The Neuroanatomy Of A Psychedelic Trip: Brain Networks

The Neuroanatomy Of A Psychedelic Trip: Brain Networks

Brain networks are collections of different regions that show functional connectivity. But how do these areas of the mind adapt when using psychedelics? That’s something worth understanding.

I’m going to assume you’ve already read the previous installment of “neuroanatomy of a psychedelic trip“, where we went over neuroreceptors and certain parts of the brain responsible for psychedelic trips.

We covered things like 5-HT2A receptors and how most psychedelics use this neuroreceptor in the brain while you trip. We also learned about the thalamus, amygdala, medial prefrontal cortex, and the cingulate cortex along with how these brain areas communicate (or stop communicating) with other parts while tripping.

This article is the sequel — and like Godfather 2, it will be better than the original.

Interested in joining a Psychedelics Clinical Trial? Sign up here now and we will connect you with a clinical trial in your area when one becomes available.

We’ll be discussing how psychedelics impact entire brain systems. We’ll also look at how certain trips may lead to brain networks communicating with one another. It’s all here, neatly packaged for you to read — so let’s get to it.

RELATED: Candy Flipping: What Is It, And Is It Safe?

How Do Psychedelics Mix With The Different Brain Networks?

When it comes to psychedelics’ interacting with the brain, modern psychedelic neuroscience refers to three networks: The Default Mode Network (DMN), the Central Executive Network (CEN), and finally the Salience Network. As you guessed it, all three networks communicate and modulate each other during a psychedelic trip. I’m also going to throw in an explanation of resting state functional connectivity (RSFC) as a bonus, like getting cheese on your nachos and cheese on the side.

Before discussing the various networks associated with psychedelic trips, you must understand that your brain is constantly trying to maintain an equilibrium.

This is an active process that involves billions of electrical and chemical interactions. A third of what you eat every day goes towards just maintaining an electrical gradient in your brain. Therefore, taking psychedelics colossally disrupts this equilibrium, sending your brain into a state of chaos.

Granted, we call it chaos because it’s so unlike the traditional homeostasis, or balance, understood in neuroscience. As psychedelic science expands, this chaos will most likely turn into a very ordered but complex process that takes an immense amount of effort to understand. For now, it’s chaos.

Intro Of The Default Mode Network (DMN) And The Central Executive Network (CEN)

In a greater sense, the DMN is a task-negative network. This means there’s not much going on while the CEN and other “working memory” networks are task-positive networks. Furthermore, it means you’re consciously doing something with your brain — like focusing on when this sentence will eventually come to an… end.

The DMN and the CEN have a “negative correlation” with one another. They’re not enemies, they just have inverse relationships — when the DMN is most active, the CEN quiets down. When it’s time for the CEN to be active, the DMN calms down. It’s also an “antagonist relationship”, because neuroscience has a ridiculous habit of developing multiple names for the same thing.

Since both networks operate so closely together, it’s difficult to discuss the DMN without referencing the CEN and obviously hard to talk about the CEN without bringing up the DMN — but we’re going to do it anyway. This is what we’re all here for. First up, the ever elusive Default Mode Network.

RELATED: I Read Every Neuroscience Study On Psychedelics Published Since 2017. Here’s What I Learned

Default Mode Network (DMN)

Undoubtedly, the most boring name for such an incredibly fascinating network.

The Default Mode Network was intentionally ignored by the scientific field until it was discovered in 2001 by Dr. Marcus Raichle. We all take risks, but Raichle does things like inject himself with radioactive xenon just to see what happens.

At a time when the entire neuroscience community would take the idle “noise” from neuroimaging and subtract it from a cognitive task, Raichle did the opposite and subtracted the neurosignals created during a cognitive task (like looking at a dot) from the “noise” when a person is not doing anything.

What he found was a low, but persistent activation of certain areas of the brain, specifically the cingulate cortex, amygdala, thalamus, and medial prefrontal cortex — all of which we covered in the previous installment of The Neuroanatomy of a Trip. The DMN also consists of the parahippocampal cortex, lateral parietal cortex, and the lateral temporal cortex.

Raichle discovered the majority of being ‘conscious’ was actually the brain being in this “default” state, or the Default Mode Network. It’s a state of being that most consider “inactivity” — like when you’re just sitting down doing self-referential processing. Things like thinking about your thoughts, daydreaming, even just sitting quietly are all activities that fall under the DMN.

Collapsing The DMN During A Trip

So you’ve taken LSD on a Tuesday afternoon and you want to see what it does to your DMN. Well, the first thing that happens is the relationship the DMN has with the CEN becomes less antagonistic and both networks build somewhat of a relationship with each other, like old high school rivals that just found each other on social media.

The structural integrity of the DMN also begins to collapse, which means brain areas that make up the DMN begin to “decouple” or “segregate” from each other. When this happens, some incredible things go down within a trip. Two areas within the DMN — the cingulate cortex and the medial prefrontal cortex — often decouple during a psychedelic experience.

Through the work of Lukasz Smigielski at University of Zurich, we know this specific decoupling is responsible for the experience of ego-dissolution, or the lofty scientific phrase “oceanic boundless,” during a trip.

The DMN and Mystical Experiences

Another part of the DMN, the lateral parietal lobe, has two sections — the superior (upper) parietal lobe and the inferior (bottom) parietal lobe. Within the bottom part is the angular gyrus and supramarginal gyrus. A gyrus is a way better name for what it actually is: A fold of brain meat.

The angular gyrus is known for processing spatial and social cognition, memory retrieval, language, and surprisingly conflict resolution. When it comes to the supramarginal gyrus, it’s involved in empathy, egocentrism, and speech perception.

Frederick Barrett of Johns Hopkins University has theorized this separation of functional connectivity between the angular gyrus and supramarginal gyrus results in a cognitive experience of “timelessness” and “spacelessness” during hefty psychedelic trips.

This neuromechanical process leads to a “mystical experience” while tripping. The concept of mystical experiences can often be a slippery slide into pseudoscience.

Nevertheless, the mystical experience is a unique subjective effect of ingesting psychedelics in moderately high doses.

Resting State Functional Connectivity (RSFC)

This is the bonus part I’ve promised you. Consider it a side quest on your main quest of understanding the neuroanatomy of a trip. So what’s the difference between resting state functional connectivity and just regular functional connectivity?

Well these two aren’t at odds, in fact RSFC is a type of functional connectivity. Resting State Functional Connectivity measures cerebral activity (through fluctuations in blood flow) between two or more parts of the brain when you’re not doing anything. It’s a resting state for a reason. In comparison, functional connectivity measures the blood flow of two or more parts of the brain. This usually happens during high cognitive activity.

In other words, functional connectivity measures the simultaneous firing of two or more parts of the brain.

While on psychedelics, resting state functional connectivity in traditional brain areas tend to spill over into other areas. So, in a sense, RSFC expands in the brain. However RSFC within the DMN has a habit of losing integrity and decreasing.

But what happens to Resting State Functional Connectivity of the DMN after a psychedelic trip?

Restructuring Of The DMN After A Trip

By now, you have a full understanding of how the DMN operates under a psychedelic. You also know the collapse of the connectivity within the DMN is a staple of the subjective effects of a psychedelic experience. Let’s get into how this phenomenon may actually have therapeutic benefits.

In 2017, Robin Carhart-Harris from Imperial College London wanted to see what psilocybin did in patients with treatment-resistant depression. He discovered that, while RSFC decreases in the DMN during a trip, the next day, RSFC within the DMN surprisingly begins to increase and gain structure. This is interesting because DMN with strong RSFC is seen in people with depressive behavior and rumination.

However, in this study, the increase in RSFC within the DMN, specifically the medial prefrontal cortex and the lateral parietal cortex, correlated with a decrease in depression lasting weeks after psilocybin administration — in people with treatment-resistant depression.

This single groundbreaking study set forth the notion that psychedelics can play a key role in treating depression. With completely different neural mechanisms from traditional Selective Serotonin Reuptake Inhibitors (SSRIs) like antidepressants Prozac and Zoloft, this is able to occur.

One may argue that psychedelics may work better than pharmaceutical antidepressants at helping patients with treatment-resistant depression. This is a conversation Big Pharma CEOs are not yet ready to have, however.

RELATED: What Causes Visuals In Psychedelic Trips?

Central Executive Network (CEN)

The Central Executive Network (CEN) is also called the Frontoparietal network (FPN). But for the sake of keeping the confusion to a minimum, we’ll refer to it as the CEN.

As mentioned earlier, the CEN is an active brain network. It is utilized when doing cognitive tasks like reading, looking for lost items, etc. In other words, literally anything that requires the use of working memory and focused cognition.

Like the DMN, the CEN has a habit of desegregating itself during a trip, while simultaneously increasing its global functional connectivity with other parts of the brain. This includes the DMN. This is interesting behavior coming from the CEN — especially when integrity disorders within the CEN are seen in people with schizophrenia and PTSD.

It’s important to note that the neurological behavior within the CEN while under psychedelics remains a mystery. However, it does show promise for the treatment of certain neurological conditions.

It took neuroscience over 100 years to even realize networks like CEN and DMN exist. The popularity of psychedelics is now pushing the need for a greater understanding of these vastly misunderstood systems. This brings us to our final brain network.

RELATED: How LSD Affects The Brain

The Salience Brain Network

The Salience Network is often incorrectly defined as the combination of the Default Mode Network and the Central Executive Network. As for the Salience Network, it’s an entirely separate network. In fact, until 2007, we didn’t even know about its existence. Neuroscience knows less about The Salience Network than it does the DMN or CEN.

The Salience Network includes parts of the hypothalamus, central striatum, thalamus, amygdala, and other brainstem nuclei. Key research on this network is still ongoing. However, the leading theory is that the Salience Network is primarily responsible for switching between the DMN and the CEN. If the DMN represents “off” and the CEN represents “on,” the Salience Network is the light switch of both networks.

Psychedelic-Induced Creativity

I know what you’re thinking, what does the Salience Network mean for my artistic creativity while I’m on psychedelics? For decades, the process of creativity was attributed to a particular cognitive state.

Kalina Christoff from the University of British Columbia developed the Dynamic Framework of Thought model. This theory states that the cognitive switch between the DMN and CEN is responsible for the development of creativity and artistic creation.

Christoff believes creativity is actually a two-part process. It consists of “idea evaluation” and “idea creation”, with both cognitive states being in constant fluctuation during the creative process. Idea creation comes from distinct activity in the DMN, while idea execution falls into the CEN.

This is a revolutionary idea of creativity that actually dates back to 2015.

However, researcher Manesh Girn was the first to consider looking into what psychedelics does to this Dynamic Framework of Thought. His theory is this: If creativity is dependent on the repeated switching from the DMN to the CEN via the Salience Network, then this creativity would be altered by the inability of the brain to be able to fully segregate from each network.

Remember, this “spilling of networks” is endemic to a psychedelic trip. Girn suggests the following when discussing the lack of full brain network segregation.

It “might facilitate the exploration of a broader search space during creative generation, which in turn leads to greater potential of discovering highly novel ideas.”


You now have a working understanding of how brain networks modulate through psychedelics. Bet you never thought that would happen when you woke up today.

The Default Mode Network, Central Executive Network, The Salience Network, and the Resting-State Functional Connectivity that connects them — all of these concepts are inside your brain. If they’re not, read the article again, or share it with a friend so they can read it for you. Better yet, share it with a friend and then read it to them, like a psychedelic neuroscience bedtime story.

Also, follow me on Twitter so you’ll know when the next installment of The Neuroanatomy of a Trip drops.

Zeus Tipado

Zeus Tipado

View all posts by Zeus Tipado

Zeus Tipado is a PhD student at Maastricht University focusing on the neuroscience of psychedelics. He’s the creator of Stonedgamer and his work has appeared in Doubleblind Magazine, Psychedelics Today, Healing Maps, and Psychedelic Support. You can reach him on Twitter, Instagram, and Twitch.

Abid Nazeer

This post was medically approved by Abid Nazeer

Dr. Nazeer is the Founder and President of APS Ketamine/Advanced Psychiatric Solutions, which he established in 2016 as the first psychiatric outpatient ketamine clinic in Illinois. He is board certified in Psychiatry as well as Addiction Medicine. He completed his psychiatry residency at Louisiana State University Health Sciences in Shreveport where he held the role of Chief Resident. Dr. Nazeer is providing medical oversight to the growth plan of Wesana Clinics, with the model of comprehensive psychiatry clinics specialized ketamine and psychedelic therapies, integrated brain health and wellness centers, and technology utilization of Wesana Solutions remote patient monitoring product.

Related Posts

Comments (2)

  • Marie James
    November 17, 2021 at 11:55 pm Reply

    Great article
    wonderful research in your area of psychedelic

  • Marie James
    November 17, 2021 at 11:58 pm Reply

    With research what’s the age someone can be in a research protocol

Leave a Reply

Your email address will not be published. Required fields are marked *

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Explore Psychedelic Therapy Regions