c- fos mRNA Induction in Acute and Chronic Audiogenic Stress: Possible Role of the Orbitofrontal Cortex in Habituation

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.

Download Full-text

Dissociable oscillatory networks support gain and loss processing in human orbitofrontal cortex

10.1101/2021.02.25.432874 ◽

2021 ◽

Author(s):

Ignacio Saez ◽

Jack Lin ◽

Edward Chang ◽

Josef Parvizi ◽

Robert T. Knight ◽

...

Keyword(s):

Neural Activity ◽

Orbitofrontal Cortex ◽

Low Frequency ◽

Brain Regions ◽

Reward Processing ◽

Neural Oscillations ◽

Beta Band ◽

Neuronal Ensembles ◽

Gain And Loss

AbstractHuman neuroimaging and animal studies have linked neural activity in orbitofrontal cortex (OFC) to valuation of positive and negative outcomes. Additional evidence shows that neural oscillations, representing the coordinated activity of neuronal ensembles, support information processing in both animal and human prefrontal regions. However, the role of OFC neural oscillations in reward-processing in humans remains unknown, partly due to the difficulty of recording oscillatory neural activity from deep brain regions. Here, we examined the role of OFC neural oscillations (<30Hz) in reward processing by combining intracranial OFC recordings with a gambling task in which patients made economic decisions under uncertainty. Our results show that power in different oscillatory bands are associated with distinct components of reward evaluation. Specifically, we observed a double dissociation, with a selective theta band oscillation increase in response to monetary gains and a beta band increase in response to losses. These effects were interleaved across OFC in overlapping networks and were accompanied by increases in oscillatory coherence between OFC electrode sites in theta and beta band during gain and loss processing, respectively. These results provide evidence that gain and loss processing in human OFC are supported by distinct low-frequency oscillations in networks, and provide evidence that participating neuronal ensembles are organized functionally through oscillatory coherence, rather than local anatomical segregation.

Download Full-text

The role of human orbitofrontal cortex in reward prediction and behavioral choice: insights from neuroimaging

The Orbitofrontal Cortex ◽

10.1093/acprof:oso/9780198565741.003.0010 ◽

2006 ◽

pp. 265-284 ◽

Cited By ~ 12

Author(s):

John P. O'Doherty ◽

Raymond J. Dolan

Keyword(s):

Orbitofrontal Cortex ◽

Behavioral Choice ◽

Reward Prediction

Download Full-text

Neuroscience: Reevaluating the Role of Orbitofrontal Cortex

Current Biology ◽

10.1016/j.cub.2019.10.063 ◽

2019 ◽

Vol 29 (24) ◽

pp. R1314-R1316

Author(s):

Brianna J. Sleezer ◽

Benjamin Yost Hayden

Keyword(s):

Orbitofrontal Cortex

Download Full-text

Role of oxidants in influenza virus-induced gene expression

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.274.1.l134 ◽

1998 ◽

Vol 274 (1) ◽

pp. L134-L142 ◽

Cited By ~ 13

Author(s):

Katharine Knobil ◽

Augustine M. K. Choi ◽

Gordon W. Weigand ◽

David B. Jacoby

Keyword(s):

Gene Expression ◽

Cell Death ◽

Influenza Virus ◽

Virus Infection ◽

A549 Cells ◽

Influenza Virus Infection ◽

Pyrrolidine Dithiocarbamate ◽

Oxygen Intermediates ◽

Mrna Induction

Influenza virus-induced epithelial damage may be mediated, in part, by reactive oxygen intermediates (ROIs). In this study, we investigated the role of ROIs in the influenza virus-induced gene expression of antioxidant enzymes and in the activation of nuclear factor-κB (NF-κB), an oxidant-sensitive transcriptional factor. Influenza virus infection increased production of intracellular ROIs in A549 pulmonary epithelial cells. Induction of manganese superoxide dismutase (MnSOD) mRNA correlated with increased MnSOD protein and enzyme activity. Influenza virus infection also activated NF-κB binding as determined by an electrophoretic mobility shift assay. Pretreatment of A549 cells with N-acetyl-l-cysteine attenuated virus-induced NF-κB activation and interleukin (IL)-8 mRNA induction but did not block induction of MnSOD mRNA. In contrast, pyrrolidine dithiocarbamate blocked activation of NF-κB and induction of MnSOD and IL-8 mRNAs. Treatment with pyrrolidine dithiocarbamate also markedly decreased virus-induced cell death. Thus oxidants are involved in influenza virus-induced activation of NF-κB, in the expression of IL-8 and MnSOD, and in virus-induced cell death.

Download Full-text

Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

Addiction Biology ◽

10.1111/adb.12927 ◽

2020 ◽

Cited By ~ 1

Author(s):

Rachel D. Altshuler ◽

Eddy S. Yang ◽

Kristine T. Garcia ◽

Ian R. Davis ◽

Adedayo Olaniran ◽

...

Keyword(s):

Orbitofrontal Cortex ◽

Male Rats

Download Full-text

Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance

International Journal of Obesity ◽

10.1038/s41366-021-00953-9 ◽

2021 ◽

Author(s):

O. Contreras-Rodriguez ◽

M. Arnoriaga-Rodríguez ◽

R. Miranda-Olivos ◽

G. Blasco ◽

C. Biarnés ◽

...

Keyword(s):

Depressive Symptoms ◽

Functional Connectivity ◽

Orbitofrontal Cortex ◽

Executive Dysfunction ◽

Structural Covariance ◽

Gut Dysbiosis ◽

Obesity Status ◽

Subcortical Nuclei ◽

Parietal Cortices

Abstract Background Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. Methods Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. Results Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. Conclusions Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.

Download Full-text

Neural Mechanisms of the Testosterone–Aggression Relation: The Role of Orbitofrontal Cortex

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21389 ◽

2010 ◽

Vol 22 (10) ◽

pp. 2357-2368 ◽

Cited By ~ 180

Author(s):

Pranjal H. Mehta ◽

Jennifer Beer

Keyword(s):

Decision Making ◽

Aggressive Behavior ◽

Orbitofrontal Cortex ◽

Impulse Control ◽

Ultimatum Game ◽

Self Regulation ◽

Neural Circuitry ◽

Neural Mechanisms ◽

Reduced Activity

Testosterone plays a role in aggressive behavior, but the mechanisms remain unclear. The present study tested the hypothesis that testosterone influences aggression through the OFC, a region implicated in self-regulation and impulse control. In a decision-making paradigm in which people chose between aggression and monetary reward (the ultimatum game), testosterone was associated with increased aggression following social provocation (rejecting unfair offers). The effect of testosterone on aggression was explained by reduced activity in the medial OFC. The findings suggest that testosterone increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation.

Download Full-text