A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ2 (11) = 39.8, p = 3.8 × 10-5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant's individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

Trunk Exercises Improve Balance in Parkinson Disease: A Phase II Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Trunk control is important for maintaining balance; hence, deficient trunk control may contribute to balance problems in people with Parkinson disease (PD). Unfortunately, this deficit is poorly managed with pharmacological therapies, emphasizing the need for alternative therapies for these patients. This randomized controlled trial sought to examine the effects of a 12-week trunk-specific exercise-based intervention on balance in people with PD. METHODS: Twenty-four people with PD and with a history of falls completed assessments of motor symptom severity, balance confidence, mobility, quality of life, and quiet-standing balance. Participants were then randomized to receive either 12 weeks of exercise or education and reassessed after 12 and 24 weeks. RESULTS: Linear mixed-models analyses showed no significant changes in clinical outcomes following the intervention. However, during quiet standing, sway area on a foam surface without vision was reduced for the exercise group at 12 (-6.9 ± 3.1 cm; 95% confidence interval [CI] = -13.1 to -0.7; P = 0.029; d = 0.66) and 24 weeks (-7.9 ± 3.1 cm; 95% CI = -14.1 to -1.7; P = 0.013; d = 0.76). Furthermore, the exercise group demonstrated reduced sway variability at 12 (-0.2 ± 0.1 cm; 95% CI = -0.4 to 0.0; P = 0.042; d = 0.62) and 24 weeks in the medial-lateral direction (-0.2 ± 0.1 cm; 95% CI = -0.4 to 0.0; P = 0.043; d = 0.62). No changes in quiet standing balance were recorded for the education group. DISCUSSION AND CONCLUSIONS: The results of this study suggest that exercise-based interventions targeting trunk strength, endurance, and mobility may be effective for improving quiet-standing balance in people with PD. However, additional research is needed to determine whether these improvements are sufficient to reduce falls risk.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A254).

A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation.

Gait freezing and postural instability are disabling features of Parkinsonian disorders, treatable with pedunculopontine nucleus stimulation. Both features are considered deficits of proximal and axial musculature, innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment. Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release. Experimentally, such accelerated release can be elicited by loud auditory stimuli--a phenomenon known as 'StartReact'. We observed StartReact in healthy and Parkinsonian controls. However, StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability. Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance. These findings suggest a relative block to triggered, pre-prepared movement in gait freezing and postural instability, relieved by pedunculopontine nucleus stimulation.

The speed of lexical activation is altered in Parkinson's disease.

Disturbed comprehension of complex noncanonical sentences in Parkinson's disease (PD) has been linked to dopamine depletion and delayed lexical retrieval. The aim of the present study was to replicate findings of delayed lexical activation in PD patients with noncanonical sentence processing difficulties, and investigate the influence of dopamine depletion on these changes to lexical access. In the first experiment, 20 patients with PD (tested whilst 'on' dopaminergic medication) and 23 controls participated in a list priming experiment. In this paradigm, stimuli are presented as a continuous list of words/nonwords, and semantic priming effects were measured across inter-stimulus intervals (ISIs) of 500 ms, 1000 ms and 1500 ms, with data analyzed using multivariate analyses of variance. The results revealed longer delays in lexical activation for PD patients with poor comprehension of noncanonical sentences, suggesting that the speed of lexical access may be compromised in PD, and that this feature may contribute to certain sentencecomprehension difficulties. In the second experiment, 7 patients with PD who participated in the first experiment, performed the same lexical decision task while 'off' their dopaminergic medication. Semantic priming effects were measured across ISIs of 500 ms and 1500 ms. Within group comparisons revealed a different pattern of semantic priming for the PD patients when 'on' compared to 'off' medication, providing further support for a dopaminergic influence on the speed of information processing and lexical activation.