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Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

ABSTRACT: Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

SUBMITTER: Jgamadze D

PROVIDER: S-EPMC9926224 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Jgamadze Dennis D Lim James T JT Zhang Zhijian Z Harary Paul M PM Germi James J Mensah-Brown Kobina K Adam Christopher D CD Mirzakhalili Ehsan E Singh Shikha S Gu Jiahe Ben JB Blue Rachel R Dedhia Mehek M Fu Marissa M Jacob Fadi F Qian Xuyu X Gagnon Kimberly K Sergison Matthew M Fruchet Oceane O Rahaman Imon I Wang Huadong H Xu Fuqiang F Xiao Rui R Contreras Diego D Wolf John A JA Song Hongjun H Ming Guo-Li GL Chen Han-Chiao Isaac HI

Cell stem cell 20230201 2

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplan ...[more]

PMID: 36736289

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Project description:ObjectiveWe explore if there are ways to characterize health systems-not already revealed by secondary data-that could provide new insights into differences in health system performance. We sought to collect rich qualitative data to reveal whether and to what extent health systems vary in important ways across dimensions of structural, functional, and clinical integration.Data sourcesInterviews with 162 c-suite executives of 24 health systems in four states conducted through "virtual" site visits between 2017 and 2019.Study designExploratory study using thematic comparative analysis to describe factors that may lead to high performance.Data collectionWe used maximum variation sampling to achieve diversity in size and performance. We conducted, transcribed, coded, and analyzed in-depth, semi-structured interviews with system executives, covering such topics as market context, health system origin, organizational structure, governance features, and relationship of health system to affiliated hospitals and POs.Principal findingsHealth systems vary widely in size and ownership type, complexity of organization and governance arrangements, and ability to take on risk. Structural, functional, and clinical integration vary across systems, with considerable activity around centralizing business functions, aligning financial incentives with physicians, establishing enterprise-wide EHR, and moving toward single signatory contracting. Executives describe clinical integration as more difficult to achieve, but essential. Studies that treat "health system" as a binary variable may be inappropriately aggregating for analysis health systems of very different types, at different degrees of maturity, and at different stages of structural, functional, and clinical integration. As a result, a "signal" indicating performance may be distorted by the "noise."ConclusionsDeveloping ways to account for the complex structures of today's health systems can enhance future efforts to study systems as complex organizations, to assess their performance, and to better understand the effects of payment innovation, care redesign, and other reforms.

Project description:BackgroundIndividuals with body dysmorphic disorder (BDD) perceive distortions in their appearance, which could be due to imbalances in global and local visual processing. The vertical occipital fasciculus connects dorsal and ventral visual stream regions, integrating global and local information, yet the role of this structural connection in BDD has not been explored. Here, we investigated the vertical occipital fasciculus's white matter microstructure in those with BDD and healthy controls and tested associations with psychometric measures and effective connectivity while viewing their face during fMRI.MethodsWe analyzed diffusion MRI and fMRI data in 17 unmedicated adults with BDD and 21 healthy controls. For diffusion MRI, bundle-specific analysis was performed, enabling quantitative estimation of neurite density and orientation dispersion of the vertical occipital fasciculus. For task fMRI, participants naturalistically viewed photos of their own face, from which we computed effective connectivity from dorsal to ventral visual regions.ResultsIn BDD, neurite density was negatively correlated with appearance dissatisfaction and negatively correlated with effective connectivity. Further, those with weaker effective connectivity while viewing their face had worse BDD symptoms and worse insight. In controls, no significant relationships were found between any of the measures. There were no significant group differences in neurite density or orientation dispersion.ConclusionThose with BDD with worse appearance dissatisfaction have a lower fraction of tissue having axons or dendrites along the vertical occipital fasciculus bundle, possibly reflecting impacting the degree of integration of global and local visual information between the dorsal and ventral visual streams. These results provide early insights into how the vertical occipital fasciculus's microstructure relates to the subjective experience of one's appearance, as well as the possibility of distinct functional-structural relationships in BDD.

Dataset Information

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Publications

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

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