HYPOTHESIS AND THEORY article

Yamakawa H., et al.:  Front. Syst. Neurosci., 19 August 2024
Abstract:

Background: “Imagination represents a pivotal capability of human intelligence. To develop human-like artificial intelligence, uncovering the computational architecture pertinent to imaginative capabilities through reverse engineering the brain’s computational functions is essential. The existing Structure-Constrained Interface Decomposition (SCID) method, leverages the anatomical structure of the brain to extract computational architecture. However, its efficacy is limited to narrow brain regions, making it unsuitable for realizing the function of imagination, which involves diverse brain areas such as the neocortex, basal ganglia, thalamus, and hippocampus.

Objective: In this study, we proposed the Function-Oriented SCID method, an advancement over the existing SCID method, comprising four steps designed for reverse engineering broader brain areas. This method was applied to the brain’s imaginative capabilities to design a hypothetical computational architecture. The implementation began with defining the human imaginative ability that we aspire to simulate. Subsequently, six critical requirements necessary for actualizing the defined imagination were identified. Constraints were established considering the unique representational capacity and the singularity of the neocortex’s modes, a distributed memory structure responsible for executing imaginative functions. In line with these constraints, we developed five distinct functions to fulfill the requirements. We allocated specific components for each function, followed by an architectural proposal aligning each component with a corresponding brain organ.

Results: In the proposed architecture, the distributed memory component, associated with the neocortex, realizes the representation and execution function; the imaginary zone maker component, associated with the claustrum, accomplishes the dynamic-zone partitioning function; the routing conductor component, linked with the complex of thalamus and basal ganglia, performs the manipulation function; the mode memory component, related to the specific agranular neocortical area executes the mode maintenance function; and the recorder component, affiliated with the hippocampal formation, handles the history management function. Thus, we have provided a fundamental cognitive architecture of the brain that comprehensively covers the brain’s imaginative capacities.

1 Introduction

Imagination is the ability to generate patterns that differ from reality, utilizing representational elements that correspond to elements in the environment acquired through experience. For intellectual systems, imagination is crucial, as it is necessary for generating hypotheses for situations that cannot be directly experienced. Furthermore, imagination forms the foundation of all meaning, understanding, and inference (Johnson, 2013). It is believed that the imaginative capabilities present in modern humans were acquired during the “Great Leap Forward,” approximately 70,000 years ago (Diamond, 1992). Given that imagination is a core function in intelligence, designing an architecture for imagination is highly beneficial for developing brain-like artificial intelligence and for the computational understanding of the brain. Here, the term “architecture” refers to a description of a system in which multiple computationally meaningful components are organically connected, thereby forming the design information for the software. …”

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Abstract:   “Animal personality, consistent individual differences in behaviour, is an important concept for understanding how individuals vary in how they cope with environmental challenges. In order to understand the evolutionary significance of animal personality, it is crucial to understand the underlying regulatory mechanisms. Epigenetic marks such as DNA methylation are hypothesised to play a major role in explaining variation in phenotypic changes in response to environmental alterations. Several characteristics of DNA methylation also align well with the concept of animal personality. In this review paper, we summarise the current literature on the role that molecular epigenetic mechanisms may have in explaining personality variation. We elaborate on the potential for epigenetic mechanisms to explain behavioural variation, behavioural development and temporal consistency in behaviour. We then suggest future routes for this emerging field and point to potential pitfalls that may be encountered. We conclude that a more inclusive approach is needed for studying the epigenetics of animal personality and that epigenetic mechanisms cannot be studied without considering the genetic background.”

van Oers K, van den Heuvel K, Sepers B. The epigenetics of animal personality. Neurosci Biobehav Rev. 2023 Jul;150:105194. doi: 10.1016/j.neubiorev.2023.105194. Epub 2023 Apr 23. PMID: 37094740.

https://www.sciencedirect.com/science/article/pii/S014976342300163X

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For Discussion: Is Epigenetics the best way to alter your personality?
https://developingchild.harvard.edu/resources/what-is-epigenetics-and-how-does-it-relate-to-child-development/
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Abstract: “Lactate is a critical metabolite during the body’s adaption to exercise training, which effectively relieves anxiety-like disorders. The biological mechanism of lactate in the exercise-mediated anxiolytic effect has, however, not been comprehensively investigated. Here, we report that exercise-induced lactate markedly potentiates the lactylation of multiple synaptic proteins, among which synaptosome-associated protein 91 (SNAP91) is the critical molecule for synaptic functions. Both anatomical evidence and in vivo recording data showed that the lactylation of SNAP91 confers resilience against chronic restraint stress (CRS) via potentiating synaptic structural formation and neuronal activity in the medial prefrontal cortex (mPFC). More interestingly, exercise-potentiated lactylation of SNAP91 is necessary for the prevention of anxiety-like behaviors in CRS mice. These results collectively suggest a previously unrecognized non-histone lactylation in the brain for modulating mental functions and provide evidence for the brain’s metabolic adaption during exercise paradigms.“

Yan L, Wang Y, Hu H, Yang D, Wang W, Luo Z, Wang Y, Yang F, So KF, Zhang L. Physical exercise mediates cortical synaptic protein lactylation to improve stress resilience. Cell Metab. 2024 Aug 9:S1550-4131(24)00289-4. doi: 10.1016/j.cmet.2024.07.018. Epub ahead of print. PMID: 39163863.

https://pubmed.ncbi.nlm.nih.gov/39163863/

 

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https://www.cell.com/cell/fulltext/S0092-8674(24)00702-5

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McCutcheon SR, Rohm D, Iglesias N, Gersbach CA. Epigenome editing technologies for discovery and medicine. Nat Biotechnol. 2024 Aug;42(8):1199-1217. doi: 10.1038/s41587-024-02320-1. Epub 2024 Jul 29. PMID: 39075148.

https://pubmed.ncbi.nlm.nih.gov/39075148/

 

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“Reactive microglia contribute to Parkinson’s disease (PD) pathogenesis. Certain cytokines such as interleukin-10 (IL-10) can restore microglia homeostasis, but targeting maladaptive immune responses without inducing systemic side effects remains a challenge. Bido et al. adopted a microRNA-detargeting system that inhibits the expression of a transgene in all but the cell type of choice. Using this system for lentiviral-mediated, local, and microglia-specific expression of IL-10 in PD mice led to reduced neuropathology and the emergence of microglial subtypes with enhanced clearance signatures. These results suggest the therapeutic potential of cell type–specific gene delivery for PD. ”

Bido S et al.: Microglia-specific IL-10 gene delivery inhibits neuroinflammation and neurodegeneration in a mouse model of Parkinson’s disease. Science Translational Medicine 16 (761), (21 Aug 2024).

https://www.science.org/doi/10.1126/scitranslmed.adm8563

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Abstract:  Lactate, a byproduct of glycolysis, was considered as a metabolic waste until identified by studies on the Warburg effect. Increasing evidence elucidates that lactate functions as energy fuel, signaling molecule, and donor for protein lactylation. Altered lactate utilization is a common metabolic feature of the onset and progression of neurodegenerative diseases, such as Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease and Huntington’s disease. This review offers an overview of lactate metabolism from the perspective of production, transportation and clearance, and the role of lactate in neurodegenerative progression, as well as a summary of protein lactylation and the signaling function of lactate in neurodegenerative diseases. Besides, this review delves into the dual roles of changed lactate metabolism during neurodegeneration and explores prospective therapeutic methods targeting lactate. We propose that elucidating the correlation between lactate and neurodegeneration is pivotal for exploring innovative therapeutic interventions for neurodegenerative diseases.

Wang MY, Zhou Y, Li WL, Liu D, Zhu LQ. Friend or foe: Lactate in neurodegenerative diseases. Ageing Res Rev. 2024 Aug 8:102452. doi: 10.1016/j.arr.2024.102452. Epub ahead of print. PMID: 39127445.

https://pubmed.ncbi.nlm.nih.gov/39127445/

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Abbreviated article…     “We’re now in the midst of a multistate outbreak of influenza A H5N1 bird flu in dairy cows and other animals. USDA has confirmed outbreaks in more than 130 dairy herds across 12 states, and also in a herd of alpacas. CDC has confirmed three human cases of bird flu in dairy farm workers.          The first case, on April 1, 2024, was the first-ever known case of cow-to-human transmission of bird flu viruses in the United States and globally, and it was the second-ever documented human case of bird flu in the United States. The first US case was in a poultry worker in Colorado in 2022. The chief complaint for the first two patients in that outbreak was conjunctivitis. The third patient had more typical flu symptoms, including a cough. All three of these patients had direct contact with infected cows. On July 3, 2024, a fourth human case of H5N1 bird flu, tied to the dairy cow outbreak, was identified in Colorado. This patient only reported eye symptoms.

Over the past 27 years, more than 900 sporadic bird flu cases in humans have been reported worldwide. Overall, 52% of them have been fatal. CDC says to avoid exposure to sick or dead animals. They also recommend wearing appropriate personal protective equipment for job-related exposure to infected or potentially infected animals. …”

Be Alert for Conjunctivitis: New Human Cases of H5N1 Bird Flu – Medscape – July 09, 2024.

https://www.medscape.com/viewarticle/be-alert-conjunctivitis-new-human-cases-h5n1-bird-flu-2024a1000cna

and

https://www.aao.org/eye-health/tips-prevention/pink-eye-conjunctivitis-bird-flu-avian-influenza#:~:text=People%20with%20H5N1%20bird%20flu,breath%2C%20difficulty%20thinking%2C%20or%20seizures

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Dementia prevention, intervention, and care 2024

Executive Summary

As life expectancies increase, the number of people living with dementia worldwide continues to rise. The 2024 report of the Lancet Commission on dementia prevention, intervention, and care adds compelling new evidence that untreated vision loss and high LDL cholesterol are risk factors for dementia. Overall, around 45% of cases of dementia are potentially preventable by addressing 14 modifiable risk factors at different stages during the life course.

The 2024 Commission update also provides updates on advances in fluid biomarkers for detection of Alzheimer’s disease, new definitions for diagnosis of Alzheimer’s disease, as well as progress on disease-modifying treatments.

2024 Commission

Gill Livingston, Jonathan Huntley, Kathy Y Liu, Sergi G Costafreda, Geir Selbæk, Suvarna Alladi, David Ames, Sube Banerjee, Alistair Burns, Carol Brayne, Nick C Fox, Cleusa P Ferri, Laura N Gitlin, Robert Howard, Helen C Kales, Mika Kivimäki, Eric B Larson, Noeline Nakasujja, Kenneth Rockwood, Quincy Samus, Kokoro Shirai, Archana Singh-Manoux, Lon S Schneider, Sebastian Walsh, Yao Yao, Andrew Sommerlad, Naaheed Mukadam
The Lancet
Published: July 31, 2024
Miia Kivipelto, Francesca Mangialasche, Kaarin J Anstey
The Lancet
Published: July 31, 2024

 

https://www.thelancet.com/commissions/dementia-prevention-intervention-care

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