It’s Time for Psychedelic Neuroscience to Face its DMNs*
About 95% of the time I read a popular science article explaining the “neuroscience of psychedelic drugs,” I cringe. Not because the topic is dull — just the contrary: I find it so interesting that I got a job studying it full-time. I cringe because the prevailing narrative on how psychedelics alter brain function is flawed, and it’s leading a lot of smart people interested in the research astray.
I know this because I used to be one of those people. An undergrad neuroscience major and self-proclaimed consciousness nerd, I couldn’t get enough of the “psychedelic renaissance.” I devoured Michael Pollan’s How to Change Your Mind and burned through episodes of Netflix’s The Mind, Explained. I came away mesmerized by the potential for psychedelic treatment. But I also inherited an idea about how psychedelics work in the brain. An idea, I’m realizing — after two years of conducting research at the world’s largest psychedelic research center — that is not grounded in fact.
I’ll call this idea — which circulates in book chapters, TV episodes, webinars, and even academic papers — the “popular account” of psychedelic action. It begins like this. Psilocybin, the chemical behind the magic in “magic mushrooms,” binds to a specific type of serotonin receptor. This binding causes a variety of network-level changes in the brain that eventually lead to a feeling of “ego-dissolution.” Before going any further, let’s define some terms (for more info, see my article on fMRI).
Brain networks are sets of neural regions that fire together when a person engages in a particular activity. The auditory network, for example, comprises a handful of areas along the right and left sides of the brain. When people listen to music — or any sounds — in an MRI scanner, these areas light up. When all of the regions in a particular network are firing together in synchrony, we’d say the network is highly connected. So we’d expect the auditory network to be more connected when a person is listening to Beethoven’s 5th, for example, than when they are lying in silence.
The “popular account” of psychedelic action hinges on one finding: psychedelic drugs cause a decrease in connectivity of a peculiar network called the Default Mode Network (DMN). In my first example, I explained that the auditory network is most connected while someone listens to sounds. And for virtually all brain networks, there is some activity during which the network is most connected. That is, except the DMN. The DMN is most strongly connected when a person engages in no activity (hence the name — the brain’s “default mode.”)
But the human mind is a tireless beast, and even when people are “doing nothing” in an MRI scanner, they’re still doing something — mind wandering or reflecting about themselves, usually. For this reason, the DMN is said to be highly connected during “self-referential thinking.”
So what does it mean for this network to become less connected, or — in neuroimaging terms — to disintegrate? After taking a psychedelic, some people report feeling “ego-dissolution”: a transient shift — or in some cases, obliteration — of their normal sense of self or identity. Psychedelic pundits sometimes contend that disintegration of the DMN is the biological basis for this feeling. “To the extent the ego can be said to have a location in the brain,” says Michael Pollan on Big Think, “it appears to be this, the Default Mode Network.”
It’s an elegant story, one that satisfyingly explains how psychedelics exert their therapeutic effects. The network in our brain that represents our identities is temporarily subdued, letting the brain go “off [its] leash,” as Pollan puts it. People with substance abuse disorders no longer see themselves as “addicts,” and people with depression no longer feel their identity bound to their illness.
Unfortunately, the “popular account” is based on faulty logic. To help understand why, consider this thought experiment (for the record, I still revere Michael Pollan).
Suppose I slide 100 people into an MRI scanner (not all at the same time) and image their brains while they watch clips of the World Cup. After analyzing the data, I observe a network of brain regions that reliably fire together while people watch the clips. Excited, I run another experiment where I show people different soccer clips — children kicking a ball around, reels from the video game FIFA — and the network is still highly connected. Did I find the “soccer network”?
Probably not. First off, everyone in the experiment was looking at people perform actions with their feet, so maybe I’ve found the “people-performing-actions-with-their-feet network.” Or, on a more basic level, everyone in the experiment had their eyes open, so likely I was observing a visual network. The point is, my findings were wholly unspecific to soccer; I’ve fallen prey to what neuroimagers call the fallacy of reverse inference.
A reverse inference is any claim that links brain data with mental states. To claim that the network we identified is the “soccer network” makes a specific prediction: if I observe someone’s brain activity, and that network lights up, then the person must be thinking about soccer. So if I instead showed people baseball clips and the network was active, we’d know that it’s not specific to soccer. Since most brain networks are involved in a myriad of mental states, valid reverse inferences are notoriously difficult to make.
Returning to psychedelics, to claim that the DMN is the neural seat of the ego — and that its disintegration represents ego loss — is an ambitious reverse inference. To prove its validity, a researcher would have to demonstrate that disintegration of the DMN and ego dissolution correlate 1:1. In other words, if a subject’s MRI scan showed a disintegration of the DMN, then that subject must have been experiencing ego dissolution.
Empirically, this couldn’t be further from the truth. It turns out that disintegration of the DMN isn’t specific to “ego-dissolving” drugs like psilocybin. It’s not even specific to hallucinogens. Among the many drugs and activities that acutely decrease connectivity of the DMN, perhaps most puzzling is alcohol. I say this because my ego does the opposite of dissolve after a pint of Blue Moon.
To link DMN disintegration to a mental state as particular as ego-dissolution is to conveniently ignore years of non-psychedelic research findings. A more likely explanation is that disintegration of the DMN is a neural correlate of being messed up on any drug, but even this may be overly-specific.
When discussing the neuroscience of psychedelics, it’s important to simplify research findings for a lay-audience, and even a certain degree of speculation is warranted in the appropriate context. But propagating an empirical inaccuracy as “our best guess” for how psychedelics work in the brain is a disservice to both the neuroscientists doing serious work on this topic, and to the curious public looking for good information.
In closing, I’ll link an alternate account of psychedelic action in the brain that goes beyond faulty reverse inferences involving the DMN. Franz Vollenweider, Katrin Preller, and the team at the University of Zurich have proposed a model of psychedelic activity that implicates the thalamus, a region involved in filtering sensory information. Psychedelics impair function of the thalamus, they suggest, which allows lights, sounds, and even thoughts that normally get “filtered out” to reach conscious awareness.
