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1.
Ergonomics ; : 1-16, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016161

ABSTRACT

As the UK's Chartered Institute of Ergonomics and Human Factors (CIEHF) celebrates its 75th anniversary, it is worth reflecting on our discipline's contribution, current state, and critical future endeavours. We present the perspectives of 18 EHF professionals who were asked to respond to five questions regarding the impact of EHF, contemporary challenges, and future directions. Co-authors were in agreement that EHF's impact has been only limited to date and that critical issues require resolution, such as increasing the number of suitably qualified practitioners, resolving the research-practice gap, and increasing awareness of EHF and its benefits. Frequently discussed future directions include advanced emerging technologies such as artificial intelligence, the development of new EHF methods, and enhancing the quality and reach of education and training. The majority felt there will be a need for EHF in 75 years; however, many noted that our methods will need to adapt to meet new needs.Practitioner statement: This article provides the perspectives of 18 Ergonomics and Human Factors (EHF) professionals on the impact of EHF, contemporary challenges and critical future directions, and changes that are necessary to ensure EHF remains relevant in future. As such, it provides important guidance on future EHF research and practice.

2.
Appl Ergon ; 117: 104245, 2024 May.
Article in English | MEDLINE | ID: mdl-38320386

ABSTRACT

There are concerns that Artificial General Intelligence (AGI) could pose an existential threat to humanity; however, as AGI does not yet exist it is difficult to prospectively identify risks and develop requisite controls. We applied the Work Domain Analysis Broken Nodes (WDA-BN) and Event Analysis of Systemic Teamwork-Broken Links (EAST-BL) methods to identify potential risks in a future 'envisioned world' AGI-based uncrewed combat aerial vehicle system. The findings suggest five main categories of risk in this context: sub-optimal performance risks, goal alignment risks, super-intelligence risks, over-control risks, and enfeeblement risks. Two of these categories, goal alignment risks and super-intelligence risks, have not previously been encountered or dealt with in conventional safety management systems. Whereas most of the identified sub-optimal performance risks can be managed through existing defence design lifecycle processes, we propose that work is required to develop controls to manage the other risks identified. These include controls on AGI developers, controls within the AGI itself, and broader sociotechnical system controls.


Subject(s)
Artificial Intelligence , Safety Management , Humans , Prospective Studies , Risk Assessment , Intelligence
3.
Animals (Basel) ; 14(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38275800

ABSTRACT

Cryptosporidium spp. and Giardia duodenalis are the main non-viral causes of diarrhoea in humans and domestic animals globally. Comparatively, much less information is currently available in free-ranging carnivore species in general and in the endangered Iberian lynx (Lynx pardinus) in particular. Cryptosporidium spp. and G. duodenalis were investigated with molecular (PCR and Sanger sequencing) methods in individual faecal DNA samples of free-ranging and captive Iberian lynxes from the main population nuclei in Spain. Overall, Cryptosporidium spp. and G. duodenalis were detected in 2.4% (6/251) and 27.9% (70/251) of the animals examined, respectively. Positive animals to at least one of them were detected in each of the analysed population nuclei. The analysis of partial ssu rRNA gene sequences revealed the presence of rodent-adapted C. alticolis (n = 1) and C. occultus (n = 1), leporid-adapted C. cuniculus (n = 2), and zoonotic C. parvum (n = 2) within Cryptosporidium, and zoonotic assemblages A (n = 5) and B (n = 3) within G. duodenalis. Subgenotyping analyses allowed for the identification of genotype VaA19 in C. cuniculus (gp60 locus) and sub-assemblages AI and BIII/BIV in G. duodenalis (gdh, bg, and tpi loci). This study represents the first molecular description of Cryptosporidium spp. and G. duodenalis in the Iberian lynx in Spain. The presence of rodent/leporid-adapted Cryptosporidium species in the surveyed animals suggests spurious infections associated to the Iberian lynx's diet. The Iberian lynx seems a suitable host for zoonotic genetic variants of Cryptosporidium (C. parvum) and G. duodenalis (assemblages A and B), although the potential risk of human transmission is regarded as limited due to light parasite burdens and suspected low excretion of infective (oo)cysts to the environment by infected animals. More research should be conducted to ascertain the true impact of these protozoan parasites in the health status of the endangered Iberian lynx.

4.
Appl Ergon ; 111: 104028, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37148587

ABSTRACT

Brain-computer interface (BCI) technologies are progressing rapidly and may eventually be implemented widely within society, yet their risks have arguably not yet been comprehensively identified, nor understood. This study analysed an anticipated invasive BCI system lifecycle to identify the individual, organisational, and societal risks associated with BCIs, and controls that could be used to mitigate or eliminate these risks. A BCI system lifecycle work domain analysis model was developed and validated with 10 subject matter experts. The model was subsequently used to undertake a systems thinking-based risk assessment approach to identify risks that could emerge when functions are either undertaken sub-optimally or not undertaken at all. Eighteen broad risk themes were identified that could negatively impact the BCI system lifecycle in a variety of unique ways, while a larger number of controls for these risks were also identified. The most concerning risks included inadequate regulation of BCI technologies and inadequate training of BCI stakeholders, such as users and clinicians. In addition to specifying a practical set of risk controls to inform BCI device design, manufacture, adoption, and utilisation, the results demonstrate the complexity involved in managing BCI risks and suggests that a system-wide coordinated response is required. Future research is required to evaluate the comprehensiveness of the identified risks and the practicality of implementing the risk controls.


Subject(s)
Brain-Computer Interfaces , Humans , Prospective Studies , Risk Assessment , Electroencephalography/methods
5.
Sci Transl Med ; 15(690): eade1779, 2023 04 05.
Article in English | MEDLINE | ID: mdl-37018416

ABSTRACT

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies.


Subject(s)
Anhedonia , Depressive Disorder, Major , Animals , Humans , Anhedonia/physiology , Callithrix , Depressive Disorder, Major/drug therapy , Anxiety , Brain
6.
Ergonomics ; 66(5): 609-626, 2023 May.
Article in English | MEDLINE | ID: mdl-35866642

ABSTRACT

Formal risk assessment is a component of safety management relating to hazardous manual tasks (HMT). Systems thinking approaches are currently gaining interest for supporting safety management. Existing HMT risk assessment methods have been found to be limited in their ability to identify risks across the whole work system; however, systems thinking-based risk assessment (STBRA) methods were not designed for the HMT context and have not been tested in this area. The aim of this study was to compare the performance of four state-of-the-art STBRA methods: Net-HARMS, EAST-BL, FRAM and STPA to determine which would be most useful for identifying HMT risks. Each method was independently applied by one of four analysts to assess the risks associated with a hypothetical HMT system. The outcomes were assessed for alignment with a benchmark analysis. Using signal detection theory (SDT), overall STPA was found to be the best performing method having the highest hit rate, second lowest false alarm rate and highest Matthews Correlation Coefficient of the four methods.Practitioner summary: A comparison of four systems thinking risk assessment methods found that STPA had the highest level of agreement with the benchmark analysis and is the most suitable for practitioners to use to identify the risks associated with HMT systems.


Subject(s)
Safety Management , Systems Analysis , Humans , Safety Management/methods , Risk Assessment
8.
Appl Ergon ; 104: 103827, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35753228

ABSTRACT

Maritime incidents occurring during pilotage are of international concern. Maritime pilots control most pilotage operations worldwide, yet despite the safety criticality of their role, research examining pilot decision-making processes during these complex and dynamic operations is scarce. This article describes the findings from two studies that utilised an integrated systems thinking framework to understand how pilots make decisions and what factors are perceived to influence their decisions. Interviews were held with 22 pilots (Study 1) and 17 maritime safety stakeholders (Study 2) in the New Zealand maritime context. The findings illustrate the challenges pilots face during pilotage and provide insights into their decision-making processes and the systemic factors that can be addressed to improve maritime safety. Given the multiple causal pathways to incidents occurring during pilotage identified by this research, it is suggested that multiple systems-wide interventions are needed, which is likely to require a long-term, strategic approach.


Subject(s)
Accidents , Decision Making , Water Sports , Humans , New Zealand
9.
Antioxidants (Basel) ; 11(4)2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35453368

ABSTRACT

The cytosolic branched-chain aminotransferase (BCAT1) has received attention for its role in myeloid leukaemia development, where studies indicate metabolic adaptations due to BCAT1 up-regulation. BCAT1, like the mitochondria isoform (BCAT2), shares a conserved CXXC motif ~10 Å from the active site. This CXXC motif has been shown to act as a 'redox-switch' in the enzymatic regulation of the BCAT proteins, however the response to reactive oxygen species (ROS) differs between BCAT isoforms. Studies indicate that the BCAT1 CXXC motif is several orders of magnitude less sensitive to the effects of ROS compared with BCAT2. Moreover, estimation of the reduction mid-point potential of BCAT1, indicates that BCAT1 is more reductive in nature and may possess antioxidant properties. Therefore, the aim of this study was to further characterise the BCAT1 CXXC motif and evaluate its role in acute myeloid leukaemia. Our biochemical analyses show that purified wild-type (WT) BCAT1 protein could metabolise H2O2 in vitro, whereas CXXC motif mutant or WT BCAT2 could not, demonstrating for the first time a novel antioxidant role for the BCAT1 CXXC motif. Transformed U937 AML cells over-expressing WT BCAT1, showed lower levels of intracellular ROS compared with cells over-expressing the CXXC motif mutant (CXXS) or Vector Controls, indicating that the BCAT1 CXXC motif may buffer intracellular ROS, impacting on cell proliferation. U937 AML cells over-expressing WT BCAT1 displayed less cellular differentiation, as observed by a reduction of the myeloid markers; CD11b, CD14, CD68, and CD36. This finding suggests a role for the BCAT1 CXXC motif in cell development, which is an important pathological feature of myeloid leukaemia, a disease characterised by a block in myeloid differentiation. Furthermore, WT BCAT1 cells were more resistant to apoptosis compared with CXXS BCAT1 cells, an important observation given the role of ROS in apoptotic signalling and myeloid leukaemia development. Since CD36 has been shown to be Nrf2 regulated, we investigated the expression of the Nrf2 regulated gene, TrxRD1. Our data show that the expression of TrxRD1 was downregulated in transformed U937 AML cells overexpressing WT BCAT1, which taken with the reduction in CD36 implicates less Nrf2 activation. Therefore, this finding may implicate the BCAT1 CXXC motif in wider cellular redox-mediated processes. Altogether, this study provides the first evidence to suggest that the BCAT1 CXXC motif may contribute to the buffering of ROS levels inside AML cells, which may impact ROS-mediated processes in the development of myeloid leukaemia.

10.
Ergonomics ; 65(2): 161-187, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34865613

ABSTRACT

This state of the science review brings together the disparate literature of effective strategies for enhancing and accelerating team performance. The review evaluates and synthesises models and proposes recommended avenues for future research. The two major models of the Input-Mediator-Output-Input (IMOI) framework and the Big Five dimensions of teamwork were reviewed and both will need significant development for application to future teams comprising non-human agents. Research suggests that a multi-method approach is appropriate for team measurements, such as the integration of methods from self-report, observer ratings, event-based measurement and automated recordings. Simulations are recommended as the most effective team-based training interventions. The impact of new technology and autonomous agents is discussed with respect to the changing nature of teamwork. In particular, whether existing teamwork models and measures are suitable to support the design, operation and evaluation of human-nonhuman teams of the future. Practitioner summary: This review recommends a multi-method approach to the measurement and evaluation of teamwork. Team models will need to be adapted to describe interaction with non-human agents, which is what the future is most likely to hold. The most effective team training interventions use simulation-based approaches.


Subject(s)
Patient Care Team , Humans
11.
Cereb Cortex ; 32(7): 1319-1336, 2022 03 30.
Article in English | MEDLINE | ID: mdl-34494095

ABSTRACT

Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in the processing of distal and proximal threat. Temporary inactivation of both aOFC and pOFC heightened responses to distal threat in the form of an unknown human, but not to proximal threat assessed in a discriminative Pavlovian conditioning task. Inactivation of the aOFC, however, did unexpectedly blunt conditioned threat responses, although the effect was not valence-specific, as conditioned appetitive responses were similarly blunted and appeared restricted to a discriminative version of the task (when both CS- and CS+ are present within a session). Inactivation of the pOFC did not affect conditioned responses to either proximal threat or reward and basal cardiovascular activity was unaffected by manipulations of activity in either subregion. The results highlight the contribution of aOFC and pOFC to regulation of responses to more distal uncertain but not proximal, certain threat and reveal their opposing contribution to that of the immediately adjacent medial OFC, area 14.


Subject(s)
Callithrix , Reward , Animals , Conditioning, Classical/physiology , Frontal Lobe/physiology , Prefrontal Cortex/physiology
12.
Ergonomics ; 65(3): 348-361, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34266371

ABSTRACT

While several competency frameworks have been proposed for Human Factors and Ergonomics (HFE) practitioners, these are not commonly based on structured analyses. The aim of this research was to develop a sociotechnical systems model of the HFE practitioner role in Australia and identify the competencies required to fulfil the role. Study One applied the Work Domain Analysis phase of cognitive work analysis (CWA) to model the HFE practitioner role. Model refinement was undertaken with seven subject matter experts. In Study Two, the model was used to elicit the competencies (knowledge, skills, abilities, other characteristics) required for successful performance, via a survey of 28 HFE practitioners. Most competencies related to skills (i.e. communication skills) and knowledge (i.e. domain knowledge). Gaps in competencies were also identified, linked to a lack of HFE education pathways in Australia. The findings have practical utility for designing HFE practitioner roles and educational programs. Practitioner summary: Cognitive work analysis provided a structured analysis of the role of the Human Factors and Ergonomics (HFE) practitioner and to support the identification of competencies. The results suggest that HFE practitioners are generalists rather than specialists and have implications for the job design and education of HFE practitioners. Abbreviations: BCPE: board of certification in professional ergonomics; CIEHF: chartered institute of ergonomics and human factors; CWA: cognitive work analysis; HFE: human factors and ergonomics; HFESA: human factors and ergonomics society of Australia; IEA: International Ergonomics Association; KSAO: knowledge, skills, abilities and other characteristics; O*NET: occupation information network; SME: subject matter expert; SRK: skills, rules, knowledge; UK: United Kingdom; USA: United States of America; WDA: work domain analysis.


Subject(s)
Cognition , Ergonomics , Australia , Ergonomics/methods , Humans , United Kingdom
13.
Appl Ergon ; 99: 103643, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34781180

ABSTRACT

Ecological Interface Design (EID) is a framework for developing dynamic interfaces that support operators to understand and take appropriate actions within highly-complex systems. This two-part study involved the development and evaluation of a novel EID-based static aviation risk management display. A within-subjects survey-based experiment employed measures of decision accuracy, situation awareness, user workload, usability, and user perceptions. Results from 23 participants showed that when compared to a risk interface utilised by a large aviation company, the EID display achieved higher usability and lower workload ratings with large effect sizes, with no differences in decision accuracy and situation awareness. The findings provide evidence that the EID framework can improve upon static traditional displays. Research contributions also include a novel model of an aviation ground operations system and an example application of EID to the development of a static display. Further research is necessary to identify the extent of the applications and benefits to static displays.


Subject(s)
Aviation , User-Computer Interface , Awareness , Humans , Risk Management
14.
Ergonomics ; 64(9): 1091-1114, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34243698

ABSTRACT

This paper reviews the key perspectives on human error and analyses the core theories and methods developed and applied over the last 60 years. These theories and methods have sought to improve our understanding of what human error is, and how and why it occurs, to facilitate the prediction of errors and use these insights to support safer work and societal systems. Yet, while this area of Ergonomics and Human Factors (EHF) has been influential and long-standing, the benefits of the 'human error approach' to understanding accidents and optimising system performance have been questioned. This state of science review analyses the construct of human error within EHF. It then discusses the key conceptual difficulties the construct faces in an era of systems EHF. Finally, a way forward is proposed to prompt further discussion within the EHF community. Practitioner statement This state-of-science review discusses the evolution of perspectives on human error as well as trends in the theories and methods applied to understand, prevent and mitigate error. It concludes that, although a useful contribution has been made, we must move beyond a focus on an individual error to systems failure to understand and optimise whole systems.


Subject(s)
Accidents , Ergonomics , Humans
15.
Hum Factors Ergon Manuf ; 31(4): 412-424, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34230798

ABSTRACT

Following strict "lockdown" restrictions designed to control the spread of the COVID-19 virus, many jurisdictions are now engaged in a process of easing restrictions in an attempt to stimulate economic and social activity while continuing to suppress virus transmission. This is challenging and complex, and in several regions, new outbreaks have emerged. We argue that systems Human Factors and Ergonomics methods can assist in understanding and optimizing the return from lockdown. To demonstrate, we used work domain analysis to develop an abstraction hierarchy model of a generic "return from lockdown restrictions" system. The model was assessed to identify (a) issues preventing a successful return from lockdown; and (b) leverage points that could be exploited to optimize future processes. The findings show that the aim of continuing to suppress virus transmission conflicts with the aims of returning to pre-virus economic and social activity levels. As a result, many functions act against each other, ensuring that the system cannot optimally achieve all three of its primary aims. Potential leverage points include modifying the goals and rules of the system and enhancing communications and feedback. Specifically, it is argued that moderating economic aims and modifying how social and community activities are undertaken will result in longer term suppression of the virus.

16.
Front Hum Neurosci ; 15: 673342, 2021.
Article in English | MEDLINE | ID: mdl-34194306

ABSTRACT

It is widely recognised that children with Down syndrome have a broad range and a high prevalence of visual deficits and it has been suggested that those with Down syndrome are more likely to exhibit visual perception deficits indicative of cerebral visual impairment. This exploratory study aims to determine the prevalence of behavioural features suggestive of cerebral visual impairment (CVI) occurring with Down syndrome and whether the visual problems can be ascribed to optometric factors. A cohort of 226 families of children with Down syndrome (trisomy 21), aged 4-17, were invited to participate in a validated question inventory, to recognise visual perception issues. The clinical records of the participants were then reviewed retrospectively. A five-question screening instrument was used to indicate suspected CVI. The majority of the 81 families who responded to the questionnaire reported some level of visual perceptual difficulty in their child. Among this cohort, the prevalence of suspected CVI as indicated by the screening questionnaire was 38%. Only ametropia was found to have a significant association with suspected CVI, although this increased the correct prediction of suspected CVI outcome by only a small amount. Results suggest that children with Down syndrome are more likely to experience problems consistent with cerebral visual impairment, and that these may originate from a similar brain dysfunction to that which contributes to high levels of ametropia and failure to emmetropise. It is important that behavioural features of CVI are recognised in children with Down syndrome, further investigations initiated and appropriate management applied.

17.
Cereb Cortex ; 31(10): 4765-4780, 2021 08 26.
Article in English | MEDLINE | ID: mdl-34076234

ABSTRACT

The midcingulate cortex (MCC) is associated with cognition and emotion regulation. Structural and correlational functional evidence suggests that rather than being homogenous, the MCC may have dissociable functions that can be mapped onto distinct subregions. In this study, we use the marmoset monkey to causally investigate the contributions of two proposed subregions of the MCC: the anterior and posterior midcingulate cortices (aMCC and pMCC) to behavioral and cardiovascular correlates of threat processing relevant to anxiety disorders. Transient inactivation of the aMCC decreased anxiety-like responses to a postencounter distal threat, namely an unfamiliar human intruder, while inactivation of the pMCC showed a mild but opposing effect. Furthermore, although inactivation of neither MCC subregions had any effect on basal cardiovascular activity, aMCC inactivation blunted the expression of both cardiovascular and behavioral conditioned responses to a predictable proximal threat (a rubber snake) during the extinction in a Pavlovian conditioning task, with pMCC inactivation having again an opposing effect, but primarily on the behavioral response. These findings suggest that the MCC is indeed functionally heterogeneous with regards to its role in threat processing, with aMCC providing a marked facilitative contribution to the expression of the emotional response to both proximal and distal threat.


Subject(s)
Fear/physiology , Gyrus Cinguli/physiology , Animals , Anxiety/psychology , Behavior, Animal , Brain Mapping , Callithrix , Cardiovascular Physiological Phenomena , Conditioning, Classical , Emotions , Female , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male
18.
Nature ; 593(7859): 351-361, 2021 05.
Article in English | MEDLINE | ID: mdl-34012079

ABSTRACT

High-energy-density physics is the field of physics concerned with studying matter at extremely high temperatures and densities. Such conditions produce highly nonlinear plasmas, in which several phenomena that can normally be treated independently of one another become strongly coupled. The study of these plasmas is important for our understanding of astrophysics, nuclear fusion and fundamental physics-however, the nonlinearities and strong couplings present in these extreme physical systems makes them very difficult to understand theoretically or to optimize experimentally. Here we argue that machine learning models and data-driven methods are in the process of reshaping our exploration of these extreme systems that have hitherto proved far too nonlinear for human researchers. From a fundamental perspective, our understanding can be improved by the way in which machine learning models can rapidly discover complex interactions in large datasets. From a practical point of view, the newest generation of extreme physics facilities can perform experiments multiple times a second (as opposed to approximately daily), thus moving away from human-based control towards automatic control based on real-time interpretation of diagnostic data and updates of the physics model. To make the most of these emerging opportunities, we suggest proposals for the community in terms of research design, training, best practice and support for synthetic diagnostics and data analysis.

19.
Hum Factors Ergon Manuf ; 31(4): 438-444, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33821127

ABSTRACT

The rail industry, as with all sectors worldwide, has faced disruptions due to the global COVID-19 pandemic. This commentary considers how rail organizations in Australia have engaged within the early stages of the crisis, outlining the challenges faced and how they were addressed. Relying on our observations, and anecdotes obtained from others across the Australian rail industry, we identified a range of impacts including determining service delivery levels (and the associated running of "ghost trains"), implementing hygiene measures and social distancing, managing training and medical assessments, and changes in the behavior of passengers and members of the public (including aggression toward staff and increased instances of trespass). Within rail organizations, we saw changes to communication and control structures, new challenges related to balancing priorities (managing risk of rail accidents vs. virus transmission risk), and negative impacts on job design offset by increased informal support for frontline workers. Importantly, from the crisis, we gained new insights about culture. Finally, we provide recommendations regarding how the Human Factors and Ergonomics discipline can support safe and effective rail operations in the context of both widespread crises such as pandemics as well as the less dramatic, but ever present, shifts in the physical, social, economic, and political environments in which rail organizations operate.

20.
Proc Natl Acad Sci U S A ; 117(40): 25116-25127, 2020 10 06.
Article in English | MEDLINE | ID: mdl-32958652

ABSTRACT

The ventromedial prefrontal cortex (vmPFC) is a key brain structure implicated in mood and anxiety disorders, based primarily on evidence from correlational neuroimaging studies. Composed of a number of brain regions with distinct architecture and connectivity, dissecting its functional heterogeneity will provide key insights into the symptomatology of these disorders. Focusing on area 14, lying on the medial and orbital surfaces of the gyrus rectus, this study addresses a key question of causality. Do changes in area 14 activity induce changes in threat- and reward-elicited responses within the nonhuman primate, the common marmoset, similar to that seen in mood and anxiety disorders? Area 14 overactivation was found to induce heightened responsivity to uncertain, low-imminence threat while blunting cardiovascular and behavioral anticipatory arousal to high-value food reward. Conversely, inactivation enhanced the arousal to high-value reward cues while dampening the acquisition of cardiovascular and behavioral responses to a Pavlovian threat cue. Basal cardiovascular activity, including heart rate variability and sympathovagal balance, which are dysfunctional in mood and anxiety disorders, are insensitive to alterations in area 14 activity as is the extinction of conditioned threat responses. The distinct pattern of dysregulation compared to neighboring region area 25 highlights the heterogeneity of function within vmPFC and reveals how the effects of area 14 overactivation on positive and negative reactivity mirror symptoms of anhedonia and anxiety that are so often comorbid in mood disorders.


Subject(s)
Anxiety/diagnostic imaging , Brain Mapping , Callithrix/physiology , Prefrontal Cortex/diagnostic imaging , Animals , Anxiety/physiopathology , Conditioning, Classical/physiology , Heart Rate/physiology , Humans , Magnetic Resonance Imaging , Prefrontal Cortex/physiology , Reward
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