A group of researchers from around the world, led by Sofya Kulikova, Senior Research Fellow at the HSE University-Perm, has revealed that ketamine, an NMDA receptor inhibitor, increases the background noise in the brain. Increased background noise raises the entropy of incoming sensory signals and interferes with their transmission between the thalamus and the cortex. This discovery could lead to a better understanding of the causes of psychosis in schizophrenia.
One in every 300 people worldwide suffers from a schizophrenic spectrum disorder. Perceptual disturbances such as hallucinations, delusions, and psychoses are the most common manifestations of these disorders.
In healthy people, ketamine can cause a mental state resembling psychosis. Ketamine blocks NMDA receptors involved in the brain’s excitatory signal transmission. An imbalance of excitation and inhibition in the central nervous system can affect the precision of sensory perception.
It is thought that similar modifications in NMDA receptor function are one of the factors contributing to schizophrenia-related perception problems. How precisely this process takes place in the involved brain regions is still unknown.
Gamma And Beta Brain Waves
Researchers from France, Austria, and Russia examined how the brains of laboratory rats given ketamine processed sensory signals to learn the answer.
The thalamo-cortical system of the rodent brain, a neural network connecting the cerebral cortex with the thalamus, is responsible for transmitting sensory information from the organs of perception to the brain. The researchers looked at this system’s beta and gamma oscillations when it was stimulated.
Gamma waves are those between 30 and 80 Hz, while beta oscillations fall between 15 and 30 Hz. These frequencies are thought to be essential for encoding and integrating sensory data.
Rats were implanted with microelectrodes to record electrical activity in the thalamus and the somatosensory cortex, a brain region responsible for processing sensory information from the thalamus. Before and after giving the rats ketamine, researchers stimulated their whiskers (vibrissae) and took notes on how the brain responded.
A comparison of the two datasets revealed that ketamine increased the power of beta and gamma oscillations in the cortex and thalamus before a stimulus was presented. The amplitude of beta/gamma oscillations in the 200-700 ms post-stimulus period was significantly lower at all recorded cortical and thalamic sites after ketamine administration.
The 200-700 ms post-stimulation time-lapse is sufficient to encode, integrate, and perceive the incoming sensory signal. The observed reduction in the power of sensory stimulus-induced oscillations can be linked to impaired perception.
NMDA Receptor Malfunction
Ketamine administration also increased noise in the post-stimulation 200-700 ms period in one thalamic nucleus and one layer of the somatosensory cortex by inhibiting NMDA receptors. This observed increase in noise, i.e. a decrease in the signal-to-noise ratio, may also indicate the neurons’ impaired ability to process incoming sensory signals.
These findings suggest that an increase in background noise may trigger psychosis by impairing the function of thalamo-cortical neurons. This, in turn, could be caused by NMDA receptor malfunction, which alters the balance of inhibition and excitation in the brain.
Because of the noise, sensory signals become less defined or pronounced. Furthermore, this may result in spontaneous bursts of activity linked to a distorted perception of reality.
“The discovered alterations 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,”
said Sofya Kulikova.
- Qin, Y., Mahdavi, A., Bertschy, M., Anderson, P. M., Kulikova, S., & Pinault, D. (2022). The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network. European Journal of Neuroscience, 1– 16 DOI: 10.1111/ejn.15845
- Reilly, T. J. (2022). Ketamine: Linking NMDA receptor hypofunction, gamma oscillations and psychosis (commentary on Qin et al., 2022). European Journal of Neuroscience, 1– 2. DOI: 10.1111/ejn.15872