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Cortical signatures of sleep are altered following effective deep brain stimulation for depression | Translational Psychiatry
eep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This is a crucial gap in knowledge, given the link between depression and sleep disturbances, and an emerging interest in the interaction between DBS, sleep, and circadian rhythms. We therefore sought to characterize changes in electrophysiological markers of sleep associated with DBS treatment for depression. We analyzed key electrophysiological signatures of sleep—slow-wave activity (SWA, 0.5–4.5 Hz) and sleep spindles—in LFPs recorded from the SCC of 9 patients who responded to DBS for TRD. This allowed us to compare the electrophysiological changes before and after 24 weeks of therapeutically effective SCC DBS. SWA power was highly correlated between hemispheres, consistent with a global sleep state. Furthermore, SWA occurred earlier in the night after chronic DBS and had a more prominent peak. While we found no evidence for changes to slow-wave power or stability, we found an increase in the density of sleep spindles.
Note 'average' number of treatments?!
The 16 participants in the FORSEE-II study had suffered from severe depression for 8 to 22 years and had previously undergone an average of 18 drug therapies, 20 electroconvulsive therapies, and 70 hours of psychotherapy -- without success.
Prof. Dr. Volker A. Coenen, first author of the study and director of the Stereotactic and Functional Neurosurgery Unit at the Department of Neurosurgery of the Medical Center -- University of Freiburg, and his team implanted the deep brain stimulation systems in the patients medial forebrain bundle of the brain and used them to stimulate the medial forebrain bundle. This brain region is involved in the perception and regulation of pleasure and reward and is thus also significant for motivation and the perceived quality of life.
Clear Relief Often within Days
The doctors evaluated the success of the therapy monthly with the help of the established Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS scores of ten study participants already decreased significantly within the first week and remained at a low level. All study participants reacted to the stimulation in the course of the study. Eight of the 16 patients had a MADRS score of under 10 points at the end of the study and thus were regarded as non-depressive. "Our patients had struggled with severe depression for years with no signs of improvement. Deep brain stimulation brought most of them significant relief within days, which lasted throughout the course of the therapy. Other forms of treatment like medication and psychotherapy often lose their effectiveness over the course of time. Absolutely sensational about the study data is that the effect seems to be long lasting, with the positive effects continuing for years," says Prof. Schläpfer.
"We know from a pilot study that the stimulation of this brain region is very promising and we are delighted about the replication of these significant effects," says Prof. Coenen.
Effective new target for mood-boosting brain stimulation found -- ScienceDaily
"Stimulation induced a pattern of activity in brain regions connected to OFC that was similar to patterns seen when patients naturally experienced positive mood states," says Vikram Rao, of the University of California, San Francisco. "Our findings suggest that OFC is a promising new stimulation target for treatment of mood disorders."
The team led by Rao and Kristin Sellers in the lab of Edward Chang studied 25 patients with epilepsy who had electrodes placed in the brain for medical reasons to pinpoint the origin of their seizures. Many of those patients also suffered from depression, which is often seen in people with epilepsy. With the patients' consent, Chang's team took advantage of those electrodes to deliver small electrical pulses to areas of the brain thought to be involved in regulating mood.
Previous studies have explored deep brain stimulation (DBS) for mood disorders, but its success depends critically on target selection. Targets in other mood-related areas deep in the brain hadn't always led to reliable improvements.
In the new study, the researchers focused their attention and the electrical stimulation on the OFC. The OFC is a key hub for mood-related circuitry. But it's also widely regarded as one of the least well-understood brain regions.
"Although OFC is a more superficial target, it shares rich interconnections with several brain regions implicated in emotion processing," Sellers says. That made this relatively small brain area an attractive target for therapeutic stimulation.
The researchers used the implanted electrodes to stimulate OFC and other brain regions while collecting verbal mood reports and questionnaire scores. Those studies found that unilateral stimulation of the lateral OFC produced acute, dose-dependent mood-state improvement in subjects with moderate-to-severe baseline depression. The changes in brain activity the researchers observed after stimulation closely resembled those seen when people are in a good mood.
Brain stimulation reduces suicidal thinking in people with hard-to-treat depression: Findings indicate promising directions to prevent suicide across mental illnesses -- ScienceDaily
A non-invasive form of brain stimulation, rTMS directs magnetic pulses at a targeted area of the brain. In these studies, rTMS was applied to the dorsolateral prefrontal cortex, an area in the frontal lobes, five times a week for either three or six weeks. Participants were randomized to receive rTMS in one of three ways: to both the right and left frontal lobes (bilateral rTMS), the left frontal lobe only (unilateral rTMS) or, as a comparison group, sham rTMS, which is similar to a placebo.
Bilateral rTMS showed the biggest effect, and outperformed both other types. Forty per cent of people who received bilateral rTMS reported that they no longer experienced suicidal thoughts by the study end. By comparison, 27 per cent of those who received unilateral rTMS, and 19 per cent of those who received sham rTMS no longer experienced suicidal thoughts. Bilateral rTMS was also the most effective at preventing the development of suicidal thoughts in people who were not experiencing suicidal thinking at the start of the study.
Monthly brain cycles predict seizures in patients with epilepsy: Implanted electrodes reveal long-term patterns of seizure risk -- ScienceDaily
The new study, based on recordings from the brains of 37 patients fitted with NeuroPace implants, confirmed previous clinical and research observations of daily cycles in patients' seizure risk, explaining why many patients tend to experience seizures at the same time of day. But the study also revealed that brain irritability rises and falls in much longer cycles lasting weeks or even months, and that seizures are more likely to occur during the rising phase of these longer cycles, just before the peak. The lengths of these long cycles differ from person to person but are highly stable over many years in individual patients, the researchers found.
In a Host of Ailments, Seeing a Brain Out of Rhythm - The New York Times
Dr. Llinás, the chairman of neuroscience and physiology at the N.Y.U. School of Medicine, believes that abnormal brain rhythms help account for a variety of serious disorders, including Parkinson’s disease, schizophrenia, tinnitus and depression. His theory may explain why the technique called deep brain stimulation — implanting electrodes into particular regions of the brain — often alleviates the symptoms of movement disorders like Parkinson’s.