Published February 28, 2026 | Version v1
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Theoretical Delimitation of Emotional Neural Circuit Modulation Through the Introduction of Functional Adult Human Cortical Tissue

Authors/Creators

  • 1. ROR icon Universidade de São Paulo

Description

This article presents a conceptual framework that explores the theoretical viability of employing functional adult human cortical tissue as an exogenous modulating node in emotional neural circuits. Grounded in well-established principles of synaptic plasticity, network-level modulation, and receptor-system-dependent neural integration, the proposed model does not presuppose the transfer of cognition, memory, or identity, nor does it imply immediate clinical applicability. Instead, the framework conceptualizes the grafted cortical tissue as a biologically active substrate, capable of indirectly influencing dysfunctional emotional dynamics through adaptive interactions with the recipient neural system. By distinguishing this approach from stem cell-based strategies and brain organoid models, the article seeks to clarify its theoretical boundaries and neurobiological plausibility. The proposed hypothesis aims to stimulate interdisciplinary discussions in theoretical neuroscience and neuroengineering, while outlining core conceptual limitations and potential directions for future investigations.

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Delimitação teórica da modulação de circuitos neurais emocionais por meio da introdução de tecido cortical humano adulto funcional.pdf

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Additional details

Additional titles

Translated title (Spanish)
Delimitación teórica de la modulación de circuitos neuronales emocionales mediante la introducción de tejido cortical humano adulto funcional

Identifiers

DOI
10.70271/260227.1432

References

  • 1- Kandel ER, Dudai Y, Mayford MR. The molecular and systems biology of memory. Cell. 2014;157(1):163–186. doi:10.1016/j.cell.2014.03.001 2 Mountcastle VB. The columnar organization of the neocortex. Brain. 1997;120(4):701–722. doi:10.1093/brain/120.4.701 3- Friston KJ. The free-energy principle: a unified brain theory? Nat Rev Neurosci. 2010;11(2):127–138. doi:10.1038/nrn2787 4 Hebb DO. The Organization of Behavior: A Neuropsychological Theory. New York: Wiley; 1949. 5 -Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361(6407):31–39. doi:10.1038/361031a0 6- Markram H, Muller E, Ramaswamy S, et al. Reconstruction and simulation of neocortical microcircuitry. Cell. 2015;163(2):456–492. doi:10.1016/j.cell.2015.09.029 7- Rolls ET. Emotion explained. Oxford: Oxford University Press; 2005. 8- LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184. doi:10.1146/annurev.neuro.23.1.155 9- Sporns O. Networks of the Brain. Cambridge (MA): MIT Press; 2011. 10- Bassett DS, Sporns O. Network neuroscience. Nat Neurosci. 2017;20(3):353–364. doi:10.1038/nn.4502 11- Björklund A, Lindvall O. Cell replacement therapies for central nervous system disorders. Nat Neurosci. 2000;3(6):537–544. doi:10.1038/75705 12- Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders—time for clinical translation? J Clin Invest. 2010;120(1):29–40. doi:10.1172/JCI40543 13- Grealish S, Diguet E, Kirkeby A, et al. Human ESC-derived dopamine neurons grafted in a rat model of Parkinson's disease. Nat Neurosci. 2014;17(8):1061–1069. doi:10.1038/nn.3765 14- Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433–1438. doi:10.1126/science.287.5457.1433 15- Arlotta P, Pasca SP. Cell diversity in the human cerebral cortex: from the embryo to brain organoids. Curr Opin Neurobiol. 2019;56:194–198. doi:10.1016/j.conb.2019.03.003 16- Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345(6194):1247125. doi:10.1126/science.1247125 17- Buzsáki G. Rhythms of the Brain. Oxford: Oxford University Press; 2006. 18- Deco G, Jirsa VK, McIntosh AR. Emerging concepts for the dynamical organization of resting-state activity in the brain. Nat Rev Neurosci. 2011;12(1):43–56. doi:10.1038/nrn2961 19- Pessoa L. Understanding brain networks and brain organization. Phys Life Rev. 2014;11(3):400–435. doi:10.1016/j.plrev.2014.03.005 20; Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8(9):700–711. doi:10.1038/nrn2201 21; Deisseroth K. Optogenetics. Nat Methods. 2011;8(1):26–29. doi:10.1038/nmeth.f.324 22= Mayberg HS. Targeted electrode-based modulation of neural circuits for depression. J Clin Invest. 2009;119(4):717–725. doi:10.1172/JCI38454 23- Lozano AM, Lipsman N. Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron. 2013;77(3):406–424. doi:10.1016/j.neuron.2013.01.020 24- Anderson ML. Neural reuse: a fundamental organizational principle of the brain. Behav Brain Sci. 2010;33(4):245–266. doi:10.1017/S0140525X10000853 25- Changeux JP, Dehaene S. Neuronal models of cognitive functions. Cognition. 1989;33(1–2):63–109. doi:10.1016/0010-0277(89)90010-2 26- Tononi G. Consciousness as integrated information. Biol Bull. 2008;215(3):216–242. doi:10.2307/25470707 27- McEwen BS, Morrison JH. The brain on stress: vulnerability and plasticity. Nat Rev Neurosci. 2013;14(10):741–752. doi:10.1038/nrn3381 28- Zilles K, Amunts K. Cytoarchitectonic and receptor architectonic mapping of the human brain. Brain Struct Funct. 2009;213(1–2):1–17. doi:10.1007/s00429-008-0185-4 29-Fuster JM. The Prefrontal Cortex. 5th ed. London: Academic Press; 2015. 30 - Northoff G, Duncan NW. How do abnormal brain dynamics help explain the symptoms of schizophrenia? Schizophr Bull. 2016;42(1):135–145. doi:10.1093/schbul/sbv149