BACKGROUND STN-DBS is well established to improve motor symptoms and quality of life in patients with PD. While non-motor symptoms are crucial for quality of life in these patients, only neuropsychiatric and neuropsychological symptoms have been systematically studied in a longitudinal design thus far. However, these are only a part of the spectrum of non-motor symptoms in PD. We hypothesized that STN-DBS is associated with a beneficial effect on a range of non-motor symptoms. METHODSIn this multicenter, open, prospective, international study we investigated non-motor effects of STN-DBS in "real-life" use. We evaluated Non-motor Symptom Scale, and Questionnaire, PD Questionnaire-8, Scales for Outcomes of PD motor examination and complications, and activities of daily living preoperatively and at 6 months follow-up in 60 consecutive patients (35 male, mean age: 61.64 ±7.84 years, mean disease duration: 10.45 ±4.22 years) undergoing STN-DBS. RESULTSAll outcomes improved significantly at 6 months follow-up (PD Questionaire-8, p=0.006; activities of daily living, p=0.012; all others, p<0.001; Wilcoxon signedrank, respectively paired t-test; Bonferroni-correction). Post-hoc analyses of Nonmotor Symptom Scale domains showed a significant reduction of sleep/fatigue and miscellaneous domains (p≤0.001), perceptual problems/hallucinations (p=0.036), and urinary (p=0.018) scores. Effect sizes were "moderate" effect for Non-motor Non-motor effects of subthalamic DBS -5 -Symptom Scale, and motor complications, "large" for motor examination, and "small" for other outcomes. CONCLUSIONSThis study provides first evidence that bilateral STN-DBS improves non-motor burden in patients with PD and opens the door to a more balanced evaluation of DBS outcomes. Further randomized studies are needed to confirm these findings and compare DBS non-motor effects to other therapies such as infusion based treatments of advanced PD.

The synRas transgenic mice express constitutively activated Valin12-Harvey Ras in postnatal neocortical pyramidal neurons. This leads to somatodendritic hypertrophy, higher densities of spines and synapses, and an enhancement of synaptic long-term potentiation associated with an increased glutamate receptor-mediated activity. It was less clear how the interneurons respond to these alterations, and this prompted the quantitative assessment of interneuron neurochemistry. Interneurons rarely expressed the transgene, however, several interneuron types displayed a transient somatic hypertrophy. Furthermore, NPY mRNA expression was persistently increased as were the laminar percentages of labeled neurons. The expression of parvalbumin and voltage-gated potassium channels Kv3.1b/3.2 was unchanged. A significant decline of GAD-67, but not GAD-65, mRNA expressing neurons was observed in layer VI in animals older than P60. This suggested that subtle deficits in inhibition and enhanced excitation evoke the interneuronal changes in the synRastransgenic mouse cortex.