Electroconvulsive therapy and how it works in severe depression: Study

By Dr. Ananya Mandal, MDMar 20 2012

Electroconvulsive therapy, or ECT, has been used in severely and persistently depressed patients from their disabling mood state for more than seven decades. Researchers have searched for the reason why this technique sometimes works in these patients.

A new study reveals what ECT therapy does in the brain. Researchers say they may have found a promising and more objective new way to diagnose depression — by looking for evidence of too much crosstalk among distinct networks that make up the brain.

In a report published Monday in the Proceedings of the National Academies of Science, a group of researchers in Scotland used a brain scanner fMRI to look at the brains of nine severely depressed patients before and after they received electroconvulsive therapy. The researchers first divided up the brain into component pieces and then measured the electronic message traffic among those pieces to see how the patterns changed before and after ECT.

There have been studies that have shown that in depression and several other psychiatric disorders, there is a pattern of “hyperconnectivity” between three widely scattered “networks” in the brain:

• the network of structures in which we process emotion and response to threats (“the affective network”);
• the network of structures that allows us to focus our attention, to reason and make higher-order judgments (“the cognitive control network”);
• and a cluster of regions that comes alive as a group when our minds are at rest — brain structures that help us ponder the intentions and mental states of others, consider our personal experiences and assess our emotions (dubbed the “default mode network”).

In healthy people, those three networks more or less take turns being dominant, and interference from the others is suppressed. In depressed people, the chatter among those three networks appears to be too noisy. On the fMRI, these hallmark symptoms of severe depression look like too much cross talk between areas.

And one other quirk appears to characterize the depressed brain: the dorsolateral prefrontal cortex — an area associated with cognitive control and conflict monitoring — is in constant communication with all the brain regions of the three big networks. It may be a central hub or switching station for all their crosstalk, or it may be constantly activated in a vain effort to override the chaos and restore order.

Electroconvulsive therapy actually succeeds in restoring that order. After several sessions of ECT, the researchers in Scotland began to see a healthy pattern of brain networks “taking turns” again in subjects' brains. Under the effects of a strong sedative and a muscle relaxant, researchers placed electrodes roughly at each subject's temples, on both sides. They administered ECT therapy — a pulse of electrical charge sufficient to induce an electrical storm (a seizure) in the brain. Twice a week, subjects got the ECT until they reported their depressive symptoms had lifted (on average, it took 8.3 sessions).

Prof Ian Reid, who led the research, said, “ECT is a controversial treatment, and one prominent criticism has been that it is not understood how it works and what it does to the brain. However we believe we've solved a 70-year-old therapeutic riddle because our study reveals that ECT affects the way different parts of the brain involved in depression connect with one another. For all the debate surrounding ECT, it is one of the most effective treatments, not just in psychiatry, but in the whole of medicine, because 75% to 85% of patients recover from the symptoms.”

He explained, “Over the last couple of years there has been an emerging new perspective on how depression affects the brain…This theory has suggested 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. Our key finding is that if you compare the connections in the brain before and after ECT, ECT reduces the connection strength between these same areas - it reduces this hyperconnectivity. 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.”

After just a few sessions of ECT, the researchers began to see the patterns of hyperconnectivity reduced and, in particular, saw that the dorsolateral prefrontal cortex was not in constant communication with far-flung regions of the brain. And as evidence of crosstalk in the brain declined, subjects were likely to report greater relief of their depressive symptoms.

The particularly dramatic reduction of "hyperconnectivity" in the dorsolateral prefrontal cortex led researchers to suggest that that brain structure may indeed be a hub of activity linking disparate brain networks and that ECT's effectiveness in restoring patients' emotional balance may be due to its effects on the dorsolateral prefrontal cortex.

The ECT-induced changes in the brain also may help to explain why ECT patients often suffer from memory and other cognitive problems, often for months after treatment, the researchers wrote. The dorsolateral prefrontal cortex plays an important role in the transfer of memories from short-term to long-term storage, as well as helping to focus attention among competing demands. If ECT dampens the structure's activity, the authors wrote, such effects might be anticipated.

The researchers now hope to continue monitoring the patients to see if the depression and hyperconnectivity returns. Prof Reid said, “If we understand more about how ECT works, we will be in a better position to replace it with something less invasive and more acceptable. At the moment only about 40% of people with depression get better with treatment from their GP. Our findings may lead to new drug targets which match the effectiveness of ECT without an impact on memory.”

Prof David Nutt, of Imperial College London, said, “These findings make a lot of sense. Indeed, the disabling of connections between different areas of the brain is what I would have predicted from the depression literature. This is why my research group is progressing psilocybin - which also disrupts this network, as we showed in PNAS recently - as a treatment for depression.”