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Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes

Clinical studies have shown that patients with anxiety disorders exhibited coactivation of limbic cortices and basal ganglia, which together form a large-scale brain network. The mechanisms by which such a large-scale network could induce or modulate anxiety-like states are largely unknown. This art...

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Autores principales: Amemori, Satoko, Graybiel, Ann M., Amemori, Ken-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277931/
https://www.ncbi.nlm.nih.gov/pubmed/34276282
http://dx.doi.org/10.3389/fnins.2021.649167
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author Amemori, Satoko
Graybiel, Ann M.
Amemori, Ken-ichi
author_facet Amemori, Satoko
Graybiel, Ann M.
Amemori, Ken-ichi
author_sort Amemori, Satoko
collection PubMed
description Clinical studies have shown that patients with anxiety disorders exhibited coactivation of limbic cortices and basal ganglia, which together form a large-scale brain network. The mechanisms by which such a large-scale network could induce or modulate anxiety-like states are largely unknown. This article reviews our experimental program in macaques demonstrating a causal involvement of local striatal and frontal cortical sites in inducing pessimistic decision-making that underlies anxiety. Where relevant, we related these findings to the wider literature. To identify such sites, we have made a series of methodologic advances, including the combination of causal evidence for behavioral modification of pessimistic decisions with viral tracing methods. Critically, we introduced a version of the classic approach-avoidance (Ap-Av) conflict task, modified for use in non-human primates. We performed microstimulation of limbic-related cortical regions and the striatum, focusing on the pregenual anterior cingulate cortex (pACC), the caudal orbitofrontal cortex (cOFC), and the caudate nucleus (CN). Microstimulation of localized sites within these regions induced pessimistic decision-making by the monkeys, supporting the idea that the focal activation of these regions could induce an anxiety-like state, which subsequently influences decision-making. We further performed combined microstimulation and tract-tracing experiments by injecting anterograde viral tracers into focal regions, at which microstimulation induced increased avoidance. We found that effective stimulation sites in both pACC and cOFC zones projected preferentially to striosomes in the anterior striatum. Experiments in rodents have shown that the striosomes in the anterior striatum project directly to the dopamine-containing cells in the substantia nigra, and we have found evidence for a functional connection between striosomes and the lateral habenular region in which responses to reward are inhibitory. We present here further evidence for network interactions: we show that the pACC and cOFC project to common structures, including not only the anterior parts of the striosome compartment but also the tail of the CN, the subgenual ACC, the amygdala, and the thalamus. Together, our findings suggest that networks having pACC and cOFC as nodes share similar features in their connectivity patterns. We here hypothesize, based on these results, that the brain sites related to pessimistic judgment are mediated by a large-scale brain network that regulates dopaminergic functions and includes striosomes and striosome-projecting cortical regions.
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spelling pubmed-82779312021-07-15 Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes Amemori, Satoko Graybiel, Ann M. Amemori, Ken-ichi Front Neurosci Neuroscience Clinical studies have shown that patients with anxiety disorders exhibited coactivation of limbic cortices and basal ganglia, which together form a large-scale brain network. The mechanisms by which such a large-scale network could induce or modulate anxiety-like states are largely unknown. This article reviews our experimental program in macaques demonstrating a causal involvement of local striatal and frontal cortical sites in inducing pessimistic decision-making that underlies anxiety. Where relevant, we related these findings to the wider literature. To identify such sites, we have made a series of methodologic advances, including the combination of causal evidence for behavioral modification of pessimistic decisions with viral tracing methods. Critically, we introduced a version of the classic approach-avoidance (Ap-Av) conflict task, modified for use in non-human primates. We performed microstimulation of limbic-related cortical regions and the striatum, focusing on the pregenual anterior cingulate cortex (pACC), the caudal orbitofrontal cortex (cOFC), and the caudate nucleus (CN). Microstimulation of localized sites within these regions induced pessimistic decision-making by the monkeys, supporting the idea that the focal activation of these regions could induce an anxiety-like state, which subsequently influences decision-making. We further performed combined microstimulation and tract-tracing experiments by injecting anterograde viral tracers into focal regions, at which microstimulation induced increased avoidance. We found that effective stimulation sites in both pACC and cOFC zones projected preferentially to striosomes in the anterior striatum. Experiments in rodents have shown that the striosomes in the anterior striatum project directly to the dopamine-containing cells in the substantia nigra, and we have found evidence for a functional connection between striosomes and the lateral habenular region in which responses to reward are inhibitory. We present here further evidence for network interactions: we show that the pACC and cOFC project to common structures, including not only the anterior parts of the striosome compartment but also the tail of the CN, the subgenual ACC, the amygdala, and the thalamus. Together, our findings suggest that networks having pACC and cOFC as nodes share similar features in their connectivity patterns. We here hypothesize, based on these results, that the brain sites related to pessimistic judgment are mediated by a large-scale brain network that regulates dopaminergic functions and includes striosomes and striosome-projecting cortical regions. Frontiers Media S.A. 2021-06-30 /pmc/articles/PMC8277931/ /pubmed/34276282 http://dx.doi.org/10.3389/fnins.2021.649167 Text en Copyright © 2021 Amemori, Graybiel and Amemori. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Amemori, Satoko
Graybiel, Ann M.
Amemori, Ken-ichi
Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes
title Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes
title_full Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes
title_fullStr Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes
title_full_unstemmed Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes
title_short Causal Evidence for Induction of Pessimistic Decision-Making in Primates by the Network of Frontal Cortex and Striosomes
title_sort causal evidence for induction of pessimistic decision-making in primates by the network of frontal cortex and striosomes
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277931/
https://www.ncbi.nlm.nih.gov/pubmed/34276282
http://dx.doi.org/10.3389/fnins.2021.649167
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