Thursday, April 18, 2013

On Dead Salmon, Drugs, and “Lighting Up” the Brain


Are fMRIs truly useful in addiction medicine?

What would it take to make neuroimaging a truly valuable tool for addiction medicine? Pictures of brain regions “lighting up” have always been exciting, as the early phase of neuroimaging predictably inspired rapture. Phase 2 arrived when a group of U.S. postdocs created the infamous dead salmon fMRI scan, showing that an exciting and colorful picture of false positives was entirely possible. As Neuroskeptic put it to the Globe and Mail, “Scientific journals prefer to publish results that are positive and ‘sexy,’ just like other media.”

That is nice to hear, since it takes the full blast of the heat lamp off journalists and directs it at those scientists with a habit of overamping MRI studies, even when the sample in the studies is exceedingly small. Plenty of blame to go around. Moreover, both scientists and journalists must contend with the fact that the bulk of the scientific world’s research resides behind steep pay walls—steep enough that even prestigious universities have been wailing lately about the cost of just getting one’s hands on the research reports, let along doing the research. “Media literacy in science journalism is really stunted by the fact that we don’t have access to primary sources,” said a spokesperson for the Electronic Frontier Foundation.

So much blame going around, in fact, that enthusiasm for President Obama’s recently announced brain initiative seems particularly muted among one group universally expected to rally around the project—neuroscientists themselves. Having helped to create the hype, some brain scientists are now suggesting that the only appropriate attitude is healthy skepticism about where the money will be used, and whose pockets will be picked to come up with the $100 million in kickoff funds.  Rather than jumping in unison when Obama said the program would allow us to “better understand how we think and how we learn and how we remember,” skeptical neuroscientists note that “Manhattan Project”-style programs are out of fashioned in today’s distributed, system-wide landscape of experiment. “Without specific goals, hypotheses, or endpoints,” said an Emory University neuroscientist in the Globe and Mail article, “the research effort becomes a fishing expedition.”

Myself, I like to fish. But not if the pond’s too small. In a recent post at National Geographic’s blog, “Not Exactly Rocket Science,” Ed Yong quoted a neuroscientist at the University of Bristol: “If you have lots of people running studies that are too small to get a clear answer, that’s more wasteful in the long-term.”

Exactly so, and one might think that a large, coordinated, possibly international initiative at studying the architecture and function of the human brain might serve as a powerful antidote to a micro-universe of tiny studies and insignificant findings.

But forget the big and little pictures for a moment. Let’s focus on what’s in it for addiction studies. What would have to happen—how would fMRIs, PETs and EEGs have to be used in order to advance our understanding of drug and alcohol abuse?

In a recent editorial —“What neuroimaging has and has not yet added to our understanding of addiction”—Martina Reske of the Institute of Neuroscience and Medicine in Julich, Germany, argues that we must take “three critical steps to implement neuroimaging as a new basis for diagnostics and treatment of substance use disorders: first, we need to merge diverse imaging findings into one comprehensive brain imaging perspective of addiction. Next, we need to identify prediction algorithms for individual substance users.” And finally, Reske writes in Addiction, “The ultimate goal has to be the development of treatment regimens based on neuroimaging results.” The interested lay public may be forgiven for assuming that all three of these conditions were already being met.

Specifically, Reske argues for “multi-modal approaches to overcome technological shortcomings. Simultaneous EEG-fMRI, for instance, combines high temporal and spatial resolution of exactly the same mental process, and hybrid MR-PET imaging allows for functional/structural and molecular characterizations.” What might stand in the way of such solutions, you ask? Reske answers that it is likely to be “the existing researchers’ hesitation, unwillingness or inability to consolidate findings from different imaging modalities.” In this case, she suggests, it is the scientists themselves, perhaps overly protective of individual turfs and research fiefdoms, who are hemming and hawing about large-scale collaborative efforts.

To reach a level of clinical relevance for addiction, neuroimaging must be used to delineate and identify “occasional versus habitual versus compulsive use or intoxication versus abstinence versus relapse.” These are not things that existing neuroimagery can do for us, but Reske believes one promising avenue will be the identification of subjects with an abnormally high risk for relapse, something neither patients nor therapists are very good at predicting. (This immediately brings neuroimaging up against a ripe field of ethical questions having to do with the identification and disclosure of high-risk subjects.)

What other payoffs might there be? Reske can think of a few: “First, linkage of neuroimaging and pharmacological studies will prove useful for predicting response to medication. Secondly, knowledge of the biological differences between responders and non-responders to available treatments might facilitate identification of the best-suited therapy for that particular individual. Thirdly, understanding which brain regions show alterations in functioning should spur the development of specific medications, cognitive-behavioral or neuroimaging-based trainings that target optimal activation levels in these regions.”

Neuroimaging is not yet specific or sensitive enough, and its practitioners not yet practiced enough, to accomplish these tasks except in a tantalizingly patchwork fashion. Neuroimaging-based predictions of addiction liability and damage and relapse make up an infant science, ripe for both growth and abuse. Obviously, it will take the gold standard of longitudinal studies involving enormous samples of participants, who would ideally be followed and scanned for decades. But such studies are, as Reske reminds us, “methodologically challenging, expensive and not promising in terms of short-term publication of results.” It sounds like the kind of Big Project that might fit under the umbrella of, say, a major, well-funded, multi-year brain research initiative endorsed by the President of the United States….

Photo Credit: https://docs.uabgrid.uab.edu/

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