Ketamine has been found to increase noise in the brain
Abstract: By inhibiting NMDA receptors, ketamine increases noise to gamma frequencies in one layer of the thalamic nucleus and one layer of the somatosensory cortex. The findings suggest that psychosis may be triggered by an increase in background noise that damages thalamocortical neurons, which may be caused by a malfunction in NMDA receptors that affect the balance of inhibition and excitation in the brain.
An international team of researchers including Sofya Kulikova, a senior research associate at HSE University in Perm, found that ketamine, being an inhibitor of the NMDA receptor, increases the brain’s background noise, causing greater entropy of incoming sensory signals and disrupting their transmission between the thalamus and the cortex.
This discovery may contribute to a better understanding of the causes of psychosis in schizophrenia.
An article with the findings of the study was published in European Journal of Neuroscience.
Schizophrenic spectrum disorders affect approximately one in 300 people worldwide. The most common manifestations of these disorders are perceptual disorders such as hallucinations, delusions and psychoses.
A drug called ketamine can cause a mental state similar to psychosis in healthy people. Ketamine inhibits NMDA receptors involved in the transmission of excitatory signals in the brain. An imbalance of excitation and inhibition in the central nervous system can affect the accuracy of sensory perception.
It is currently believed that similar changes in the functioning of NMDA receptors are one of the causes of perception disorders in schizophrenia. However, it is still not clear how exactly this process takes place in the brain regions involved.
To find out, neuroscientists from France, Austria and Russia studied how the brains of lab rats on ketamine process sensory signals. The researchers examined beta and gamma oscillations that occur in response to sensory stimuli in the thalamo-cortical system of the rodent brain, the neural network that connects the cerebral cortex to the thalamus responsible for transmitting sensory information from the organs of perception to the brain.
Beta oscillations are brain waves in the range of 15 to 30 Hz, and gamma waves are those in the range of 30 to 80 Hz. These frequencies are believed to be crucial for encoding and integrating sensory information.
In the experiment, rats were implanted with microelectrodes to record electrical activity in the thalamus and somatosensory cortex, the area of the brain responsible for processing sensory information coming from the thalamus. The researchers stimulated the whiskers (vibrissae) of the rats and recorded brain responses before and after the administration of ketamine.
A comparison of the two data sets revealed that ketamine increased the power of beta and gamma oscillations in the cortex and thalamus even in the resting state before the stimulus was presented, while the amplitude of the beta/gamma oscillations in the 200-700 ms post-stimulus period was significantly shorter in all recorded cortical and thalamic sites after ketamine administration.
A post-stimulation time lag of 200–700 ms is long enough to encode, integrate, and perceive the incoming sensory signal. The observed decrease in the power of oscillations induced by a sensory stimulus can be related to impaired perception.
The analysis also revealed that by inhibiting NMDA receptors, ketamine administration added noise to gamma frequencies in the period 200-700 ms after stimulation in one nucleus of the thalamus and in one layer of the somatosensory cortex. It can be assumed that this observed increase in noise, i.e. decrease in the signal-to-noise ratio, also indicates an impaired ability of neurons to process incoming sensory signals.
These findings suggest that psychosis may be induced by an increase in background noise that impairs the function of thalamo-cortical neurons. This, in turn, could be caused by the failure of the NMDA receptor, which affects the balance of inhibition and excitation in the brain. Noise makes sensory signals less defined or more distinct. In addition, it can cause spontaneous outbursts of activity associated with a distorted perception of reality.
“The detected changes in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotics or predicting disease course in patients with psychotic spectrum disorders,” says Sofya Kulikova.
About this neuroscience research news
Original research: Open access.
“The psychotomimetic ketamine disrupts the transmission of late sensory information in the corticothalamic network” Yi Qin et al. European Journal of Neuroscience
The psychotomimetic ketamine disrupts the transmission of late sensory information in the corticothalamic network
In prodromal and early schizophrenia, disturbances of attention and perception are associated with structural and chemical abnormalities of the brain and with dysfunctional corticothalamic networks showing disturbed brain rhythms. The underlying mechanisms are elusive.
The noncompetitive NMDA receptor antagonist ketamine simulates symptoms of prodromal and early schizophrenia, including disturbances in ongoing wide-band beta-/gamma-frequency (17-29 Hz/30-80 Hz) oscillations in task- and sensor-related corticothalamic networks.
In normal healthy subjects and rodents, complex integrative processes, such as sensory perception, induce transient, large-scale synchronized beta/gamma oscillations in a time window of a few hundred ms (200–700 ms) after the presentation of an object of attention (eg, sensory stimulation).
Our aim was to use a multisite electrophysiological network approach to investigate, in lightly anesthetized rats, the effects of a single psychotomimetic dose (2.5 mg/kg, subcutaneously) of ketamine on sensory-evoked oscillations.
Ketamine transiently increased the power of baseline beta/gamma oscillations and decreased sensory-evoked beta/gamma oscillations. In addition, it disrupted information transmission in the somatosensory thalamus and associated cortex and reduced sensory-induced thalamocortical connectivity in the broadband gamma range.
The present findings support the hypothesis that NMDA receptor antagonism disrupts the transmission of perceptual information in the somatosensory cortico-thalamo-cortical system.