Nano-oxidation of silicon surfaces: Comparison of noncontact and contact atomic-force microscopy methods

3 pages, 4 figures.Local oxidation lithography by atomic-force microscopy is emerging as a powerful method for nanometer-scale patterning of surfaces. Here, we perform a comparative study of contact and noncontact atomic-force microscopy (AFM) oxidation experiments. The comparison of height and width dependencies on voltage and pulse duration allows establishing noncontact AFM as the optimum local oxidation method. For the same electrical conditions, noncontact AFM oxides exhibit higher aspect ratios (0.04 vs 0.02). The smallness of the liquid meniscus in noncontact AFM oxidation produces smaller oxide widths. We also report a slower oxidation rate in contact AFM oxidation. We explain this result by introducing an effective energy barrier (~0.14 eV) that includes the mechanical work done by the growing oxide against the cantilever (~0.01 eV).This work was financially supported by the Dirección General de Enseñanza Superior e Investigación (PB98-0471) and the European Commission (GR5D-CT- 2000-00349).Peer reviewe

Subthalamic responses to motor cortex stimulation:Selective targeting of the subthalamic motor area

Introduction: Over the last decades, it has been shown consistently that deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson (PD) patients. However, in a substantial number of patients the beneficial effects of STN DBS are overshadowed by cognitive and/or limbic alterations. These side effects of STN DBS are thought to be caused by stimulation of the associative and limbic pathways that run through the STN. We hypothesize that an optimal effect of STN DBS on the motor symptoms without inducing cognitive and limbic side effects can be achieved by selective stimulation of the STN motor region by improved targeting. To achieve this goal, we made use of the cortico-subthalamic projection. We hypothesize that in PD patients motor cortex stimulation (MCS) evokes a specific response in the dorsolateral part of the STN, supposedly the STN motor area, that can be seen in both single unit activity and local field potentials (LFP). Material and Methods: Here we describe the results of one PD patient in which we performed MCS during the intra-operative STN microrecordings. In total, we measured single unit activity of eight neurons at various locations in the STN and LFP’s at the same locations. Data were analyzed using Matlab. All recordings were high pass filtered, the stimulus artifact was removed by time shifting, peristimulus time histograms were constructed from which significant excitatory and inhibitory responses were determined using the change point analysis. Results: The STN neurons had an average spontaneous firing rate of 64.6±36.3 Hz. Within the STN responses to MCS were seen, while outside the borders of the STN no responses were found. Responses differed between ventro-dorsal regions in the anterior-posterior and medio-lateral plane. In the anterior and lateral electrode at dorsal levels of the STN a significant early excitation (~10-50ms) and subsequent inhibition (50-110ms) were seen. The lateral electrode also showed a late excitation (~115-170ms). The responses we found were partially similar to reports in animal studies, but we did not observe the typical triphasic response. Conclusion: We found responses in the STN during MCS, which were significantly different in the dorsally recorded neurons in the lateral and anterior trajectory compared to the neurons recorded in other regions of the STN. In the near future MCS could be a novel tool to determine the motor area of the STN to optimize targeting for DBS in PD patients, thereby preventing cognitive and limbic side effect

Formal inverse integrating factors and the nilpotent center problem

We are interested in deepening knowledge of methods based on formal power series applied to the nilpotent center problem of planar local analytic monodromic vector fields X. As formal integrability is not enough to characterize such a centers we use a more general object, namely, formal inverse integrating factors V of X. Although by the existence of V is not possible to describe all nilpotent centers strata, we simplify, improve and also extend previous results on the relationship between these concepts. We use in the performed analysis the so-called Andreev number n N with n > 2 associated to X which is invariant under orbital conjugacy of X. Besides the leading terms in the (1,n)-quasihomogeneous expansions that V can have we also prove the following: (i) If n is even and there exists V then X has a center; (iii) If the existence of V characterizes all the centers; (iii) If there is a V with minimum ``vanishing multiplicity' at the singularity then, generically, X has a center.The author is partially supported by a MINECO grant number MTM2014-53703-P and by a CIRIT grant number 2014 SGR 1204

Subthalamic nucleus deep brain stimulation in elderly patients – analysis of outcome and complications

BACKGROUND: There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. METHODS: Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age ≥ 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. RESULTS: Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. CONCLUSION: DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate

A Unified Functional Network Target for Deep Brain Stimulation in Obsessive-Compulsive Disorder

BACKGROUND: Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. METHODS: First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. RESULTS: While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. CONCLUSIONS: Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected-regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part IV: deep brain stimulation

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients

Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson's disease

BACKGROUND Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and sleep symptoms in Parkinson’s disease (PD). However, the long-term effects of STN-DBS on sleep and its relationship with QoL outcome are unclear. METHODS In this prospective, observational, multicenter study including 73 PD patients undergoing bilateral STN-DBS, we examined PDSleep Scale (PDSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, -activities of daily living, and -complications (SCOPA-A, -B, -C), and levodopa-equivalent daily dose (LEDD) preoperatively, at 5 and 24 months follow-up. Longitudinal changes were analyzed with Friedman-tests or repeated-measures ANOVA, when parametric tests were applicable, and Bonferroni-correction for multiple comparisons. Post-hoc, visits were compared with Wilcoxon signed-rank/t-tests. The magnitude of clinical responses was investigated using effect size. RESULTS Significant beneficial effects of STN-DBS were observed for PDSS, PDQ-8, SCOPA-A, -B, and -C. All outcomes improved significantly at 5 months with subsequent decrements in gains at 24 months follow-up which were significant for PDSS, PDQ-8, and SCOPA-B. Comparing baseline and 24 months follow-up, we observed significant improvements of PDSS (small effect), SCOPA-A (moderate effect), -C, and LEDD (large effects). PDSS and PDQ-8 improvements correlated significantly at 5 and 24 months follow-up. CONCLUSIONS In this multicenter study with a 24 months follow-up, we report significant sustained improvements after bilateral STN-DBS using a PD-specific sleep scale and a significant relationship between sleep and QoL improvements. This highlights the importance of sleep in holistic assessments of DBS outcomes

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease.

To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy