Growing Human Brains

           Though originally published in August, some exciting neuroscience research is just starting to hit the news now. A lab in Austria has created a cerebral organoid, a very small - less complex - embryonic human brain from stem cells. Stem cells have already been used to make single neurons (the cells that make up your brain), but the brain is not simply a pile of neurons. Neurons are organized into different structures within the brain, as well as specific layers in the cerebral cortex. Each structure and layer has a different formation and therefore function. Because of its complexity and specificity, it is important to have human brain models instead of relying on lab animals.
            The basic process is the same for any stem cell research. Stem cells are generalized (pluripotent) cells that have no destination yet. By bathing them in a bath of different nutrients and signaling chemicals, you can make them grow into whatever type of cell you like: skin cells, blood cells or nerve cells. In this study, a base of stem cells were bathed in a mix of neuronal chemical signals. After a few days, pluripotent tests were done to see if the cells were on their way to becoming neurons. Days 8-10 showed neuronal identity. Days 15-20 showed continuous neuronal tissue surrounding a fluid filled cavity reminiscent of the vesicles found in a human brain. The real test of this experiment’s success came at day 20, when tests for regional markers showed specific structures developing. Markers for regions like the hindbrain (which is not as pronounced in humans) shrunk while those for regions like the forebrain (which is larger in humans) grew. Markers for different layers of the brain even showed up, with their signature inside-out development. By two months, a 4mm diameter cerebral organoid with all the markers of a human embryonic brain had formed. Because of lack of a circulatory system, tissue in the center of the brain started to die out, and development stopped.

            This lab did not stop there though. It wasn’t enough just to create the first cerebral organoid, they had to put it to the test too. Microcephaly is a disorder causing brains to stop growing before they reach full size, and can cause serious mental defects. Genetic tests on mice have been unsuccessful because of the specific differences in genes and brain structures. The Austrian team took skin cells from a patient with severe Microcephaly, reprogrammed them back to pluripotent stem like cells, then used the same technique to create a ‘personalized cerebral organioid’. Indeed, they found the patient’s cerebral organoid was smaller than a normal one. By performing genetic and physical tests on the organoid, they found the cause of the patients condition; a genetic mutation causing certain developmental cells in the brain to stop dividing too early. Armed with this knowledge, there is hope of early intervention halting the progress of Microcephaly in future patients.

            The possibilities of uses for cerebral organoids are endless. Not only can they be used to decode genetic disorders, but testing drugs on an organoid made from non-embryonic stem cells is preferable to any current option both scientifically and ethically. This is not to mention the possibilities of personalized cerebral organoids. Have a headache? Let the doctor take some flakes of your skin, and build you a mini-brain to see what the problem is. We are of course a long way from anything like this, but this progress is a huge leap in the right direction.

To read more about this research, here are articles from:

The Economist http://www.economist.com/news/science-and-technology/21584319-group-stem-cell-biologists-have-grown-organoid-resembles-brain

CNN http://www.cnn.com/2013/08/28/health/stem-cell-brain/index.html

The Scientist http://www.the-scientist.com/?articles.view/articleNo/37262/title/Lab-Grown-Model-Brains/

Or read the original article from Nature:

http://www.nature.com/nature/journal/v501/n7467/full/nature12517.html

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Your crazed neuroscientist,
Sierra

Improvisation and Creativity

      On January 28^th, 2010, Jonah Lehrer and Holly Sidford discussed neuroscience and art after Jonah’s talk at the San Francisco Dynamic Adaptability Conference in one of my favorite neuroscience interviews. Jonah was on the way towards writing his third book, Imagine, which has recently been pulled off shelves due to some fabricated quotes, though can still be found in second hand stores and such (I would not let this deter you from reading Jonah’s work. Even if there is some fabrication, his main ideas are still valid, and his writing style lets non-scientists ponder these great concepts. I will refer to him often in this blog). In his talk, he discussed the connection between neuroscience, art and creativity (the basis for Imagine).

          Jonah starts off with an amazing study on arguably the most creative act humans can manage, improvisation. This study was done by Bengtsson et al at the Karolinska Institutet in Stockholm, Sweden as well as Charles Limb at the University of Southern California. Professional jazz pianists were put into an fMRI (functional MRI, a machine that captures someone’s brain activity while they are doing a task). They were given a piano, and first asked to play a previously learned jazz piece. Then they were asked to make up a similar type of piece. Comparing the brains, the researchers found that improvising brains showed a decrease in activity in the Dorsolateral Prefrontal Cortex and an increase in the activity of the Medial Frontal Cortex (see image below). 

According to a previous study by Ridderinkhof and his team at the University of Amsterdam, “medial frontal cortex is found to be involved in performance monitoring: evaluating outcome vis-a-vis expectancy, and detecting performance errors or conflicting response tendencies.” It would make sense that this part of the brain is more active during improvisation. When creating a new piece of music, the medial frontal cortex listens to the music coming out, compares it to what it knows it wants to hear, and adjusts its commands to the fingers accordingly.

          The dorsolateral prefrontal cortex on the other hand was somewhat of a mystery before these experiments. It is believed it have something to do with self monitoring, acting as a filter. If this is correct, the experiment shows that to improvise, pianists turn off their filter, inhibit their inhibitory area, “silence the silencer”.

          This does not only apply to jazz improvisation. Liu et al at the National Institute on Deafness and Other Communication Disorders showed the same results for free style rappers, meaning that these same areas are activated/deactivated for language.

          The key to creativity is not grandiose moments of insight or great muses. It is training yourself not to worry about doing something wrong, and trust yourself. This is not something given to only a select few. It is something that can be learned and taught. This is how Jonah ends his discussion, with a call to teach these ideas of creativity in school. Let kids go off on their own, improvise, create something new. Creativity will get you farther than any type of algebra could, even if not measurable on a standardized test.

Jonah and Holly’s full interview can be found at this link (it is broken into 4 parts, but well worth a watch):

http://www.youtube.com/watch?v=BP9-VjOBwDE

Neural Correlates of Lyrical Improvisation: An fMRI Study of Freestyle Rap. Siyuan Liu,   Ho Ming Chow, Yisheng Xu,      Michael G. Erkkinen, Katherine E. Swett, Michael W. Eagle,         Daniel A. Rizik-Baer & Allen R. Braun. Scientific Reports 2, Article number: 834 doi:10.1038/srep00834. Received 20 June 2012 Accepted 19 October 2012 Published 15 November 2012

Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation. Charles J. Limb, Allen R. Braun. PLoS One

Cortical regions involved in the generation of musical structures during improvisation in pianists. Bengtsson SL, Csíkszentmihályi M, Ullén F. Karolinska Institutet, Stockholm, Sweden. 2007 May;19(5):830-42.

Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning. K. Richard Ridderinkhof, Wery P.M. van den Wildenberga,c, Sidney J. Segalowitzd, Cameron S. Carter. Brain and Cognition.