Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD).

BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). METHODS: The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning. DISCUSSION: We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial. TRIAL REGISTRATION: ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021.

The Effect of Prefrontal Transcranial Direct Current Stimulation on Attention Network Function in Healthy Volunteers.

OBJECTIVES: The effect of acute transcranial direct current stimulation (tDCS) on cortical attention networks remains unclear. We examined the effect of 20 min of 2 mA dorsolateral prefrontal cortex tDCS (bipolar balanced montage) on the efficiency of alerting, orienting and executive attention networks measured by the attention network test. MATERIALS AND METHODS: A between-subjects stratified randomized design compared active tDCS vs. sham tDCS on attention network function in healthy young adults. RESULTS: Executive attention was greater following active vs. sham stimulation (d = 0.76) in the absence of effects on alerting, orienting, or global RT or error rates. Group differences were not moderated by state-mood. CONCLUSION(S): Twenty minutes of active 2 mA tDCS over left DLPFC is associated with greater executive attention in healthy humans.

Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE). OBJECTIVES: We address the efficacy and safety of tDCS in MDE. METHODS: The outcome measures were Hedges' g for continuous depression ratings, and categorical response and remission rates. RESULTS: A random effects model indicated that tDCS was superior to sham tDCS (k=11, N=393, g=0.30, 95% CI=[0.04, 0.57], p=0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k=9, LOR=0.36, 95% CI[-0.16, 0.88], p=0.176, remission: k=9, LOR=0.25, 95% CI [-0.42, 0.91], p=0.468). We estimated that for a study to detect the pooled continuous effect (g=0.30) at 80% power (alpha=0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively). CONCLUSIONS: tDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed.

Evaluating psychological interventions in a novel experimental human model of anxiety.

Inhalation of 7.5% carbon dioxide increases anxiety and autonomic arousal and provides a novel experimental model of anxiety with which to evaluate pharmacological and psychological treatments for anxiety. To date several psychotropic drugs including benzodiazepines, SSRIs and SNRIs have been evaluated using the 7.5% CO2 model; however, it has yet to be used to evaluate psychological interventions. We compared the effects of two core psychological components of mindfulness-meditation (open monitoring and focused attention) against general relaxation, on subjective, autonomic and neuropsychological outcomes in the 7.5% CO2 experimental model. 32 healthy screened adults were randomized to complete 10 min of guided open monitoring, focused attention or relaxation, immediately before inhaling 7.5% CO2 for 20 min. During CO2-challenge participants completed an eye-tracking measure of attention control and selective attention. Measures of subjective anxiety, blood pressure and heart rate were taken at baseline and immediately following intervention and CO2-challenge. OM and FA practice reduced subjective feelings of anxiety during 20-min inhalation of 7.5% CO2 compared to relaxation control. OM practice produced a strong anxiolytic effect, whereas the effect of FA was more modest. Anxiolytic OM and FA effects occurred in the absence of group differences in autonomic arousal and eye-movement measures of attention. Our findings are consistent with neuropsychological models of mindfulness-meditation that propose OM and FA activate prefrontal mechanisms that support emotion regulation during periods of anxiety and physiological hyper-arousal. Our findings complement those from pharmacological treatment studies, further supporting the use of CO2 challenge to evaluate future therapeutic interventions for anxiety.

The effect of focused attention and open monitoring meditation on attention network function in healthy volunteers.

Mindfulness meditation techniques are increasingly popular both as a life-style choice and therapeutic adjunct for a range of mental and physical health conditions. However, little is known about the mechanisms through which mindfulness meditation and its constituent practices might produce positive change in cognition and emotion. Our study directly compared the effects of Focused Attention (FA) and Open-Monitoring (OM) meditation on alerting, orienting and executive attention network function in healthy individuals. Participants were randomized to three intervention groups: open-focused meditation, focused attention, and relaxation control. Participants completed an emotional variant of the Attention Network Test (ANT) at baseline and post-intervention. OM and FA practice improved executive attention, with no change observed in the relaxation control group. Improvements in executive attention occurred in the absence of change in subjective/self-report mood and cognitive function. Baseline levels of dispositional/trait mindfulness were positively correlated with executive control in the ANT at baseline. Our results suggest that mindfulness meditation might usefully target deficits in executive attention that characterise mood and anxiety disorders.

The overlap of obsessive-compulsive disorder and social phobia and its treatment.

Both obsessive-compulsive disorder (OCD) and social phobia are common in community and clinical settings, and it should be expected that a proportion of patients with one of these conditions will also fulfill either current or lifetime criteria for the other condition. However, comorbid social phobia is more common among patients with a primary diagnosis of OCD than is comorbid OCD in patients with a primary diagnosis of social phobia. This article explores the extent of the association of OCD and social phobia in epidemiological studies, and examines the possible role of underlying depression and other disorders in mediating the appearance of the comorbid condition. Although there have been no published randomized controlled trials in patients with this particular pattern of co-morbidity, it seems sensible to adopt pharmacologic and psychologic treatment approaches which have been found efficacious in both OCD and social phobia. Pharmacologic management therefore centers on first-line treatment with a selective serotonin reuptake inhibitor. Psychologic intervention should draw on the range of cognitive and behavioral approaches required for optimal outcomes in OCD and social phobia, as discrete conditions.

A pilot randomized control trial investigating the effect of mindfulness practice on pain tolerance, psychological well-being, and physiological activity.

OBJECTIVE: To investigate the effect of mindfulness training on pain tolerance, psychological well-being, physiological activity, and the acquisition of mindfulness skills. METHODS: Forty-two asymptomatic University students participated in a randomized, single-blind, active control pilot study. Participants in the experimental condition were offered six (1-h) mindfulness sessions; control participants were offered two (1-h) Guided Visual Imagery sessions. Both groups were provided with practice CDs and encouraged to practice daily. Pre-post pain tolerance (cold pressor test), mood, blood pressure, pulse, and mindfulness skills were obtained. RESULTS: Pain tolerance significantly increased in the mindfulness condition only. There was a strong trend indicating that mindfulness skills increased in the mindfulness condition, but this was not related to improved pain tolerance. Diastolic blood pressure significantly decreased in both conditions. CONCLUSION: Mindfulness training did increase pain tolerance, but this was not related to the acquisition of mindfulness skills.