OCD symptoms reduced by targeted deep brain stimulation

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Deep Brain Stimulation (DBS) at two areas of the brain significantly reduced OCD symptoms, with significantly improved cognitive flexibility from one area and a greater positive effect on depressed mood from the other. These were the findings from a UK study starting in 2013, with six treatment-refractory Obsessive Compulsive Disorder (OCD) patients.

OCD is characterised by unwanted intrusive thoughts (obsessions) and repetitive stereotyped behaviours (compulsions- sometimes called rituals) and often means everyday activities become impossible for those with the condition. This repetitive and compulsive behaviour is commonly associated with either depressed mood or impairment in cognitive flexibility – an inability to flexibly adapt to changing situations.

Deep brain stimulation (DBS) is an emerging treatment for a small number of people with extremely severe OCD who have not responded to available treatment, such as cognitive behavioural therapy or medication. It requires neurosurgical implantation of electrodes.

In a study, six patients with treatment-refractory OCD were recruited from NHS England Highly Specialised OCD Services.

As part of the study, in a double-blind cross over trial, each patient received DBS stimulation to brain areas previously associated with OCD, the anteromedial subthalamic nucleus (amSTN) for three months and DBS stimulation to the ventral capsule/ventral striatal area (VC/VS) for three months, followed by DBS stimulation to both amSTN and VC/VS. The neurosurgery and clinical assessments were carried out at the Unit of Functional Neurosurgery and Hughlings Jackson Ward, The National Hospital for Neurology and Neurosurgery, Queen Square, London (part of University College London Hospitals).

The study found that DBS at each site significantly and equivalently reduced OCD symptoms. However, amSTN but not VC/VS DBS significantly improved cognitive flexibility, but VC/VS DBS had a greater positive effect on depressed mood.

Furthermore, MRI tractography (a form of brain imaging) from optimally activated electrode contacts showed that the two DBS sites affected different neural circuits within the brain. This finding provides clues as to the roles that those specific brain regions play in OCD, and has potentially important implications for treatment.

Lead author, Professor Eileen Joyce (UCL Queen Square Institute of Neurology), said: “This is the first study to compare directly the effects of deep brain stimulation at two brain sites and has discovered important information about how the brain changes in severe OCD responsible for obsessions and compulsions, depressed mood and cognitive inflexibility might be alleviated.

“The finding that amSTN but not VC/VS DBS improved cognitive flexibility and that the effect of DBS on mood was significantly greater for VC/VS DBS, implicates the involvement of different neural circuitries associated with distinct symptoms in OCD. MRI tractography findings revealed that VC/VS and amSTN DBS modulate distinct brain networks implicated in OCD and are compatible with these clinical and cognitive observations.”

Cognitive flexibility was measured by the CANTAB IED test, and undertaken by researchers at Cambridge University. Their previous studies have shown that impaired cognitive flexibility is a marker of OCD and improvement implies that patients can break out of maladaptive routines and habits and take on new and rewarding experiences.

All patients had been ill for at least 20 years and failed to respond to high doses of medication plus intensive CBT. Patients were recruited from NHS England Specialised OCD Services, at South West London St Georges Mental Health NHS and Hertfordshire NHS partnership. Additional patient expertise was provided by the Advanced Interventions Service at the University of Dundee and NHS Tayside.

The trials’ first patient was recruited in 2013 and the sixth and final patient finished the study in November 2016. The study was by funded by grants from the MRC and Wellcome Trust.

One of the trial participants was first diagnosed at the age of 26 years with OCD but had symptoms since the age of 7. Prior to the trial, the participant had been ‘profoundly debilitated’ by OCD for 10 years and had been living continuously in psychiatric units for 6 years, receiving treatment from numerous specialist OCD services and specialists.

“I was getting worse and nothing was helping. I had no quality of life and the only tasks I attempted were the basics: I ate, drank, used the loo and slept. When I used the toilet I would be in the bathroom for up to 14 hours each time because of my OCD rituals,” the participant said.

“My overwhelming symptoms were feeling contaminated, obsessional slowness and mentally reviewing every single action.

“The reviewing affected all things I undertook and my slowness was so bad it would take me two to three hours to cross the bedroom and another hour to gets my legs in bed. I showered, changed my clothes and brushed my teeth only once a month as they were such arduous tasks.”

“I didn’t feel anything for a few days but then I did. I felt inexplicably excited and happy with the great sense of looking forward to life. I recognised the feeling from 20 years before when I had been completely well.

“I found I could walk from room-to-room much more quickly and, miraculously, my need to review subsided and I was soon performing tasks much quicker and on my own. I started getting dressed again and went shopping in London, something I hadn’t done for 10 years.

“The surgery has transformed my life. I am living completely independently and doing volunteer work.”

There are several limitations to the study, the main one being the small sample size. However, when comparing the effectiveness of the two DBS sites, patients served as their own controls in an innovative design, and the conclusions were robust to adjustment for multiple comparisons and parametric and non-parametric analyses.

Nevertheless, it would be important to test this hypothesis in a larger group of patients when the mechanistic actions of amSTN and VC/VS DBS on recovery from OCD can be evaluated in more detail.

Abstract
Background: Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored.
Methods: Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts.
Results: DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD.
Conclusions: Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.

Authors
Himanshu Tyagi, Annemieke M Apergis-Schoute, Harith Akram, Tom Foltynie, Patricia Limousin, Lynne M Drummond, Naomi A Fineberg, Keith Matthews, Marjan Jahanshahi, Trevor W Robbins, Barbara J Sahakian, Ludvic Zrinzo, Marwan Hariz, Eileen M Joyce

University College London material
Biological Psychiatry abstract


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