The combination of neuronal activity and neurotransmitters helped to clarify the effect of psilocybin

British researchers combined several neuroimaging techniques and created a model of the interaction of neural activity with the activity of neurotransmitters in the brain. To demonstrate its effectiveness, they measured the brain activity of participants under the influence psilocybin: a model that considers the location of the serotonergic receptors 5-HT2A was clearly the one in which was only used to visualize the activity obtained using fMRI. The new method will help, for example, to clarify the therapeutic effect of the use of psychedelics to treat depression and other affective disorders, write the scientists in the journal Proceedings of the National Academy of Sciences.

Methods now used to study brain activity, based on a variety of aspects of its work. The principle of operation of functional MRI, for example, is based on the fact that the flow of oxygen-rich blood to various parts of the brain correlates with neural activity in it: by the interaction of the molecules of oxyhemoglobin with the magnetic field of the scanner can be visualized activity with high spatial resolution. Electroencephalography (EEG), in turn, allows the display of the electrical activity of the brain during the activation of separate neural networks, and positron emission tomography (PET) — activity of neurotransmitters (this uses radioactive tracers that bind to specific receptors — e.g., serotonin).

The choice of imaging technique depends entirely on the methodology of conducted research and formulated hypotheses, so none of them can be completely universal. On the other hand, some of them could be combined and this will allow to study comprehensively the brain: at the level of anatomical structures, activity of neural networks involved in their neurotransmitter function.

To do this it was decided by scientists under the leadership of Kringelbach Morten (Morten Kringelbach) from Oxford University. In his neurovisualization they joined, on the one hand, the activity of brain neurons in certain parts, and on the other the work of neurotransmitters that this activity defines. For this purpose they used the data obtained by three methods: diffusion MRI (insfcs) for anatomical reconstruction of the paths of neural connections, fMRI for visualizing activity in them, and PET for assessment of concentration of neurotransmitters.

To develop a method and demonstrate its effectiveness, the researchers decided to visualize the activity of the brain under the action of psilocybin — alkaloid, psychoactive substances, hallucinogenic mushrooms. At the level of neurotransmitters its activity should be simple enough: psilocybin acts on serotoninergicescuu system (mainly on serotonin receptor 5-HT2A), and its neurons, the projection of which go up to the limbic system, the cerebellum and the cortex, located in the nuclei of the seam in the medulla.

The challenge, therefore, is to combine the activity of the brain obtained by fMRI, with the location of receptors for 5-HT2A, which can be determined using PET: the density of the location of the receptor depends on led serotonin electrical activity. After this combined data can then be visualized on certain neural tracts, which are obtained using insfcs.

To visualize the tracts of the brain, the researchers used insfcs-data received from 16 people, and to visualize the location of the 5-HT2A—receptor — PET data, conducted with 210 volunteers. an fMRI experiment was performed on a separate group of people: nine volunteers were administered either psilocybin or saline as a placebo, and looked at the activity of their brains at rest.

Obtained using fMRI, the brain activity (or rather, the amplitude of the BOLD signal) was klasterizatsii using k-means: they have made three different cluster activity (sebastiania), which with a certain probability appear either under the action of psilocybin or placebo (saline). The relationship between the obtained sebastianelli and brain activity in an fMRI experiment was assessed using the distance the Kullback — Leibler information measure, which allows to measure the distance apart of the two probabilistic events. Sebastiania statistically significant (p < 0.0001) correlated with localization of activity in one group or another. In that case, if a probabilistic model for added data on the receptors 5-HT2A, the correlation was higher (p < 0.000001). Interestingly, data on the density of the location and the work of other serotonergic receptors probabilistic model did not improve.

In other words, better to explain the dynamics of the activity of the brain under the action of psilocybin (compared to placebo) failed in the case when the data about activity of certain areas of the brain were combined with the density (and therefore activation) key for the action of this substance receptors 5-HT2A. In addition, scientists believe, such imaging in the future will help to clarify the therapeutic effect of psilocybin in particular — the propriety of its use in the treatment of depression, the occurrence of which the serotonergic system plays a key role.

One explanation for the therapeutic effects of some psychedelics might be that under their action the neurons in the faster growing dendrites and spines, which helps the cells better to give each other the signal, and the brain — to restore the atrophied connections.

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