There is an oped in the NYTimes today about cigarette labels. The author, Martin Lindstrom, talks about graphic labels on cigarette containers and their effectiveness for encouraging people to quit smoking. He concludes that they don’t work. Guess why? Functional imaging of course…
We’ve been down this road before, extraordinary claims based on an fMRI experiment. Mr. Lindstrom says the following about his fMRI experiment:
A brain-imaging experiment I conducted in 2006 explains why antismoking scare tactics have been so futile. I examined people’s brain activity as they reacted to cigarette warning labels by using functional magnetic resonance imaging, a scanning technique that can show how much oxygen and glucose a particular area of the brain uses while it works, allowing us to observe which specific regions are active at any given time.
We tested 32 people (from Britain, China, Germany, Japan and the United States), some of whom were social smokers and some of whom were two-pack-a-day addicts. Most of these subjects reported that cigarette warning labels reduced their craving for a cigarette, but their brains told us a different story.
Each subject lay in the scanner for about an hour while we projected on a small screen a series of cigarette package labels from various countries — including statements like “smoking kills” and “smoking causes fatal lung cancers.” We found that the warnings prompted no blood flow to the amygdala, the part of the brain that registers alarm, or to the part of the cortex that would be involved in any effort to register disapproval.
To the contrary, the warning labels backfired: they stimulated the nucleus accumbens, sometimes called the “craving spot,” which lights up on f.M.R.I. whenever a person craves something, whether it’s alcohol, drugs, tobacco or gambling.
Now, to his credit, he does say that more work is needed:
Further investigation is needed, but our study has already revealed an unintended consequence of antismoking health warnings. They appear to work mainly as a marketing tool to keep smokers smoking.
I think that I would like to question his primary claim which is that an increased BOLD signal (or “lighting up” as he calls it) in the nucleus accumbens is somehow indicative of engagement of the reward pathway in these people. This increased BOLD signal is almost always taken as an indication that excitatory transmission is happening. In this case, they are probably thinking dopamine release in the nucleus accumbens. This idea comes from the fact that excitatory transmission requires energy so there is more blood flow and more oxygen consumption happening in the area. What some of these researchers neglect to tell you is that inhibition also requires a great deal of energy consumption. Why you ask? Well the answer is simple. When GABA-A receptors are activated (at least in the adult CNS) chloride flows into the cell. In order to keep the chloride gradient intact (and inhibition going) the neuron has to get rid of this chloride load. To do this, it pumps out chloride, largely through a potassium, chloride transporter called KCC2. Now this transporter is electroneutral; however, in order for it to work, our old friend the sodium-potassium ATPase has to bump up its activity. This requires a good deal of energy, energy expenditure that would likely contribute to a BOLD response. Wanna know more, check out this great review in Neuron that is freely available on PMC.
So, the NYTimes editorial says that the graphic warnings are causing reward. I say not so fast, they may actually be inhibiting the accumbens via an increase in GABAergic activity. Either of us could be right but in the absence of pharmacological data, I will say the jury is out. Like so many other fMRI-based studies, this one is certainly interesting but it is completely open to interpretation and mine is quite the opposite of the author’s in this case. Finally, what about the evidence that these graphic labels actually work? I think we should not ignore these findings all because of one fMRI experiment. Moreover, the limp cigarette Canadian label is totally awesome!
UPDATE: To be clear, the mechanism that I cite (Na+-K+-ATPase) is only one of many mechanisms that may lead to a BOLD response via an increase in inhibitory neurotransmission. I find these lines from the Neuron review particularly intriguing:
Here, it is interesting to note that observations in normal human subjects using PET have shown that administration of the specific GABAA receptor agonist, 4, 5, 6, 7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; an agonist known to induce a tonic GABA conductance) leads to an increase in glucose metabolism, even though clinical and electroencephalographic monitoring showed a sedative effect and sleepiness after drug administration (Peyron et al., 1994a). In temporal lobe epilepsy patients, the THIP-induced increase of glucose metabolism was highest in the electrically hypoactive focus (Peyron et al., 1994b).