Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study

Abstract Background Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. Methods The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. Results Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. Conclusions Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients’ genotype in a sample from a Mexican population.

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Working Memory Deficits in Schizophrenia Are Associated With the Rs34884856 Variant and Expression Levels of the NR4A2 Gene in a Sample Mexican Population: A Case Control Study

10.21203/rs.3.rs-53517/v1 ◽

2020 ◽

Author(s):

Elizabeth Ruiz-Sánchez ◽

Janet Jiménez-Genchi ◽

Yessica M. Alcántara-Flores ◽

Carlos J. Castañeda-González ◽

Carlos L. Aviña-Cervantes ◽

...

Keyword(s):

Working Memory ◽

Mrna Expression ◽

Genetic Variants ◽

Mononuclear Cells ◽

Memory Performance ◽

Mexican Population ◽

High Resolution Melt ◽

Expression Levels ◽

Neuropsychiatric Diseases ◽

Significant Difference

Abstract Background Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. Methods The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. Results Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. In these patients, a decrease of NR4A2 mRNA expression was related to working memory impairment. Conclusions Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients´ genotype in a sample from a Mexican population.

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Working Memory Performance after Daily Caffeine Intake: Compromised Performance and Reduced Hippocampal Activity.

10.1101/2021.04.19.440520 ◽

2021 ◽

Author(s):

Yu-Shiuan Lin ◽

Janine Weibel ◽

Hans-Peter Landolt ◽

Francesco Santini ◽

Helen Christina Slawik ◽

...

Keyword(s):

Working Memory ◽

Memory Performance ◽

Error Rates ◽

Caffeine Intake ◽

Cognitive State ◽

Placebo Condition ◽

Memory Functions ◽

Acute Withdrawal ◽

Caffeine Withdrawal ◽

Significant Difference

Neuroprotective effects of caffeine have been frequently reported in the context of disease and cognitive dysfunction as well as in epidemiological studies in humans. However, evidence on caffeine effects on neural and memory functions during daily intake in a healthy cognitive state remains scarce. This randomized double-blind placebo-controlled crossover study investigated working memory functions by N-back tasks and functional magnetic resonance imaging (fMRI) after daily caffeine intake compared to a placebo baseline and to acute caffeine withdrawal in 20 young healthy volunteers. Each volunteer was given 3 times 150 mg caffeine for 10 days in the daily caffeine condition, 3 times 150 mg mannitol for 10 days in the placebo condition, and 9-day caffeine plus 1-day mannitol in the acute withdrawal condition. During the 10th day, participants performed 4 N-back sessions (two loads each: 0- and 3-back) under controlled laboratory conditions. During the 4th session of N-Back (i.e. at 5.5 h, 36.5 h and > 10 days after the last caffeine intake in the caffeine, withdrawal, and placebo condition, respectively) we assessed blood-oxygen-level-dependent (BOLD) activity. During the entire 10th day, in 0-back tasks, we observed longer reaction times (RTs) in the withdrawal compared to the placebo (Cohens d = 0.7) and caffeine condition (Cohens d = 0.6), but no significant effects of conditions on error rates. In contrast, in 3-back tasks (controlled for 0-back), the RTs in the caffeine condition were longer compared to placebo (Cohens d = 0.6) and withdrawal (Cohens d = 0.5). Error rates were higher during both caffeine and withdrawal conditions compared to placebo (Cohens d of both contrasts = 0.4). Whole-brain analyses on fMRI data did not reveal significant condition-dependent differences in activities between task loads. Across task loads, however, we observed a reduced hippocampal activation (Cohens d = -1.3) during the caffeine condition compared to placebo, while no significant difference in brain activities between withdrawal and placebo conditions. Taken together, the worse working memory function and the hippocampal hypoactivation implicate a potential detrimental effect of daily caffeine intake on neurocognitive functions of healthy adults. Moreover, they echo the hippocampal volumetric reduction reported previously in the same volunteers. Lastly, acute withdrawal from daily caffeine intake impairs both low-order cognitive processes and working memory performance. Taking earlier studies on acute caffeine effects into account, our findings indicate that daily caffeine intake elicits a dynamic change in cerebral activities during the course of repeated consumption, with unknown consequences in the long run.

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Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene

International Journal of Genomics ◽

10.1155/2014/950903 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Qingqing Jiao ◽

Cuiping Liu ◽

Ziliang Yang ◽

Qiang Ding ◽

Miaomiao Wang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Activity Index ◽

Disease Activity Index ◽

Peripheral Tolerance ◽

Systemic Lupus ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Significant Difference

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.

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Investigating Chronotype Orientation on Daily and Weekly Rhythm Fluctuations in Preschoolers Working Memory Performance

International Clinical Neuroscience Journal ◽

10.15171/icnj.2018.27 ◽

2019 ◽

Vol 5 (4) ◽

pp. 150-157

Author(s):

Zohre Nasiri Zarch ◽

Massoud Sharifi ◽

Mahmood Heidari ◽

Shahla Pakdaman

Keyword(s):

Working Memory ◽

Cognitive Processes ◽

Training Programs ◽

Memory Performance ◽

Time Of Day ◽

Time Intervals ◽

Mixed Analysis ◽

Significant Difference ◽

Data Collection Instrument ◽

Day Of The Week

Background: Chronopsychology researches claim that cognitive processes performance during learning in the educational environment in times of the day and days of the week fluctuate, and working memory is essential among these cognitive processes. The research aimed to study the rhythm of daily and weekly working memory performance of preschoolers based on their chronotype (morningness and eveningness) orientation. Methods: The research method is causal-comparative. The participants are 100 preschool children in Tehran that were selected based on purposive sampling. Their working memory was tested at different time intervals of (8, 11, 13, and 15) and weekly (Saturday, Sunday, Monday, Tuesday and Wednesday). Saturday also considered as the first day of the week. Data collection instrument were children morningness-eveningness preference (CMEP) in the form of questionnaire and working memory test. Data analysis based on a mixed analysis of variance. Results: The results showed that preschoolers working memory performance during different days of the week and time of day was different (P<0.01). There was a significant difference between children in different groups regarding memory at different hours of the day, but on different days of the week, there was no significant difference in memory performance (P<0.01). Conclusion: According to the findings, teachers and clinicians are suggested to consider the importance of circadian rhythm parameters in assessing cognitive function in patients and healthy people. Awareness of individual differences of the morningness-eveningness type can be very effective in designing training programs and preventive health associated matters with each type.

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The Protective Effects of 18β-Glycyrrhetinic Acid onHelicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils

BioMed Research International ◽

10.1155/2016/4943793 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Donghui Cao ◽

Jing Jiang ◽

Lili You ◽

Zhifang Jia ◽

Tetsuya Tsukamoto ◽

...

Keyword(s):

Mononuclear Cells ◽

Ph Value ◽

Glycyrrhetinic Acid ◽

Therapeutic Drug ◽

Mongolian Gerbils ◽

Protective Effects ◽

Expression Levels ◽

Significant Difference ◽

Cox 2 ◽

H Pylori

18β-Glycyrrhetinic acid (GRA), a major component ofGlycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA onHelicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbilsin vivo. The gerbils were randomly divided into groups: uninfected;H. pylori-infected;H. pylori+ antibiotics (clarithromycin, amoxicillin, and esomeprazole); andH. pylori+ GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in theH. pylori+ GRA group, the intraluminal gastric pH value was lower (2.14±0.08versus3.17±0.23,P<0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P<0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P<0.05) compared with theH. pylori-infected group. There was no significant difference in results between theH. pylori+ GRA group and theH. pylori+ antibiotics group. This study indicated that GRA significantly attenuatedH. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug.

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Working memory task performance and chunking in early Alzheimer's disease

The British Journal of Psychiatry ◽

10.1192/bjp.bp.110.083857 ◽

2011 ◽

Vol 198 (5) ◽

pp. 398-403 ◽

Cited By ~ 29

Author(s):

Jonathan Huntley ◽

Daniel Bor ◽

Adam Hampshire ◽

Adrian Owen ◽

Robert Howard

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Working Memory ◽

Spatial Working Memory ◽

Memory Performance ◽

Verbal Working Memory ◽

Control Group ◽

Mild Disease ◽

Significant Difference ◽

Encoding Strategy

BackgroundChunking is a powerful encoding strategy that significantly improves working memory performance in normal young people.AimsTo investigate chunking in patients with mild Alzheimer's disease and in a control group of elderly people without cognitive impairment.MethodPeople with mild Alzheimer's disease (n = 28) were recruited and divided according to Mini-Mental State Examination score into mild and very mild disease groups. A control group of 15 elderly individuals was also recruited. All participants performed digit and spatial working memory tasks requiring either unstructured sequences or structured sequences (which encourage chunking of information) to be recalled.ResultsThe control group and both disease groups performed significantly better on structured trials of the digit working memory tasks, indicating successful use of chunking strategies to improve verbal working memory performance. The control and very mild disease groups also performed significantly better on structured trials of the spatial task, whereas those with mild disease demonstrated no significant difference between the structured and unstructured spatial conditions.ConclusionsThe ability to use chunking as an encoding strategy to improve verbal working memory performance is preserved at the mild stage of Alzheimer's disease, whereas use of chunking to improve spatial working memory is impaired by this stage. Simple training in the use of chunking might be a beneficial therapeutic strategy to prolong working memory functioning in patients at the earliest stage of Alzheimer's disease.

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Cannabidiol Does Not Cause Significant Changes to Working Memory Performance in the N-Back Task

Pharmaceuticals ◽

10.3390/ph14111165 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1165

Author(s):

Éamon Jones ◽

Styliani Vlachou

Keyword(s):

Working Memory ◽

Online Survey ◽

Memory Performance ◽

Demographic Data ◽

Analysis Of Covariance ◽

Long Term Effects ◽

Significant Difference ◽

Common Era ◽

Back Task

Cannabis use can be traced back to several centuries before the Common Era, when it was used for industrial, medicinal and recreational purposes. More recently, over 100 different cannabinoid compounds have been identified, one of which is cannabidiol (CBD), a compound widely used for anti-inflammatory and anxiolytic treatment. The literature surrounding the cognitive effects of CBD is limited, with most studies focusing on the effects of other cannabinoids on cognition. To expand this literature, this study investigated whether CBD causes significant differences to working memory (WM) functioning, as measured by the N-back task. It was hypothesised that CBD does not cause statistically significant differences to WM. In all, 54 participants, 33 females and 21 males, were recruited, with a mean age of 32.63 years. Of these 54 participants, 26 reported using CBD and no other cannabinoids, while 28 reported not using any cannabinoid. The participants were instructed to answer a short online survey to gather basic demographic data and to complete an online N-back task to measure WM. For the computerised N-back task, the participants completed a practice and three test blocks, where they were instructed to respond to whether a series of letter stimuli were presented one trial back (1-back), two trials back (2-back) or three trials back (3-back). Multivariate analysis of covariance yielded no statistically significant difference on either response time or response accuracy data between groups after controlling for how long the participants use CBD and for what reason they use CBD. These results support our hypothesis that CBD does not cause significant changes to WM functioning. Further research is greatly needed to investigate the long-term effects of CBD use on WM and on general cognitive functioning.

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128 Raw Scores Best Differentiate Resilience and Vulnerability to Sleep Loss for Cognitive Throughput and Working Memory

SLEEP ◽

10.1093/sleep/zsab072.127 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A52-A52

Author(s):

Tess Brieva ◽

Courtney Casale ◽

Erika Yamazaki ◽

Caroline Antler ◽

Namni Goel

Keyword(s):

Working Memory ◽

Digit Span ◽

Memory Performance ◽

Sleep Loss ◽

Vulnerable Groups ◽

Critical Question ◽

Average Performance ◽

Time In Bed ◽

Significant Difference ◽

Optimal Approach

Abstract Introduction Substantial individual differences exist in cognitive deficits due to sleep restriction (SR) and total sleep deprivation (TSD), but the best approach to define such resilience and vulnerability remains a critical question. We compared multiple approaches and cutoff thresholds to define resilience and vulnerability using the Digit Symbol Substitution Task (DSST) and the Digit Span Task (DST). Methods Forty-one healthy adults (mean±SD ages,33.9±8.9y) participated in a 13-night experiment [two baseline nights (10h-12h time-in-bed, TIB), 5 SR nights (4h TIB), 4 recovery nights (12h TIB), and 36h TSD]. The DSST [measuring cognitive throughput] and DST [measuring working memory] were administered every 2h during wakefulness. Resilient/vulnerable groups were defined by average performance (DSST: number correct; DST: total correct from forward and backward versions) during SR1-5, average performance change from baseline during SR1-5, and variance in performance during SR1-5. Within each approach, groups were defined by +/-1 standard deviation (SD) and the top and bottom 12.5%, 20%, 25%, 33%, 50%. Bias-corrected and accelerated bootstrapped t-tests compared performance between resilient and vulnerable groups during baseline and SR1-5. Kendall’s tau correlations compared the ranking of individuals in each group. Results T-tests showed significant differences between resilient/vulnerable groups at all raw score cutoffs for DSST and DST performance during SR and at baseline. Change from baseline t-tests showed significant differences during SR between the DSST groups only at 12.5%, 20%, and SD whereas DST t-tests showed significant differences at all cutoffs. Variance t-tests revealed a significant difference between the DSST groups only at 25% during SR. For the DSST, the variance vs. change from baseline comparison at all cutoffs and between raw score vs. change from baseline for the SD cutoff showed moderate correlations, and for the DST, the raw score vs. change from baseline correlation was moderate for 25% and 33%. Conclusion The resilient/vulnerable groups defined by raw score were more consistent than those defined by change from baseline or variance, and raw score did not track these approaches well. As such, raw score is the optimal approach to define cognitive throughput and working memory performance resiliency/vulnerability during sleep loss. Support (if any) ONR Award No. N00014-11-1-0361;NIH UL1TR000003;NASA NNX14AN49G and 80NSSC20K0243;NIH R01DK117488

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A-153 Working Memory Performance and Brain Activity in the context of Opioid Withdrawal and Relapse

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acaa068.153 ◽

2020 ◽

Vol 35 (6) ◽

pp. 947-947

Author(s):

Surprenant B ◽

Grimone K ◽

Wagner T ◽

Sarles-Whittlesey H ◽

Jones E ◽

...

Keyword(s):

Working Memory ◽

Brain Activity ◽

Memory Performance ◽

Brain Activation ◽

Opioid Use Disorder ◽

Opiate Withdrawal ◽

Opioid Use ◽

Behavioral Measures ◽

Significant Difference

Abstract Objective Working memory (WM) deficits are associated with opioid use disorder (OUD). However, little research addresses WM during withdrawal. We used the N-back WM paradigm to assess whether differences exist between persons in withdrawal versus stable opioid doses. We also examined whether N-back performance or associated brain activity during either withdrawal or satiation predict subsequent abstinence versus relapse. Method We evaluated N-Back performance and associated brain function of 20 OUD patients during 3 T fMRI. Participants were actively using opioids during the first scan (SOWS M = 8.10, SD = 9.22) and abstained 24 hours before the second scan (SOWS M = 28.26, SD = 11.64), buprenorphine treatment began afterwards. Twelve participants (age: M = 33.92, SD = 5.99) completed both scans and were included in within-subject contrasts. Sixteen participants (age: M = 34.38, SD = 5.38) completed at least one scan and were evaluated on whether brain activation or performance was associated with relapse. Results Paired-sample t-tests revealed no significant difference on N-back accuracy (0-back: t = 0.78, p = .45, d = 0.23; 2-back: t = −0.28, p = .78, d = 0.08) or brain activation (2-back versus 0-back) across regions of interest (ROIs) associated with WM in prior studies between satiated and abstinent assessments (ts < 0.5, ps > .05). Contrasting relapsing and abstinent groups at follow-up revealed no significant difference in N-back accuracy (0-back: t = −0.30, p = .77, d = 0.14; 2-back: t = 0.43, p = .67, d = 0.22) or associated ROI brain activation (ts < 1.29, ps > .05). Conclusion This is the first investigation of brain and behavioral measures of WM in opiate withdrawal and relapse. No significant differences were found, and effect sizes were small. Further research that investigates direct (compensatory activation) and task-indirect systems (default network, motivation) during cognitive challenges is needed.

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The Modulation of Working-Memory Performance Using Gamma-Electroacupuncture and Theta-Electroacupuncture in Healthy Adults

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2062718 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Meng Ren ◽

Jingjing Xu ◽

Jingjun Zhao ◽

Sicong Zhang ◽

Wenjing Wang ◽

...

Keyword(s):

Working Memory ◽

Memory Performance ◽

Reaction Times ◽

High Load ◽

Central Component ◽

Human Beings ◽

Daily Lives ◽

Significant Difference ◽

Before And After ◽

Transcranial Alternating Current Stimulation

Working memory (WM), a central component of general cognition, plays an essential role in human beings’ daily lives. WM impairments often occur in psychiatric, neurodegenerative, and neurodevelopmental disorders, mainly presenting as loss of high-load WM. In previous research, electroacupuncture (EA) has been shown to be an effective treatment for cognitive impairments. Frequency parameters are an important factor in therapeutic results, but the optimal frequency parameters of EA have not yet been identified. In this study, we chose theta-EA (θ-EA; 6 Hz) and gamma-EA (γ-EA; 40 Hz), corresponding to the transcranial alternating-current stimulation (tACS) frequency parameters at the Baihui (DU20) and Shenting (DU24) acupoints, in order to compare the effects of different EA frequencies on WM. We evaluated WM performance using visual 1-back, 2-back, and 3-back WM tasks involving digits. Each participant (N = 30) attended three different sessions in accordance with a within-subject crossover design. We performed θ-EA, γ-EA, and sham-EA in a counterbalanced order, conducting the WM task both before and after intervention. The results showed that d-prime (d′) under all three stimulation conditions had no significance in the 1-back and 2-back tasks. However, in the 3-back task, there was a significant improvement in d′ after intervention compared to d′ before intervention under θ-EA (F [1, 29] = 22.64; P < 0.001 ), while we saw no significant difference in the γ-EA and sham-EA groups. Reaction times for hits (RT-hit) under all three stimulation conditions showed decreasing trends in 1-, 2-, and 3-back tasks but without statistically significant differences. These findings suggest that the application of θ-EA might facilitate high-load WM performance.

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