Comparison between control-based continuation and phase-locked loop methods for the identification of backbone curves and nonlinear frequency responses

Control-based continuation (CBC) and phase-locked loops (PLL) are two experimental testing methods that have demonstrated great potential for the non-parametric identification of key nonlinear dynamic features such as nonlinear frequency responses and backbone curves. Both CBC and PLL exploit stabilizing feedback control to steer the dynamics of the tested system towards the responses of interest and overcome important difficulties experienced when applying conventional testing methods such as sine sweeps to nonlinear systems. For instance, if properly designed, the feedback controller can prevent the system from exhibiting untimely transitions between coexisting responses or even losing stability due to bifurcations. This contribution aims to highlight the similarities that exist between CBC and PLL and present the first thorough comparison of their capabilities. Comparisons are supported by numerical simulations as well as experimental data collected on a conceptually simple nonlinear structure primarily composed of a thin curved beam. The beam is doubly clamped and exhibits nonlinear geometric effects for moderate excitation amplitudes

Comparison between control-based continuation and phase-locked loop methods for the identification of backbone curves and nonlinear frequency responses

Control-based continuation (CBC) and phase-locked loops (PLL) are two experimental testing methods that have demonstrated great potential for the non-parametric identification of key nonlinear dynamic features such as nonlinear frequency responses and backbone curves. Both CBC and PLL exploit stabilizing feedback control to steer the dynamics of the tested system towards the responses of interest and overcome important difficulties experienced when applying conventional testing methods such as sine sweeps to nonlinear systems. For instance, if properly designed, the feedback controller can prevent the system from exhibiting untimely transitions between coexisting responses or even losing stability due to bifurcations. This contribution aims to highlight the similarities that exist between CBC and PLL and present the first thorough comparison of their capabilities. Comparisons are supported by numerical simulations as well as experimental data collected on a conceptually simple nonlinear structure primarily composed of a thin curved beam. The beam is doubly clamped and exhibits nonlinear geometric effects for moderate excitation amplitudes

A tool to improve pre-selection for deep brain stimulation in patients with Parkinson’s disease

Determining the eligibility of patients with Parkinson’s disease (PD) for deep brain stimulation (DBS) can be challenging for general (non-specialised) neurologists. We evaluated the use of an online screening tool (Stimulus) that aims to support appropriate referral to a specialised centre for the further evaluation of DBS. Implementation of the tool took place via an ongoing European multicentre educational programme, currently completed in 15 DBS centres with 208 referring neurologists. Use of the tool in daily practice was monitored via an online data capture programme. Selection decisions of patients referred with the assistance of the Stimulus tool were compared to those of patients outside the screening programme. Three years after the start of the programme, 3,128 patient profiles had been entered. The intention for referral was made for 802 patients and referral intentions were largely in accordance with the tool recommendations. Follow-up at 6 months showed that actual referral took place in only 28%, predominantly due to patients’ reluctance to undergo brain surgery. In patients screened with the tool and referred to a DBS centre, the acceptance rate was 77%, significantly higher than that of the unscreened population (48%). The tool showed a sensitivity of 99% and a specificity of 12% with a positive and negative predictive value of 79 and 75%, respectively. The Stimulus tool is useful in assisting general neurologists to identify appropriate candidates for DBS consideration. The principal reason for not referring potentially eligible patients is their reluctance to undergo brain surgery

Multi-task learning for subthalamic nucleus identification in deep brain stimulation

Deep brain stimulation (DBS) of Subthalamic nucleus (STN) is the most successful treatment for advanced Parkinson’s disease. Localization of the STN through Microelectrode recordings (MER) is a key step during the surgery. However, it is a complex task even for a skilled neurosurgeon. Different researchers have developed methodologies for processing and classification of MER signals to locate the STN. Previous works employ the classical paradigm of supervised classification, assuming independence between patients. The aim of this paper is to introduce a patient-dependent learning scenario, where the predictive ability for STN identification at the level of a particular patient, can be used to improve the accuracy for STN identification in other patients. Our inspiration is the multi-task learning framework, that has been receiving increasing interest within the machine learning community in the last few years. To this end, we employ the multi-task Gaussian processes framework that exhibits state of the art performance in multi-task learning problems. In our context, we assume that each patient undergoing DBS is a different task, and we refer to the method as multi-patient learning. We show that the multi-patient learning framework improves the accuracy in the identification of STN in a range from 4.1 to 7.7%, compared to the usual patient-independent setup, for two different datasets. Given that MER are non stationary and noisy signals. Traditional approaches in machine learning fail to recognize accurately the STN during DBS. By contrast in our proposed method, we properly exploit correlations between patients with similar diseases, obtaining an additional information. This information allows to improve the accuracy not only for locating STN for DBS but also for other biomedical signal classification problems

Combined STN/SNr-DBS for the treatment of refractory gait disturbances in Parkinson's disease: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Severe gait disturbances in idiopathic Parkinson's disease (PD) are observed in up to 80% of all patients in advanced disease stages with important impact on quality of life. There is an unmet need for further symptomatic therapeutic strategies, particularly as gait disturbances generally respond unfavourably to dopaminergic medication and conventional deep brain stimulation of the subthalamic nucleus in advanced disease stages. Recent pathophysiological research pointed to nigro-pontine networks entrained to locomotor integration. Stimulation of the pedunculopontine nucleus is currently under investigation, however, hitherto remains controversial. The substantia nigra pars reticulata (SNr) - entrained into integrative locomotor networks - is pathologically overactive in PD. High-frequent stimulation of the substantia nigra pars reticulata preferentially modulated axial symptoms and therefore is suggested as a novel therapeutic candidate target for neuromodulation of refractory gait disturbances in PD.</p> <p>Methods</p> <p>12 patients with idiopathic Parkinson's disease and refractory gait disturbances under best individual subthalamic nucleus stimulation and dopaminergic medication will be enroled into this double-blind 2 × 2 cross-over clinical trial. The treatment consists of two different stimulation settings using <it>(i) </it>conventional stimulation of the subthalamic nucleus [STNmono] and <it>(ii) </it>combined stimulation of distant electrode contacts located in the subthalamic nucleus and caudal border zone of STN and substantia nigra pars reticulata [STN+SNr]. The primary outcome measure is the change of the cumulative 'axial score' (UPDRS II items '13-15' and UPRDS III items '27-31') at three weeks of constant stimulation in either condition. Secondary outcome measures include specific scores on freezing of gait, balance function, quality of life, non-motor symptoms, and neuropsychiatric symptoms. The aim of the present trial is to investigate the efficacy and safety of a three week constant combined stimulation on [STN+SNr] compared to [STNmono]. The results will clarify, whether stimulation on nigral contacts additional to subthalamic stimulation will improve therapeutic response of otherwise refractory gait disturbances in PD.</p> <p>Trial registration</p> <p>The trial was registered with the clinical trials register of <url>http://www.clinicaltrials.gov</url> (<a href="http://www.clinicaltrials.gov/ct2/show/NCT01355835">NCT01355835</a>)</p

Comparative classical and ab initio Molecular Dynamics study of molten and glassy germanium dioxide

A Molecular Dynamics (MD) study of static and dynamic properties of molten and glassy germanium dioxide is presented. The interactions between the atoms are modelled by the classical pair potential proposed by Oeffner and Elliott (OE) [Oeffner R D and Elliott S R 1998, Phys. Rev. B, 58, 14791]. We compare our results to experiments and previous simulations. In addition, an ab initio method, the so-called Car-Parrinello Molecular Dynamics (CPMD), is applied to check the accuracy of the structural properties, as obtained by the classical MD simulations with the OE potential. As in a similar study for SiO2, the structure predicted by CPMD is only slightly softer than that resulting from the classical MD. In contrast to earlier simulations, both the static structure and dynamic properties are in very good agreement with pertinent experimental data. MD simulations with the OE potential are also used to study the relaxation dynamics. As previously found for SiO2, for high temperatures the dynamics of molten GeO2 is compatible with a description in terms of mode coupling theory.Comment: 27 pages, 16 figure

Functional Dissection of the Proton Pumping Modules of Mitochondrial Complex I

A catalytically active subcomplex of respiratory chain complex I lacks 14 of its 42 subunits yet retains half of its proton-pumping capacity, indicating that its membrane arm has two pump modules

Long-term effects of STN DBS on mood: psychosocial profiles remain stable in a 3-year follow-up

<p>Abstract</p> <p>Background</p> <p>Deep brain stimulation of the subthalamic nucleus significantly improves motor function in patients with severe Parkinson's disease. However, the effects on nonmotor aspects remain uncertain. The present study investigated the effects of subthalamic nucleus deep brain stimulation on mood and psychosocial functions in 33 patients with advanced Parkinson's disease in a three year follow-up.</p> <p>Methods</p> <p>Self-rating questionnaires were administered to 33 patients prior to surgery as well as three, six, twelve and 36 months after surgery.</p> <p>Results</p> <p>In the long run, motor function significantly improved after surgery. Mood and psychosocial functions transiently improved at one year but returned to baseline at 36 months after surgery. In addition, we performed cluster and discriminant function analyses and revealed four distinct psychosocial profiles, which remained relatively stable in the course of time. Two profiles featured impaired psychosocial functioning while the other two of them were characterized by greater psychosocial stability.</p> <p>Conclusion</p> <p>Compared to baseline no worsening in mood and psychosocial functions was found three years after electrode implantation. Moreover, patients can be assigned to four distinct psychosocial profiles that are relatively stable in the time course. Since these subtypes already exist preoperatively the extent of psychosocial support can be anticipatory adjusted to the patients' needs in order to enhance coping strategies and compliance. This would allow early detection and even prevention of potential psychiatric adverse events after surgery. Given adequate psychosocial support, these findings imply that patients with mild psychiatric disturbances should not be excluded from surgery.</p