Neural deactivation caused by Psilocybin as determined by fMRI scans
- vzuluagacuartas
- Oct 9, 2019
- 5 min read
I came along with this video that explains, in a very simplistic way, the effect that psilocybin has on the brain. I found that Dr. Nutt did an amazing job at explaining in simple terms the mechanisms of action that occur in the brain when consuming psilocybin.
According to Dr. Nutt, the activation of the 5-HT2A receptors with psilocybin was expected to exhibit an increase of activation in the visual cortex, but it did not. It actually did something totally opposite to what was expected. The brain scans exhibited a decreased blood flow to many areas of the brain, including the thalamus and the Default Mode Network (DMN). Moreover, the subjective psychedelic effects stated by the individuals demonstrated a significant negative correlation with the brain's blood flow in the cortex.
The results of the study supported that psilocybin turns off brain activity in the anterior and posterior cingulate cortex, which integrates many functions of the brain.
According to Dr. Nutt, the most important effect regarding the decrease of blood flow in the cortex is that it allows the brain to "do its own thing" and develop connections that were not seen before.
To support past findings, magnetoencephalography scans were done to measure neuronal activity instead of brain flow. The scans obtained revealed very similar results; there was a very significant decrease in neuronal activity in the anterior and the posterior cingulate cortexes. Furthermore, the scans revealed that psilocybin also switched off the Subgenual Anterior Cingulate Cortex. The Subgenual Anterior Cingulate Cortex is known to be involved in depression, as many antidepressant therapies act on this part of the brain.
This video summarizes the findings that I have also talked about in past posts. Researchers are highly interested in the effects that psilocybin has on parts of the brain that have been liked to depression and anxiety. Changes in the Default Mode Network and the Anterior Cingulate Cortex are related to structural changes in depression. Such findings are promising, as they illustrate that psychedelics could allow for structural changes in the brains of depressed patients.
The Default Mode Network:
I realized that even though I have explained the functions of the Default Mode Network (DMN), I have not truly explained which structures are associated with it. There are three main hubs associated with the DMN, as explained by Andrews-Hanna, Smallwood, and Spreng (2015) :
Functional hubs: Involved in information regarding the self
Posterior cingulate cortex (PCC): It is an integral part of the limbic system, which is involved with emotion formation and processing, learning, and memory.
Medial prefrontal cortex: Memory and decision making
Angular gyrus: involved in a number of processes related to language, number processing and spatial cognition, memory retrieval, attention, etc...
Dorsal medial subsystem hub: Involved when it comes to thinking about others.
Dorsal medial prefrontal cortex (dmPFC): Mostly associated with the ability to reason about other people's mental states and form impressions of them.
Temporoparietal junction (TPJ): Reflects on beliefs about others.
Lateral temporal cortex: Retrieval of social semantic and conceptual knowledge.
Medial temporal subsystem hub: Autobiographical memory and future simulations.
Hippocampus: Involved in the formation of new memories as well as remembering the past and imagining the future.
Parahippocampus: Spatial and scene recognition and simulation.
Retrosplenial cortex: Spatial navigation.
Posterior inferior parietal lobe : Auditory, visual, and somatosensory information and attention.
The DMN involves many structures of the brain; most of them are involved in awareness and introspective thought. It has been shown that psychedelics decrease the activity among the connections in the DMN, allowing for plasticity, as the brain creates different connections that will alleviate depressive symptoms in patients.
Article Summary:
A study performed by Carhard-Harris et al. (2012) sought to address the effects of psilocybin in the brain by using functional MRI (fMRI) techniques and a protocol design to picture the change from formal consciousness to psychedelic's state consciousness. There were a total of 30 subjects in the study. The scans were performed on hallucinogen-experienced subjects, with a mean age average of 34 years old. The scans were done with arterial spin labeling (ASL) perfusion and blood-oxygen level-dependent (BOLD) fMRIs during intravenous infusion of psilocybin. The dose injected was 2mg of psilocin along with 10ml of saline solution.
Firstly, subjects received a placebo solution (10ml of saline with no psilocin). During the second scan, the experimental dose was administered. The effects of psilocin began within five seconds after the administration of the experimental dose. After the trip, subjects were asked on their subjective interpretations of the effects of the drug. The subjects reported their surroundings to change in unusual ways. They reported things as looking strange, their imagination as being vivid and wild, and that their experiences had dream-like qualities, among others. Moreover, the results of the scans demonstrated a significant decrease of cerebral blood flow in the subcortical thalamus, putamen, and hypothalamus. The scans also exposed decreased blood flow in the cortical regions such as the posterior cingulate cortex, precuneus, bilateral angular gyrus, supramarginal gyrus, rostral and dorsal anterior cingulate cortex, and medial prefrontal cortex lateral orbitofrontal cortex. Hence, the administration of Psilocin significantly decreased brain blood flow and venous oxygenation in a manner that correlated with its subjective effects. This significantly decreased the activity of the medial prefrontal cortex and the posterior cingulate cortex.
Different studies have stated that psychedelics increase neural activity, but the study performed by Carhard-Harris et al. (2012) states the opposite. According to the researchers, it is possible that the deactivations of the structure were caused by the stimulation of 5-HT receptors other than 5-HT2A. Nevertheless, it is questionable, as psychedelics have high affinity to 5-HT2A receptor and such areas have high numbers of these receptors. An important aspect to note is that the regions that showed the most consistent deactivation of the posterior cingulate cortex and the medial prefrontal cortex are known to be highly active during wakening (metabolism in the PCC is ∼20% higher than most other brain regions, yet psilocybin decreased its blood flow by up to 20% in some subjects (Buckner, Andrews-Hanna, & Schacter, 2008)).The deactivation of these brain structures may explain the effect that hallucinogens have on consciousness.
As shown in Figure 5., the activity of the ventromedial prefrontal cortex (vmPFC) decreased after the administration of psyclocin. The vmPFC is known to regulate depressive-like behaviour.
Carhart-Harris, R., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., . . . Nutt, D. J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. PNAS Proceedings of the National Academy of Sciences of the United States of America, 109(6), 2138-2143. doi:http://dx.doi.org.proxy1.lib.trentu.ca/10.1073/pnas.1119598109
Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: Anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38.
Horn, A., Ostwald, D., Reisert, M., & Blankenburg, F. (2014). The structural–functional connectome and the default mode network of the human brain. Neuroimage, 102, 142-151. Andrews-Hanna, J. R.,
Smallwood, J., & Spreng, R. N. (2014). The default network and self-generated thought: component processes, dynamic control, and clinical relevance. Annals of the New York Academy of Sciences, 1316(1), 29–52. doi:10.1111/nyas.12360 Nutt, D. (2016). 5HT-2a Receptor Stimulation by Psilocybin Benefits Mental Health. Retrieved from: https://www.youtube.com/watch?v=8poiZH3MOSY
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