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This work was supported by Grant PVE 400730/2014-6 from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brasil; to J.S.C.) and Grant PHB-H2012-0011 Ministerio de Educacion (Spain; to F.C.). We thank Professor John F. Araujo (Federal University of Rio Grande do Norte) for support in the first steps of this project and Begona Rodriguez (Universidad Autonoma de Madrid) for expert technical help.

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The arousal-related "central thalamus" stimulation site simultaneously innervates multiple high-level frontal and parietal areas

Publicado en:JOURNAL OF NEUROSCIENCE. 43 (46): 7812-7821 - 2023-01-01 43(46), DOI: 10.1523/JNEUROSCI.1216-23.2023

Autores: Morais, PLAG; Rubio-Garrido, P; de Lima, RM; Córdoba-Claros, A; de Nascimento, ES ; Cavalcante, JS; Clascá, F

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In human and non-human primates, deep brain stimulation (DBS) applied at or near the internal medullary lamina of the thalamus (a region referred to as "central thalamus", CT), but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally-conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal and cingulate cortical areas. Some populations simultaneously target the frontal, parietal and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the brain's attention, executive control, and working-memory networks. Increased functional connectivity in these networks has been previously described as a signature of consciousness.Significance StatementIn human and non-human primates, deep brain stimulation (DBS) at a specific site near the internal medullary lamina of the thalamus ("central thalamus", CT) had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the brain's attention, executive control, and working-memory networks. Increased functional connectivity in these networks has been previously described as a signature of consciousness.Copyright © 2023 the authors.

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