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Researchers at the University of California, San Francisco (UCSF) have revealed results suggesting that personalized deep brain stimulation (DBS) may produce a sustained antidepressant effect by targeting a brain circuit linked to bad mood.
The proof of concept study involved a patient named Sarah, who had lived with major depressive disorder (MDD) since her childhood. Researchers first implanted electrodes into Sarah’s brain which mapped different areas related to mood and identified an area which, if stimulated by pulses through the electrode, gave Sarah immediate relief. suicidal thoughts and bad mood.
The study, published in Natural medicine, was described during a press briefing attended by Sarah and two academics from UCSF, professor of psychiatry Dr Katherine Scangos and neurosurgeon Dr Edward Chang. During the briefing, Sarah highlighted the impact of stimulation on life. Prior to enrolling in the trial, Sarah, who had tried unsuccessfully to recover using multiple combinations of antidepressants and even electroconvulsive therapy, suffered greatly from her illness. “My daily life had become so restricted and impoverished by depression that I felt tortured every day I forced myself to resist the suicidal urges that overwhelmed me several times an hour,” Sarah explained.
After the first round of targeted stimulation, Sarah felt an incredible and unprecedented change. “When I first received the stimulation, the ‘Ah-hah’ moment happened. I felt the most intensely happy feeling and my depression was a distant nightmare for a while, ”she said.
The reason Sarah felt this improved mood was because Chang had implanted an array of ten EEG electrodes in her brain, dotted around areas related to mood and emotions, such as the hippocampus and amygdala. .
Over a ten-day period, the researchers monitored Sarah’s mood as she had the electrodes fitted and identified an area of the brain called the ventral striatum that consistently induced an improvement in mood when stimulated. They also identified, using machine learning techniques, that brain waves produced in the amygdala increased when Sarah was in a bad mood.
Putting this information together, the Scangos and Chang team designed a personalized stimulation to Sarah’s brain networks. “We implanted a small chronic neuromodulation device to continuously monitor abnormal amygdala activity and automatically trigger a stimulation pulse when detected,” Scangos explained. This created a “closed loop,” where stimulation was only delivered when Sarah’s brain told the device that it was needed. This contrasts with previous brain stimulation methods which, when activated, provide a constant level of stimulation. The level of personalization achieved in this study was also unprecedented, acting as a demand stimulator for the brain.
Once the chronic implant was activated, the momentary lift Sarah had previously experienced became a sustained improvement in her mood that changed her entire lifestyle, making the hobbies she previously only used to distract from his suicidal thoughts seems pleasurable to him.
A battery of questionnaires used to assess clinical symptoms showed Sarah’s mood improved significantly. Sarah scored 36 on the Montgomery-Åsberg Depression Rating Scale (MADRS) before treatment, indicating severe depression, but several months after turning on the device, she is fell below 10 points, indicating remission. Sarah has now had the device implanted for 15 months and has felt the benefits of the device throughout this time.
To make the stimulation as effective as possible, the team titrated the signal to Sarah’s brain, eventually settling on a 1mA dose lasting six seconds. This stimulation, which is delivered hundreds of times a day up to a maximum of 30 minutes of stimulation, is imperceptible to Sarah.
The technology, although never before used to treat depression, was largely inspired by Chang’s earlier work in the treatment of epilepsy, where monitoring the electrical currents inside the brain is a critical technique. “This device’s battery and pulse generator are about the size of a matchbox,” Chang said.
The next steps for the researchers are to deploy the technique in more patients. The technique will need to be personalized using brain mapping for each patient, a technique Chang hopes one day can do non-invasively. “Each electrode contact we used registers about a millimeter to a millimeter and a half of brain area and what’s quite striking about what we’ve seen is that if you look at a centimeter away, the signals can be very different.… We hope that this kind of knowledge about the circuits of depression will give us the common ground truth we need to develop more targeted non-invasive approaches.
Reference:
Scangos KW, Khambhati AN, Daly PM, et al. Closed-loop neuromodulation in an individual with treatment-resistant depression. Nat Med. Published online 4 Oct 2021: 1-5. doi: 10.1038 / s41591-021-01480-w
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