Addiction connections

First published in eLife earlier in 2019, Chris Smith spoke to Edmund Rolls from the Oxford Centre for Computational Neuroscience about brain connectivity, smoking and drinking...

Edmund - We're very interested in the brain mechanisms of certain sorts of behaviour, including addictive behaviour. In this particular paper smoking and drinking. And what we have discovered is one part of the brain - the medial orbital frontal cortex - has different connectivity in people who drink; and the lateral orbital frontal cortex has different connectivity in those who smoke.

Chris - Who did you look at and how?

Edmund - We studied very large samples - of eight hundred thirty one participants, in one case from a US project called the Human Connectome Project, and we followed that up with eleven hundred and seventy six participants from London. What we did was to measure the connectivity between different brain regions while people were resting in a brain scanner. We used functional magnetic resonance imaging. What we found is that just when we measured the connectivity between different brain regions - when they weren't doing anything: they weren't smoking or drinking at the time - we found that we could predict who, later on in life, would smoke and who would drink.

Chris - Now what fraction of the people you studied were smokers and drinkers and what fraction were not?

Edmund - The youngest participants were 14 in this study. At that stage very few of them had started smoking or drinking. They were brain scanned again at the age of 19, and at 19 some of them had started to drink. And we correlated their brain connectivity with their smoking and drinking. The lateral orbital frontal cortex had low functional connectivity in smokers, and we think smokers were giving themselves nicotine in order to increase the connectivity between brain regions. And we think that that is the basis for that type of semi-addictive behaviour: that it makes one more alert because perhaps one's connectivity of the lateral orbital frontal cortex but also in fact overall of all brain areas is slightly low in smokers.

Chris - This is like functionally self medicating isn't it to pep up the areas which are underperforming?

Edmund - That's one of the ideas that resulted from this particular study. One could consider that that's what happens in smoking. The other interesting thing that happens in this investigation is that, associated with the smoking, and the undergone activity of the lateral orbital frontal cortex, people were more impulsive. So we think that one thing that may facilitate smoking is impulsiveness. And it's important to have discovered this, because that has implications for helping people.

Chris - Now if someone is making up for - for want of a better phrase - a paucity of functional connectivity between two brain regions and the nicotine is doing that, when a person who has been an entrenched smoker gives up, what are the consequences for their cognition?

Edmund - We don't know. My advice to someone would be that if you feel that you need a bit more stimulation then don't smoke but take a small amount of nicotine in the form of a patch and that might restore your alertness that perhaps previously you sought by smoking.

克里斯,因为人会从你的年代aying that if there is this reduction in connectivity and that the the smokers are doing this in order to improve the communication between these disparate brain areas, that if you don't have the nicotine signal there then there would be a consequence for cognition either either an IQ decrement or an attentional decrement. That would suggest then that if that's manifest at 14 because you're saying that when you looked at the youngest participants who hadn't yet become smokers and they showed similar patterns, do you see underperformance or a tendency towards attentional problems in those young people?

Edmund - That's not clear yet. The overall point would be that it's possible that those who choose to smoke may have slightly less sort of activation of their brains, and so they may be likely to benefit from stimulation of their brains. But we haven't taken it further than that. What I could say is that we made a second discovery: the same individuals were reporting how much drinking they performed. Those individuals had slight over-connectivity of the whole of their brain, and in particular for the medial orbital frontal cortex. Now that's extremely interesting because the medial orbital frontal cortex is a part of the brain involved in rewards. The account we came to, therefore, is that it's possible that those who drink have a particularly sensitive reward system and it's that that attracts them to alcohol. Now the interesting point here, in relation to addiction in general, is that we now have two types of addictive behaviour which have quite different underlying brain mechanisms.

Chris - And what do you think, putting all this together, the take home message is? How should cognitive neuroscientists think differently about people who use these agents, and how might doctors and clinicians dealing with people who do, approach their subjects differently because of what you've found?

Edmund - I think this has very important implications for understanding addiction in general. There's been an emphasis in the field of neuroscience research on addiction to think primarily of a chemical called dopamine which may underlie a lot of addictive behaviour. But if so, that would be a unitary phenomenon. But here we have two other types of addictive behaviour - smoking and drinking - which can't be accounted for by a simple unitary explanation. There are different things that are happening in different parts of the brain. That then leads us towards potential treatments for different types of addictive behaviour. And the sort of treatment that then could be helpful for those who have smoked is that it may be helpful to suggest a nicotine patch until their brain perhaps normalises its sensitivity a little bit after they haven't smoked for some time. And similarly, for those who may have an oversensitive medial orbital frontal cortex to rewards, which attracts them to alcohol, then at least some cognitive understanding of what's happening in their brain would help individuals to understand their own behaviour better.