Value Representations in the Rodent Orbitofrontal Cortex Drive Learning, not Choice

AbstractHumans and animals make predictions about the rewards they expect to receive in different situations. In formal models of behavior, these predictions are known as value representations, and they play two very different roles. Firstly, they drive choice: the expected values of available options are compared to one another, and the best option is selected. Secondly, they support learning: expected values are compared to rewards actually received, and future expectations are updated accordingly. Whether these different functions are mediated by different neural representations remains an open question. Here we employ a recently-developed multi-step task for rats that computationally separates learning from choosing. We investigate the role of value representations in the rodent orbitofrontal cortex, a key structure for value-based cognition. Electrophysiological recordings and optogenetic perturbations indicate that these representations do not directly drive choice. Instead, they signal expected reward information to a learning process elsewhere in the brain that updates choice mechanisms.

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TRANSGENIC MOUSE MODELS OF ALZHEIMER’S DISEASE

Innovation in Aging ◽

10.1093/geroni/igz038.3077 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S835-S835

Author(s):

Charnae A Henry-Smith ◽

Xianlin Han

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Models ◽

Myelin Sheath ◽

Thinking Skills ◽

Drug Dosage ◽

Whole Body ◽

To Receive ◽

The Brain

Abstract Alzheimer’s disease is a progressive brain disease that slowly destroys memory and thinking skills. Alzheimer’s is characterized by an increase in Aβ plaques , and tau tangles. Neurons in the brain have axons covered in myelin sheath that connect microglia and astrocytes. The myelin sheath is composed of about 70% lipid composition; Sulfatide contributing to 30% overall. Sulfatide changes the morphology of primary microglia to their activated form. To study the role of microglia activation and sulfatide levels, three different mouse models were created: APP KI mice, CST Whole Body Ko mice, and cCST (conditional) KO. In order to create the genotype of the APP KI mice, a breeding mouse line was created. The APP KI gene had to be introduced in Plp1-Cre and cCST KO crossed mice to receive a working mouse model. During the duration of breeding for the APP KI mice, a preliminary experiment was performed on the CST KO mice. These mice were given the PLX3397 diet with the aim to remove the microglia and to see the effect of Aβ plaques. The PLX3397 will reduce the microglia targeting the CSF1R. After consuming the diet, the mice were harvested to collect tissues from the brain and spinal cord. Lipidomics and immunohistology were performed. In conclusion, we will continue the breeding of the CST flox/flox / Plp1-Cre / APP KI mice, and the drug dosage and treatment to be used in our APP KI mice will be based on preliminary data from our CST mice.

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Orthogonal Representations of Reward Magnitude, Certainty, and Volatility in the Macaque Orbitofrontal Cortex

10.1101/365080 ◽

2018 ◽

Author(s):

Tianming Yang ◽

Elisabeth A. Murray

Keyword(s):

Reward Magnitude ◽

Orbitofrontal Cortex ◽

Stimulus Presentation ◽

Two Dimensions ◽

Foraging Strategies ◽

General Role ◽

Decision Variables ◽

Categorical Knowledge ◽

Reward Information ◽

The Brain

AbstractCategorical knowledge about the probabilistic and volatile nature of resource availability can improve foraging strategies, yet we have little understanding of how the brain represents such knowledge. Neurons in the orbitofrontal cortex (OFC) of macaques encode several decision variables (e.g., reward magnitude, probability) that could influence choice behavior. Here we investigated whether OFC neurons also represent two aspects of reward predictability: certainty and volatility. Rhesus monkeys performed a visual stimulus-reward association task in which a set of simple shapes preceded the delivery of reward, and they learned the nature of each shape’s reward association along two dimensions. One involved the certainty of a reward outcome; rewards can be either deterministic (and therefore certain) or probabilistic (uncertain). A second dimension reflected the volatility of an outcome; reward schedules can be either stable over time or volatile. During stimulus presentation, the activity of OFC neurons reflected both categorical certainty and categorical volatility, in addition to reward magnitude. These three characteristics were represented orthogonally by three distinct neural populations of similar size. These findings point to a more general role for OFC in processing reward information than one restricted to encoding parametric valuations such as reward magnitude and probability.

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Prenatal Visual Exposure to a Predator Influences Lateralization in Goldbelly Topminnows

Symmetry ◽

10.3390/sym12081257 ◽

2020 ◽

Vol 12 (8) ◽

pp. 1257

Author(s):

Marco Dadda ◽

Veronica Vendramin ◽

Christian Agrillo

Keyword(s):

Prenatal Exposure ◽

Genetic Basis ◽

Brain Lateralization ◽

Light Stimulation ◽

Visual Exposure ◽

Motor Tests ◽

Genetic And Environmental Factors ◽

Open Question ◽

The Brain

The role of genetic and environmental factors in modulating the development of brain lateralization is far from being fully understood, and the presence of individual differences in several lateralized functions is still an open question. In goldbelly topminnows, the genetic basis of asymmetrical functions in the brain has been studied, and recently it has been found that light stimulation influences the expression of lateralization of newborns. Here, we investigated whether prenatal exposure to predators affects the development of lateralization in 10-day-old topminnows born from females exposed to a real or to a simulated predator during pregnancy. Offspring from females exposed to a real predator were lateralized in both visual and motor tests, whereas fish from females exposed to a simulated predator were not and did not differ from controls. Prenatal exposure to a real predator might promote the alignment of lateralization in the same direction in different individuals.

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The role of cytokines in the processes of adaptive integration of immune and neuroendocrine reactions of the human body

Problems of Endocrinology ◽

10.14341/probl12744 ◽

2021 ◽

Vol 67 (2) ◽

pp. 4-9

Author(s):

E. A. Troshina

Keyword(s):

Immune Responses ◽

Therapeutic Strategies ◽

Main Task ◽

Combined Effects ◽

Immune Stimulation ◽

Adaptive Integration ◽

The Subject ◽

To Receive ◽

The Brain

The immune, endocrine and nervous systems are integrated due to the existence of reciprocal pathways for transmitting information about changes in their actual functional state. The main task of the brain is to receive, integrate and store information, and there is strong evidence that this also applies to information obtained through the body’s immune responses. It has been proven that the production of cytokines in the brain can be caused not only by peripheral immune stimulation, but also by the nerve cells themselves, stimulated by certain neurosensory signals. Evolutionarily preserved antihomeostatic mechanisms characteristic of specific diseases are the subject of further research, the results of which may be very important for the development of therapeutic strategies that would prevent the undesirable combined effects of immune and neuroendocrine mediators.

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Multivariate spatial feature selection in fMRI

Social Cognitive and Affective Neuroscience ◽

10.1093/scan/nsab010 ◽

2021 ◽

Author(s):

E Jolly ◽

L J Chang

Keyword(s):

Spatial Scale ◽

Cognitive Processes ◽

Multivariate Analyses ◽

Spatial Spectrum ◽

Psychological Processes ◽

Spatial Feature ◽

Neural Representations ◽

Open Question ◽

Local Representations ◽

The Brain

Abstract Multivariate neuroimaging analyses constitute a powerful class of techniques to identify psychological representations. However, not all psychological processes are represented at the same spatial scale throughout the brain. This heterogeneity is apparent when comparing hierarchically organized local representations of perceptual processes to flexible transmodal representations of more abstract cognitive processes such as social and affective operations. An open question is how the spatial scale of analytic approaches interacts with the spatial scale of the representations under investigation. In this article, we describe how multivariate analyses can be viewed as existing on a spatial spectrum, anchored by searchlights used to identify locally distributed patterns of information on one end, whole brain approach used to identify diffuse neural representations at the other and region-based approaches in between. We describe how these distinctions are an important and often overlooked analytic consideration and provide heuristics to compare these different techniques to choose based on the analyst’s inferential goals.

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Hope and the brain: Trait hope mediates the protective role of medial orbitofrontal cortex spontaneous activity against anxiety

NeuroImage ◽

10.1016/j.neuroimage.2017.05.056 ◽

2017 ◽

Vol 157 ◽

pp. 439-447 ◽

Cited By ~ 20

Author(s):

Song Wang ◽

Xin Xu ◽

Ming Zhou ◽

Taolin Chen ◽

Xun Yang ◽

...

Keyword(s):

Spontaneous Activity ◽

Orbitofrontal Cortex ◽

Protective Role ◽

Trait Hope ◽

The Brain

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Dynamic interactions between top-down expectations and conscious awareness

10.1101/151019 ◽

2017 ◽

Cited By ~ 1

Author(s):

Erik L. Meijs ◽

Heleen A. Slagter ◽

Floris P. de Lange ◽

Simon van Gaal

Keyword(s):

Attentional Blink ◽

Conscious Awareness ◽

Prediction Errors ◽

Top Down ◽

Dynamic Interactions ◽

Electrophysiological Recordings ◽

Stimulus Perception ◽

The Relationship ◽

The Brain

AbstractIt is well known that top-down expectations affect perceptual processes. Yet, remarkably little is known about the relationship between expectations and conscious awareness We address three crucial questions that are outstanding: 1) How do predictions affect the likelihood of conscious stimulus perception?; 2) Does the brain register violations of predictions nonconsciously?; and 3) Do predictions need to be conscious to influence perceptual decisions? We performed three experiments in which we manipulated stimulus predictability within the attentional blink paradigm, while combining visual psychophysics with electrophysiological recordings. We found that valid stimulus expectations increase the likelihood of conscious access of stimuli. Furthermore, our findings suggest a clear dissociation in the interaction between expectations and consciousness: conscious awareness seems crucial for the implementation of top-down predictions, but not for the bottom-up generation of stimulus-evoked prediction errors. These results constrain and update influential theories about the role of consciousness in the predictive brain.

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Differential attentional control mechanisms by two distinct noradrenergic coeruleo-frontal cortical pathways

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2015635117 ◽

2020 ◽

Vol 117 (46) ◽

pp. 29080-29089

Author(s):

Andrea Bari ◽

Sangyu Xu ◽

Michele Pignatelli ◽

Daigo Takeuchi ◽

Jiesi Feng ◽

...

Keyword(s):

Response Inhibition ◽

Orbitofrontal Cortex ◽

Attentional Control ◽

Control Mechanisms ◽

Impulsive Behavior ◽

Pathological Conditions ◽

Neuron Activation ◽

Medial Pfc ◽

The Brain

The attentional control of behavior is a higher-order cognitive function that operates through attention and response inhibition. The locus coeruleus (LC), the main source of norepinephrine in the brain, is considered to be involved in attentional control by modulating the neuronal activity of the prefrontal cortex (PFC). However, evidence for the causal role of LC activity in attentional control remains elusive. Here, by using behavioral and optogenetic techniques, we investigate the effect of LC neuron activation or inhibition in operant tests measuring attention and response inhibition (i.e., a measure of impulsive behavior). We show that LC neuron stimulation increases goal-directed attention and decreases impulsivity, while its suppression exacerbates distractibility and increases impulsive responding. Remarkably, we found that attention and response inhibition are under the control of two divergent projections emanating from the LC: one to the dorso-medial PFC and the other to the ventro-lateral orbitofrontal cortex, respectively. These findings are especially relevant for those pathological conditions characterized by attention deficits and elevated impulsivity.

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Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

Clinical and Developmental Immunology ◽

10.1155/2012/937253 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 10

Author(s):

Theodore S. Johnson ◽

David H. Munn ◽

Bernard L. Maria

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tumor Infiltrating Lymphocytes ◽

Tolerance Mechanism ◽

Antigen Presenting ◽

Open Question ◽

Infiltrating Lymphocytes ◽

The Impact ◽

The Brain

Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

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