Memory deficit in patients with cerebral small vessel disease: evidence from eye tracking technology.

Cerebral small vessel disease is the one of the most prevalent causes of vascular cognitive impairment. We aimed to find objective and process-based indicators related to memory function to assist in the detection of memory impairment in patients with cerebral small vessel disease. Thirty-nine cerebral small vessel disease patients and 22 healthy controls were invited to complete neurological examinations, neuropsychological assessments, and eye tracking tasks. Eye tracking indicators were recorded and analyzed in combination with imaging features. The cerebral small vessel disease patients scored lower on traditional memory task and performed worse on eye tracking memory task performance compared to the healthy controls. The cerebral small vessel disease patients exhibited longer visit duration and more visit count within areas of interest and targets and decreased percentage value of total visit duration on target images to total visit duration on areas of interest during decoding stage among all levels. Our results demonstrated the cerebral small vessel disease patients performed worse in memory scale and eye tracking memory task, potentially due to their heightened attentional allocation to nontarget images during the retrieval stage. The eye tracking memory task could provide process-based indicators to be a beneficial complement to memory assessment and new insights into mechanism of memory impairment in cerebral small vessel disease patients.

Features of attention network impairment in patients with temporal lobe epilepsy: Evidence from eye-tracking and electroencephalogram.

AIM: To explore multiple features of attention impairments in patients with temporal lobe epilepsy (TLE). METHODS: A total of 93 patients diagnosed with TLE at Xiangya Hospital during May 2022 and December 2022 and 85 healthy controls were included in this study. Participants were asked to complete neuropsychological scales and attention network test (ANT) with recording of eye-tracking and electroencephalogram. RESULTS: All means of evaluation showed impaired attention functions in TLE patients. ANT results showed impaired orienting (p < 0.001) and executive control (p = 0.041) networks. Longer mean first saccade time (p = 0.046) and more total saccadic counts (p = 0.035) were found in eye-tracking results, indicating abnormal alerting and orienting networks. Both alerting, orienting and executive control networks were abnormal, manifesting as decreased amplitudes (N1 & P3, p < 0.001) and extended latency (P3, p = 0.002). The energy of theta, alpha and beta were all sensitive to the changes of alerting and executive control network with time, but only beta power was sensitive to the changes of orienting network. CONCLUSION: Our findings are helpful for early identification of patients with TLE combined with attention impairments, which have strong clinical guiding significance for long-term monitoring and intervention.

Event-related potentials reveal visual episodic memory deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) patients usually suffer from impaired episodic memory (EM), but its underlying electrophysiologic mechanism and impacted cognitive performance are unclear. We aim to investigate the association between episodic memory reserve and physiological measures of memory workload in TLE patients using Event-related potentials (ERP). METHODS: A change detection task with image stimuli assesses visual episodic memory. During the memory encoding and decoding phases, the ERP signals were analyzed from twenty-nine TLE patients (twelve with left TLE patients, seventeen with TLE), and thirty healthy controls. Given that EM is a complex process involving many fundamental cognitive processes, the amplitudes and latencies of EM-related ERP (FN400, late positive potential (LPC), and late posterior negativity (LPN)), and the ERP reflecting the fundamental processes (P100, N100, P200, and P300) were calculated. Then we used a three-by-two factorial design on the ERP metrics for interaction and main effects. The correlation analysis among Wechsler Memory Scales-Chinese Revision (WMS-RC) results, behavioral data, and the ERPs was carried out. RESULTS: The TLE patients performed worse in WMS-RC and the memory task. The increased P200 and decreased P300 amplitudes were observed in the TLE patients, and LPN was abnormal in only LTLE patients. For EM-related components, differences were observed in both the LTLE and RTLE patients: the lack of the FN400 effect, the lack of the reversed LPC effect, and the reduced FN400. No significant inter-group difference was detected for the latencies of all the ERPs. Additionally, there were significant correlations among WMS-RC scores, behaviors, and some ERP amplitudes. CONCLUSIONS: The impaired EM is linked to the increased P200 and decreased P300 amplitudes. LPN seems to be sensitive to left temporal lobe dysfunction. More importantly, the abnormal old or new effects of the FN400 and LPC, and the reduced FN400 amplitude might be associated with the visual EM deficit in the TLE patients. These findings may assist in the deep understanding of the EM disorder and the evaluation of the side effects of antiepileptic drugs.

Validity and reliability of the Chinese version of the epilepsy stigma scale.

OBJECTIVE: This study was conducted to test the validity and reliability of the Chinese version of the epilepsy stigma scale (ESS), which aims to better understand the stigma of patients with epilepsy (PWEs), lays the foundation for future investigation and explores appropriate strategies to mitigate PWEs' stigma in Chinese culture. METHODS: The scale was translated following standard procedures. For psychometric validation, the Chinese version of the ESS was administered to 214 PWEs above the age of 16 who were diagnosed with epilepsy by two trained epileptologists and were taking anti-seizure drugs for at least a month. All of the patients were recruited from Xiangya Hospital of Central South University of China from August 2021 to September 2021. RESULTS: The Cronbach's alpha coefficient was 0.893 for the entire scale, 0.903 for felt stigma, and 0.688 for enacted stigma. Exploratory and confirmatory factor analyses were conducted and showed that the scale was grouped under two dimensions, and the results of confirmatory factor analysis support the structure. CONCLUSION: The Chinese version of the ESS is a valid and reliable tool to assess epilepsy-related stigma in Chinese culture.

Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase.

4-Hydroxylphenylpyruvate dioxygenase (HPPD) catalyzes the conversion of 4-hydroxylphenylpyruvate (HPP) to homogentisate, the important step for tyrosine catabolism. Comparison of the structure of human HPPD with the substrate-bound structure of A. thaliana HPPD revealed notably different orientations of the C-terminal helix. This helix performed as a closed conformation in human enzyme. Simulation revealed a different substrate-binding mode in which the carboxyl group of HPP interacted by a H-bond network formed by Gln334, Glu349 (the metal-binding ligand), and Asn363 (in the C-terminal helix). The 4-hydroxyl group of HPP interacted with Gln251 and Gln265. The relative activity and substrate-binding affinity were preserved for the Q334A mutant, implying the alternative role of Asn363 for HPP binding and catalysis. The reduction in kcat/Km of the Asn363 mutants confirmed the critical role in catalysis. Compared to the N363A mutant, the dramatic reduction in the Kd and thermal stability of the N363D mutant implies the side-chain effect in the hinge region rotation of the C-terminal helix. The activity and binding affinity were not recovered by double mutation; however, the 4-hydroxyphenylacetate intermediate formation by the uncoupled reaction of Q334N/N363Q and Q334A/N363D mutants indicated the importance of the H-bond network in the electrophilic reaction. These results highlight the functional role of the H-bond network in a closed conformation of the C-terminal helix to stabilize the bound substrate. The extremely low activity and reduction in Q251E's Kd suggest that interaction coupled with the H-bond network is crucial to locate the substrate for nucleophilic reaction.

Novel PHOX2B germline mutation in childhood medulloblastoma: a case report.

BACKGROUND: Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported. CASE PRESENTATION: We present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening. CONCLUSIONS: This case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.

Distinct fine-root responses to precipitation changes in herbaceous and woody plants: a meta-analysis.

Precipitation is one of the most important factors that determine productivity of terrestrial ecosystems. Precipitation across the globe is predicted to change more intensively under future climate change scenarios, but the resulting impact on plant roots remains unclear. Based on 154 observations from experiments in which precipitation was manipulated in the field and root biomass was measured, we investigated responses in fine-root biomass of herbaceous and woody plants to alterations in precipitation. We found that root biomass of herbaceous and woody plants responded differently to precipitation change. In particular, precipitation increase consistently enhanced fine-root biomass of woody plants but had variable effects on herb roots in arid and semi-arid ecosystems. In contrast, precipitation decrease reduced root biomass of herbaceous plants but not woody plants. In addition, with precipitation alteration, the magnitude of root responses was greater in dry areas than in wet areas. Together, these results indicate that herbaceous and woody plants have different rooting strategies to cope with altered precipitation regimes, particularly in water-limited ecosystems. These findings suggest that root responses to precipitation change may critically influence root productivity and soil carbon dynamics under future climate change scenarios.

Beyond resource limitation: an expanded test of the niche dimension hypothesis for multiple types of niche axes.

The niche dimension hypothesis predicts that more species can coexist given a greater number of niche axes along which they partition the environment. Although this hypothesis has been broadly supported by nutrient enrichment experiments, its applicability to other ecological factors, such as natural enemies and abiotic stresses, has not been vigorously tested. Here, we examined the generality of the niche dimension hypothesis by experimentally manipulating both resource and non-resource niche dimensions-nitrogen limitation, pathogens and low-temperature stress-in a Tibetan alpine meadow. We found that decreases in niche dimensions led to a significant reduction in species richness, consistent with results from nutrient addition studies. However, different niche variables uniquely affected the plant communities. While nitrogen had largest effects on both community biomass and species richness, pathogens and low-temperature stress, in combination with nitrogen, had synergistic effects on them. Our results provide direct evidence demonstrating that both resource and non-resource niche dimensions can influence species coexistence. These findings suggest that other non-resource factors need to be taken into consideration to better predict the community assembly and control over biodiversity, particularly under the future multifaceted global change scenarios.

Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network.

BACKGROUND: Long non-coding RNAs (lncRNAs) have previously been emerged as key players in a series of biological processes. Dysregulation of lncRNA is correlated to human diseases including neurological disorders. Here, we developed a multi-step bioinformatics analysis to study the functions of a particular Down syndrome-associated gene DSCR9 including the lncRNAs. The method is named correlation-interaction-network (COIN), based on which a pipeline is implemented. Co-expression gene network analysis and biological network analysis results are presented. METHODS: We identified the regulation function of DSCR9, a lncRNA transcribed from the Down syndrome critical region (DSCR) of chromosome 21, by analyzing its co-expression genes from over 1700 sets and nearly 60,000 public Affymetrix human U133-Plus 2 transcriptional profiling microarrays. After proper evaluations, a threshold is chosen to filter the data and get satisfactory results. Microarray data resource is from EBI database and protein-protein interaction (PPI) network information is incorporated from the most complete network databases. PPI integration strategy guarantees complete information regarding DSCR9. Enrichment analysis is performed to identify significantly correlated pathways. RESULTS: We found that the most significant pathways associated with the top DSCR9 co-expressed genes were shown to be involved in neuro-active ligand-receptor interaction (GLP1R, HTR4, P2RX2, UCN3, and UTS2R), calcium signaling pathway (CACNA1F, CACNG4, HTR4, P2RX2, and SLC8A3), neuronal system (KCNJ5 and SYN1) by the KEGG, and GO analysis. The A549 and U251 cell lines with stable DSCR9 overexpression were constructed. We validated 10 DSCR9 co-expression genes by qPCR in both cell lines with over 70% accuracy. CONCLUSIONS: DSCR9 was highly correlated with genes that were known as important factors in the developments and functions of nervous system, indicating that DSCR9 may regulate neurological proteins regarding Down syndrome and other neurological-related diseases. The pipeline can be properly adjusted to other applications.

Wuhu Decoction Regulates Dendritic Cell Autophagy in the Treatment of Respiratory Syncytial Virus (RSV)-Induced Mouse Asthma by AMPK/ULK1 Signaling Pathway.

BACKGROUND Dendritic cell autophagy plays a pivotal role in asthma. Wuhu decoction can significantly improve respiratory syncytial virus (RSV) bronchiolitis and delay its development into asthma. The aim of the present study was to explore the therapeutic effect and mechanism of Wuhu decoction on RSV -induced asthma in mice. MATERIAL AND METHODS Establishment of asthmatic mice model was induced by RSV. Hematoxylin-eosin staining, periodic acid-Schiff (PAS) staining, and Masson trichrome staining were performed to observe pathological changes in the lungs. The levels of CD4⁺ T, CD8⁺ T, and CD4⁺ CD25⁺ T in blood were analyzed by flow cytometry. The contents of interleukin (IL)-4, interferon-gamma (IFN-γ), IL-10, and IL-13 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The number of autophagosomes in dendritic cells (DCs) of lung tissue was observed by transmission electron microscope. The DCs of lung tissue were isolated by magnetic bead sorting. The levels of LC3-II, Beclin-1, and LC3-I in DCs and MMP-9, TIMP-1, AMPK, p-AMPK, ULK1, and LK1 expression in lung tissues were detected by western blot. Real-time polymerase chain reaction (PCR) detected the expression of AMPK and ULK1 genes. RESULTS Wuhu decoction can effectively alleviate chronic airway inflammation and airway remodeling and reduce airway hyperresponsiveness. Moreover, Wuhu decoction can significantly enhance the level of autophagy in DCs of lung tissue and promote the expression of AMPK and ULK1 in lung tissue. CONCLUSIONS Wuhu decoction may improve the RSV-induced asthmatic symptoms by enhancing autophagy of DCs in lung tissue dependent on the AMPK/ULK1 signaling pathway.

Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Precipitation- rather than temperature-driven pattern in belowground biomass and root:shoot ratio across the Qinghai-Tibet Plateau.

The Qinghai-Tibet Plateau faces dramatic global change, which can greatly affect its plant growth, biomass accumulation, and carbon cycling. However, it is still unclear how belowground plant biomass, which is the major part of vegetation biomass on the plateau, changes with different environmental factors, impeding accurate prediction of ecosystem carbon cycling under future global change scenarios. To reveal the patterns of belowground biomass and root:shoot ratio with environmental factors in different vegetation types on the Qinghai-Tibet Plateau, we synthesized data for 158 sites from 167 publications, including 585 and 379 observations for above- and below-ground biomass, respectively. Data on temperature, precipitation, soil nitrogen content, evapotranspiration and solar radiation were collected from open databases. The results showed that precipitation, rather than temperature, was closely associated with other environmental factors including soil N and solar radiation. Also, both above- and below-ground biomass significantly increased with annual precipitation and its related environmental factors, while elevation-related coldness only slightly decreased aboveground biomass. In addition, the positive effect of precipitation on belowground biomass is more obvious in higher elevations (colder areas). As a result, root:shoot ratio significantly increased with precipitation in colder areas but not in warmer areas. Finally, the positive relationship between biomass and precipitation was stronger for dryer steppes than for wetter meadows and shrublands. Our findings indicate that precipitation, as well as the associated nitrogen availability and solar radiation, together are more important drivers than temperature for ecosystem productivity and biomass allocation on the Qinghai-Tibet Plateau. Given the heterogeneous trend of precipitation change on the plateau, productivity response to global change can be highly variable across different regions and vegetation types, which can consequently impact soil carbon dynamics and regional carbon cycling.

Effects of a Nurse-Led Cognitive Behavioral Intervention for Parents of Children With Epilepsy.

BACKGROUND: This study aimed to evaluate the effects of a nurse-led cognitive behavioral intervention for parents of children with epilepsy (CWE). METHODS: The study recruited 238 CWE from the neurology ward of Xiangya Hospital from March 2019 to August 2022. According to the interventions after discharge, the children and their parents were randomly divided into 117 parent-child dyads in the intervention group and 121 parent-child dyads in the control group. The seizure severity and treatment compliance in CWE as well as the parents' psychological states and satisfaction with the care provided by nurses were compared before and after intervention. RESULTS: The follow-up six months after discharge showed that the seizure frequency among CWE in the intervention group was significantly less than the controls (P = 0.048). Compared with the controls, the intervention group also reported fewer symptoms of anxiety and depression, better sleep quality, and more positive attitudes toward epilepsy, as well as higher nursing satisfaction (P < 0.001). The correlation analysis indicated the correlation of CWE's seizure severity was correlated with the compliance, parents' psychological states, and parents' satisfaction with the care provided by nurses. CONCLUSIONS: The adoption of the nurse-led cognitive behavioral intervention on parents of CWE can improve the parents' mental health status and their satisfaction with the nurses, which can have a positive association with the seizure severity of CWE. In light of this information, this nursing intervention may be a new method for the long-term disease management of CWE.

Reduced eye gaze fixation during emotion recognition among patients with temporal lobe epilepsy.

OBJECTIVES: To investigate the facial scan patterns during emotion recognition (ER) through the dynamic facial expression task and the awareness of social interference test (TASIT) using eye tracking (ET) technology, and to find some ET indicators that can accurately depict the ER process, which is a beneficial supplement to existing ER assessment tools. METHOD: Ninety-six patients with TLE and 88 healthy controls (HCs) were recruited. All participants watched the dynamic facial expression task and TASIT including a synchronized eye movement recording and recognized the emotion (anger, disgust, happiness, or sadness). The accuracy of ER was recorded. The first fixation time, first fixation duration, dwell time, and fixation count were selected and analyzed. RESULTS: TLE patients exhibited ER impairment especially for disgust (Z = - 3.391; p = 0.001) and sadness (Z = - 3.145; p = 0.002). TLE patients fixated less on the face, as evidenced by the reduced fixation count (Z = - 2.549; p = 0.011) of the face and a significant decrease in the fixation count rate (Z = - 1.993; p = 0.046). During the dynamic facial expression task, TLE patients focused less on the eyes, as evidenced by the decreased first fixation duration (Z = - 4.322; p = 0.000), dwell time (Z = - 4.083; p = 0.000), and fixation count (Z = - 3.699; p = 0.000) of the eyes. CONCLUSION: TLE patients had ER impairment, especially regarding negative emotions, which may be attributable to their reduced fixation on the eyes during ER, and the increased fixation on the mouth could be a compensatory effect to improve ER performance. Eye-tracking technology could provide the process indicators of ER, and is a valuable supplement to traditional ER assessment tasks.

Why are graminoid species more dominant? Trait-mediated plant-soil feedbacks shape community composition.

Species traits may determine plant interactions along with soil microbiome, further shaping plant-soil feedbacks (PSFs). However, how plant traits modulate PSFs and, consequently, the dominance of plant functional groups remains unclear. We used a combination of field surveys and a two-phase PSF experiment to investigate whether forbs and graminoids differed in PSFs and in their trait-PSF associations. When grown in forb-conditioned soils, forbs experienced stronger negative feedbacks, while graminoids experienced positive feedbacks. Graminoid-conditioned soil resulted in neutral PSFs for both functional types. Forbs with thin roots and small seeds showed more-negative PSFs than those with thick roots and large seeds. Conversely, graminoids with acquisitive root and leaf traits (i.e., thin roots and thin leaves) demonstrated greater positive PSFs than graminoids with thick roots and tough leaves. By distinguishing overall and soil biota-mediated PSFs, we found that the associations between plant traits and PSFs within both functional groups were mainly mediated by soil biota. A simulation model demonstrated that such differences in PSFs could lead to a dominance of graminoids over forbs in natural plant communities, which might explain why graminoids dominate in grasslands. Our study provides new insights into the differentiation and adaptation of plant life-history strategies under selection pressures imposed by soil biota.

Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease.

Excessive hepatic lipid droplets (LDs) accumulation-induced lipid metabolism disorder contributes to the development of non-alcoholic fatty liver disease (NAFLD). Exercise is a promising therapeutic strategy for NAFLD. However, the mechanism by which exercise ameliorates NAFLD through regulating the catabolism of hepatic LDs remains unclear. In the present study, we investigated the effect of perilipin2 (PLIN2)-lysosomal acid lipase (LIPA) axis mediating exercise-triggered lipophagy in a high-fat diet (HFD)-induced NAFLD mouse model. Our results showed that exercise could reduce HFD-induced hepatic LDs accumulation and change the expression of lipolysis-related enzymes. Moreover, exercise upregulated the expression of microtubule associated protein 1 light chain 3 (LC3) and autophagy-related proteins, and downregulated sequestosome 1 (P62) expression and promoted autophagosomes formation. Interestingly, exercise downregulated PLIN2 expression, upregulated LIPA expression, and increased the activity of hepatic LIPA and serum levels of LIPA in the NAFLD mouse model. Further mechanistic studies demonstrated that adenosine monophosphate-activated protein kinase (AMPK) activator-5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) treatment significantly increased mRNA levels and protein expression of LIPA and LC3II and decreased levels of PLIN2 and P62 in palmitic acid (PA)-treated HepG2 cells. PLIN2 silencing and LIPA overexpression notably increased the mRNA level and protein expression of LC3II and decreased the mRNA level and protein expression of p62, respectively. In summary, our findings reveal novel insights into the effect of exercise on improving lipid droplet metabolism disorder in NAFLD. Enhancing the PLIN2-LIPA axis-mediated lipophagy may be one of the key mechanisms involved in NAFLD alleviation by exercise.

Impaired orienting function detected through eye movements in patients with temporal lobe epilepsy.

Objective: Patients with temporal lobe epilepsy (TLE) often exhibit attention function impairment. The orienting network is the subsystem of the attention network that has not been fully studied. In this study, we used eye-tracking technology with an attention network test (ANT)-based task to assess the orienting function of TLE patients, aiming to characterize their eye movement patterns. Methods: A total of 37 TLE patients and 29 healthy controls (HCs) completed the ANT task based on eye-tracking technology. Orienting function damage was mainly assessed by the ANT orienting effect. Eye movement metrics, such as mean first goal-directed saccade latency (MGSL), total saccades, and saccade amplitudes, were compared between groups. Results: The TLE patients had a significantly lower ANT orienting effect (HC, 54.05 ± 34.05; TLE, 32.29 ± 39.54) and lower eye-tracking orienting effect (HC, 116.98 ± 56.59; TLE, 86.72 ± 59.10) than those of the HCs. The larger orienting effects indicate that orienting responses are faster when receiving a spatial cue compared with a center cue. In the spatial cue condition, compared with HCs, the TLE group showed a longer first goal-directed saccade latency (HC, 76.77 ± 58.87 ms; TLE, 115.14 ± 59.15 ms), more total saccades (HC, 28.46 ± 12.30; TLE, 36.69 ± 15.13), and larger saccade amplitudes (HC, 0.75° ± 0.60°; TLE, 1.36° ± 0.89°). Furthermore, there was a positive correlation of the orienting-effect score between the ANT task and eye-tracking metrics (r = 0.58, p < 0.05). Conclusion: We innovatively developed a new detection method using eye-tracking technology in combination with an ANT-based task to detect the orienting function in TLE patients. The current research demonstrated that TLE patients had a significant orienting dysfunction with a specific saccade pattern characterized by a longer first goal-directed saccade latency, more total saccades, and larger saccade amplitudes. These oculomotor metrics are likely to be a better indicator of orienting function and may potentially be used for behavioral-based interventions and long-term cognition monitoring in TLE patients.

Frontal lobe epilepsy: an eye tracking study of memory and attention.

Objective: To explore the characteristics and mechanisms of working memory impairment in patients with frontal lobe epilepsy (FLE) through a memory game paradigm combined with eye tracking technology. Method: We included 44 patients with FLE and 50 healthy controls (HC). All participants completed a series of neuropsychological scale assessments and a short-term memory game on an automated computer-based memory evaluation platform with an eye tracker. Results: Memory scale scores of FLE patients including digit span (U = 747.50, p = 0.007), visual recognition (U = 766.50, p = 0.010), and logical memory (U = 544.00, p < 0.001) were significantly lower than HC. The patients with FLE took longer to complete the four levels of difficulty of the short-term memory game than healthy controls (level 1: U = 2974.50, p = 0.000; level 2: U = 3060.50, p = 0.000; level 3: U = 2465.00, p = 0.000; level 4: U = 2199.00, p = 0.000). During the memory decoding period, first fixation on the targets took significantly longer for FLE patients for all difficulty levels compared to controls (level 1: U = 3407.00, p = 0.008; level 2: U = 3618.00, p = 0.036; level 3: U = 3345.00, p = 0.006; level 4: U = 2781.00, p = 0.000). The average fixation duration per target among patients with FLE was found to be significantly longer compared to HC (level 1: U = 2994.50, p = 0.000; level 2: U = 3101.00, p = 0.000; level 3: U = 2559.50, p = 0.000; level 4: U = 2184.50, p = 0.000). The total fixation duration on AOI/total completion time of FLE patients was significantly lower than those of HC for levels 1 to 3 (level 1: U = 1557.00, p = 0.000; level 2: U = 2333.00, p = 0.000; level 3: U = 2757.00, p = 0.000). Furthermore, the eye tracking data during the memory decoding phase were correlated with neuropsychological scale scores (p < 0.05). Conclusion: Patients with FLE exhibited short-term memory impairment probably due to deficits in attentional maintenance, especially during the memory decoding phase. Eye tracking technology provided the possibility to help separate and quantify visual attention from memory processing, contributing to exploring underlying mechanisms of memory impairment in FLE.

Effects of HAR1 on cognitive function in mice and the regulatory network of HAR1 determined by RNA sequencing and applied bioinformatics analysis.

Background: HAR1 is a 118-bp segment that lies in a pair of novel non-coding RNA genes. It shows a dramatic accelerated change with an estimated 18 substitutions in the human lineage since the human-chimpanzee ancestor, compared with the expected 0.27 substitutions based on the slow rate of change in this region in other amniotes. Mutations of HAR1 lead to a different HAR1 secondary structure in humans compared to that in chimpanzees. Methods: We cloned HAR1 into the EF-1α promoter vector to generate transgenic mice. Morris water maze tests and step-down passive avoidance tests were conducted to observe the changes in memory and cognitive abilities of mice. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) between the experimental and control groups. Systematic bioinformatics analysis was used to confirm the pathways and functions that the DEGs were involved in. Results: Memory and cognitive abilities of the transgenic mice were significantly improved. The results of Gene Ontology (GO) analysis showed that Neuron differentiation, Dentate gyrus development, Nervous system development, Cerebral cortex neuron differentiation, Cerebral cortex development, Cerebral cortex development and Neurogenesis are all significant GO terms related to brain development. The DEGs enriched in these terms included Lhx2, Emx2, Foxg1, Nr2e1 and Emx1. All these genes play an important role in regulating the functioning of Cajal-Retzius cells (CRs). The DEGs were also enriched in glutamatergic synapses, synapses, memory, and the positive regulation of long-term synaptic potentiation. In addition, "cellular response to calcium ions" exhibited the second highest rich factor in the GO analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs showed that the neuroactive ligand-receptor interaction pathway was the most significantly enriched pathway, and DEGs also notably enriched in neuroactive ligand-receptor interaction, axon guidance, and cholinergic synapses. Conclusion: HAR1 overexpression led to improvements in memory and cognitive abilities of the transgenic mice. The possible mechanism for this was that the long non-coding RNA (lncRNA) HAR1A affected brain development by regulating the function of CRs. Moreover, HAR1A may be involved in ligand-receptor interaction, axon guidance, and synapse formation, all of which are important in brain development and evolution. Furthermore, cellular response to calcium may play an important role in those processes.

Memory characteristics in mesial temporal lobe epilepsy: Insights from an eye tracking memory game and neuropsychological assessments.

AIMS: To compare different patterns of memory impairment in patients with two subtypes of mesial temporal lobe epilepsy (MTLE) and healthy controls. METHODS: Thirty-five healthy controls and 41 patients with MTLE were recruited, of which 25 patients were diagnosed as hippocampal sclerosis (HS-MTLE), and the rest 16 patients were lesion-negative (MRI-neg MTLE). Participants completed the Wechsler memory assessment and a short-term memory game on an automated computer-based memory assessment platform with an eye tracker. RESULTS: Both the MRI-neg MTLE and HS-MTLE groups took longer time to complete the short-term memory game than healthy controls (p < 0.001, Cohen's d = 1.087; p = 0.047, Cohen's d = 0.787). During the memory encoding phase, the MRI-neg MTLE group spent significantly shorter time than healthy controls on the difficult levels with three (p = 0.004, Cohen's d = 0.993) and four targets (p = 0.016, Cohen's d = 0.858). During the memory decoding phase, the HS-MTLE group spent less time looking on the targets compared to controls when recalling and finding four targets (p = 0.004, Cohen's d = -0.793), while the MRI-neg MTLE group spent significantly longer time on the distractors and shorter time on the region of interests (ROIs) for all difficulty levels (all p < 0.05) than controls. Furthermore, the eye tracking data were correlated with the scores of the Wechsler Memory Scale after Bonferroni correction (p < 0.05). CONCLUSION: Patients with MRI-neg MTLE demonstrate impaired memory mostly due to attention deficits, while those with HS-MTLE show memory impairment with relative sparing of attention. Eye tracking technology has the potential of facilitating the investigation of the mechanism of memory defect in MTLE and can serve as a supplementary neuropsychological tool for clinical diagnosis and long-term monitoring.