Psycho-inactive: the effect of drugs on a resting brain

(Originally published by Edinburgh Student Newspaper, March 10, 2016)

When we stare blankly at our computer screens, zoning out on that assignment with a rapidly approaching deadline, it might feel like our thoughts are blank. But are our brains every really at rest? Have our brain cells stopped sending those signals that light up on fMRI scans?

New research from the University of Cambridge, led by Professor James Rowe studied the brains of participants who were just sitting in the fMRI scanner, not carrying out any tasks.

Lead author Robin Borchert and his colleagues showed that they could study brain at rest to understand the effect of specific drugs on the brain (5). This is important because being able to study drug treatments without participants doing anything in the scanner has important advantages, including being able to study severely mentally or physically impaired patients.

Brain imaging studies, bright and multicolored, are all over the media and hard to miss. fMRI is one particularly prevalent type of imaging. Since its introduction in 1993, nearly 30,000 scientific papers have mentioned it. Most often, studies look at participants doing something in the scanner, everything from opening and closing their eyes (2) to watching erotic images. Task-based imaging is the jargon for these types of studies. fMRIs measure oxygen use by different areas of the brain because more oxygen represent higher brain activity.

Our brain is only 2% of our body mass, but accounts for 20% of our body’s energy use. Compared to this baseline consumption of 20%, when participants carry out tasks in the fMRI machine, there is only a 5% change. The bulk of the energy is used is by the brain at rest. Studies like Borchert’s that examine resting brains are important both because they address a large chunk of our brain’s activity, but also because studying a resting brain is much more convenient. Task-free imaging, as it’s called, entails subjects lie quietly with their eyes closed in the scanner.

Borchert studied the resting brains of Parkinson’s patients after taking atomoxetine, a drug normally prescribed for ADHD but preliminarily tested as a Parkinson’s drug, or a placebo. Dopamine is famously involved in the motor defects of Parkinson’s, but in the past few years, other brain chemicals, such as noradrenaline have been shown to be involved in cognitive deficits. The drug Borchert studied causes an increase in noradrenaline.

The mechanism of how this drug works is not clear. This study looked at changes in connections between brain areas, or the end effect of the drug.

They showed that atomoxetine increases in connections between the executive control areas of the brain, which are normally impaired in Parkinson’s patients. The changes in their brain connections as compared to the control group, after taking atomoxetine mirrored the changes that happened in task-based studies.

This similarity is crucial, because it validates the technique of studying the resting brain. “It’s demonstrating that we can use resting state imaging to study the effect of drugs on brain networks,” Borchert explains.

Importantly, they also showed the drug not only correlated with changes in the brain connectivity, but also in cognitive tests of verbal fluency done outside the scanner. Originally the paper was going to focus only on the changes in connectivity. “But one day during a lab meeting, we started talking about actually trying to correlate resting state changes with cognitive performance outside the scanner,” recounts Borchert, “This got us really excited. And I ended up staying in the lab really late that night running the analysis.”

Sure enough, they found that increased connectivity correlated with whether or not participants’ cognitive performance improved or worsened on the drug. Measures outside the scanner mean that studying the brain networks could also elucidate why the drug might work for some patients and not others.

Resting-state imaging is also particularly useful for studying physically and mentally debilitating illnesses such as Parkinson’s. While being in the scanner is still difficult, the duration is shorter than for task-based studies, and the patients don’t have to carry out any tasks that might be difficult for them.

While resting state imaging is promising, there is some skepticism. “It’s still kind of an enigma. No one really knows what’s going on when the brain is at rest, “ explains Borchert.

And more specifically, we also don’t know the implications of the changes in brain connectivity during resting state. As the well-known neuroscience blogger, Neuroskeptic says, “We have a long way to go before we can properly understand what these changes mean – that is to say we don’t really know what kind of mental processes or information processing correspond to functional connectivity…So this is only one piece of the puzzle!”

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