Ketamine can Cause Psychosis in Healthy Individuals

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Highlights:

Ketamine raises noise to gamma frequencies in one layer of the thalamic nucleus and one layer of the somatosensory cortex by blocking NMDA receptors
The findings show that psychosis may be induced by an increase in background noise damaging thalamocortical neurons, which may be produced by NMDA receptor dysfunction disrupting the balance of inhibition and excitement in the brain //

Ketamine, as an NMDA receptor inhibitor, raises the brain’s background noise, increasing the entropy of incoming sensory signals and disrupting their transmission between the thalamus and the cortex, according to an international team of researchers led by Sofya Kulikova, a Senior Research Fellow at HSE University-Perm. This discovery could help researchers better understand the causes of psychosis in people with schizophrenia. The outcomes of the study were reported in the European Journal of Neuroscience.

One in every 300 people globally suffers from schizophrenia-related diseases. Perceptual abnormalities such as hallucinations, delusions, and psychoses are the most common signs of these illnesses.

Ketamine Treatment

Ketamine, a medication, can cause a mental state akin to psychosis in healthy people. Ketamine blocks NMDA receptors in the brain, which are involved in the transmission of excitatory signals. An imbalance in the central nervous system’s excitation and inhibition may impair sensory perception accuracy ().

‘Ketamine, a medication, can cause a mental state akin to psychosis in healthy people.’

Similar abnormalities in the activity of NMDA receptors are currently thought to be one of the reasons for schizophrenia-related perceptual disorders. However, it is still unknown how this process takes place in the brain regions involved.

Neuroscientists from France, Austria, and Russia investigated how the brains of laboratory rats on ketamine processed sensory inputs The researchers looked at beta and gamma oscillations in the rat brain’s thalamocortical system, a neural network that connects the cerebral cortex with the thalamus and is responsible for transmitting sensory information from the organs of perception to the brain.

Beta oscillations are brainwaves that occur between 15 and 30 hertz, while gamma waves occur between 30 and 80 hertz. These frequencies are thought to be essential for sensory encoding and integration.

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Rats were implanted with microelectrodes to record electrical activity in the thalamus and the somatosensory cortex, an area of the brain responsible for processing sensory information from the thalamus. Before and after ketamine treatment, the researchers stimulated the rats’ whiskers (vibrissae) and recorded the brain’s responses.

A comparison of the two datasets revealed that ketamine increased the power of beta and gamma oscillations in the cortex and thalamus even before a stimulus was presented, whereas the amplitude of beta and gamma oscillations in the 200–700 ms post-stimulus period was significantly lower at all recorded cortical and thalamic sites after ketamine administration.

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The 200–700 ms post-stimulation time-lapse is sufficient to encode, integrate, and comprehend the incoming sensory data. The observed reduction in the power of sensory stimulus-induced oscillations can be linked to decreased perception. Pre-stimulus beta and gamma frequencies on cortical and thalamic recordings are considerably higher with ketamine than with saline. An analysis published in the European Journal of Neuroscience also found that ketamine administration increased noise to gamma frequencies in one thalamic nucleus and one layer of the somatosensory cortex after activation by blocking NMDA receptors. It is reasonable to suppose that the observed increase in noise, i.e., a decrease in the signal-to-noise ratio, also reflects the neurons’ decreased ability to handle incoming sensory information.

These findings show that an increase in background noise may promote psychosis by affecting the activity of thalamocortical neurons. This, in turn, could be caused by NMDA receptor dysfunction, which alters the balance of inhibition and excitement in the brain. Because of the noise, sensory signals become less distinct or pronounced. Furthermore, this may result in spontaneous bursts of activity linked to a skewed view of reality.

“The discovered changes in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders,” says the study’s lead author, Dr. Sofya Kulikova.

Reference:

The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network - (https://onlinelibrary.wiley.com/doi/10.1111/ejn.15845)

Source-Medindia