Organoid Intelligence: Can We Separate Intelligent Behavior from an Intelligent Being?

Understanding how the organs form and how their cells behave is essential to finding the causes and treatment for developmental disorders, as well as understanding certain diseases. However, studying most organs in live animals or humans is technically difficult, expensive and invasive. To address this issue, scientists have developed models called ‘organoids’ that recapitulate the development of organs using stem cells in the lab. These models are easier to study and manipulate than the live organs. Brain organoids have been used to recapitulate brain formation as well as developmental, degenerative and psychiatric brain conditions such as microcephaly, autism and Alzheimer’s disease. However, these brain organoids lack the vasculature (the network of blood vessels) that supplies a live brain with nutrients and regulates its development, and which has important roles in brain disorders. Partly due to this lack of blood vessels, brain organoids also do not develop a blood brain barrier, the structure that prevents certain contents of the blood, including pathogens, toxins and even certain drugs from entering the brain. These characteristics limit the utility of existing brain organoids. To overcome these limitations, Sun, Ju et al. developed brain organoids and blood vessel organoids independently, and then fused them together to obtain vascularized brain organoids. These fusion organoids developed a robust network of blood vessels that was well integrated with the brain cells, and produced more neural cell precursors than brain organoids that had not been fused. This result is consistent with the idea that blood vessels can regulate brain development. Analyzing the fusion organoids revealed that they contain structures similar to the blood-brain barrier, as well as microglial cells (immune cells specific to the brain). When exposed to lipopolysaccharide – a component of the cell wall of certain bacteria – these cells responded by initiating an immune response in the fusion organoids. Notably, the microglial cells were also able to engulf connections between brain cells, a process necessary for the brain to develop the correct structures and work normally. Sun, Ju et al. have developed a new organoid system that will be of broad interest to researchers studying interactions between the brain and the circulatory system. The development of brain-blood-barrier-like structures in the fusion organoids could also facilitate the development of drugs that can cross this barrier, making it easier to treat certain conditions that affect the brain. Refining this model to allow the fusion organoids to grow for longer times in the lab, and adding blood flow to the system will be the next steps to establish this system.

Understanding how the organs form and how their cells behave is essential to finding the causes and treatment for developmental disorders, as well as understanding certain diseases. However, studying most organs in live animals or humans is technically difficult, expensive and invasive. To address this issue, scientists have developed models called ‘organoids’ that recapitulate the development of organs using stem cells in the lab. These models are easier to study and manipulate than the live organs. Brain organoids have been used to recapitulate brain formation as well as developmental, degenerative and psychiatric brain conditions such as microcephaly, autism and Alzheimer’s disease. However, these brain organoids lack the vasculature (the network of blood vessels) that supplies a live brain with nutrients and regulates its development, and which has important roles in brain disorders. Partly due to this lack of blood vessels, brain organoids also do not develop a blood brain barrier, the structure that prevents certain contents of the blood, including pathogens, toxins and even certain drugs from entering the brain. These characteristics limit the utility of existing brain organoids. To overcome these limitations, Sun, Ju et al. developed brain organoids and blood vessel organoids independently, and then fused them together to obtain vascularized brain organoids. These fusion organoids developed a robust network of blood vessels that was well integrated with the brain cells, and produced more neural cell precursors than brain organoids that had not been fused. This result is consistent with the idea that blood vessels can regulate brain development. Analyzing the fusion organoids revealed that they contain structures similar to the blood-brain barrier, as well as microglial cells (immune cells specific to the brain). When exposed to lipopolysaccharide – a component of the cell wall of certain bacteria – these cells responded by initiating an immune response in the fusion organoids. Notably, the microglial cells were also able to engulf connections between brain cells, a process necessary for the brain to develop the correct structures and work normally. Sun, Ju et al. have developed a new organoid system that will be of broad interest to researchers studying interactions between the brain and the circulatory system. The development of brain-blood-barrier-like structures in the fusion organoids could also facilitate the development of drugs that can cross this barrier, making it easier to treat certain conditions that affect the brain. Refining this model to allow the fusion organoids to grow for longer times in the lab, and adding blood flow to the system will be the next steps to establish this system.

Toward improved understanding of cardiac development and congenital heart disease: The advent of cardiac organoids

A Review of <i>The Rise of the Australian Neurohumanities</i>

We examine the challenging “marriage” between computational efficiency and biological plausibility—A crucial node in the domain of spiking neural networks at the intersection of neuroscience, artificial intelligence, and robotics. Through a transdisciplinary review, we retrace the historical and most recent constraining influences that these parallel fields have exerted on descriptive analysis of the brain, construction of predictive brain models, and ultimately, the embodiment of neural networks in an enacted robotic agent. We study models of Spiking Neural Networks (SNN) as the central means enabling autonomous and intelligent behaviors in biological systems. We then provide a critical comparison of the available hardware and software to emulate SNNs for investigating biological entities and their application on artificial systems. Neuromorphics is identified as a promising tool to embody SNNs in real physical systems and different neuromorphic chips are compared. The concepts required for describing SNNs are dissected and contextualized in the new no man’s land between cognitive neuroscience and artificial intelligence. Although there are recent reviews on the application of neuromorphic computing in various modules of the guidance, navigation, and control of robotic systems, the focus of this paper is more on closing the cognition loop in SNN-embodied robotics. We argue that biologically viable spiking neuronal models used for electroencephalogram signals are excellent candidates for furthering our knowledge of the explainability of SNNs. We complete our survey by reviewing different robotic modules that can benefit from neuromorphic hardware, e.g., perception (with a focus on vision), localization, and cognition. We conclude that the tradeoff between symbolic computational power and biological plausibility of hardware can be best addressed by neuromorphics, whose presence in neurorobotics provides an accountable empirical testbench for investigating synthetic and natural embodied cognition. We argue this is where both theoretical and empirical future work should converge in multidisciplinary efforts involving neuroscience, artificial intelligence, and robotics.

Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques.

Brain organoid implications have opened vast avenues in the realm of interdisciplinary research, particularly in the growing field of organoid intelligence (OI). A brain organoid is a three-dimensional (3D), lab-grown structure that mimics certain aspects of the human brain organization and function. The integration of organoid technology with computational methods to enhance the understanding of organoid behavior and to predict their responses to various stimuli is known as OI. The ability of brain organoids to adapt and memorize, is a key area of exploration. OI encapsulates the confluence of breakthroughs in stem cell technology, bioengineering, and artificial intelligence (AI). This chapter delves deep into the myriad potentials of OI, encompassing an enhanced understanding of human cognitive functions, and achieving significant biological computational proficiencies. Such advancements stand to offer a unique complementarity to conventional computing methods. The implications of brain organoids in the OI sphere signify a transformative stride towards a more intricate grasp of the human brain and its multifaceted intricacies. The intersection of biology and machine learning is a rapidly evolving field that is reshaping our understanding of life and health. This convergence is driving advancements in numerous areas, including genomics, drug discovery, personalized medicine, and synthetic biology.

JOURNAL/nrgr/04.03/01300535-202501000-00032/figure1/v/2024-05-14T021156Z/r/image-tiff Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies.

For thousands of years, human beings have been exploring the fundamental nature of the world and the self. In this process, modern science and Vedanta philosophy do not differ in conceiving the physical body as a material and mind also as a material. But now and then, the question is asked that so-called matter is not sentient, it cannot be aware or conscious, and how does matter suddenly become conscious/aware/sentient being? For this reason, consciousness studies have become very important in the last two to three decades and it has opened up. These studies are now turn out to be multidisciplinary by the interest of brain scientists, neuroscientists, psychologists, philosophers of mind, language, physicists, computer scientists, Artificial Intelligence. A lot of work has been done in this field of science to address what is this subjective conscious experience which a human being has internally. Consciousness studies are not new in the east, about two to three thousand years ago texts called Upanishads which are originated from Vedas are clearly stated about consciousness and its nature. In this article, the nature of consciousness is discussed and demonstrated according to Advaita Vedanta Philosophy. The article also encompasses the standpoint of modern science on consciousness. Finally, an attempt is made to answer the so-called hard problem of consciousness from the Advaita Vedanta perspective.

Bio of Dr. Clark: Dr. Andy Clark is a professor of philosophy and chair in logic and metaphysics at the University of Edinburgh in Scotland. Previously, he taught at Washington University at St. Louis and the University of Sussex in England. Clark is one of the founding members of the Contact collaborative research project, whose aim is to investigate the role environment plays in shaping the nature of conscious experience. Dr. Andy Clark research interests include philosophy of mind, artificial intelligence, including robotics, artificial life, embodied cognition, and mind, technology and culture. Dr. Clark's papers and books deal with the philosophy of mind and he is considered a leading scientist in mind extension. He has also written extensively on connectionism, robotics, and the role and nature of mental representation.

Feeling our way to machine minds: People's emotions when perceiving mind in artificial intelligence

Anthropologists have become increasingly interested in embodiment-that is, the ways that socio-cultural factors influence the form, behavior and subjective experience of human bodies. At the same time, social cognitive neuroscience has begun to reveal the mechanisms of embodiment by investigating the neural underpinnings and consequences of social experience. Despite this overlap, the two fields have barely engaged one another. We suggest three interconnected domains of inquiry in which the intersection of neuroscience and anthropology can productively inform our understanding of the relationship between human brains and their socio-cultural contexts. These are: the social construction of emotion, cultural psychiatry, and the embodiment of ritual. We build on both current research findings in cultural neuroscience and ethnographic data on cultural differences in thought and behavior, to generate novel, ecologically informed hypotheses for future study. In addition, we lay out a specific suggestion for operationalizing insights from anthropology in the context of cultural neuroscience research. Specifically, we advocate the development of field studies that use portable measurement technologies to connect individual patterns of biological response with socio-cultural processes. We illustrate the potential of such an approach with data from a study of psychophysiology and religious devotion in Northeastern Brazil.

The differentiation between natural intelligence and artificial intelligence represents a significant concern among intellectuals. Artificial intelligence developers, leveraging advancements in neuroscience, cognitive sciences, and advanced theories in the philosophy of mind, aim to replicate the structure and functionality of the human brain through a functionalist and behaviourist lens. Broadly speaking, artificial intelligence can be categorized into two renowned types:Classical Artificial Intelligence or the “Computational Theory of Mind”: This perspective emphasizes the computational and algorithmic side of artificial intelligence and advocates for the mechanization and computerization of the mind.Connectionist Artificial Intelligence: This viewpoint focuses on recreating the “neural networks” of the brain. Additionally, the human soul, as the source of human intelligence, possesses cognitive and motivational powers that act as the soldiers of the soul, generating a variety of actions and effects. This research attempts to re-evaluate the fundamental differences between natural intelligence and artificial intelligence from Ibn Sina's perspective using a rational-analytical approach. According to Ibn Sina, natural intelligence and artificial intelligence differ in eight key areas: composite synthesis, intentionality, creativity and inventiveness, specialization focus, self-awareness and self-discovery, the internal evolution of natural intelligence, the impulsive power of desire, ethical conduct, and the ability to recall.

Background: Sleeping sickness is caused by the extracellular parasite Trypanosoma brucei and is associated with neuroinflammation and neuropsychiatric disorders, including disruption of sleep/wake patterns, and is now recognised as a circadian disorder. Sleeping sickness is traditionally studied using murine models of infection due to the lack of alternative in vitro systems that fully recapitulate the cellular diversity and functionality of the human brain. The aim of this study is to develop a much-needed in vitro system that reduces and replaces live animals for the study of infections in the central nervous system, using sleeping sickness as a model infection. Methods: We developed a co-culture system using induced pluripotent stem cell (iPSC)-derived cortical human brain organoids and the human pathogen T. b. gambiense to model host-pathogen interactions in vitro. Upon co-culture, we analysed the transcriptional responses of the brain organoids to T. b. gambiense over two time points. Results: We detected broad transcriptional changes in brain organoids exposed to T. b. gambiense, mainly associated with innate immune responses, chemotaxis, and blood vessel differentiation compared to untreated organoids. Conclusions: Our co-culture system provides novel, more ethical avenues to study host-pathogen interactions in the brain as alternative models to experimental infections in mice. Although our data support the use of brain organoids to model host-pathogen interactions during T. brucei infection as an alternative to in vivo models, future work is required to increase the complexity of the organoids ( e.g., addition of microglia and vasculature). We envision that the adoption of organoid systems is beneficial to researchers studying mechanisms of brain infection by protozoan parasites. Furthermore, organoid systems have the potential to be used to study other parasites that affect the brain significantly reducing the number of animals undergoing moderate and/or severe protocols associated with the study of neuroinflammation and brain infections.

Organoid has become a novel in vitro model to research human development and relevant disorders in recent years. With many improvements on the culture protocols, current brain organoids could self-organize into a complicated three-dimensional organization that mimics most of the features of the real human brain at the molecular, cellular, and further physiological level. However, lacking positional information, an important characteristic conveyed by gradients of signaling molecules called morphogens, leads to the deficiency of spatiotemporally regulated cell arrangements and cell–cell interactions in the brain organoid development. In this review, we will overview the role of morphogen both in the vertebrate neural development in vivo as well as the brain organoid culture in vitro, the strategies to apply morphogen concentration gradients in the organoid system and future perspectives of the brain organoid technology.