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Fourth of July

Celebrating the Fourth with Neuroscience Fireworks

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There’s so much to celebrate about our country this Fourth of July. That includes giving thanks to all those healthcare providers who have put themselves in harm’s way to staff the ERs, hospital wards, and ICUs to care for those afflicted with COVID-19, and also for everyone who worked so diligently to develop, test, and distribute COVID-19 vaccines.

These “shots of hope,” created with rigorous science and in record time, are making it possible for a great many Americans to gather safely once again with family and friends. So, if you’re vaccinated (and I really hope you are—because these vaccines have been proven safe and highly effective), fire up the grill, crank up the music, and get ready to show your true red, white, and blue colors. My wife and I—both fully vaccinated—intend to do just that!

To help get the celebration rolling, I’d like to share a couple minutes of some pretty amazing biological fireworks. While the track of a John Philip Sousa march is added just for fun, what you see in the video above is the result of some very serious neuroscience research that is scientifically, as well as visually, breath taking. Credit for this work goes to an NIH-supported team that includes Ricardo Azevedo and Sunil Gandhi, at the Center for the Neurobiology of Learning and Memory, University of California, Irvine, and their collaborator Damian Wheeler, Translucence Biosystems, Irvine, CA. Azevedo is also an NIH National Research Service Award fellow and a Medical Scientist Training Program trainee with Gandhi.

The team’s video starts off with 3D, colorized renderings of a mouse brain at cellular resolution. About 25 seconds in, the video flashes to a bundle of nerve fibers called the fornix. Thanks to the wonders of fluorescent labeling combined with “tissue-clearing” and other innovative technologies, you can clearly see the round cell bodies of individual neurons, along with the long, arm-like axons that they use to send out signals and connect with other neurons to form signaling circuits. The human brain has nearly 100 trillion of these circuits and, when activated, they process incoming sensory information and provide outputs that lead to our thoughts, words, feelings, and actions.

As shown in the video, the nerve fibers of the fornix provide a major output pathway from the hippocampus, a region of the brain involved in memory. Next, we travel to the brain’s neocortex, the outermost part of the brain that’s responsible for complex behaviors, and then move on to explore an intricate structure called the corticospinal tract, which carries motor commands to the spinal cord. The final stop is the olfactory tubercle —towards the base of the frontal lobe—a key player in odor processing and motivated behaviors.

Azevedo and his colleagues imaged the brain in this video in about 40 minutes using their imaging platform called the Translucence Biosystems’ Mesoscale Imaging System™. This process starts with a tissue-clearing method that eliminates light-scattering lipids, leaving the mouse brain transparent. From there, advanced light-sheet microscopy makes thin optical sections of the tissue, and 3D data processing algorithms reconstruct the image to high resolution.

Using this platform, researchers can take brain-wide snapshots of neuronal activity linked to a specific behavior. They can also use it to trace neural circuits that span various regions of the brain, allowing them to form new hypotheses about the brain’s connectivity and how such connectivity contributes to memory and behavior.

The video that you see here is a special, extended version of the team’s first-place video from the NIH-supported BRAIN Initiative’s 2020 “Show Us Your BRAINS!” imaging contest. Because of the great potential of this next-generation technology, Translucence Biosystems has received Small Business Innovation Research grants from NIH’s National Institute of Mental Health to disseminate its “brain-clearing” imaging technology to the neuroscience community.

As more researchers try out this innovative approach, one can only imagine how much more data will be generated to enhance our understanding of how the brain functions in health and disease. That is what will be truly spectacular for everyone working on new and better ways to help people suffering from Alzheimer’s disease, Parkinson’s disease, schizophrenia, autism, epilepsy, traumatic brain injury, depression, and so many other neurological and psychiatric disorders.

Wishing all of you a happy and healthy July Fourth!

Links:

Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)

NIH National Research Service Award

Medical Scientist Training Program (National Institute of General Medical Sciences/NIH)

Small Business Innovation Research and Small Business Technology Transfer (NIH)

Translucence Biosystems (Irvine, CA)

Sunil Gandhi (University of California, Irvine)

Ricardo Azevedo (University of California, Irvine)

Video: iDISCO-cleared whole brain from a Thy1-GFP mouse (Translucence Biosystems)

Show Us Your BRAINs! Photo & Video Contest (Brain Initiative/NIH)

NIH Support: National Institute of Mental Health; National Eye Institute


Singing for the Fences

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Credit: NIH

I’ve sung thousands of songs in my life, mostly in the forgiving company of family and friends. But, until a few years ago, I’d never dreamed that I would have the opportunity to do a solo performance of the Star-Spangled Banner in a major league ballpark.

When I first learned that the Washington Nationals had selected me to sing the national anthem before a home game with the New York Mets on May 24, 2016, I was thrilled. But then another response emerged: yes, that would be called fear. Not only would I be singing before my biggest audience ever, I would be taking on a song that’s extremely challenging for even the most accomplished performer.

The musician in me was particularly concerned about landing the anthem’s tricky high F note on “land of the free” without screeching or going flat. So, I tracked down a voice teacher who gave me a crash course about how to breathe properly, how to project, how to stay on pitch on a high note, and how to hit the national anthem out of the park. She suggested that a good way to train is to sing the entire song with each syllable replaced by “meow.” It sounds ridiculous, but it helped—try it sometime. And then I practiced, practiced, practiced. I think the preparation paid off, but watch the video to decide for yourself!

Three years later, the scientist in me remains fascinated by what goes on in the human brain when we listen to or perform music. The NIH has even partnered with the John F. Kennedy Center for the Performing Arts to launch the Sound Health initiative to explore the role of music in health. A great many questions remain to be answered. For example, what is it that makes us enjoy singers who stay on pitch and cringe when we hear someone go sharp or flat? Why do some intervals sound pleasant and others sound grating? And, to push that line of inquiry even further, why do we tune into the pitch of people’s voices when they are speaking to help figure out if they are happy, sad, angry, and so on?

To understand more about the neuroscience of pitch, a research team, led by Bevil Conway of NIH’s National Eye Institute, used functional MRI imaging to study activity in the region of the brain involved in processing sound (the auditory cortex), both in humans and in our evolutionary relative, the macaque monkey [1]. For purposes of the study, published recently in Nature Neuroscience, pitch was defined as the harmonic sounds that we hear when listening to music.

For humans and macaques, their auditory cortices lit up comparably in response to low- and high-frequency sound. But only humans responded selectively to harmonic tones, while the macaques reacted to toneless, white noise sounds spanning the same frequency range. Based on what they found in both humans and monkeys, the researchers suspect that macaques experience music and other sounds differently than humans. They also go on to suggest that the perception of pitch must have provided some kind of evolutionary advantage for our ancestors, and has therefore apparently shaped the basic organization of the human brain.

But enough about science and back to the ballpark! In front of 33,009 pitch-sensitive Homo sapiens, I managed to sing our national anthem without audible groaning from the crowd. What an honor it was! I pass along this memory to encourage each of you to test your own pitch this Independence Day. Let’s all celebrate the birth of our great nation. Have a happy Fourth!

Reference:

[1] Divergence in the functional organization of human and macaque auditory cortex revealed by fMRI responses to harmonic tones. Norman-Haignere SV, Kanwisher N, McDermott JH, Conway BR. Nat Neurosci. 2019 Jun 10. [Epub ahead of print]

Links:

Our brains appear uniquely tuned for musical pitch (National Institute of Neurological Diseases and Stroke news release)

Sound Health: An NIH-Kennedy Center Partnership (NIH)

Bevil Conway (National Eye Institute/NIH)

NIH Support: National Institute of Neurological Diseases and Stroke; National Eye Institute; National Institute of Mental Health