Neuroimaging study helps explain why LSD makes the familiar seem more surprising

Scientists at the Psychedelic Research Group at Imperial College London are learning more about how the drug LSD impacts sensory perception and learning. A new study, published in Neuropharmacology, sheds light on why things seem to become less predictable under the influence of LSD.

The study indicates that LSD decreases the neural response to unexpected stimuli while increasing it for familiar stimuli.

“Within neuroscience the field of perception is of major interest as it deals with some of the most fundamental aspects regarding conscious experience, and psychedelic drugs provide us with a window into looking at those mechanisms that underlie perception,” explained study author Christopher Timmermann, a PhD student.

“A fairly recently developed theory states that perception is the result of a sort of dance occurring between predictions and surprise mechanisms processed in the brain. To put it simply, more evolved brain areas are constantly imposing their model (or predictions) of the world on less-evolved areas that process sensory information.”

“Whenever something in the world happens that fails to live up to these models, surprise signals form in these less evolved sensory areas and are passed up to these more evolved brain areas so that they update their model of the world,”┬áTimmermann said. “The objective of the study was to understand how the mechanisms that underlie perception are modified under LSD, as we know that it radically alters the mechanisms of perception in really interesting ways.”

The researchers recorded the brain activity of 20 healthy participants using magnetoencephalography (MEG) while they completed an auditory oddball paradigm task. In the task, they responded to unexpected “oddball” tones that occurred infrequently and irregularly within a series of standard tones.

The participants received either LSD or a placebo about 3.5 hours prior to the experiment.

Normally, the auditory cortex and frontal lobe regions of the brain automatically generate a particular electrical wave called mismatch negativity upon hearing an unexpected tone.

But Timmermann and his colleagues found that this mismatch negativity was significantly reduced under the influence of LSD. They also found an increased mismatch negativity for the standard tones.

“The main take home message of the study is that we found that in our study LSD altered the way in which the brain processes familiar and surprising stimuli,” he told PsyPost. “Surprising stimuli was processed as being more familiar, and familiar stimuli was processed as more surprising.”

“The interesting bit is that when we modelled the results, we saw that these more evolved areas were less effective in imposing its models of the world on elementary sensory areas, while sensory areas were less effective in generating a context of familiarity that allows surprise to occur,” Timmermann explained.

“So these results suggest that the altered mechanisms of familiarity and surprise under LSD are closely related to these modifications in the interactions between brain areas which drive predictions and surprise mechanisms that underlie perception.”

There is still much to be learned about how LSD produces a psychedelic experience.

“The main caveat of the study is how the results that we are seeing in the brain, under a specific task, relate to what people actually experience under LSD,” Timmermann said. “It is tempting to assume that we are probing directly into mechanisms that underlie the experience, but it is hard to reach a major conclusion in this regard and it thus should be considered as one of many stepping stones in this field.”

“These results open a range of research questions worth investigating,” Timmermann added. “For example: does these alterations in our models of perception provided by LSD have an impact on the way that people make meaning of larger areas of experience? Do these modifications we see in our study relate to the therapeutic benefits that we are seeing with psychedelic drugs? These are interesting questions as they attempt to bridge these results with areas that have broader implications.”

The study, “LSD modulates effective connectivity and neural adaptation mechanisms in an auditory oddball paradigm“, was co-authored by Meg J. Spriggs, Mendel Kaelen, Robert Leech, David J. Nutt, Rosalyn J. Moran, Robin L. Carhart-Harris and Suresh D. Muthukumaraswamy.