were stimulated by HMGB1 (10 microg/ml). At various time points after HMGB1 stimulation, macrophages were denatured directly in cell culture flasks to detect activation of Janus kinase-2 (JAK2), signal transducer and activator of transcription-1 (STAT1) and STAT3 by immunoprecipitation, Western blotting and electrophoretic mobility shift assay, respectively. RESULTS: HMGB1 stimulation could activate STAT1 and STAT3 in peritoneal macrophages in 2 hours, among them the activation of STAT3 appeared to be the quickest, peaking as early as 10 minutes after stimulation. But no marked change in JAK2 activity was observed within 2 hours following HMGB1 stimulation. CONCLUSION: These data suggest that Janus kinase-signal transducer and activator of transcription pathway might be involved in regulation of HMGB1-induced inflammatory response in peritoneal macrophages.

Relationship between high-mobility group box 1 protein release and T-cell suppression in rats after thermal injury.

To study whether high-mobility group box 1 protein (HMGB1) has an effect on T-cell-mediated immunity secondary to burn injury, 96 male Wistar rats weighing 250 to 300 g were randomly divided into three groups as follows:sham burn group, burn group, and burn with ethyl pyruvate treatment group, and they were killed on postburn days (PBDs)1, 3, 5, and 7, respectively, with 8 animals at each time point. Columns of nylon wool were used to isolate splenic T cells. T-Cell proliferation was analyzed with thiazolyl blue and expression of IL-2 receptor alpha (IL-2Ralpha) on the surface of T cell with flow cytometry. Levels of HMGB1 were determined using Western blot analysis. IL-2, soluble IL-2R, IL-4, and interferon-gamma were determined with enzyme-linked immunosorbent assay kits. Gene expressions of HMGB1, IL-2, and IL-2R were assessed using reverse-transcription polymerase chain reaction, and activation of nuclear factor of activated T cell was determined with gel mobility shift assay. The levels of HMGB1 in plasma were significantly elevated on PBDs 1 to 5. Significant proliferation of splenic T cells and IL-2, as well as IL-2Ralpha expression on T cells, were simultaneously suppressed to a certain extent on PBDs 1 to 7. Nuclear factor of activated T-cell activity of splenic T cells was markedly down-regulated on PBDs 1 to 3. Administration of ethyl pyruvate to inhibit HMGB1 can significantly restore proliferative activity, nuclear factor of activated T-cell activity, and expression levels of IL-2 and IL-2Ralpha on T cells. High-mobility group box 1 protein released after major burns might be associated with the pathogenesis of immunosuppression in splenic T lymphocytes in rats.

[The role of Janus kinase-signal transducer and transcription activator pathway in the regulation of synthesis and release of lipopolysaccharide-induced high mobility group box-1 protein].

OBJECTIVE: To investigate the role of Janus kinase-signal transducer and transcription activator (JAK-STAT) pathway in the regulation of synthesis and release of lipopolysaccharide-induced high mobility group box-1 protein (HMGB1). METHODS: Peritoneal macrophages harvested from male Wistar rats were incubated for 3 days before the experiment. The activation of Janus kinase-2 (JAK2), signal transducer and activator of transcription-1 (STAT1) and STAT3 was observed before and 10, 30, 60 and 120 mins after LPS stimulation (4 determinations at each time point) and it was expressed as A value (absorption). In addition, the cells were divided into normal control, LPS stimulation, JAK2 inhibition (with AG490 treatment 2 hours before LPS stimulation), STAT1 inhibition (with fludarabine treatment 2 hours before LPS stimulation) and STAT3 inhibition (with rapamycin treatment 2 hours before LPS stimulation) groups. The cells in all groups except control group were stimulated with LPS 3 days after culture. The expression of HMGB1 gene and its protein release in each group were determined for 4 times and were expressed as A value. RESULTS: LPS could activate JAK2, STAT1 and STAT3 within 2 hours, especially the activation of STAT3 appeared more quickly, peaking at 10 minutes after LPS stimulation (7.47 +/- 0.56). Pretreatment with the inhibitors of JAK-STAT pathway could markedly reduce the expression of HMGB1 mRNA (P < 0.01), but exerted no effect on HMGB1 release. CONCLUSION: JAK-STAT pathway can be activated early during endotoxin challenge, and it may play a role in the regulation of HMGB1 synthesis.