‘We’ve never seen that before’: Experiment with drug Ketamine reveals possible ‘reset button’ inside the brain

A recent experiment conducted during research into Huntington's disease shows the anesthetic Ketamine may trigger a ‘reset’ of electrical activity in our brains, providing a possible explanation for the so-called ‘K-hole.’

Huntington's disease is an inherited, degenerative neurological disorder that results in the death of brain cells, leading to impaired coordination which can eventually render those living with the condition unable to speak. 

In order to better understand this and a host of other neurological diseases and psychiatric conditions, researchers examine the mechanics of our neural pathways and, in particular, their reaction to certain therapeutic medicines, such as ketamine. 

Ketamine is an anaesthetic with pain-numbing and dissociative effects, making it a popular medicine as well as a recreational drug. However, recent tests performed on sheep found that when the animals were given high doses, brain activity stopped completely, and almost instantaneously. 

Electroencephalography (EEG) tests showed a complete cessation of cortical activity, which lasted for up to several minutes before brain activity returned to normal, something which has not been observed before now.

“This wasn't just reduced brain activity. After the high dose of ketamine the brains of these sheep completely stopped. We’ve never seen that before,” says neurobiologist Jenny Morton from the University of Cambridge.

“A few minutes later their brains were functioning normally again – it was as though they had just been switched off and on.”

Ketamine was first synthesized in the 1960s and has been used as a sedative and as pain relief medication for humans and animals ever since. More recently, it has also shown promise in treating depression, PTSD and even migraines. 

In recreational drug use, an extremely dissociative state, commonly referred-to as a “K-hole,” known for hallucinations, distortion of time and space, changes in mood and sensations of floating, has been reported throughout the drug’s history.

The University of Cambridge team is exploring the effect of therapeutic drugs on the brain in a sheep model of Huntington's disease. However, the experiments thus far have been conducted on healthy sheep; the ketamine revelations were surprising, secondary findings from the research.

The team observed three distinct states when the ketamine was administered regardless of dosage levels: an initial period of sedation, followed by dissociative consciousness without voluntary movement, followed by full alertness, though voluntary movement was still slow to return. 

During the second stage, researchers observed highly volatile shifts in brain activity, in which the output of the entire cerebral cortex switched between bursts of low- and high-frequency oscillations (or waves within waves of brain activity).

At even higher doses, more akin to those taken by recreational drug users, the activity ceased altogether, roughly two minutes after the drug was administered. 

"It seems likely that the total cessation of cortical activity underpins the phenomenon known as the 'K-hole,'" the team explains. 

It doesn't necessarily mean that all brain activity has stopped, just the cessation of normal electrical activity associated with regular brain activity. 

"Understanding how different brain regions engage and disengage is key to understanding the function of neural networks," the authors write, providing an avenue of further study which may also help science better understand conditions such as schizophrenia. 

"Ketamine-evoked changes in the EEG provide an interesting tool for studying such networks, not only in the normal brain but also in neurological diseases in which cognitive and psychiatric disorder are prominent."

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