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Scientists suggest a new way to treat depression with brain implants



An x-ray of someone who has had electrodes implanted in his brain to treat Parkinson's disease.
Image: Hellerhoff (Wikimedia Commons)

In recent years, physicians have been studying an unorthodox method to address cases of depression that have not responded to other treatments: sending precise electrical shocks directly into a patient's brain, also known as deep Brain Stimulation (DBS). While the technique is promising, its positive effects tend to be inconsistent.

But a recent study by the University of California, San Francisco, published in Current Biology on Thursday seems to offer an interesting step for DBS as a therapy for depression. Her research suggests that there is another potential target for stimulation that could provide more reliable mood enhancements. Better still, the new target could be free from the disturbing side effects seen with conventional DBS, such as mania.

DBS is generally used to treat neurological conditions such as Parkinson's and epileptic seizures. These states are characterized by erratic electrical activity in certain brain regions, and the pulses used in the DBS – which are surgically implanted in the brain and controlled by a device that is normally implanted elsewhere in the body – act as a pacemaker, temporarily restore healthy brain patterns and relieve people's symptoms. People with depression also tend to have abnormal brain activity, so it has been suggested that DBS might be helpful in difficult, treatment-resistant cases of depression.

The researchers behind the current study had the opportunity to conduct a unique experiment. They were able to examine 25 patients with chronic epilepsy who were scheduled to undergo surgery to temporarily implant electrodes into their brains. The implants let the doctors find out where the brain seizures came from by recording the local nerve activity of a particular brain region (by locating the seizures, the doctors could then plan how to safely remove the affected parts) the brain at a later stage Time). However, for their experiment, researchers could use the same implants to essentially mimic a session with DBS.

Patients had implants placed in different areas of the brain, including near the lateral part of the orbitofrontal cortex (OFC). a region directly behind the eye. It is well known that the OFC plays a role in decision-making, emotion processing and mood regulation. And although this is also involved in depression, it has not been extensively studied as a stimulation goal.

For several days volunteers had different brain regions stimulated by DBS, including the OFC. Sometimes, instead, the patients received sham stimulation that acted as a control. After each stimulation session, they talked about how they felt and responded to questionnaires to gauge their mood.

Patients had different symptoms of depression, from minimal to severe (based on a common screening test) for their surgery). Those who had no or little signs of depression did not experience mood swings thereafter, regardless of where the stimulation took place or whether it was received at all. In people with moderate to severe depression symptoms, mood seemed to improve within minutes of stimulating OFC. Compared to sessions where other areas of the brain associated with depression were stimulated, these mood enhancements seemed more reliable, meaning that people felt a major boost in larger shocks.

"Our results are important because they have a positive effect A new potential target for the treatment of mood symptoms from brain stimulation therapies," said author Heather Dawes, co-director of UCSF's System-Based Neurotechnology for Emerging Therapies -Mail to Gizmodo.

patients' brain activity outside of DBS sessions, allowing them to better understand exactly what DBS did to the OFC. In particular, the brain activity observed after a patient's sessions seemed to be at the activity level which was observed when the patient was naturally in a good mood.

"This suggests that the stimulation promotes the natural brain activity that underlies the positive mood rather than induce an unnatural activity pattern," said Dawes.

And this without the pendulum swinging too far back and the patia hyperactive or manic, a side effect occasionally seen in DBS.

There have already been several targets for DBS therapy for depression, eg the subgenual cingulate cortex, a brain region that is often associated with emotions and mood regulation. However, studies have shown no consistent benefit from DBS treatment. An important clinical study on DBS was completed in early 2013, after an early analysis had shown that the first wave of the patient did not improve as much as the researchers had predicted. Some people got even worse.

This study is technically a mistake, but has not closed the door to DBS therapy. For example, many patients in the study who did not respond to DBS within the first six months (the cut-off point to decide whether to continue enrolling more patients) showed significant improvements over the long term. Further clinical trials with DBS are already in progress. However, it has led to questions as to whether there are ways to refine the treatment better.

As the OFC interacts with other brain regions that coordinate mood and emotion, the team could provide a more consistent benefit in stimulating. There is even limited evidence that non-invasive forms of stimulation (including electrodes attached to the surface of the head) in which the OFC is involved can also help people with depression.

But there is still much to do at the moment before we can rely on anything.

"We are really excited about the promising results presented in this paper, but more work is needed before this becomes a clinical treatment," said Dawes. This work also includes testing whether the same effect occurs in patients who are clinically depressed and have not responded to other treatments.

"There is also a lot to do to see if this stimulation approach can help depression patients actually recover from their disease – so far we have been able to study only short-term effects," she added. "This is an area that we and others will explore further."

[Current Biology]


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