Parkinsonian motor symptoms are linked to pathologically increased beta-oscillations in the basal ganglia. While pharmacological treatment and deep brain stimulation (DBS) reduce these pathological oscillations concomitantly with improving motor performance, we set out to explore neurofeedback as an endogenous modulatory method. We implemented real-time processing of pathological subthalamic beta oscillations through implanted DBS electrodes to provide deep brain electrical neurofeedback. Patients volitionally controlled ongoing beta-oscillatory activity by visual neurofeedback within minutes of training. During a single one-hour training session, the reduction of beta-oscillatory activity became gradually stronger and we observed improved motor performance. Lastly, endogenous control over deep brain activity was possible even after removing visual neurofeedback, suggesting that neurofeedback-acquired strategies were retained in the short-term. Moreover, we observed motor improvement when the learnt mental strategies were applied 2 days later without neurofeedback. Further training of deep brain neurofeedback might provide therapeutic benefits for Parkinson patients by improving symptom control using strategies optimized through neurofeedback.
IntroductionOutcomes rated on impairment scales are satisfactory after burr hole trepanation for chronic subdural haematoma (cSDH). However, the surgery leads to bony defects in the skull with skin depressions above that are frequently considered aesthetically unsatisfactory by the patients. Those defects could be covered by the approved medical devices (burr hole covers), but this is rarely done today. We wish to assess, whether the application of burr hole covers after trepanation for the evacuation of cSDH leads to higher patient satisfaction with the aesthetical result at 90 days postoperative, without worsening disability outcomes or increasing the complication rate.Methods and analysisThis is a prospective, single-blinded, randomised, controlled, investigator-initiated clinical trial enrolling 80 adult patients with first-time unilateral or bilateral cSDH in Switzerland. The primary outcome is the difference in satisfaction with the aesthetic result of the scar, comparing patients allocated to the intervention (burr hole cover) and control (no burr hole cover) group, measured on the Aesthetic Numeric Analogue scale at 90 days postoperative. Secondary outcomes include differences in the rates of skin depression, complications, as well as neurological, disability and health-related quality of life outcomes until 12 months postoperative.Ethics and disseminationThe institutional review board (Kantonale Ethikkommission Zürich) approved this study on 29 January 2019 under case number BASEC 2018–01180. This study determines, whether a relatively minor modification of a standard surgical procedure can improve patient satisfaction, without worsening functional outcomes or increasing the complication rate. The outcome corresponds to the value-based medicine approach of modern patient-centred medicine. Results will be published in peer-reviewed journals and electronic patient data will be safely stored for 15 years.Trial registration number
NCT03755349.
Many efforts targeting amyloid-β (Aβ) plaques for the treatment of Alzheimer's Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aβ treatments through high-resolution light-sheet imaging of electrophoretically cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1-APP/PS1 mice subjected to β-secretase inhibitors, polythiophenes, or anti-Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance, with polythiophenes emerging as a potent anti-Aβ compound. Furthermore, aligning with a spatial-transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aβ therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aβ plaques. This may also contribute to the clinical trial failures of Aβ-therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition.
Parkinsonian motor symptoms are linked to pathologically increased beta-oscillations in the basal ganglia. While pharmacological treatment and deep brain stimulation (DBS) reduce these pathological oscillations concomitantly with improving motor performance, we set out to explore neurofeedback as an endogenous modulatory method. We implemented deep brain electrical neurofeedback to provide real-time visual neurofeedback of pathological subthalamic oscillations measured through implanted DBS electrodes. All 8 patients volitionally controlled ongoing beta-oscillatory activity within minutes of training. During a single one-hour training session, the reduction of beta-oscillatory activity became gradually stronger and accelerated hand movements. Lastly, endogenous control over deep brain activity was possible even after removing visual neurofeedback, suggesting that neurofeedback-acquired strategies were retained in the short-term. We observed a similar motor improvement when the learnt mental strategies were applied 2 days later. Further improvement of deep brain neurofeedback might benefit Parkinson patients by improving symptom control, even in the absence of real-time neurofeedback.
Background
Brain biopsies are crucial diagnostic interventions, providing valuable information for treatment and prognosis, but largely depend on a high accuracy and precision. We hypothesized that through the combination of neuronavigation-based frameless stereotaxy and MRI-guided trajectory planning with intraoperative CT examination using a mobile unit, one can achieve a seamlessly integrated approach yielding optimal target accuracy.
Methods
We analyzed a total of 7 stereotactic biopsy trajectories for a variety of deep-seated locations and different patient positions. After rigid head fixation, an intraoperative pre-procedural scan using a mobile CT unit was performed for automatic image fusion with the planning MRI images and a peri-procedural scan with the biopsy cannula in situ for verification of the definite target position. We then evaluated the radial trajectory error.
Results
Intraoperative scanning, surgery, computerized merging of MRI and CT images as well as trajectory planning were feasible without difficulties and safe in all cases. We achieved a radial trajectory deviation of 0.97 ± 0.39 mm at a trajectory length of 60 ± 12.3 mm (mean ± standard deviation). Repositioning of the biopsy cannula due to inaccurate targeting was not required.
Conclusion
Intraoperative verification using a mobile CT unit in combination with frameless neuronavigation-guided stereotaxy and pre-operative MRI-based trajectory planning was feasible, safe and highly accurate. The setting enabled single-millimeter accuracy for deep-seated brain lesions and direct detection of intraoperative complications, did not depend on a dedicated operating room and was seamlessly integrated into common stereotactic procedures.
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