scholarly journals The role of the rodent lateral orbitofrontal cortex in simple Pavlovian cue-outcome learning depends on training experience

2020 ◽  
Author(s):  
Marios C. Panayi ◽  
Simon Killcross
Keyword(s):  
Orbitofrontal Cortex ◽  
Behavioural Control ◽  
Complex Environments ◽  
Training Experience ◽  
Flexible Control ◽  
Null Effect ◽  
Outcome Relationship ◽  
Associative Blocking ◽  
Critical Structure

AbstractThe orbitofrontal cortex (OFC) is a critical structure in the flexible control of value-based behaviours. OFC dysfunction is typically only detected when task or environmental contingencies change, against a backdrop of apparently intact initial acquisition and behaviour. While intact acquisition following OFC lesions in simple Pavlovian cue-outcome conditioning is often predicted by models of OFC function, this predicted null effect has not been thoroughly investigated. Here we test the effects of lesions and temporary muscimol inactivation of the rodent lateral OFC on the acquisition of a simple single cue-outcome relationship. Surprisingly, pre-training lesions significantly enhanced acquisition after over-training whereas post-training lesions and inactivation significantly impaired acquisition. This impaired acquisition to the cue reflects a disruption of behavioural control and not learning since the cue could also act as an effective blocking stimulus in an associative blocking procedure. These findings suggest that even simple cue-outcome representations acquired in the absence of OFC function are impoverished. Therefore, while OFC function is often associated with flexible behavioural control in complex environments, it is also involved in very simple Pavlovian acquisition where complex cue-outcome relationships are irrelevant to task performance.

scholarly journals The Role of the Rodent Lateral Orbitofrontal Cortex in Simple Pavlovian Cue-Outcome Learning Depends on Training Experience

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Marios C Panayi ◽  
Simon Killcross
Keyword(s):  
Orbitofrontal Cortex ◽  
Behavioral Control ◽  
Complex Environments ◽  
Training Experience ◽  
Flexible Control ◽  
Outcome Relationship ◽  
Associative Blocking ◽  
And Behavior ◽  
Critical Structure

Abstract The orbitofrontal cortex (OFC) is a critical structure in the flexible control of value-based behaviors. OFC dysfunction is typically only detected when task or environmental contingencies change, against a backdrop of apparently intact initial acquisition and behavior. While intact acquisition following OFC lesions in simple Pavlovian cue-outcome conditioning is often predicted by models of OFC function, this predicted null effect has not been thoroughly investigated. Here, we test the effects of lesions and temporary muscimol inactivation of the rodent lateral OFC on the acquisition of a simple single cue-outcome relationship. Surprisingly, pretraining lesions significantly enhanced acquisition after overtraining, whereas post-training lesions and inactivation significantly impaired acquisition. This impaired acquisition to the cue reflects a disruption of behavioral control and not learning since the cue could also act as an effective blocking stimulus in an associative blocking procedure. These findings suggest that even simple cue-outcome representations acquired in the absence of OFC function are impoverished. Therefore, while OFC function is often associated with flexible behavioral control in complex environments, it is also involved in very simple Pavlovian acquisition where complex cue-outcome relationships are irrelevant to task performance.

scholarly journals Cortical and thalamic influences on striatal involvement in instructed, serial reversal learning; implications for the organisation of flexible behaviour.

2021 ◽  
Author(s):  
Brendan Williams ◽  
Anastasia Christakou
Keyword(s):  
Functional Connectivity ◽  
Cognitive Flexibility ◽  
Reversal Learning ◽  
Orbitofrontal Cortex ◽  
Dorsal Striatum ◽  
Response Strategy ◽  
Flexible Control ◽  
The Right ◽  
Serial Reversal

Cognitive flexibility is essential for enabling an individual to respond adaptively to changes in their environment. Evidence from human and animal research suggests that the control of cognitive flexibility is dependent on an array of neural architecture. Cortico-basal ganglia circuits have long been implicated in cognitive flexibility. In particular, the role of the striatum is pivotal, acting as an integrative hub for inputs from the prefrontal cortex and thalamus, and modulation by dopamine and acetylcholine. Striatal cholinergic modulation has been implicated in the flexible control of behaviour, driven by input from the centromedian-parafascicular nuclei of the thalamus. However, the role of this system in humans is not clearly defined as much of the current literature is based on animal work. Here, we aim to investigate the roles corticostriatal and thalamostriatal connectivity in serial reversal learning. Functional connectivity between the left centromedian-parafascicular nuclei and the associative dorsal striatum was significantly increased for negative feedback compared to positive feedback. Similar differences in functional connectivity were observed for the right lateral orbitofrontal cortex, but these were localised to when participants switched to using an alternate response strategy following reversal. These findings suggest that connectivity between the centromedian-parafascicular nuclei and the striatum may be used to generally identify potential changes in context based on negative outcomes, and the effect of this signal on striatal output may be influenced by connectivity between the lateral orbitofrontal cortex and the striatum.

scholarly journals A triple combination of treatments on moderate COVID-19

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 769-772
Author(s):  
ChunMiao Bao ◽  
BinBin Li ◽  
YuFeng Zhou
Keyword(s):  
Medical Records ◽  
Clinical Characteristics ◽  
Smoking Status ◽  
Length Of Hospital Stay ◽  
Convincing Evidence ◽  
Triple Combination ◽  
Viral Shedding ◽  
Null Effect ◽  
Treatment Start

Abstract Objective A triple combination of interferon (IFN) α-2b, lopinavir tablets, and umifenovir was used to treat COVID-19 patients. It is important to explore whether the benefit of this therapy is time dependent. Methods A cohort of moderate COVID-19 patients (n = 54) was admitted for hospitalization. The demographic (age, gender, and smoking status) and clinical characteristics (epidemiological trace and comorbidity) were collected from the digital medical records. The length of hospital stay (LOS) and the viral shedding time (VST) were set as the outcomes for COVID-19 cases. Results After control for age, sex, epidemiological trace, smoking, and comorbidity, the time of treatment start had null effect on VST (IRR = 1.09; 95% CI = 0.91–1.30; p = 0.33) or LOS (IRR = 1.10; 95% CI = 0.94–1.28; p = 0.23). Conclusion There is no convincing evidence to support a pivotal role of the timing of the therapy in the prognosis of moderate COVID-19 cases.

scholarly journals The role of salient beliefs in graduates’ intention to apply

2015 ◽  
Vol 41 (1) ◽  
Author(s):  
Samantha Adams ◽  
François De Kock
Keyword(s):  
Empirical Support ◽  
Behavioural Control ◽  
Control Beliefs ◽  
Future Research ◽  
Research Approach ◽  
Application Process ◽  
Perceived Behavioural Control ◽  
Latent Variable Analysis ◽  
Study Results

Orientation: Organisations compete fiercely to recruit the best graduates, because they consider them a rich source of future talent. In the recruitment literature, it has become increasingly important to understand the factors that influence graduate applicant intentions. Research purpose: Drawing on the theory of planned behaviour (TPB), we tested a model proposing that applicant intention is a function of their attitude towards applying, beliefs about referent other’s expectations (subjective norms) and perceived behavioural control with respect to this behaviour.Motivation for the study: The study was motivated by the need to shed light on graduate applicants’ decisions to apply to an organisation of their choice. Research approach, design and method: The study used a quantitative design to test hypotheses that attitudes towards behaviour, norms and control beliefs would influence intention to apply. We surveyed prospective job seekers (N = 854) studying at a South African university about their beliefs regarding the job application process. Main findings: Structural equation modelling showed reasonable fit of the proposed model to the survey data. Latent variable analysis demonstrated that perceived behavioural control and subjective norm explained intention to apply. With the combination of all three variables, only attitude towards applying did not play a significant role in the prediction of intention to apply, which is contrary to previous research. Practical/managerial implications: The findings highlight the role of salient control beliefs in the application process. Efforts by universities and organisations to affect intentions to apply may potentially benefit from focusing on support services that could enhance feelings of control and minimise perceived obstacles. Recruiters could focus on control to increase potential recruitment pools. Contribution/value-add: The study contributes to the recruitment literature in three ways. Firstly, TPB is shown to be a useful framework to explain graduate applicants’ intention to apply, as this theoretical model found empirical support. In doing so, the present study advances our understanding of how graduates’ intentions to apply are formed. Secondly, the results showed that applicants’ control and normative beliefs dominate when considering applying. Lastly, the study results open up interesting avenues for future research on applicant intentions.

Exploring the lived experience of endoscopy trainees and their perceptions of nurse endoscopists as trainers

2021 ◽  
Vol 19 (Sup8) ◽  
pp. S14-S21
Author(s):  
Leigh Donnelly ◽  
Alison Steven
Keyword(s):  
Lived Experience ◽  
Emotional Impact ◽  
Training Experience ◽  
Endoscopy Training ◽  
Constructive Feedback ◽  
Self Confidence ◽  
Therapeutic Procedures ◽  
Emerging Themes ◽  
Increasing Demand

Background UK endoscopy services face considerable workforce pressures from an increasing demand for procedures. To meet this need, health services have introduced the role of nurse endoscopist (also known as clinical, non-medical or non-physician endoscopist). These roles have grown and developed to include performing many complex diagnostic and therapeutic procedures, as well as the provision of endoscopy training. Aims This study examines the lived experiences of (nurse and medical) endoscopy trainees, especially regarding being trained by nurse endoscopists. Methods The study employed interpretive phenomenological analysis (IPA). Data were collected through semi-structured in-depth interviews of 10 participants, who were selected from a sample of trainees attending a basic colonoscopy skills course. Interviews were preceded by observations to gain contextual insights into the training experience. The data were analysed in stages through a process of reading and re-reading the transcripts, making initial descriptive observations and then annotating with discursive, linguistic and conceptual comments. Findings Four emerging themes were identified. A lack self-confidence was a barrier to progression, compounded by the emotional impact of making mistakes without comprehensible constructive feedback. Attitudes of trainers and other endoscopy staff, as well as their relationships with trainees, had an impact on self-confidence and educational experience. Pressure on endoscopy units to perform procedures led to a tendency to treat training like a burden, although training was seen as an important investment. Trainees sought to differentiate nurse endoscopist and medical endoscopist roles and justify their skills and value, with comparisons between different nurse and medical trainers. Conclusion The emerging themes illustrate the requirement for a collegiate approach to endoscopy training.

scholarly journals Phosphoregulation of the intracellular termini of K+-Cl− cotransporter 2 (KCC2) enables flexible control of its activity

2018 ◽  
Vol 293 (44) ◽  
pp. 16984-16993 ◽  
Author(s):  
Antje Cordshagen ◽  
Wiebke Busch ◽  
Michael Winklhofer ◽  
Hans Gerd Nothwang ◽  
Anna-Maria Hartmann
Keyword(s):  
Intrinsic Activity ◽  
Hek 293 ◽  
Flexible Control ◽  
Mediated Effects ◽  
293 Cells ◽  
Bona Fide ◽  
Graded Activity ◽  
First Time ◽  
Increased Activity

The pivotal role of K+-Cl− cotransporter 2 (KCC2) in inhibitory neurotransmission and severe human diseases fosters interest in understanding posttranslational regulatory mechanisms such as (de)phosphorylation. Here, the regulatory role of the five bona fide phosphosites Ser31, Thr34, Ser932, Thr999, and Thr1008 was investigated by the use of alanine and aspartate mutants. Tl+-based flux analyses in HEK-293 cells demonstrated increased transport activity for S932D (mimicking phosphorylation) and T1008A (mimicking dephosphorylation), albeit to a different extent. Increased activity was due to changes in intrinsic activity, as it was not caused by increased cell-surface abundance. Substitutions of Ser31, Thr34, or Thr999 had no effect. Additionally, we show that the indirect actions of the known KCC2 activators staurosporine and N-ethylmaleimide (NEM) involved multiple phosphosites. S31D, T34A, S932A/D, T999A, or T1008A/D abrogated staurosporine mediated stimulation, and S31A, T34D, or S932D abolished NEM-mediated stimulation. This demonstrates for the first time differential effects of staurosporine and NEM on KCC2. In addition, the staurosporine-mediated effects involved both KCC2 phosphorylation and dephosphorylation with Ser932 and Thr1008 being bona fide target sites. In summary, our data reveal a complex phosphoregulation of KCC2 that provides the transporter with a toolbox for graded activity and integration of different signaling pathways.

scholarly journals The leadership and followership challenges of doctors in training during the COVID-19 pandemic

2021 ◽  
pp. 1-9
Author(s):  
Nathan Boardman ◽  
Jack Munro-Berry ◽  
Judy McKimm
Keyword(s):  
Early Career ◽  
Formal Training ◽  
Clinical Environment ◽  
Training Experience ◽  
Healthcare Leadership ◽  
Leadership Culture ◽  
Team Working ◽  
Medical Education And Training ◽  
And Training

Research carried out in 2016 by the authors investigated the challenges that doctors in training experience around leadership and followership in the NHS. The study explored contemporary healthcare leadership culture and the role of followership from the perspective of early career doctors. It found that the leadership and followership challenges for these doctors in training were associated with issues of social and professional identity, communication, the medical hierarchy, and relationships with senior colleagues (support and trust). These challenges were exacerbated by the busy and turbulent clinical environment in which they worked. To cope with various clinical situations and forms of leadership, doctors in training engage in a range of different followership behaviours and strategies. The study raised implications for medical education and training and suggested that followership should be included as part of formal training in communication and team working skills. The importance of both leadership and followership in the delivery of safe and effective patient care has been brought sharply into focus by the COVID-19 pandemic. This article revisits these challenges in light of the pandemic and its impact on the experiences of doctors in training.

scholarly journals Interacting roles of lateral and medial Orbitofrontal cortex in decision-making and learning : A system-level computational model

2019 ◽  
Author(s):  
Bhargav Teja Nallapu ◽  
Frédéric Alexandre
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Computational Model ◽  
Orbitofrontal Cortex ◽  
Temporal Dynamics ◽  
System Level ◽  
Interacting Networks ◽  
Cortical Regions ◽  
Experimental Findings

AbstractIn the context of flexible and adaptive animal behavior, the orbitofrontal cortex (OFC) is found to be one of the crucial regions in the prefrontal cortex (PFC) influencing the downstream processes of decision-making and learning in the sub-cortical regions. Although OFC has been implicated to be important in a variety of related behavioral processes, the exact mechanisms are unclear, through which the OFC encodes or processes information related to decision-making and learning. Here, we propose a systems-level view of the OFC, positioning it at the nexus of sub-cortical systems and other prefrontal regions. Particularly we focus on one of the most recent implications of neuroscientific evidences regarding the OFC - possible functional dissociation between two of its sub-regions : lateral and medial. We present a system-level computational model of decision-making and learning involving the two sub-regions taking into account their individual roles as commonly implicated in neuroscientific studies. We emphasize on the role of the interactions between the sub-regions within the OFC as well as the role of other sub-cortical structures which form a network with them. We leverage well-known computational architecture of thalamo-cortical basal ganglia loops, accounting for recent experimental findings on monkeys with lateral and medial OFC lesions, performing a 3-arm bandit task. First we replicate the seemingly dissociate effects of lesions to lateral and medial OFC during decision-making as a function of value-difference of the presented options. Further we demonstrate and argue that such an effect is not necessarily due to the dissociate roles of both the subregions, but rather a result of complex temporal dynamics between the interacting networks in which they are involved.Author summaryWe first highlight the role of the Orbitofrontal Cortex (OFC) in value-based decision making and goal-directed behavior in primates. We establish the position of OFC at the intersection of cortical mechanisms and thalamo-basal ganglial circuits. In order to understand possible mechanisms through which the OFC exerts emotional control over behavior, among several other possibilities, we consider the case of dissociate roles of two of its topographical subregions - lateral and medial parts of OFC. We gather predominant roles of each of these sub-regions as suggested by numerous experimental evidences in the form of a system-level computational model that is based on existing neuronal architectures. We argue that besides possible dissociation, there could be possible interaction of these sub-regions within themselves and through other sub-cortical structures, in distinct mechanisms of choice and learning. The computational framework described accounts for experimental data and can be extended to more comprehensive detail of representations required to understand the processes of decision-making, learning and the role of OFC and subsequently the regions of prefrontal cortex in general.

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