In certain circles, the potent psychedelic N,N-dimethyltryptamine (DMT) is known as the 鈥渟pirit molecule鈥� for its peculiar ability to transport people into other worlds. Those who take it commonly experience vibrant colours, abstract geometric patterns 鈥� and even meet elves and aliens 鈥� all in a way that feels completely real.
That might all sound about as far from the realm of empirical science as you can get 鈥� but not for neuroscientist . In his lab in听Maastricht, the Netherlands, he is planning an outlandish experiment in which he will monitor the brains of people dosed with DMT while they wear a virtual reality headset. The hope is that by observing what happens when we slip into another form of reality, we can fathom how our minds construct the one we experience in everyday life. 鈥淥ur brain is easily deceived as to what reality is,鈥� says Tipado.
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Already, he has found tantalising hints of a new brain network that he thinks might underlie the feeling we have of being immersed in a world 鈥� be that real life, VR or a听drug-induced trip. He hopes to identify and perhaps even learn to control this hypothetical 鈥渋mmersion circuit鈥�. If he can, it might enable us to dial up or down how believable an experience is, create more effective therapies for mental ill-health and produce more visceral听training worlds for surgeons or firefighters. It would also, of course, be a听huge听breakthrough in neuroscience.
Prediction machines
We don鈥檛 fully understand how our minds create the seamless experience of the world around us. But one leading idea is that the brain is a kind of 鈥減rediction machine鈥� that actively constructs reality by contrasting personal expectations, based on past events, with direct data from our senses.
When there is a difference between internal predictions and our senses, we are left with a 鈥減rediction error鈥�, which the body tries to minimise by gradually updating our internal model of ourselves and the world as new sense data comes in. 鈥淓verything we experience is a kind of pragmatic construct,鈥� says cognitive philosopher at the University of Sussex in the UK. 鈥淎ll of our predictions are geared towards smoothly guiding actions, because it鈥檚 only actions that will keep us alive.鈥�
This predictive model of ourselves is built in a hierarchy of layers. The so-called higher levels contain abstract ideas such as who we are and what reality is, whereas the lower levels are concerned with more concrete things like colour and shape. There is a two-way flow of information, with predictions cascading down from these higher levels in a series of feedback loops, while sense data from our eyes, ears, nose and skin rises up from the lower levels.
Psychedelics are widely thought to exert some of their strongest effects at higher levels of predictive processing, says Clark. For example, activity in the brain鈥檚 default mode network听鈥� which is broadly thought to help us听assess past events, plan for the future and construct our sense of self-awareness and ego听鈥� is dampened by many psychedelics. Recent research by at Imperial College London found that DMT specifically while also regions and collapsing the organisation of the brain鈥檚 hierarchies.
鈥淲henever you take psychedelics, the location of this information gets mixed up,鈥� says Tipado. Simple, low-level concepts like colours and shapes are processed in higher levels of the visual cortex. Meanwhile, complex听concepts, like the details of faces, are听processed in lower-level regions of the visual cortex. 鈥淚t鈥檚 like putting a PlayStation 5 disc in a PlayStation 2. It鈥檚 not compatible,鈥� he says. 鈥淭hat鈥檚 why we have visual experiences that are very counterintuitive.鈥�
This disruption makes some sense within an听overarching model of how psychedelics act on the mind 鈥� called (REBUS). Computational neuroscientist at University College London and at the University of California San Francisco, who听came up with the model, suggest that psychedelics specifically relax the grip of听our听high-level expectations of what reality听should be like. Reducing top-down control听in听this way then frees up the flow of听bottom-up sensory information so that听it听exerts more influence.
Psychedelic therapy
All of which could help explain the therapeutic effects of psychedelics, which are combined with talking therapy in promising treatments for depression, PTSD and addiction. According to REBUS, relaxing high-level beliefs allows us to reframe the unremitting thought patterns and behaviours that occur in mental health conditions like these.
By building on predictive processing models听like this, Tipado aims to figure out what happens when we become so immersed in our perceptions of alternate realities that we听accept them as physically real. He agrees that the relaxation of high-level beliefs can dramatically alter our experience of reality, but听argues that the influential and causal role played by lower levels in the hierarchy has been overlooked. at the University of Exeter, UK, has thought about these processes independently and is broadly on the same page. 鈥淭here鈥檚 not just processes from the top听down or bottom up,鈥� he says. 鈥淭here鈥檚 an听interplay. It鈥檚 more dialogical.鈥�
Tipado鈥檚 research considers how this dialogue plays out in the brain鈥檚 visual system. 鈥淥ut of all the perceptual domains, the听single thing that is a global experience in听psychedelic trips is an intense visual experience,鈥� he says. A听2018 study by Roseman and Carhart-Harris found that positive therapeutic outcomes in psychedelic-assisted therapy , among other things.
Psychedelics suddenly give access to an almost raw feed听of our visual听world
This has taken Tipado on an unexpected detour into the realm of ocular science and the intricate way that . 鈥淲e鈥檙e trying to draw attention to the bottom-up processing of the eye,鈥� he says, and听how it alters our subjective experience of听immersion听鈥� broadly defined as the perception of being physically present in听a听non-physical world.
In particular, he is focusing on the role played by amacrine cells in the retina, which are thought to act as inhibitory filters for the visual data we receive from the outside world.听In 2015, and his collaborators at Osaka University in Japan . They found these 鈥渇ilterless鈥� mice performed better at tests involving identifying the edges and outlines of objects in darkness. 鈥淚f you don鈥檛 have amacrine cells, then you can detect significantly lower-contrast objects,鈥� says Tipado. However, there are many different types of amacrine cells, and the precise filtering mechanisms are unknown.
Tipado also suspects that amacrine cells are听the key to understanding the immersive visuals experienced in psychedelic trips. In a , he pointed to the similarity between the behaviour of mice bred听to lack these cells and the common psychedelic phenomenon of 鈥渃losed-eye visuals鈥�, whereby incredibly vivid colours, shapes and even entire worlds are perceived behind shut eyelids. Amacrine cells also contain a lot of 5HT2a receptors, which are the听same type activated by psychedelics like DMT and psilocybin. The alteration of amacrine cells by psychedelics through their 5HT2a receptors may enhance the amount of听visual sensitivity in darkness, including behind closed eyelids, leading to these unusual听visual experiences. 鈥淲e鈥檙e suddenly given access to an almost raw feed of our visual听world,鈥� says Tipado.
He suggests that these cells might even be the gateway to the wholesale disruption and alteration of the brain鈥檚 predictive processing hierarchies, which underpin all immersive visual perceptions听鈥� psychedelic or otherwise. 鈥淭he possibility that a trip might be initially triggered because amacrine cells aren鈥檛 inhibiting visual information could open up听a听whole new realm of understanding,鈥� he听says. Roseman agrees that amacrine cells play a role in visual psychedelic experiences but adds that he 鈥渨ouldn鈥檛 go as far as saying they are the source of visions鈥�.
Virtual reality
To test these ideas, next year Tipado plans听to听observe how the visual cortex is activated during an immersive VR experience before, during and after a DMT trip. He has designed the experiment to try to modulate amacrine cell activity. Rather than mind-blowing visuals melting into each other, the VR听world is sparse: a 360-degree surrounding of Eigengrau听鈥� German for intrinsic grey听鈥� which replicates the darkness you see when you close your eyes.听This low-quality, low-contrast visual information increases the听likelihood that the brain makes a听prediction error, says Tipado. 鈥淚t鈥檚 like听when听you鈥檙e in a dark room, you might听mistake听a coatrack for a person.鈥�
Is immersion an听actual network of brain areas that can be dialled up and dialled down?
By combining DMT听with VR, he hopes to听draw people into a series of immersive realities that they believe are real to greater or听lesser degrees. 鈥淲e can really play around with this sort of state of visual ambiguity,鈥� he says. A functional near-infrared spectroscopy headset, which assesses brain activity by shining light through the skull and observing how much is absorbed by brain tissue, will then be used to search for possible hallmarks of immersion in the visual cortex. 鈥淲e鈥檙e investigating the areas of the brain responsible听for immersion,鈥� he says.
Tipado says his unpublished pilot studies suggest that there is overlap in activity in the visual cortex in people experiencing either immersive VR or DMT realities. These common signals could hint at a new brain network specifically related to immersion. 鈥淲e鈥檙e assuming that this could represent some sort of circuit of brain connectivity,鈥� he says. 鈥淚s immersion an actual network of brain areas, just like how the default mode network is a network of brain areas that can be dialled up听and dialled down?鈥� he asks.
However, it is fair to say there is still听no听published evidence to back up Tipado鈥檚听claims of an overarching immersion network.听And , a neuroscientist at the Spinoza Centre for Neuroimaging in the Netherlands, suggests that the underlying architecture of VR immersion may differ from psychedelic immersion.
Still, Tipado is upbeat. 鈥淔iguring out if the brain constructs reality in the same way regardless of it being actual reality, virtual reality or a pharmacological reality induced by psychedelics, could help us comprehend augmented reality as a whole,鈥� he says. 鈥淎nd potentially how our minds construct day鈥憈o-day reality, too.鈥�
From an entertainment perspective, this听could enable gaming worlds that are听fundamentally more believable. 鈥淭hat鈥檚听a听low鈥慼anging fruit,鈥� says Tipado. It听could also lead to more effective virtual offices or training programmes for pilots or听doctors, for example.
Then there is psychedelic-assisted therapy, during which people are often given blindfolds to reduce their visual stimulation. Some other approaches go even further, attempting to remove the subjective experiences of psychedelics altogether. However, Roseman points out that 鈥渁 lot of the emotional insights of the spiritual experience have a visual or imaginary quality鈥�. Tipado agrees that more attention should be paid to the importance of vision in these therapies and he hopes to use immersive VR to precisely guide the experience. 鈥淭he future needs to be a little bit weirder,鈥� he says.
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