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LSD “Frees the Brain” From Its Usual Neural Pathways, Study Finds

By Alexander Beadle

Published: Jul 12, 2021   
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Researching how the mind works is no easy task. In fact, because of the brain’s astounding complexity, one of the most effective ways to assess what is really going on inside our heads is to completely flip the script and instead take a look at what happens when normal brain function is disrupted.

In a new study led by researchers from the University of Cambridge, scientists aimed to do just that. Using functional magnetic resonance imaging (fMRI) scans of the brain, the researchers studied the effects of LSD on a group of healthy volunteers. They found that the hallucinogenic drug was able to weaken the relationship between anatomical brain structure and functional connectivity, allowing the brain to explore new connectivity patterns.

The researchers also found that the drug increased the complexity of only certain brain states, known as segregated brain states, indicating that the effects of LSD on brain function and subjective experience are non-uniform in time.

Together, the researchers say that these findings provide important new insight into the relationship between brain function and consciousness.

Studying consciousness

The study was published earlier this year in the journal NeuroImage.

“My main interest, and the focus of my research, is on understanding the neuroscience of human consciousness,” Andrea Luppi, a consciousness researcher at the University of Cambridge and the first author of the study, told PsyPost.

“Most studies of consciousness focus on its loss: sleep, anesthesia, or coma. But we think that a complementary way to obtain insights is to study states of altered consciousness, such as the psychedelic state induced by LSD.”

For this study, Luppi and his colleagues invited 20 healthy participants with previous experience of drug use to undergo two short experimental sessions inside an fMRI machine. During one session, the participants were given a placebo drug, while in the other they were given an active dose of LSD. No tasks were given to the participants during the fMRI scanning – they were simply instructed to lie there with their eyes closed for the duration. One participant aborted their session due to anxiety; four more were excluded due to excessive head movement while they were being scanned, leaving 15 valid participant results to be studied.

LSD frees functional connectivity from the constraints of structural connectivity

As the saying from the great neuropsychologist Donald Hebb goes, “neurons that fire together, wire together.” But it appears that this might not always hold true under the influence of LSD.

“We know that brain structure has a large influence on brain function under normal conditions,” Luppi explained to PsyPost.

“Our research shows that under the effects of LSD, this relationship becomes weaker: function is less constrained by structure. This is largely the opposite of what happens during anesthesia.”

Under the influence of LSD, the brain appears to be less constrained by either the presence or absence of pre-existing connections between different parts of the brain. Instead, the brain is able to more freely explore different connectivity patterns. The researchers theorize that these unusual connectivity patterns, reflected in the increased functional complexity of the brain, might be the underlying cause behind some of the unusual beliefs and experiences that occur during a psychedelic trip.

LSD’s effects on the brain change with time

Interestingly, the researchers also noted that the administration of LSD caused different subjective effects depending on the particular state of the brain at any given point, meaning LSD’s effects were non-uniform in time.

“From introspection, we know that the subjective stream of consciousness is a constant ebb and flow – so we explored the dynamic effects of LSD on human brain function, focusing on two key properties: integration and segregation of information in the brain,” Luppi explained in a statement.

In relatively simple terms, we can think of the brain as being made up of many different specialized regions that each deal with a particular skill. To function properly, the brain needs to be able to deal with the specialized local (segregated) processes in each region and the wider distributed (integrated) processes. Using fMRI, it is possible to study these functional relationships, and hence identify any differences in how these states operate under the influence of LSD compared to how they operate under normal conditions.

“Our main finding is that the effects of LSD on brain function and subjective experience are not uniform in time,” Luppi said. “In particular, the well-known feeling of ‘ego dissolution’ induced by LSD correlates with [the] reorganization of brain networks during a state of high global integration. These results reveal a new, dynamic dimension of psychedelic action on the human brain.”

On the flip side, the decoupling of brain function from its structural constraints was predominately seen for the globally segregated brain sub-states. It was also observed that LSD reduced the functional connectivity of the anterior medial prefrontal cortex – a part of the brain thought to be involved in reality monitoring – in globally segregated brain sub-states. This again hints at a possible neurobiological explanation for some of the more hallucinogenic subjective experiences seen with psychedelics use.

“Studying psychoactive substances offers a unique opportunity for neuroscience: we can study their effects in terms of brain chemistry, but also at the level of brain function and subjective experience,” Luppi added, speaking to PsyPost. “In particular, the mind is never static, and neither is the brain: we are increasingly discovering that when it comes to brain function and its evolution over time, the journey matters just as much as the destination.”


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