scholarly journals Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jose A Fernandez-Leon ◽  
Douglas S Engelke ◽  
Guillermo Aquino-Miranda ◽  
Alexandria Goodson ◽  
Maria N Rasheed ◽  
...  
Keyword(s):  
Individual Variability ◽  
Complete Suppression ◽  
Risky Decision ◽  
Defensive Responses ◽  
Increased Risk ◽  
Conflict Model ◽  
Approach Behaviors ◽  
Single Unit Recordings ◽  
Threat Avoidance ◽  
Food Seeking

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic cortex (PL) respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals' decision depends on previously associated memories. Using a conflict model in which male Long-Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: i) rats that continued to press a lever for food (Pressers); and ii) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision making by regulating threat-avoidance vs. reward-approach behaviors.

scholarly journals Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex

2021 ◽  
Author(s):  
Jose A. Fernandez-Leon ◽  
Douglas S. Engelke ◽  
Guillermo Aquino-Miranda ◽  
Alexandria Goodson ◽  
Fabricio H. Do Monte
Keyword(s):  
Individual Variability ◽  
Complete Suppression ◽  
Risky Decision ◽  
Defensive Responses ◽  
Increased Risk ◽  
Conflict Model ◽  
Approach Behaviors ◽  
Single Unit Recordings ◽  
Threat Avoidance ◽  
Food Seeking

The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic cortex (PL) respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animal decision depends on previously associated memories. Using a conflict model in which rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: i) rats that continued to press a lever for food (Pressers); and ii) rats that exhibited a complete suppression in food seeking (Non-Pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-Pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision making by regulating threat-avoidance vs. reward-approach behaviors.

scholarly journals Conflict-mediated tasks for studying the act of facing threats in pursuit of rewards

2020 ◽  
Author(s):  
Elizabeth Illescas-Huerta ◽  
Leticia Ramirez-Lugo ◽  
Rodrigo Ordonez Sierra ◽  
Jorge A. Quillfeldt ◽  
Francisco Sotres-Bayon
Keyword(s):  
Choice Behavior ◽  
Open Field Test ◽  
Straight Alley ◽  
Conflict Task ◽  
Motivational Systems ◽  
Defensive Responses ◽  
Approach Behaviors ◽  
The Face ◽  
Threat Avoidance ◽  
Taking Action

AbstractSurvival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly occur simultaneously. When threat- and reward-eliciting stimuli (learned or unlearned) co-occur, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Previous animal models using approach-avoidance conflicts have often focused on the ability to avoid threats by forgoing the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are lacking. Thus, we developed three conflict-mediated tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict-mediated behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this validated set of innate/learned conflict-mediated tasks could help understand the underlying brain mechanisms that allow animals to confront threats, by actively suppressing defensive responses, to achieve goals.

scholarly journals Tumor cell total mRNA expression shapes the molecular and clinical phenotype of cancer

2021 ◽  
Author(s):  
Shaolong Cao ◽  
Jennifer Wang ◽  
Shuangxi Ji ◽  
Peng Yang ◽  
Matthew Montierth ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Mrna Expression ◽  
Genetic Alterations ◽  
Individual Variability ◽  
Cancer Type ◽  
Sequencing Data ◽  
Increased Risk ◽  
Mrna Content ◽  
Risk Of Disease ◽  
Pan Cancer

Abstract Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, differences in tumor cell total mRNA content have not been comprehensively assessed. Technical and analytical challenges have impeded examination of total mRNA expression at scale across cancers. To address this, we developed a model for quantifying tumor-specific total mRNA expression (TmS) from bulk sequencing data, which performs transcriptomic deconvolution while adjusting for mixed genomes. We used single-cell RNA sequencing data to demonstrate total mRNA expression as a feature of tumor phenotype. We estimated and validated TmS in 5,015 patients across 15 cancer types identifying significant inter-individual variability. At a pan-cancer level, high TmS is associated with increased risk of disease progression and death. Cancer type-specific patterns of genetic alterations, intra-tumor genetic heterogeneity, as well as pan-cancer trends in metabolic dysregulation and hypoxia contribute to TmS. Taken together, our results suggest that measuring cell-type specific total mRNA expression offers a broader perspective of tracking cancer transcriptomes, which has important biological and clinical implications.

scholarly journals Sensitivity to gains during risky decision-making differentiates chronic cocaine users from stimulant-naïve controls

2019 ◽  
Author(s):  
B. Kluwe-Schiavon ◽  
A. Kexel ◽  
G. Manenti ◽  
D.M. Cole ◽  
M.R. Baumgartner ◽  
...  
Keyword(s):  
Decision Making ◽  
Neuropsychological Test ◽  
Risky Decision Making ◽  
Risky Decision ◽  
Cocaine Use ◽  
Risk Seeking ◽  
Chronic Cocaine ◽  
Increased Risk ◽  
Cocaine Users ◽  
The Individual

AbstractBackgroundAlthough chronic cocaine use has been frequently associated with decision-making impairments that are supposed to contribute to the development and maintenance of cocaine addiction, it has remained unclear how risk-seeking behaviours observed in chronic cocaine users (CU) come about. Here we therefore test whether risky decision-making observed in CU is driven by alterations in individual sensitivity to the available information (gain, loss, and risk).MethodA sample of 96 participants (56 CU and 40 controls) performed the no-feedback (“cold”) version of the Columbia Card Task. Structured psychiatric interviews and a comprehensive neuropsychological test battery were additionally conducted. Current and recent substance use was objectively assessed by toxicological urine and hair analysis.ResultsCompared to controls, CU showed increased risk-seeking in unfavourable decision scenarios in which the risk was high and the returns were low, and a tendency for increased risk aversion in favourable decision scenarios. These differences arose from the fact that CU were less sensitive to gain, but similarly sensitive to loss and risk information in comparison to controls. Further analysis revealed that individual differences in sensitivity to loss and risk were related to cognitive performance and impulsivity.ConclusionThe reduced sensitivity to gain information in people with CU may contribute to their propensity for making risky decisions. While these alterations in the sensitivity to gain might be directly related to cocaine use per se, the individual psychopathological profile of CU might moderate their sensitivity to risk and loss impulsivity.

scholarly journals EPIGENETICS OF STRESS AND ADAPTATION ACROSS HEALTHSPAN AND LIFESPAN

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S735-S735
Author(s):  
Luigi Ferrucci ◽  
Shabnam Salimi ◽  
Luigi Ferrucci
Keyword(s):  
Stress Response ◽  
Chronic Diseases ◽  
Accelerated Aging ◽  
Premature Mortality ◽  
Individual Variability ◽  
Biological Aging ◽  
Increased Risk ◽  
Approaches To Study ◽  
Rate Of Decline ◽  
Aging Phenomena

Abstract Any stimulus that endangers body integrity (stressor) results in an adaptive response to resolve stressful state and determine adaptive or and maladaptive responses. Both chronic extrinsic and intrinsic stressors can produce long-lasting, epigenetic changes in various organs that can eventually result in accelerated changes in bio-physio-pathology. There is initial evidence that stress response involves mechanisms of the epigenetic basis of adaptation and stress response to biological aging and chronic diseases. With aging, homeostasis stability declines causing augmented vulnerability to the external and internal stress. Individuals in whom vulnerability trespass a certain threshold experience accelerated aging and deterioration of health and/ or “secondary aging” phenomena such as premature mortality. Because of substantial heterogeneity of the rate of decline in homeostatic stability, there is inter-individual variability in the age of appearance of chronic diseases and the increased risk of disability and mortality. Thus, tools for the quantification of a stress response would be clinically valuable. Therefore, this symposium suggests approaches to study the epigenetic basis of molecular adaptations across various age, organs’ health-span, and life-span.

scholarly journals Conflict Test Battery for Studying the Act of Facing Threats in Pursuit of Rewards

2021 ◽  
Vol 15 ◽  
Author(s):  
Elizabeth Illescas-Huerta ◽  
Leticia Ramirez-Lugo ◽  
Rodrigo O. Sierra ◽  
Jorge A. Quillfeldt ◽  
Francisco Sotres-Bayon
Keyword(s):  
Choice Behavior ◽  
Open Field Test ◽  
Straight Alley ◽  
Test Battery ◽  
Conflict Task ◽  
Motivational Systems ◽  
Approach Behaviors ◽  
The Face ◽  
Threat Avoidance ◽  
Taking Action

Survival depends on the ability of animals to avoid threats and approach rewards. Traditionally, these two opposing motivational systems have been studied separately. In nature, however, they regularly compete for the control of behavior. When threat- and reward-eliciting stimuli (learned or unlearned) occur simultaneously, a motivational conflict emerges that challenges individuals to weigh available options and execute a single behavioral response (avoid or approach). Most previous animal models using approach/avoidance conflicts have often focused on the ability to avoid threats by forgoing or delaying the opportunity to obtain rewards. In contrast, behavioral tasks designed to capitalize on the ability to actively choose to execute approach behaviors despite threats are scarce. Thus, we developed a behavioral test battery composed of three conflict tasks to directly study rats confronting threats to obtain rewards guided by innate and conditioned cues. One conflict task involves crossing a potentially electrified grid to obtain food on the opposite end of a straight alley, the second task is based on the step-down threat avoidance paradigm, and the third one is a modified version of the open field test. We used diazepam to pharmacologically validate conflict behaviors in our tasks. We found that, regardless of whether competing stimuli were conditioned or innate, a low diazepam dose decreased risk assessment and facilitated taking action to obtain rewards in the face of threats during conflict, without affecting choice behavior when there was no conflict involved. Using this pharmacologically validated test battery of ethologically designed innate/learned conflict tasks could help understand the fundamental brain mechanisms underlying the ability to confront threats to achieve goals.

scholarly journals Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

2020 ◽  
Vol 21 (4) ◽  
pp. 1421 ◽  
Author(s):  
Elena Azzini ◽  
Stefania Ruggeri ◽  
Angela Polito
Keyword(s):  
Pathological Condition ◽  
Age Groups ◽  
Autism Spectrum ◽  
Individual Variability ◽  
Dietary Factors ◽  
Experimental Designs ◽  
Vitamin Supplementation ◽  
Population Groups ◽  
Increased Risk ◽  
Adverse Pregnancy

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case–control experimental designs and the study of interactions between different factors it should be emphasized.

Maternal Care and Individual Differences in Defensive Responses

2005 ◽  
Vol 14 (5) ◽  
pp. 229-233 ◽  
Author(s):  
Carine Parent ◽  
Tie-Yuan Zhang ◽  
Christian Caldji ◽  
Rose Bagot ◽  
Frances A. Champagne ◽  
...  
Keyword(s):  
Maternal Care ◽  
Stress Reactivity ◽  
Brain Regions ◽  
Biological Psychiatry ◽  
Epigenetic Mechanisms ◽  
Familial Transmission ◽  
Autonomic Responses ◽  
Defensive Responses ◽  
Sustained Effects ◽  
Increased Risk

Familial transmission of mental illness is common. Recent studies in behavioral neuroscience and biological psychiatry reveal the importance of epigenetic mechanisms of transmission that center on the developmental consequences of variations in parental care. Studies with rats suggest that environmental adversity results in patterns of parent–offspring interactions that increase stress reactivity through sustained effects on gene expression in brain regions known to regulate behavioral, endocrine, and autonomic responses to stress. While such effects might be adaptive, the associated cost involves an increased risk for stress-related illness.

scholarly journals Regulatory VCAN polymorphism is associated with shoulder pain and disability in breast cancer survivors

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Trevor S. Mafu ◽  
Alison V. September ◽  
Delva Shamley
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Shoulder Pain ◽  
Breast Cancer Survivors ◽  
Individual Variability ◽  
Nucleotide Polymorphisms ◽  
Related Factors ◽  
Cross Sectional ◽  
Pain Disability ◽  
Increased Risk

Abstract Background and purpose Shoulder morbidity following breast cancer treatment is multifactorial. Despite several treatment- and patient-related factors being implicated, unexplained inter-individual variability exists in the development of such morbidity. Given the paucity of relavant genetic studies, we investigate the role of polymorphisms in candidate proteoglycan genes. Patients and methods We conducted a cross-sectional study on 254 South African breast cancer survivors, to evaluate associations between shoulder pain/disability and ten single nucleotide polymorphisms (SNPs) within four proteoglycan genes: ACAN (rs1126823 G>A, rs1516797 G>T, rs2882676 A>C); BGN (rs1042103 G>A, rs743641 A>T, rs743642 G>T); DCN rs516115 C>T; and VCAN (rs11726 A>G, rs2287926 G>A, rs309559). Participants were grouped into no–low and moderate–high shoulder pain/disability based on total pain/disability scores: < 30 and ≥ 30, respectively using the Shoulder Pain and Disability Index (SPADI). Results The GG genotype of VCAN rs11726 was independently associated with an increased risk of being in the moderate-to-high shoulder pain (P = 0.005, OR = 2.326, 95% CI = 1.259–4.348) or disability (P = 0.011, OR = 2.439, 95% CI = 1.235–4.762) categories, after adjusting for participants’ age. In addition, the T-T-G inferred allele combination of BGN (rs74364–rs743642)–VCAN rs11726 was associated with an increased risk of being in the moderate-to-high shoulder disability category (0 = 0.002, OR = 2.347, 95% CI = 1.215–4.534). Conclusion Our study is first to report that VCAN rs11726, independently or interacting with BGN polymorphisms, is associated with shoulder pain or disability in breast cancer survivors. Whereas our findings suggest an involvement of proteoglycans in the etiology of shoulder pain/disability, further studies are recommended.

Validation of the Activity Room: An Ecologically Valid Assessment of Young Children’s Risk-Taking

2021 ◽  
pp. 263207702098814
Author(s):  
Casie H. Morgan ◽  
Claire Estep ◽  
Barbara A. Morrongiello ◽  
David C. Schwebel
Keyword(s):  
Risk Taking ◽  
Convergent Validity ◽  
Assessment Tool ◽  
Unintentional Injury ◽  
The United States ◽  
Child Injury ◽  
Risky Decision ◽  
Increased Risk ◽  
Physical Risk ◽  
Play Behaviors

Physical risk-taking is associated with increased risk of unintentional injury, a global health challenge and the leading cause of death for children in the United States. To assess risk and develop prevention programs, valid tools to assess children’s physical risk-taking are needed. No ecologically valid behavioral measures are widely available. This study describes the development and validation of the “Activity Room” to measure children’s physical risk-taking while presenting low risk of actual injury. Participants were 59 children aged 4 to 6 years old (51% female; 51% non-Hispanic White) and their parents. Children completed two tasks to assess physical risk-taking: (a) vignettes (short stories presenting risk situations) and (b) the “Activity Room” (unsupervised engagement for 5 min in a room with apparatus designed to stimulate potential physical risk-taking). Parents responded to a questionnaire concerning children’s active play behaviors. Correlational analyses evaluated convergent validity of the Activity Room risk-taking outcome. The Activity Room proved feasible; all children engaged eagerly and safely. Convergent validity was demonstrated through two strategies. First, risk-taking in the Activity Room correlated with observed play behaviors, such as climbing and falling. Second, risk-taking in the Activity Room correlated with children’s risk-taking responses in the vignettes and with parent-reported child risk-taking. Results indicate the Activity Room task is a valid technique to assess young children’s risk-taking in an ecologically valid real-world behavioral task. Incorporation of the task as an assessment tool may benefit a range of studies investigating children’s physical risk-taking behavior, risky decision-making, and child injury prevention strategies.

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