Scientists have discovered how electroconvulsive or electric shock therapy - a controversial but effective treatment - acts on the brains of severely depressed people and say the finding could help improve diagnosis and treatment of mental illness.
Electroconvulsive therapy (ECT) involves first anaesthetizing the patient and then electrically inducing a seizure.
It has a controversial reputation - gained in part because of its role in the 1975 film "One Flew Over The Cuckoo's Nest" starring Jack Nicholson - but is a potent and effective treatment for patients with mood disorders like severe depression.
Yet despite it being used successfully in clinical practice around the world for more than 70 years, scientists have until now not been entirely clear how or why it works.
Now a team from Aberdeen University in Scotland has shown for the first time that ECT affects the way different parts of the brain involved in depression communicate with each other.
In a study published in the Proceedings of the National Academy of Sciences (PNAS) journal they found ECT appears to turn down overactive connections between parts of the brain that control mood and parts that control thinking and concentrating.
This stops the overwhelming impact that depression has on patients' ability to enjoy life and carry out day-to-day activities, they said.
"We've solved a 70-year-old therapeutic riddle," said Ian Reid, a professor of psychiatry at the University of Aberdeen who led the study.
"Our key finding is that if you compare the connections in the brain before and after ECT, ECT reduces the connection strength," he said in a statement.
"For the first time we can point to something that ECT does in the brain that makes sense in the context of what we think is wrong in people who are depressed."
In recent years, experts have developed a new theory on how depression affects the brain that suggests there is a "hyperconnection" between the areas of the brain involved in emotional processing and mood change and the parts of the brain involved in thinking and concentrating.
David Nutt, a professor of neuropsychopharmacology at Imperial College London who was not involved in the ECT study, said its findings "make a lot of sense.
"The disabling of connections between different areas of the brain is what I would have predicted from the depression literature," he said in an emailed comment.
He said the results also chime with a study Nutt published in January which found that psilocybin, the active ingredient in the psychedelic drug known as magic mushrooms, also disrupts this network of connections and may also be effective in treating severe depression.
The electrotherapy study involved using functional magnetic resonance imaging (fMRI) to scan the brains of nine severely depressed patients before and after ECT and then applying complex mathematical analysis to investigate brain connectivity.
Aberdeen University's chair of neuroimaging Christian Schwarzbauer, who devised the new method for analyzing the connectivity data, said it enabled the team to see to what extent more than 25,000 different brain areas communicated with each other.
He said the new method could also be applied to a wide range of other brain disorders such as schizophrenia, autism, or dementia, and "may lead to a better understanding of the underlying disease mechanisms and the development of new diagnostic tools."
The researchers said they now hope to continue monitoring the patients to see if the depression and hyperconnectivity returns. They also want to compare their ECT findings with the effects of other therapies used to treat depression such as psychotherapy and anti-depressants.