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Electroconvulsive therapy (ECT), a treatment for major depressive disorder with a mild shock to the brain, has been a mystery. The latest research has found that this therapy may work by adjusting the balance of excitability and inhibition within the brain.
Electroconvulsive therapy, which is considered a cruel treatment by delivering electrical currents to the brain to trigger brief seizures, has been controversial due to its negative portrayal in movies. For example, in the movie One Flew Over the Asylum, it is portrayed as a cruel punishment. But in reality, for those with depression who don't respond to medication, this therapy can be remarkable.
Studies have found that approximately 50% to 70% of patients with major depressive disorder experience an improvement in symptoms after electroconvulsive therapy [1]. In contrast, medications designed to alter the balance of chemicals in the brain only help 10% to 40% of people with depression [2].
Although electroconvulsive therapy has been used for decades, scientists still do not fully understand the biological basis of its effects on the brain. Bradley Voytek, a neuroscientist at the University of California, San Diego, was told by a psychiatrist that the therapy was like "rebooting" the brain, but Wojtek dismissed the explanation as too simplistic to be satisfactory.
▷Why can electroconvulsive therapy alleviate depressive symptoms? New research links treatment to inhibition of neuronal firing in the brain. Picture: Myriam Wares
Recently, Wojtek and his team explored how electroconvulsive therapy produces antidepressant effects by studying patterns of electrical activity in the brain and combining it with data from patients. In two studies published last fall, they found that electroconvulsive therapy and its related therapies were able to increase "background noise" in the brain that is not easily detected under the mask of brain waves. Scientists refer to this noise as "aperiodic activity."
The research team believes that this therapy may produce antidepressant effects by increasing non-cyclical activity in the brain, helping to restore the balance between excitation and inhibition in the brain.
Sydney Smith, a graduate student at the Wojtek Lab, said that whenever she explained the study to lay lay people, people were always surprised to ask, "Are they still using electroshock therapy?" This misconception and stigma has prompted them to work harder to uncover how electroconvulsive therapy works.
About eight years ago, Wojtek worked with psychiatrist Maryam Soltani and her colleagues, who collected EEG data from patients treated with electroconvulsive therapy. The researchers installed electrodes in the patient's head to measure electrical activity in the brain before and after treatment.
Years of EEG research have revealed that the electrical activity of a healthy brain produces a certain pattern, known as brain waves (for example, when we are deeply relaxed or sleeping, the brain produces a type of brain wave called α waves). Previous research linked α waves to depression, which led Soltani and Wojtek to initially speculate that electroconvulsive therapy may have affected α waves. If this hypothesis is true, then it could also help explain why electroconvulsive therapy slows down certain frequencies on EEGs [3].
However, a preliminary analysis of the first two patients revealed a different finding: a significant increase in acyclical activity ("background noise") in the brain.
This non-cyclical activity has become a research hotspot in the Wojtek laboratory in recent years. Instead of focusing on those regular brain waves, such as α waves, they study those that seem chaotic. Although there is no clear pattern in aperiodic activity on EEG, Wojtek's team has developed statistical tools that can reveal its underlying structure. It is this acyclical structure that the researchers observed in data from Soltani's electroconvulsive therapy patients.
In a study published in the journal Translational Psychiatry in November 2023 [4], the researchers found an increase in acyclic activity of brain waves in nine patients with electroconvulsive therapy. In a subsequent study [5], neuroscientists analyzed a large amount of data previously collected from 22 patients who received electroconvulsive therapy and 23 patients who received magnetic epilepsy therapy (magnetic epilepsy therapy uses a magnetic field rather than an electric current to induce seizures). These analyses also found that acyclic activity of brain waves also increased after treatment.
Non-cyclical activity is thought to be related to the balance of excitation and inhibition in the brain. When one neuron receives a signal from another neuron, it may be excited or inhibited, i.e., it becomes easier or less likely to emit the signal. In 2017, Wojtek and collaborators published a study in the journal NeuroImage that aperiodic activity reflects the inhibition process [6].
More research is needed to verify the link between acyclical activity and inhibition. However, when the researchers combined this finding with their new clinical study, they speculated that epilepsy treatment may have suppressed some neuronal populations, and that this inhibition may manifest as an increase in acyclic activity on EEG.
The investigators speculate that the inhibitory effect in electroconvulsive therapy may be associated with a reduction in depressive symptoms. "Electroconvulsive therapy may alleviate depressive symptoms by restoring the level of inhibition in the prefrontal cortex," Smith and colleagues wrote in their November 2023 preliminary study of electroconvulsive therapy. ”
The research team did not design these experiments to demonstrate a link between acyclical activities and depression. K. Krishnan, Senior Advisor to Rush University Health System in Chicago Ranga Rama Krishnan said that the connection may exist, but it will take a lot of effort to prove it. Krishnan has been managing programs including electroconvulsive therapy at Duke University for decades, but has not been involved in these studies.
To demonstrate this definitively, researchers need to study a broader patient population and design sophisticated protocols. But Krishnan sees the papers as "a step in the right direction."
Sarah Lisanby, director of the non-invasive neuromodulation unit at the National Institute of Mental Health, noted that electrotherapy and magnetotherapy have shown similar effects in regulating non-cyclic activities. She stresses that this means that it is not the electric field that alleviates depressive symptoms in electroconvulsive therapy, but the seizures it triggers.
Recent studies by Lisa Bi have shown that magnetic epilepsy treatment is as effective as electroconvulsive therapy [7], but with fewer side effects and less severe. Although electroconvulsive therapy has been widely used in clinical practice, magnetic epilepsy therapy has not yet been approved by the Food and Drug Administration and is currently limited to investigational use.
Smith and Wojtek hope that if future studies validate their results, acyclical activity could be an indicator that could help doctors predict which patients would benefit from such treatments. They believe that while current electroconvulsive therapy acts directly on the brain "like a sledgehammer", a deeper understanding of its mechanism has the potential to lead to the development of more precise, less stressful and comfortable treatments for patients.
In addition to clinical applications, this research can help patients better understand the changes that occur in the brain during electroconvulsive therapy and what their benefits are. "At least when discussing the risks and benefits of these treatments, we can explain to patients that we're trying to improve their brain function," Smith said. ”
For the patient, such an explanation allows the patient to understand the effects of the treatment more concretely, rather than feeling like they are being pressed the "reset button" and treated like a cold machine.
Original: https://www.quantamagazine.org/brains-background-noise-may-explain-value-of-shock-therapy-20240318/
Bibliography:
- 1 https://www.nature.com/articles/s41398-021-01560-y
- 2 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2680312
- 3 https://www.nature.com/articles/s41598-020-74103-y
- 4 https://www.nature.com/articles/s41398-023-02634-9
- 5 https://www.nature.com/articles/s41398-023-02631-y
- 6 https://www.sciencedirect.com/science/article/abs/pii/S1053811917305621?via%3Dihub
- 7 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2812444