I have so far described ECT and rTMS as methods for stimulating the brain and thereby influencing mental well-being. ECT induces an epileptic seizure, and thus, the placement of the electrodes does not play a particularly crucial role in the outcome. rTMS, on the other hand, targets a specific part of the brain cortex where there is evidence that it leads to a reduction in depressive symptoms. Deep Brain Stimulation (DBS) is even more targeted and, for that matter, more invasive. By placing an electrode with multiple active points inside the brain itself, one directly affects the activity. In this section, I will delve into the technology and its application, but first, let's provide a background on how researchers have identified where in the brain to place the electrode.
Where is depression located?
Naturally, depression is not localized in any specific area of the brain, as the common understanding is that the brain consists of a large number of closely interconnected networks extending to both hemispheres and subcortically. What researchers refer to is the part of the brain where they observe either an anatomical or functional difference between groups of patients with depression and healthy controls. Neurologist Helen S. Mayberg has played a crucial role in this work. She and her team, using various brain imaging methods such as PET and fMRI, have investigated changes in activity in different parts of the brain due to depression and successful antidepressant treatment. In a review article from 2009, she describes many of the findings. Generally, hypoactivity in the frontal cortex is observed, but it can vary for different parts of the lobe. The first area suspected to be significant was the most ventral part of the cingulate cortex (SCC below). Here, hyperactivity was observed in depressed patients, and the activity decreased after treatment with both antidepressant medications and ECT. SCC has also been implicated in the regulation of negative emotions.
Several different forms of evidence thus pointed towards SCC as a target for DBS treatment. From DBS in Parkinson's disease, it is known that high-frequency stimulation (in a different part of the brain) leads to inhibited endogenous neural activity and thus clinical effects.
How is it done in practical terms?
DBS as a technique has been implemented for a long time and involves the insertion of electrodes into the brain. To achieve precision in localization, a map of the individual's brain is first created using MRI. Then, stereotactic techniques are used to find the right coordinates in the brain and the angle for the electrode (see image below). To access the brain, incisions are made in the scalp, holes are drilled in the skull, and then the dura is opened. During these initial steps, the patient is typically under anesthesia. However, when inside the brain parenchyma with the electrodes, there may be value in having the patient awake. This is because it is the time when the electrode can be activated to observe the patient's reaction. In DBS for motor conditions such as tremor or Parkinson's, one can receive immediate feedback on their location in the brain by observing a reduction in tremors. This is naturally more challenging when dealing with a psychiatric indication.
he electrodes are connected to a device that is located somewhere under the skin on the body, for example, under the collarbone. Following the procedure, there is a period of adjusting the stimulation to find the optimal effect.
Does it work?
DBS is regularly used in highly specialized healthcare for Parkinson's disease and essential tremor. It has also shown effectiveness in various forms of dystonia. Clinical trials are ongoing for obsessive-compulsive disorder and depression. In an initial proof-of-principle study on six treatment-resistant depressed patients, Mayberg tested DBS targeted at the aforementioned SCC area (more precisely, towards white matter). According to the authors, a clear antidepressant effect was found in four out of six patients, and it decreased during blinded deactivation of the stimulation. This open-label study was followed by several others, all reporting positive results. In 2015, two randomized controlled trials (RCTs) for DBS in treatment-resistant depression were published. One study included 30 patients randomized to active or sham stimulation targeting the ventral striatum. No difference was observed between sham and real stimulation. In the other study, they targeted the aforementioned SCC area for five patients who had previously responded to DBS treatment and achieved remission. They were randomized to either continue stimulation or turn it off. The conclusion was that genuine DBS was indeed more effective than sham stimulation. The latter study is, of course, very small but still provides insights into:
The target area for treatment, SCC, or striatum.
The stimulation regimen.
The dynamics of treatment response. There seems to be an acute and a chronic effect.
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