Psychedelics induce “hypersynchrony” in multiple brain regions

New research provides evidence that psychedelic experiences are related to “hypersynchrony” in the brain. The study, published in the journal Communication Biology, found that substances like LSD or ketamine produced “aberrantly strong” patterns of electrical brain activity that were characterized by unusually synchronized high-frequency oscillations across different regions.

One of the most intriguing aspects of psychedelics is their ability to induce altered states of consciousness, which are characterized by profound changes in perception, cognition, and self-awareness. These altered states offer a unique opportunity to investigate how brain activity gives rise to subjective experiences. By examining the neural correlates of altered states, the researchers hoped to shed light on the neural basis of consciousness and the mechanisms through which it can be altered.

“Consciousness is one of those fundamental questions that have always fascinated me. I think that psychedelics is a great tool to study the neural basis of consciousness in laboratory animals, since we share most of the same neural ‘hardware’ with other mammals,” said study author Pär Halje, a cognitive neuroscientist and researcher in neurophysiology at Lund University.

To conduct the study, the researchers used awake rats as their experimental subjects. They developed a technique to simultaneously record electrical signals from 128 different areas of the rats’ brains. This involved implanting microelectrode arrays with multiple wires into specific brain regions.

These arrays allowed the researchers to measure both local field potentials (LFPs) and single unit activities from various brain areas. LFPs are electrical signals generated by the collective activity of thousands of neurons, while single unit activities represent the firing patterns of individual neurons.

The researchers administered different psychoactive substances to the rats, including LSD, DOI (2,5-dimethoxy-4-iodoamphetamine), ketamine, and PCP (phencyclidine).

LSD and DOI are known to interact with serotonergic receptors, particularly the 5-HT2A receptor. On the other hand, ketamine and PCP are agonists of another type of receptor called NMDAR, which stands for N-Methyl-D-Aspartate receptor. This receptor is associated with the neurotransmitter glutamate and is involved in processes like learning, memory, and neural communication.

The researchers also included amphetamine as a non-psychedelic psychoactive control. The effects of these substances on brain activity were recorded and analyzed.

Halje and his colleagues found that 5-HT2AR psychedelics and NMDAR psychedelics had distinct effects on neuronal firing rates. However, despite these differences at the level of individual cells, both types of psychedelics induced similar changes in the collective activity of neuronal populations in the form of high-frequency oscillations, which are rapid and repetitive patterns of electrical activity in the brain.

What was particularly striking was that these high-frequency oscillations occurred almost simultaneously in different parts of the brain, particularly in the ventral striatum and cortical areas. The signals from different brain regions were firing almost perfectly in sync with each other, with incredibly small delays between them, often less than 1 millisecond. This suggested a unique synchronization pattern that wasn’t solely reliant on the relatively slow communication through chemical synapses.

“We assumed that a single brain structure was generating the waves and that it then spread to other locations,” Halje explained. “But instead, we saw that the waves went up and down almost simultaneously in all parts of the brain where we could detect them – a phenomenon called phase synchronization.”

In other words, even though the individual brain cells were behaving differently under the influence of LSD and ketamine, the overall way that different parts of the brain were communicating showed a striking similarity, with very fast and synchronized signals.

“Our study shows that psychedelics radically change the way that neurons interact,” Halje told PsyPost. “Interestingly, the most significant change happens not on the level of individual neurons, but in how they behave collectively – we observe that psychedelics induce highly synchronized brain waves in multiple brain regions.”

The study challenges models that directly link changes in firing rates to the psychedelic state. The appearance of high-frequency oscillations was largely independent of neuron population firing rates, suggesting that firing rate changes alone might not fully explain the altered states induced by psychedelics.

The findings offer potential implications for researching and modeling psychoses. The distinctive oscillatory pattern observed in rats during the psychedelic state could potentially serve as a valuable research model for understanding certain aspects of psychotic disorders. This could be particularly useful since the manifestations of psychoses are often complex and difficult to model in laboratory settings.

“Given how drastically a psychosis manifests itself, there ought to be a common pattern that we can measure. So far, we have not had that, but we now see a very specific oscillation pattern in rats that we are able to measure,” Halje said in a news release.

The study also opened up an exciting avenue for understanding consciousness. The synchronized oscillatory pattern observed in the brain during the psychedelic state might serve as a tool for studying the neural underpinnings of consciousness.

“In light of the development of AI, it is becoming increasingly important to clarify what we mean by intelligence and what we mean by consciousness,” Halje said. “Can self-awareness occur spontaneously, or is it something that needs to be built in? We do not know this today, because we do not know what the required ingredients for consciousness in our brains are. This is where it is exciting, the synchronized pattern we see, and whether this can help us to track down the neural foundations of consciousness.”

While the study’s findings suggest a potential link between hypersynchrony and altered consciousness, direct comparisons between animal models and human psychedelic experiences require caution due to interspecies differences. Animal models often provide useful information, especially when dealing with phenomenon at the cellular level, but the findings may not directly translate to human experiences.

“Since the study was done with rats, the link to human consciousness is only speculative,” Halje told PsyPost. “There is really no way of knowing what aspects of conscious experience we share with the rats.”

The study, “5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive limbic cortex-basal ganglia system“, was authored by Ivani Brys, Sebastian A. Barrientos, Jon Ezra Ward, Jonathan Wallander, Per Petersson, and Pär Halje.

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