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Brains react differently to ADHD medication than expected

A tried and tested medication for treating ADHD works differently than expected in the brains of healthy individuals during rest: rather than stimulating brain activity, it suppresses it.

Co-fluctuations

Even when we ourselves are at rest, our brains are anything but resting.  Activity is fluctuating in all brain areas simultaneously according to a specific pattern. What causes these co-fluctuations? Neuroscientists, including Leiden cognitive psychologist Rudy van den Brink, have carried out research on this phenomenon. 'The combined fluctuations of all brain areas at the same time offer a unique look into how the brain is organised when the person is at rest,' Van den Brink explains. 'What causes these fluctuations and the factors that influence them has been a mystery for a long time.'

No external stimuli

The question that the researchers wanted to answer was whether particular substances can influence brain activity if there are no external stimuli. To test this they gave healthy human subjects a medicine that is used to treat ADHD: atomoxetine. The subjects were then placed in a scanner and were asked to keep loooking at a cross on a screen and to just let their thoughts flow freely. 'This put the subjects in a restful state, something like daydreaming,' Van den Brink explained.

Neurotransmitters

Atomoxetine is known to increase noradrenaline and dopamine, both of which are neurotransmitters that influencce the way nerves transmit signals. Noradrenaline improves concentration. ADHD patients have too little of this hormone, which is why they are given a medication that promotes the production of noradrenaline. Dopamine has a similar effect elsewhere in the brain, but it affects motivation.

Unexpected outcome

To the surprise of the researchers, the medication administered to the test subjects suppressed the co-fluctuations in the brain strongly, more in some brain areas than others. This indicates that noradrenaline and dopamine reduce communication between different areas throughout the whole brain - an effect that had never previously been demonstrated. The researchers were amazed at the findings of their research as they had assumed that administering noradrenaline and dopamine would lead to stronger co-fluctuations. The effect of the drug therefore seems to depend on the state of the brain.

Catecholaminergic Neuromodulation Shapes Intrinsic MRI Functional Connectivity in the Human Brain. Ruud L. van den Brink, Thomas Pfeffer, Christopher M. Warren, Peter R. Murphy, Klodiana-Daphne Tona, Nic J. A. van der Wee, Eric Giltay, Martijn S. van Noorden, Serge A.R.B. Rombouts, Tobias H. Donner and Sander Nieuwenhuis. The Journal of Neuroscience, 27 July 2016, 36(30): 7865-7876

Illustration: the same image from above and from the side. The picture shows the effect of atomoxetine on communication  (co-fluctuations) between different brain regions. The blue connections indicate where the atomoxetine reduced the co-fluctuiations, and the red line shows where the atomoxetine increased the co-fluctuations.