Neuroscience Exploring The Brain Review Question Answers

[Mandy Geise]

TheBrain Bee is a live Q&A neuroscience competition for high schoolers. The Brain Bee motivates students to learn about the brain, captures their imaginations, and inspires them to pursue neuroscience-related careers in order to help treat and find cures for neurological and psychological disorders. The Brain Bee competition hosted by Rice University will consist of two rounds: the written round and an oral round. All participants will first take a written test, composed of multiple choice, True/False, and short answer questions. The top 10 students from the written round will then advance to the oral round, wherein they will compete for cash prizes and a chance to advance to the national competition. In addition to our competition, we will have guest speakers and exciting, interesting neuroscience demonstrations.

To help you better prepare for the competition, we are planning to host a free WORKSHOP on February 18th, 2023. We will be playing some themed jeopardy, watching some demonstrations, and reviewing general neuroscience information. All high school students interested in participating in the competition are welcome, but this opportunity is completely optional and not a prerequisite to the competition!

How does our brain switch between different behaviors? A new study has now provided the first answers to this key question in neuroscience. Using mice, the researchers investigated electrical activity in a certain area within the brain. Results were then analyzed with the help of an adaptive computer algorithm. This artificial intelligence identified a type of typical fingerprint in the signals.

Analyzing this signal allowed researchers to predict which behavior the animals would switch to next, two seconds before they actually made the change. The results have now been published in the journal Nature Neuroscience.

The rest of the brain keeps the hypothalamus informed about the external world. Based on this information, the hypothalamus regulates innate behaviors such as eating, exploring surroundings or interacting with others. But how does it do so?

To answer this question, a tandem of research groups lead by Prof. Dr. Alexey Ponomarenko at the Institute of Physiology and Pathophysiology at FAU and Prof. Dr. Tatiana Korotkova at the University Clinic of Cologne and the MPI for Metabolism Research combined several cutting-edge techniques of neuroscience and mathematics.

The researchers investigated the hypothalamus in mice, as this part of the brain is very similar in mice and humans. "We used AI to analyze the electrical activity in a certain region within the hypothalamus," explains data scientist Mahsa Altafi, a doctoral candidate at FAU.

Initial findings revealed that the hypothalamus oscillates at a rhythm known as a beta oscillation. The nerve cells in the hypothalamus are particularly active 20 times a second, with activity levels falling again between these peaks. It is like an orchestra in which all the musicians concentrate on the conductor's baton in order to play in unison.

What is particularly interesting is that some cells do not become active on tact, but just before, in the offbeat. These cells play a certain melody. And the order of the notes they play influences which piece of music the orchestra plays next. "Reading the electrical signal allows us to predict which behavior the mouse will switch to two seconds later," explains Altafi.

But what happens if the offbeat melody is suppressed? Changwan Chen at the Max Planck Institute for Metabolism Research and the University Clinic of Cologne used light to manipulate the activity of the hypothalamic neurons.

The effect was surprising: The mice remained stuck in their current behavior until the light was switched off. For example, they interacted persistently with other mice even if these mice showed no interest. "It was striking how persistently a mouse with the inhibited transition state interacted with another mouse that was trying to avoid this prolonged communication," Chen recalls.

The "offbeat melody" appears to put the hypothalamus in a transition state, thereby enabling the animals to switch to another behavior. Which behavior that is, however, does not depend solely on the hypothalamus.

It turns out that the hypothalamus is instructed by the medial prefrontal cortex, a region responsible for cognitive control of behavior. For example, it considers, which option is best in a particular situation. Should I eat? Or should I rather interact with another mouse, or collect new experiences?

In order to communicate with the hypothalamus, the medial prefrontal cortex oscillates in tact with the rhythm set by the hypothalamus, following the beta oscillation like a conductor's baton. "Signals from the prefrontal cortex help the hypothalamus to promote transitions between behaviors," explains Prof. Korotkova from the University Clinic of Cologne.

"It is particularly fascinating that the hypothalamus starts a preparation to transition between behaviors around two seconds before it actually occurs. It is likely that the mice are not even consciously aware at this point that they are about to switch to a different behavior."

"Our findings indicate the importance of beta oscillations in orchestrating the activity of the myriad of neurons that drive specific behaviors, and for smooth transitions between them," states Prof. Ponomarenko.

"These findings may guide the development of new medications and therapies for serious psychiatric brain disorders. I look forward to the day when patients with anorexia nervosa or obsessive-compulsive disorder can benefit from this."

How many brain cell types are there? What is their form, function, and how do they connect? Teams at the Allen Institute for Brain Science are working to answer these foundational neuroscience questions. By cataloguing and genetically profiling cell types of the brain with incredible precision and detail, we are working to improve our fundamental understanding of brain development, evolution, and disease.

Using a team science approach, we are exploring the mammalian brain at a molecular level and sharing our insights with the world. We do this through advanced single-cell molecular analysis techniques, such as single-cell RNA sequencing and electrophysiology, combined with cutting-edge imaging technologies that provide a comprehensive view of how our brains are organized; what their cellular makeup is; how those cells connect, develop, and function; and the complex relationship between these factors.

The breadth of the NIH definition is intentional, given the nature of the NIH portfolio and imperatives for maximal transparency. Transparency shows respect for the participants who put their trust in us, in the face of unknown outcomes, to help advance science. Our concerns about transparency stem in part from the issues surrounding the reporting of clinical trials data. For both NIH-funded and non-NIH funded trials, unreported data and untimely dissemination of results has been documented over and over again. Others have expressed concern that the NIH has not collected needed trans-NIH data to enable it to function as proper stewards of clinical trials.

Why is it important to know whether you are proposing to conduct a clinical trial? Correctly identifying whether your study is a clinical trial is crucial to complying with NIH policies, many of which are now in effect, such as registering and reporting all NIH supported clinical trials in ClinicalTrials.gov and good clinical practice training. Very soon, your answer will be crucial to picking the appropriate NIH funding opportunity for your application, writing your research plan correctly (since some information will be captured in the new human subjects and clinical trials form), and ensuring that your application includes all the information required for peer review.

I hope as other institutes implement/improve the requirements for clinical trials, they are considerate of the variety of types of trials and are flexible regarding timing for planning/enrollment/implementation.

That is, this new regulation will potentially decimate basic neuroscience research in humans, putting us years behind where we could be in understanding the brain and really treating neural disease clinically. Worse, it will make the public think that thousands of clinical trials are leading to no clinical outcomes, suggesting to them that medical science as a whole is faltering, and should not be funded. I do hope NIH will reconsider the implications and consequences of this decision.

More generally, basic research that does not produce a long-lasting change on the body or behavior should not be classified as a clinical trial. The goal of these studies IS NOT to produce a permanent change. They are MEASURING the body or the mind, not CHANGING them.

Applying these policies to psychopathology and other basic research studies as in case 18 will put an undue burden on such studies with no benefit that I can see. I think that the definition of an intervention has to be restricted to one that is designed to reduce or prevent symptoms rather than leaving it so broad as to include any manipulation that is designed to have some measurable impact on the participants.

Including mechanistic studies of basic brain function (whether in healthy individuals or patient groups) in clinicaltrials.gov will undermine the utility of that website, because it will swell with thousands of studies that will not be relevant to meaningful, disease-related outcomes. As other commentators mention, the burden on investigators will be considerable. I have entered studies in clinicaltrials.gov, and it is not a trivial task. Most importantly, the rigid format, designed for real clinical trials, cannot accommodate the complex data analysis for mechanistic studies. Investigators will have to spend many hours trying to shoe-horn their data into ill-specified fields. Because it will be virtually impossible to design data fields that will generalize to the huge variety of mechanistic studies, it will not be possible to use the data in meta-analyses.

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