MOSCOW, Russia — Ketamine’s ability to cause hallucinations is helping scientists understand what causes schizophrenics to experience delusions. A new study finds that the anesthetic — which some use as a recreational drug — can trigger the same kind of “brain noise” seen in patients with schizophrenia.
Ketamine, an inhibitor of excitatory brain signals, can disrupt communication between the thalamus and the cortex, according to an international team. The interference from ketamine could help scientists understand why people with schizophrenia experience delusions and hallucinations and potentially introduce new ways to produce antipsychotics.
“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,” says Sofya Kulikova, PhD, a senior research fellow at the National Research University Higher School of Economics in Russia, in a media release.
One in every 300 people globally has a schizophrenic spectrum disorder. The most common symptoms of these disorders range from hallucinations, to delusions and psychoses. In the current research, the study authors found that ketamine increases background noise in the brain, making it harder for neurons to send over their messages from one brain area to another.
How does ketamine affect the brain?
Ketamine is a drug that creates a mental state similar to psychosis. It works by blocking NMDA receptors which send over excitatory signals to the brain. Having an imbalance of excitation and inhibition in the central nervous system can affect how the brain processes sensory perception.
One hypothesis underlying perception disorders in schizophrenia are changes to NMDA receptor function. However, until now, scientists did not understand how blocking excitatory signals occurs in the brain’s thalamus and cortex.
An international team from France, Austria, and Russia dosed lab rats with ketamine and then used microelectrodes to study the electrical activity of their brains in response to sensory signals. They paid close attention to beta and gamma oscillations — brain waves involved in encoding and integrating sensory information — which was released in the rat’s thalamocortical system after touching the rat’s whiskers. The thalamocortical system is a neural network in charge of sending over sensory information to other brain areas involved in sensory perception.
Results show ketamine increased the power of beta and gamma oscillations in the cortex and thalamus before touching the rat’s whiskers. The size of the brainwaves also lowered at all cortical and thalamic sites while the animals were high on ketamine, suggesting ketamine disrupts the brain’s ability to process sensory information. After stimulating the rat’s whiskers, the research team noticed a lapse in beta and gamma oscillations, suggesting impaired perception.
This could reveal what causes psychosis
A closer analysis showed that ketamine’s inhibition of NMDA receptors created noise to gamma frequencies in the thalamus and in one layer of the somatosensory cortex. The increase in noise makes it harder for neurons to “hear” and execute the sensory message coming from other brain areas.
In terms of psychosis, the researchers hypothesize that psychosis could come from this increased signal-to-noise ratio that impairs thalamocortical neurons. Blocking excitatory NMDA receptors is potentially one of the contributors to noise as it skews the brain to have more inhibitory signals. The changes in activity and impaired processing of sensory information would then be associated with a distorted view of reality.
The study is published in the European Journal of Neuroscience.