By Kathleen Berger

Neuroscientists are examining the brain in a new way, with a modern twist, in hopes of finding answers to the many mysteries of the human brain.

“The human brain is the most complicated thing there is and we understand it very poorly,” said senior author Nico Dosenbach, MD, PhD,an assistant professor of neurology, of occupational therapy and of pediatrics at Washington University School of Medicine in St. Louis.

The neuroscientist is hoping his team’s research will improve the future of precision mapping and high quality scanning, as well as improve drug therapies for many conditions including neurological and psychiatric disorders.

Dosenbach is a founding member of the Midnight Scan Club, a group of Washington University neuroscientists who have taken turns in an MRI scanner late at night, scanning their own brains for hours to generate a massive amount of high-quality data for their research.

Dosenbach remembered the day his brain processed the idea.  His goal has been to analyze the unique features and connections in individual human brains and evaluate the brain networks that control functions. But the research, involving the MRI scanner and a kind of brain scan called functional connectivity MRI, is expensive. He said the money wasn’t there until the realization of a dramatically discounted price for the scanner after midnight.

“I was walking to my friend’s car and we were talking about how this was the future of neuroimaging and how we couldn’t afford it,” said Dosenbach.  “And he went, ‘Nico, you know that after midnight scan charges are 90% off’. In my memory, I slapped him on his back really hard and I looked at him and said, ‘That’s it! We’re doing it!’ ”

And so the Midnight Scan Club was born.  But it wasn’t called ‘Midnight Scan Club’ just yet. Dosenbach recalled when he realized his club needed a name. He happened to be watching a popular TV show, Sons of Anarchy.

“They had a club, a logo and were kind of cool. And scientists usually aren’t that cool. So eventually, when we had more members, we made a logo that’s like a brain that looks like a skull and we put it on t-shirts, and we decided to be a club,” he said.

Not outlaws, just out-of-the-box thinkers.

“Scientists are a bunch of geeks and it’s just for fun!” Dosenbach laughed. “None of us have motorcycles, I assure you, or even leather jackets.”

By creating a club, Dosenbach believed he could lure more members.

“We’re up in the middle of the night doing science; to some people that’s appealing.”

The club discovered groundbreaking data about the underestimated, and often neglected, cerebellum. It’s all based on the brains of 10 volunteers, including Dosenbach’s.

To better understand the inner workings of individual brains, the MRI scanner became a big part of their nightlife. They used functional connectivity MRI to reliably detect fundamental differences in how individual brains are wired.

“It was kind of mind-blowing how different people were; one paper carefully analyzed this,” Dosenbach explained. “To me, that suggests there are potentially multiple ways of achieving a similar level of performance.”

He used the example of a math problem.

“The way my brain does it is actually very different from yours,” he said. “That’s very important for medical research and how we treat people with therapy or with drugs.”

The club also discovered there is so much more to the cerebellum than anyone knew before their data set was published. The cerebellum was previously thought to be limited to controlling movement, involved with only motor function. It has long been treated like an afterthought by researchers studying higher brain functions until the Midnight Scan Club provided new data.

The cerebellum is inconveniently located in the back of the brain, on the underside.

“For technical reasons, it’s always the hardest part to get good functional MRI measurements. Because we overloaded the acquisition on these subjects, we were actually able to get a pretty decent signal down there with some seriously major discoveries without really expecting that much,” Dosenbach explained.

Postdoctoral researcher and first author Scott Marek, PhD, was brought into the club to focus on the cerebellum. He explained the club’s discoveries and he defined the cerebellum as the mind’s quality control center for our thoughts.

“The more posterior parts of the cerebellum are the regions involved in all sorts of executive functions; whether it be working memory, language, abstract thinking, forward planning,” said Marek. “What we think in studying the structure is that the entire cerebellum, whether it’s the motor parts of it or these more cognitive parts, is acting as the brain’s quality control unit.”

Marek measured the timing of brain activity and found that the cerebellum was consistently the last step in neurologic circuits.

“When you have a signal that’s occurring in the cerebral cortex, we can look at where it’s functionally hooked up with in the cerebellum. It’s when we see activity in a region of the prefrontal cortex, about 500 milliseconds later we see activity pop up in a region that’s functionally connected with the cerebral cortex in the cerebellum,” explained Marek. “The cerebellum is sort of checking that output and then sending signals back to the cerebral cortex to tell it if the output was correct or if it needs to be modified.”

Involved in higher function, the researchers said the cerebellum serves as executive function of the brain.

“You can never have top performance in anything without a functioning cerebellum,” said Dosenbach. “80 percent of the volume of the cerebellum is taken up by networks that are responsible for higher-order cognitive functions.”

Using the cortex’s networks as a template, Marek could identify the networks in the cerebellum. Notably, the sensory networks are missing — vision, hearing and touch — and only 20 percent of the cerebellum is devoted to movement, roughly the same amount as in the cerebral cortex. The remaining 80 percent is occupied by networks involved in higher-order cognition: the attention network; the default network, which has to do with daydreaming, recalling memories and just idly thinking; and two networks that oversee executive functions such as decision-making and planning.

After the findings were published, the Midnight Scan Club received emails from people who claim to have a lesion, a damaged or missing part of the cerebellum. In the emails, people claimed to have concerns that were disregarded by medical professionals.

“Getting emails from people saying ‘I’ve had cloudy thoughts after having damaged my cerebellum, I can’t do a cross word puzzle anymore.’ Having a basic science study translate immediately to those types of people and to actually make an impact was very rewarding for me,” said Marek.

Marek also performed individualized network analyses on the 10 people in the data set. He found that while brain functions are arranged in roughly the same pattern in everyone’s cerebellum, there is enough individual variation to distinguish brain scans performed on any two participants. The researchers are now investigating whether such individual differences in cerebellar networks correlate with intelligence, behavior, personality traits such as adaptability, or psychiatric conditions.

The cerebellum also is sensitive to alcohol. Dosenbach said this is one of the reasons why people who have had too many drinks stumble around. He said the new data helps explain why someone who is inebriated also shows poor judgment. Just as a person staggers drunkenly because his or her compromised cerebellum is unable to perform the customary quality checks on motor function, alcohol-fueled bad decisions might also reflect a breakdown of quality control over executive functions.