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A randomized, controlled trial is performed over a six-month period to compare the effects of neurostimulation of the subthalamic nucleus of the brain with the best medical management on the changes in the quality of life and motor functions in patients with advanced Parkinson's disease. Findings imply that subthalamic neurostimulation is more effective than medical management alone in patients under 75 years of age with severe motor complications of Parkinson's disease.

Background and Objectives: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR., Methods: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (OR IVW per 4.8 kg/m 2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI., Results: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (OR IVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, OR IVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, OR IVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (OR IVW 0.85 [0.74-0.99], p = 0.032) than men (OR IVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant ( p -interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association., Discussion: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

PET and fMRI studies have revealed that excitation of the vestibular system by caloric or galvanic stimulation not only activates the parietoinsular vestibular cortex but also bilaterally deactivates the occipital visual cortex. Likewise, visual motion stimulation not only activates the visual cortex but also deactivates the parietoinsular vestibular cortex. These findings are functionally consistent with the hypothesis of an inhibitory reciprocal visual-vestibular interaction for spatial orientation and motion perception. Transcallosal visuovisual interaction between the two hemispheres was found by using half-field visual motion stimulation: activation of motion-sensitive areas hMT/V5 and deactivations of the primary visual cortex contralateral to the stimulated hemisphere. The functional significance of these inter- and intra-sensory interactions could be that they (A) allow a shift of the sensorial weight between two incongruent sensory inputs and (B) ensure a correspondence of the two hemispheres during evaluation of contradictory motion stimulation of the right and left hemifields. In terms of mathematical modeling, these findings may reflect the concepts of a sensory conflict mechanism or a mismatch between expected and actual sensory input.