Psychedelics, Virtual Reality, & Experiential Medicine Part I: Predictive Processing

Part IIIa of the Unbundling Psychedelic Therapy Series

Welcome to Part I of Part III of Unbundbling of Psychedelic Therapy, a series of essays on how we should expect Psychedelic Assisted Therapy (PAT) to evolve over the next several years and the political, economic, and technological forces driving this evolution.

If you missed Part I and Part II I encourage you to check them out, but they’re not prerequisite for this essay.

What’s motivating this examination of Virtual Reality (VR) is the auspicious similarities to psychedelics in that it is in the midst of a renaissance whereby the technology has reached a sufficient threshold to be:

1. Therapeutically useful and

2. Culturally and commercially adopted at a scale¹

Two data points to support this notion include the recent FDA clearance of Applied VR’s chronic low back pain treatment and the accelerating consumer sales of the most advanced VR headsets.

Initially, I thought I would explore how we might see VR be used to support Psychedelic Medicine—for example, as adjuncts to preparation and integration, as a medium of connecting therapists and patients, or even while on is tripping—but it wasn’t quite coming together as I had hoped, I was missing a piece of the theoretical puzzle that connected psychedelics and VR, and it was bothering me.

Fortunately, this line from VR pioneer Jaron Lanier nudged me in the right direction (emphasis added):

“VR is not about simulating reality, really, but about stimulating neural expectations.”

With this in mind and by the grace of the internet, I made my way to Predictive Processing—a concept which I had been aware of but never explored in earnest—and I am now forced to sheepishly admit overlooking such a fundamental piece of the psychedelic science puzzle.

VR and psychedelics are deep, technical, and complex domains, rife with enthusiasm. I often feel that any explanatory motifs that merely allude to ‘resetting neural connections’ or ‘neuroplastic changes’ or some other buzzy phrase of how VR or Psychedelics work—let alone the two in combination—feels insufficient, even if they’re true.

And so to ground my own enthusiasm for this particular nexus of emerging technologies and to help support an informed psychedelic industry, I want to explore the concept of Predictive Processing in the context of these interventions because it doesn’t get as much attention as the more often invoked neuroplasticity and the Default Mode Network but is nevertheless a core concept of both technologies.

Predictive Processing (PP) has become the leading unified model of brain function.

PP is key to understanding how VR and psychedelics create altered states and treat mental illness. Thus, a rudimentary understanding of this theory would behoove psychedelic stakeholders, which I hope to accomplish in this post—Wish me luck since this post is more technical than anything I’ve written, and so I imagine responses to this piece might be “This guy has no idea what he’s talking about” or “I have no idea what this guy is talking about,” maybe both.

TL;DR:

• As Anil Seth notes: “Our conscious experiences of the world and the self are forms of brain-based prediction—controlled hallucinations.” Rather than merely taking in senses (sight, sound, emotion, perception, etc.) and experiencing them as one views images projected onto a screen, the conscious experience starts with a prediction from the brain.

• These predictions originate from a model of our bodies and our surroundings which is “stored” in the higher levels of the brain. This “model of reality” is under constant revision and changes over time.

• The development of one’s character, personality, traits, habits, behaviors, and mental illness occur along a pathway that looks something like this:

  • The moment-to-moment predictions about our body, the environment, and incoming sensory information generate a conscious experience

  • These experiences form beliefs that mediate our behavior, personality, traits, and habits

  • When the model, predictions, and neural circuits become maladaptive, it forms the neurobiological basis of what we call mental illness

• Finally, the dual theory that psychedelics relax the model that forms our top-down predictions and VR hijacks the model via bottom-up sensory stimulation makes VR compatible with psychedelics in ways that other neurostimulation techniques are not.

Special thanks to Joe Hardy, Christian Ulstrup, Robin Arnott, and Sandeep Prakash for thoughtful conversations at the nexus of psychedelics and VR—despite this expert input, any errors/misinterpretations are 100% mine.

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Predictive Processing, Experience Dependent Neuroplasticity, & Mental Illness

In the movie Ace Ventura: Pet Detective, the protagonist, played by Jim Carrey, is tasked with finding the Miami Dolphin’s star mascot Snowflake the Dolphin, who has gone missing just before the Super Bowl.

After much investigative work without progress, the scene in which Ventura makes the crucial connection that will solve the crime is reminiscent of how I have spent the last several weeks ruminating on the relationship between psychedelics and Virtual Reality (VR).

In this scene, Ventura is racking his brain to make the connection between the two prime suspects, Ray Finkle, a former field goal kicker for the Miami Dolphins—who is blamed for losing the Super Bowl for missing a last-minute field goal many years ago—and the lead detective on the case from the Miami Police Department, Lois Einhorn whom Ventura is sure is corrupt.

After much consternation, the truth eventually dawns on him that Finkle, who has been missing for years, underwent a sex change and became a woman and is, in fact, Einhorn.

Finkle is Einhorn and Einhorn is Finkle.

Finkle & Einhorn

These two suspects are actually the same person, and this critical insight allows Ventura to go on to solve the crime, find Snowflake, and return him just in time for the Super Bowl.

Just as Finkle is Einhorn and Einhorn is Finkle—psychedelics are VR and VR is Psychedelic.

In Isness: Using Multi-Person VR to Design Peak Mystical-Type Experiences Comparable to Psychedelics, the authors note (emphasis added):

“The word ‘psychedelic’ was coined by Osmond in correspondence with Huxley in 1956. Derived from the combination of the Greek words psyche (yuch, translated ‘soul’ or ‘mind’) and delein (dhlein, ‘to reveal’, ‘to make visible’, or ‘to manifest’), ‘psychedelic is often translated as ‘mind-manifesting’ or ‘mind-revealed’. Crucially, we highlight that the word’s roots are agnostic to the particular form of technology used in order to achieve ‘mind-manifesting.

Practices, Rituals, Drugs, and Technology

Throughout history, people have been exploring their minds with psychoactive plants, breathwork, meditation, prayer, chanting, dancing, and fasting.

There is a mind to explore, and drugs are one of many ways to do so; however, they might be the most reliable.

But that may not always be the case as increasingly powerful computing enables immersive technologies to consistently and reliably invoke altered states.

As we’ll explore below, VR ‘tricks’ the mind with images, tactile sensations, and sound that responds to one’s eye, head, and body movement so as to depict a realistic scene, thus convincing the brain that it is real.

So just as Finkle was a man and Einhorn is a woman—but they are the same person—psychedelics and VR represent the different polarities from which experiences can act on the brain to effect change.

The major piece of this conceptual puzzle is Predictive Processing.

Predictive Processing & the Hallucination of Reality

“Brains…are bundles of cells that support perception and action by constantly attempting to match incoming sensory inputs with top-down expectations or predictions.”—Andy Clark

As someone looking at PP with “fresh eyes,” I think we can grasp the basic premise in four steps:

1. The brain creates a model of the body, the space around it, and the environment, including the causes of sensory information

2. Top-down predictions from the brain’s model

3. Bottom-up incoming sensory information

4. Prediction error minimization

Usually, we think of our conscious experience as the result of our sense organs (eyes, ears, etc.) sensing stimuli from the environment (sound waves, light rays, etc.) and projecting them into the associated parts of the brain (visual cortex, auditory cortex, etc.) and from which we experience these senses in conscious awareness like a movie projected onto a screen.

The Brain’s Model of Reality

However, PP turns this concept on its head—pun intended—and claims that our conscious experience—what we see, hear, feel, etc.— is not necessarily an accurate representation of the environment as it is, but rather a prediction about— or a hallucination of—the sensory information based on a model of the world that we have built from past experiences.

Karl Friston, a computational Neuroscientist at University College London and collaborator with psychedelic researcher Robin Carhart-Harris notes:

“In this view, the brain is an inference machine that actively predicts and explains its sensations. Central to this hypothesis is a probabilistic model that can generate predictions, against which sensory samples are tested to update beliefs about their causes”

PP posits the brain is constantly generating and updating a mental model (often referred to as a generative model) of one’s body, the space around it, and the environment. This model develops throughout one’s life in a trial-and-error fashion in response to incoming sensory stimulation like objects and sounds and sensations from the body (like hunger, the urge to pee or poop, etc.) and interactions with others. This world model is constantly revising and updating according to the moment-to-moment comparison of the model’s predictions with incoming sensory information.

Top-Down Predictions & Bottom-Up Sensory Information

The predictions are based on prior beliefs (priors, beliefs, and assumptions are used interchangeably for our purposes) about the cause and significance of incoming sensory input and are referred to as top-down because the model is stored in higher brain levels.

These predictions are what we experience, not the actual sensory stimulus.

These moment-to-moment predictions travel “down” and meet the moment-to-moment incoming sensory stimuli traveling “bottom-up” from the external and internal environments.

These predictions are compared against the actual sensory input, and the results of this comparison are used to revise the model on an ongoing basis. When a prediction is way off, the model is updated accordingly.

Model Revision: Prediction Error Minimization

The meeting of the top-down and bottom-up information streams is the process by which the brain’s model of the world is constantly updated and revised through Prediction Error Minimization.

In this phase of the PP cycle, the brain’s predictions are evaluated against the incoming sensory information for accuracy. If the prediction was accurate, it reaffirms the brain’s model. If the prediction was wrong, the model is updated to reflect this new information.

What does this have to do with psychedelics and VR?

Quite a bit, but first, we have to understand the connection between PP and mental illness.

Predictive Processing and Mental Illness: Stress and Uncertainty

As a defensive response to some overwhelmingly stressful and intolerable event or environment—such as exposure to abuse, violence, parental neglect or anxiety, etc.—our models of reality develop beliefs that might have short-term survival value but over time become maladaptive.

Overwhelming uncertainty can lead to the same result.

Uncertainty as a state (“where is my next meal coming from? Can I make rent? Is my spouse cheating on me? Will my father come home drunk again? etc.) can act like trauma in that they both breed priors and beliefs that are maladaptive, self-destructive and resistant to change.

Mental illnesses like depression, addiction, OCD, and PTSD can be understood as the manifestations of the beliefs that have become maladaptively dominant (wrong) and resistant to change (rigid).

In this way, faulty circuits—which have become the newly adopted biological model of mental illness (replacing chemical imbalance) are downstream of “faulty models,” which itself is downstream from environmental and social determinants such as those identified above, as well as hereditary elements.

In the footnotes² are a few quotes (and sources) from scientific publications exploring this connection.

Top-Down: Predictive Processing in Psychedelics

So far, we’ve established that conscious experience originates from our brains’ model that makes moment-to-moment “top-down” predictions about the incoming, “bottom-up” sense data from our sensory and interoceptive receptors, and this model is revised whenever these predictions are wrong.

So, where do psychedelics fit in?

It just so happens that the primary receptor the classical psychedelics act on, the 5-HT2A, happens to be most dense in higher levels of the brain that encodes priors, beliefs, and assumptions and stores our model of reality.

When psychedelics act on these receptors, it relaxes the model and the beliefs upon which the top-down predictions are based—in other words, when our normal model of reality breaks down and we experience things like ego dissolution, states of unitive awareness, and a perturbation of cognitive capacities and sensory experience that we have come to call a “trip.”

Here’s how Robin Carhart-Harris and Karl Friston describe this concerning psychedelics for the treatment of mental illness (emphasis added):

“With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors.”

Illustrations by Pedro Oliveira, courtesy of Favo Studio. From REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics: “In this figure, we show compromised bottom-up signaling via a thin arrow with a red cross over its center. The graphic on the top right depicts a pathologically rigid or frozen system, insensitive to perturbation, represented in this figure as a heavy ball dropped on a solid surface having a minimal effect on the system, i.e., the ball lands with an uneventful thud. The bottom row depicts brain organization under a psychedelic. In this figure, the top-down arrow has been made translucent to reflect a deweighting or relaxation of high-level priors or beliefs (this component of the model is referred to by the acronym REBUS). The effect of this deweighting is to enable bottom-up information intrinsic to the system, to travel up the hierarchy with greater latitude and compass.”

In other words, psychedelics replace one hallucination with another—they disrupt the hallucination of everyday-waking life generated by the neural model of our body, surroundings, and incoming sensory information. The resulting experience is an altogether different type of hallucination resulting from the relaxation of the breakdown of normal perception.

The therapeutic potential lies in the capacity for revision to this model that can happen during or following a trip during the so-called “neuroplastic window.”

Bottom-Up: Predictive Processing in Virtual Reality

So if psychedelics relax high-level beliefs, priors, and assumptions that form our top-down predictions, then VR hijacks the model via bottom-up sensory stimulus (visual, tactile, auditory, etc.) that “tricks” our brains into believing that the VR simulation is real.

What makes the VR experience believable is the head-mounted display that depicts a scene that changes as one moves. In this sense, a VR system attempts to predict the sensory consequences of an individual’s movement and depicts an accurate scene that matches the brain’s prediction about how the scene should change in response to one’s movement, just like the generative model.

As the authors of Neuroscience of Virtual Reality: From Virtual Exposure to Embodied Medicine put it

“Specifically, VR hardware tracks the motion of the user, while VR software adjusts the images on the user's display to reflect the changes produced by the motion in the virtual world.”

Furthermore, VR systems accomplish this the same way our brains do by maintaining a model of the body, the space around it, and incoming sensory stimuli.

This prediction is then used to provide the expected sensory input using the VR hardware. Obviously, to be realistic, the VR model tries to mimic the brain model as much as possible: the more the VR model is similar to the brain model, the more the individual feels present in the VR world.”

In instances where VR helps chronic pain or PTSD, the generative model that encodes priors and beliefs is revised through the prediction error minimization process, thereby creating new neural beliefs.

Again, to make the comparison to psychedelics, which dissolve or relax our model and allow for bottom-up sensory input to make revisions to the model—VR leverages computer-generated bottom-up sensory stimulus that is all too real and which studies are showing modulate the models enough to mediate positive changes when the models have become pathological.

Closing the Loop

This top-down/bottom-up symbiotic relationship between the action of classical psychedelics and VR is a compelling area of academic, commercial, and self-directed research.

As Matthew Moroz and Robin Carhartt-Harris note in Employing Synergistic Interactions of Virtual Reality and Psychedelics in Neuropsychopharmacology:

“The individual interventions not only complement each other but offer synergistic interactions whereby each increases the efficacy of the other…

We propose that for certain pathologies researchers need not bother themselves as to which medium offers greater hope. Instead, we hypothesize that the most effective interventions shall necessarily come from a composite approach utilizing both.”

Thanks for reading, I hope it gets you thinking.

Always remember, laces out.

1. not to mention the shared capacity altering states of consciousness

PTSD

“Trauma-related disorders in particular have begun to be identified as disorders of excessive accumulated prediction errors (uncertainty) over life.”

—Predictive processing in mental illness: Hierarchical circuitry for perception and trauma

Depression

“…healthy human learning is normally based on making predictions and experiencing discrepancies between predicted and actual events or experiences. We present evidence suggesting that this learning mechanism is distorted in depression: current research indicates that people with depression tend to negatively reappraise or disregard positive information that disconfirms negative expectations, thus resulting in sustained negative predictions and biased learning.”

—Distorted Cognitive Processes in Major Depression: A Predictive Processing Perspective

Addiction

“We’ll argue that predictive processing implies a view of addiction not as a brain disease, but rather as a breakdown in the dynamics of the wider agent-environment system…We suggest that addiction can prove harmful to the person because as their addiction progressively takes hold, the addict comes to embody a predictive model of the environment that fails to adequately attune them to a volatile, dynamic environment. The use of an addictive substance produces illusory feedback of being well-attuned to the environment when the reality is the opposite.”

—Embodying addiction: A predictive processing account

2.