JUN 01, 2015

3-D Brain Models Could Be Diagnostic Tool for Doctors

WRITTEN BY: Will Hector
There are a few essential ways to understand the neural workings of the human brain. One is to painstakingly map the circuitry using computers. See a fascinating article in the January 8, 2015, New York Times magazine on Sebastian Seung's work for more on this.

There's the Human Connectome Project's work on building a connectome, or map of the neural connections with the goal of establishing a baseline for a healthy brain's anatomical and functional connectivity and facilitate research on disorders such as Alzheimer's, dyslexia, autism, and schizophrenia.

Then, there's the lab down the hall where the really wild stuff occurs. In this case, imagine Sergiu Pasca's name on the door. Pasca and his Stanford colleagues introduced what they call human cortical spheroids in the May 25 edition of the journal Nature Methods.

Pasca's human cortical spheroids are cultured 3-D structures that grow and function much like a miniature version of the cortex of the subject from whom the original tissue was drawn. The mini brain models, or "organoids," feature neural networks through which cells actively communicate. Theoretically, the models would show doctors, psychiatrists, and psychologists any abnormalities in connectivity that might assist with diagnosis and treatment planning.

Thomas R. Insel, M.D., Director of the NIH's National Institute of Mental Health (most of the funding for the study came from the National Institutes of Health), commented on the findings: "There's been amazing progress in this field over the past few years. The cortex spheroids grow to a state in which they express functional connectivity, allowing for modeling and understanding of mental illnesses. They do not even begin to approach the complexity of a whole human brain. But that is not exactly what we need to study disorders of brain circuitry. As we seek advances that promise enormous potential benefits to patients, we are ever mindful of the ethical issues they present."

Science has long theorized that an organism passes through embryonic development in stages that loosely mirror the evolution of that organism. This process, called recapitulation, is currently popular in somatic psychology work. It has been accomplished using stem cells in 3-D cultures. These experiments have revealed patterns similar to corticogenesis, the process through which the cerebral cortex is created.

Prior to Pasca's study, researchers had studied neurons derived from patients' skin cells using something called induced pluripotent stem cells, or iPSCs. They produced rough organoids that mimicked the brain's own architecture, but lacked the complex circuitry required to study the human brain's workings.

Pasca's team utilized an improved method to produce iPSCs that more closely resembled the neural connectivity and circuitry of the human brain, including support of glial cells and forming of layers-also a key component of corticogenesis. The model can also succumb to the process of mico thin slicing as a way to map the brain.

"While the technology is still maturing, there is great potential for using these assays to more accurately develop, test safety and effectiveness of new treatments before they are used in individuals with a mental illness," said David Panchision, Ph.D., NIMH program director for stem cell research.

Follow Will Hector on Twitter: @WriterWithHeart

(Source: Nature Methods; Science Daily)