Brain Scans and Bold Plans: Our Interview with Matt Wall

Sometimes, a conversation takes you to places you never would’ve expected. Matt Wall and I struck up a chat about brain-scanning technology early this year, and he mentioned that he’d like to do an interview for The Connectome.

Since he’s got 5+ years of published brain research under his belt, I jumped at the chance.

I figured we’d be talking about what life’s like in an fMRI lab, and maybe about some recent discoveries – but we wound up chatting about science misconceptions, the nature of pain, post-traumatic stress disorder and psychedelic drug trips (among other things). I think you’ll enjoy hearing his insights as much as I enjoyed picking his brain. –Ben

Ben Thomas:
So, Matt, how’d you get involved in fMRI research?
Matt Wall: My bachelor’s degree was actually in psychology. I earned my Ph.D. in Cambridge, and I started working with fMRI in my post-doctoral work – first in a vision lab, looking at low-level visual physiology, and then working on the spinal cord. So I keep getting further and further away from my roots as a psychologist.
BT: And you’ve done some work in cognitive neuroscience as well. So, quite a broad range of topics. What’s the unifying theme in all this work?
MW: Well, in a sense, I’ve just been moving from one field to another as I find interesting projects – but the unifying theme is really the fMRI itself. I’ve come away from each of these projects with a richer understanding of the technology. fMRI is such a technical specialty that it often takes years to become familiar enough with the technology to understand how to perform effective research with it. Once you’ve got that understanding, though, you can apply it to studying lots of different areas of neuroscience.
BT: Once you’ve reached that level of familiarity, what kinds of tasks are you expected to be involved in? What’s day-to-day life like in an fMRI lab?
MW: My latest project has been studying reactions to pain – so a lot of my day-to-day work has been strapping electrodes to people’s heads, giving them electrical shocks, and recording their brain activity. Which sounds pretty sadistic, but we’re doing it for a good reason: We’re particularly interested in the trigeminal nerve, and its role in processing pain signals. Although this nerve is technically part of the peripheral nervous system, you can – in theory – get BOLD (blood oxygen level-dependent) fMRI signals from it, as you can from, say, the cerebral cortex. Our goal has been to try to figure out where exactly in the pain system a given drug starts messing with the signal. We haven’t quite managed to get things working as we’d hoped, though, and my contract with that lab is about to be up. But it’s been an interesting project to work on.
BT: To backtrack just a bit, you mentioned looking for BOLD signals, which is a great opportunity to talk about a common source of confusion I see in articles on brain studies: fMRI doesn’t directly measure neural activity at all.
MW: Right. What fMRI is actually tracking is the ratio of oxygenated to deoxygenated hemoglobin in a given area – basically, the oxygen level in the blood pumping through that region of the brain. One thing we know about the brain’s vascular system is that it tends to overcompensate; so the more active a certain area of the brain becomes, the more oxygen it demands, and the more oxygen the vascular system dumps into it.
BT: So fMRI is measuring the level of oxygen in that area, but not what that area’s doing – it could be processing input from some other area; it could be sending out excitatory or inhibitory signals, or a mixture of the two…
MW: That’s one of the trickiest things about analyzing fMRI data. You’re comparing brain activity during a task with “control” activity – i.e., activity in that same area when that task isn’t being performed – and sometimes you notice an increase in activity in a certain region during the task, while maybe you notice a decrease in others; they were more active in the control condition. So there’s often the possibility that an increase of activity in one area could mean it’s inhibiting activity in another. But it’s very difficult to be sure about those kinds of causal interpretations.
BT: And yet every day we’re reading headlines like, “Brain Area Responsible for [X] Discovered!” All we really know is that’s an area that becomes more active during task [X]. It could be processing that task, or it could be inhibiting another region that interferes with the task.
MW: A better way to phrase it would be, “Brain Area Associated with [X] Discovered.” It’s quite a leap to say that activity in a certain area is directly causing a certain effect – especially if that supposed effect is something as complex as a whole behavior or a personality trait.
BT: Yeah, no kidding. So, now that this pain research is wrapping up, what’s on the horizon for you?
MW: Lately I’ve been getting into neuropharmacology. I recently wrapped up some work for GlaxoSmithKline, at a lab that was studying pharmaceutical drugs before they went to market. But my most recent project has actually been a TV series exploring the effects of recreational drugs on the brain. I was just a relatively small part of a large team working on the program – the major players were Prof. David Nutt of Imperial College and Prof. Val Curran of UCL, with Dr Robin Carhartt-Harris being the principal investigator. Most recently we performed fMRI scans on people who were on quite large doses of MDMA (ecstasy). So that’s been fun.
BT: Any interesting discoveries yet?
MW: A few things, actually; yeah. The point of the MDMA episode was to examine the therapeutic uses of that drug. MDMA was used in clinical settings quite a lot in the 1940s, when it was first discovered – but once it became known as a street drug, all that research stopped, and a lot of misinformation started spreading.
BT: The claims that it caused “holes in the brain” and all that.
MW: Right. But there’s some evidence that MDMA can be used to help treat PTSD (post-traumatic stress disorder). A therapist can walk patients through memories of their traumatic experiences while they’re on ecstasy; they’re still lucid about the details of the memory, but the drug seems to counteract a lot of the agitation and distress they’d normally feel. So after a few walkthroughs of the traumatic memory while on MDMA, the patients develop the ability to think through the details of the experience without suffering that intense anxiety.
BT: And what’s fMRI telling you about how that works neurologically?
MW: What we’re finding so far is that MDMA usage is correlated with increased activity in the visual cortex (vs. placebo) during recall of emotionally positive memories. And that lines up with our subjects’ reports – they generally report that those memories are much more vivid than usual when they’re on MDMA. And during recall of emotionally negative memories, we’re seeing that MDMA use is correlated with much lower activity in the parahippocampal gyrus, which is involved in memory retrieval, and in the amygdala, which is associated with negative emotions like fear and disgust. So it’s possible that MDMA inhibits the negative emotions associated with those memories.
BT: Sounds like MDMA shows some promise for clinical treatment.
MW: I think that’s likely. Oh, and there was also another episode where we were studying the effects of psilocybin, the chemical in “magic mushrooms.” I took part in that one myself, which was quite interesting. It was a crazy experience, actually. A real roller coaster.
BT: The last time a lot of these drugs were seriously studied was back in the ’60s, when they were still legal. And back in those days, we didn’t have fMRI; we had EEG (electroencephalography), which really just measures electrical activity across the scalp. So I’m really excited to see what we’ll discover now that we can correlate activity in a specific brain region with all these perceptual distortions and expansions that psychedelic drug users describe.
MW: I think the tide of public opinion is starting to shift. MDMA, psilocybin, LSD, and so on are really powerful mind-altering compounds. There’s a lot of anecdotal evidence about them; and so far, only a few studies demonstrating that, say, psilocybin can alleviate depression in people who aren’t responsive to other treatments. These are very small studies; it’s tough to get bigger funding and wider sample groups, because, as you say, these drugs are still illegal in many parts of the world. But over the past few years, I’m hearing more and more researchers saying, “Hey, if these drugs have potential therapeutic benefits, we really should be investigating them further.” Any powerful mind-altering compound carries certain risks, of course – but there’s no reason they shouldn’t be tested in clinical environments.
BT: Absolutely. This sounds like a fascinating project; when I asked you to talk with me about fMRI research, I had no idea we’d wind up talking about psychedelic drug trips.
MW: Yeah; it’ll be interesting to see where this research takes us.
Thanks again, Matt, for taking the time to chat. We’ve got more interviews with big names in neuroscience on the way, so stay tuned for lots more exciting times!




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