Umeå University's logo

Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. As a crucial part of the anxiety circuit in the brain, the bed nucleus of stria terminalis (BNST) has been proposed as a target for DBS in OCD. However, the mechanism of action of BNST DBS in OCD is not yet fully understood. In our studies, the aim was to evaluate the effect and side effects of DBS in the BNST in severe OCD, to investigate which anatomical areas are being affected by the stimulation and what could be the potential mechanism of action of DBS in this target. We also explored the knowledge and concerns regarding DBS in OCD among psychiatrists, psychotherapists and patients suffering from the disorder. We investigate clinical outcomes and safety of DBS in the BNST in a series of 11 participants with severe therapy-refractory OCD. The primary outcome was a change in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores one year after surgery. Using image and stimulation parameter data from the study above, we investigate through participant-specific simulation of the electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Six of the participants were evaluated with symptom provocation fMRI pre-operatively and in DBS ON and OFF conditions. A web-based study surveyed psychiatrists, patients, and cognitive-behavioural therapists regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy.

At baseline, the mean±SD YBOCS score was 33±3.0. One year after DBS, mean±SD YBOCS score was 20±4.8 (38% improvement (range 10- 60%) p <0.01). Of the 11 participants, six were considered responders (decrease in YBOCS ≥35%) and four partial responders (decrease in YBOCS 25-34%). Surgical adverse events included one case of skin infection leading to reimplantation. The most common transient stimulation-related side-effects were anxiety and insomnia. The individual electric stimulation fields by stimulation in the BNST were similar at the 12 and 24-months follow up, involving mainly the anterior limb of the internal capsule (ALIC), genu of the internal capsule, BNST, fornix, anteromedial globus pallidus externa (GPe) and the anterior commissure. A statistically significant correlation (p < 0.05) between clinical effect measured by the YBOCS and simulation was found at the 12-month follow-up in the ventral ALIC and anteromedial GPe. A significant decrease in anxiety-related brain activity in the pre-supplementary motor area (pre-SMA) and the anterior insula was seen in 3/6 participants, with a comparable reduction (below significance level) in the other three participants. Results from the survey found that the primary source of information was from scientific sources among psychiatrists and psychotherapists. The patients' primary source of information was the media. Common concerns among the groups included complications from surgery, anaesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists and ethical concerns among psychiatrists.

BNST DBS is a promising therapy in severe therapy-refractory OCD. Our results are in line with previous publications regarding effect and safety profiles. We hypothesise that possible mechanisms of BNST DBS in OCD could be modulation of anxiety-related activity in the pre-SMA and anterior insula, two regions that play an important role in the pathophysiology of OCD. Many of the targets under investigation for OCD are in anatomical proximity, and as seen in our study, offtarget effects overlap. Therefore, DBS in the region of ALIC, NA, and BNST may perhaps be considered to be stimulation of the same target. DBS challenges in obsessive-compulsive disorder consist of source and quality of information, potential long-term adverse effects and eligibility. A broad research agenda is needed for studies as we advance in this field.