• Deep brain stimulation
• Major depressive disorder
• Midbrain
• Obsessive-compulsive disorder
• Superolateral medial forebrain bundle
• Ventral tegmental area

• Deep Brain Stimulation/methods
• Humans
• Medial Forebrain Bundle/physiology
• Ventral Tegmental Area/diagnostic imaging
• Ventral Tegmental Area/physiology
• Male
• Cadaver
• Female
• Mesencephalon/diagnostic imaging
• Mesencephalon/physiology
• Middle Aged
• Aged
• Electrodes, Implanted
• Obsessive-Compulsive Disorder/therapy
• Obsessive-Compulsive Disorder/diagnostic imaging
• Adult

• behavioral task
• deep brain stimulation
• electrophysiology
• non-human primate
• subthalamic nucleus

• Agence Nationale de la Recherche

• DBS
• Parkinson’s disease
• STN
• dyskinesia
• stimulation-induced dyskinesia

• Aged
• Female
• Humans
• Dyskinesias
• Parkinson Disease/complications
• Parkinson Disease/therapy
• Subthalamic Nucleus
• Tremor

• U01 NS119562 NINDS NIH HHS
• R01 NS096008 NINDS NIH HHS
• UH3 NS119844 NINDS NIH HHS
• R25 NS108939 NINDS NIH HHS
• KL2 TR001429 NCATS NIH HHS
• R01 NR014852 NINR NIH HHS

• Anteromedial STN
• Case report
• DBS
• Directional
• Focal
• Mesencephalic ventral tegmentum
• Obsessive–compulsive disorder
• slMFB

• Deep Brain Stimulation/methods
• Dyskinesias/etiology
• Dyskinesias/therapy
• Female
• Humans
• Obsessive-Compulsive Disorder/therapy
• Subthalamic Nucleus

• Albert-Ludwigs-Universität Freiburg im Breisgau (1016)

Twenty years after its first use in a patient with obsessive-compulsive disorder (OCD), the results confirm that deep brain stimulation (DBS) is a promising therapy for patients with severe and resistant forms of the disorder. Nevertheless, many unknowns remain, including the optimal anatomical targets, the best stimulation parameters, the long-term (LT) effects of the therapy, and the clinical or biological factors associated with response. This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response.

To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD.

A comprehensive search was conducted in the PubMed, Cochrane, Scopus, and ClinicalTrials.gov databases from inception to December 31, 2020, using the following strategy: “(Obsessive-compulsive disorder OR OCD) AND (deep brain stimulation OR DBS).” Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool. The inclusion criteria were as follows: a main diagnosis of OCD, DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale (Y-BOCS) as primary outcome. Data were analyzed with descriptive statistics.

Forty articles identified by the search strategy met the eligibility criteria. Applying a follow-up threshold of 36 mo, 29 studies (with 230 patients) provided information on short-term (ST) response to DBS in, while 11 (with 155 patients) reported results on LT response. Mean follow-up period was 18.5 ± 8.0 mo for the ST studies and 63.7 ± 20.7 mo for the LT studies. Overall, the percentage of reduction in Y-BOCS scores was similar in ST (47.4%) and LT responses (47.2%) to DBS, but more patients in the LT reports met the criteria for response (defined as a reduction in Y-BOCS scores > 35%: ST, 60.6% vs LT, 70.7%). According to the results, the response in the first year predicts the extent to which an OCD patient will benefit from DBS, since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation. Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients; but it is still controversial whether this improvement persists, increases or decreases in the long term. Three different patterns of LT response emerged from the analysis: 49.5% of patients had good and sustained response to DBS, 26.6% were non responders, and 22.5% were partial responders, who might improve at some point but experience relapses during follow-up. A significant improvement in depressive symptoms and global functionality was observed in most studies, usually (although not always) in parallel with an improvement in obsessive symptoms. Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters; however, some severe adverse events including intracranial hemorrhages and infections were also described. Hypomania was the most frequently reported psychiatric side effect. The relationship between DBS and suicide risk is still controversial and requires further study. Finally, to date, no clear clinical or biological predictors of response can be established, probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed.

The present review confirms that DBS is a promising therapy for patients with severe resistant OCD, providing both ST and LT evidence of efficacy.

• Deep brain stimulation
• Obsessive-compulsive disorder
• Predictors of response
• Side effects
• Short-term
• Long-term

• deep brain stimulation
• dystonia
• isolated dystonia
• stimulation‐induced dyskinesia

• K23 NS099441 NINDS NIH HHS
• UH3 NS128297 NINDS NIH HHS

The underlying mechanisms behind the therapeutic and side effects of deep brain stimulation (DBS) need further investigation. The utilization of transgenic mouse lines is a suitable approach to better understand the cellular and network effects of DBS. However, not many bilateral DBS studies have been conducted in mice. This might be due to a lack of commercially available bilateral DBS constructs.

We developed an approach to perform repetitive long‐term DBS in freely moving mice. In this study, we implanted an in‐house custom‐made DBS construct containing two bipolar concentric electrodes to target the subthalamic nucleus (STN) bilaterally. Subsequently, we stimulated half of the animals with clinically relevant parameters three to five times a week with a duration of 20 min for ten weeks. Several behavioral tests were conducted of which the open field test (OFT) is shown to validate the reliability of this electrode construct and implantation method. Furthermore, we performed fiber photometry measurements to show the acute effect of STN‐DBS on serotonin network activity in the dorsal raphe nucleus.

Repetitive DBS and long‐term behavioral testing were performed without complications. STN‐DBS resulted in an increase of the distance traveled in the OFT and a reduction of calcium levels in serotonergic neurons of the dorsal raphe nucleus. None of the mice had lost their electrodes and postmortem evaluation of the tissue showed accurate targeting of the STN without excessive gliosis.

The DBS electrode construct and implantation method described can be used for long‐term DBS studies to further investigate the mechanisms underlying DBS.

• DBS
• deep brain stimulation
• electrodes
• implantation
• method
• mice

• Deep brain stimulation
• chorea
• essential tremor
• subthalamic nucleus

• Anterior commissure
• Deep brain stimulation
• Internal capsule
• Nucleus accumbens
• Obsessive-compulsive disorder
• Reward circuitry
• Ventral striatum

• Tourette syndrome
• etiology
• natural history
• pathophysiology
• review
• tic disorders

• Animals
• Biomedical Research
• Humans
• Tourette Syndrome/metabolism
• Tourette Syndrome/pathology
• Tourette Syndrome/therapy

• R01 MH104030 NIMH NIH HHS