Information processing-like phenotype of human brain organoids

Human brain organoids possess a remarkable capability to mimic key physiological aspects of the human brain, offering a promising avenue for investigating neurological disorders. Despite evidence indicating that neurodegenerative diseases like Alzheimer's impair the human brain's information-processing ability, the information-processing potential of brain organoids and its connection to neural network function have not been comprehensively examined.

In this study, researchers employed a task-based functional phenotyping framework (Brainopheno) to assess and quantify the information-processing-like properties of human cortical organoids. They discovered that these organoids exhibit a pattern-processing-like phenotype, characterized by the representation and classification of evoked neural activities in response to various spatial input stimulation patterns using a microelectrode array (MEA) system.

Furthermore, this functional phenotype emerges as the neural network matures and is disrupted by pharmacological interventions, indicating a direct link between classification performance and the functional integrity of organoid neural networks (ONNs). Notably, the researchers observed functional deficits in ONNs when they were altered by a familial Alzheimer's disease-associated gene mutation (APP) and by monocytes from patients with sporadic AD.

This groundbreaking work establishes a quantifiable functional phenotype of neural organoids, bridging molecular and cellular profiles with neural circuit function. The findings pave the way for a new framework to analyze disease phenotyping and therapeutic development in the realm of basic neurology.