The Origins of Human Functional Stereotaxis: A Reappraisal

In order to shed light on the first application of human functional stereotactic neurosurgery, whether it was in the realm of movement disorders, as has been claimed repeatedly, or in the realm of psychiatry, a review of the original scholarly literature was conducted. Tracking and scrutinising original publications by Spiegel and Wycis, the pioneers of human stereotactic neurosurgery, it was found that its origin and the very incentive for its development and first clinical use were to avoid the side effects of frontal leucotomy. The first applications of functional stereotactic neurosurgery were in performing dorsomedial thalamotomies in psychiatric patients; it was only later that the stereotactic technique was applied in patients with chronic pain, movement disorders and epilepsy. Spiegel and Wycis' first functional stereotactic operations were for obsessive-compulsive disorder, schizophrenia, and other psychiatric conditions

Severe Bilateral Kinetic Tremor Due to Unilateral Midbrain Lesions

Background: The dentatothalamic tract connects the dentate nucleus of the cerebellum with the contralateral thalamus and plays a major role in the pathogenesis of tremor. Unilateral lesions of the dentatothalamic pathway may affect its ipsilateral predecussational or its contralateral postdecussational course, which results either in ipsilateral or in contralateral tremor. Case Report: Here, we present two patients with a unilateral midbrain lesion resulting in bilateral tremor. Both patients presented with severe kinetic tremor. Discussion: The corresponding unilateral mesencephalic lesion affected both the ipsilateral predecussational and the ipsilateral postdecussational dentatothalamic tract originating from the contralateral dentate nucleus, which is very unusual and has not been outlined clearly before

High Performance Liquid Chromatography on Calixarene-Bonded Silica Gels. III. Separations of cis/trans Isomers of Proline-Containing Peptides

The liquid chromatographic behavior of p-tert-butylcalix[n]arene (n = 4,5,6, and 8) for the separation of cis/trans peptide bond isomers of proline-containing peptides is studied to demonstrate the chromatographic selectivity of calixarene stationary phases. The results are compared with the elution patterns obtained on RP18 and β-cyclodextrin, as well as on a monomeric p-tert-butylphenoxyacetic acid. The chromatographic data are established by rechromatography and 1H-NMR spectroscopy. The results support the assumption that inclusion complexation seems to be a possible separation principle because of the size of the calixarene cavitie

Reinforcement magnitudes modulate subthalamic beta band activity in patients with Parkinson's disease

We set out to investigate whether beta oscillations in the human basal ganglia are modulated during reinforcement learning. Based on previous research, we assumed that beta activity might either reflect the magnitudes of individuals' received reinforcements (reinforcement hypothesis), their reinforcement prediction errors (dopamine hypothesis) or their tendencies to repeat versus adapt responses based upon reinforcements (status-quo hypothesis). We tested these hypotheses by recording local field potentials (LFPs) from the subthalamic nuclei of 19 Parkinson's disease patients engaged in a reinforcement-learning paradigm. We then correlated patients' reinforcement magnitudes, reinforcement prediction errors and response repetition tendencies with task-related power changes in their LFP oscillations. During feedback presentation, activity in the frequency range of 14 to 27 Hz (beta spectrum) correlated positively with reinforcement magnitudes. During responding, alpha and low beta activity (6 to 18 Hz) was negatively correlated with previous reinforcement magnitudes. Reinforcement prediction errors and response repetition tendencies did not correlate significantly with LFP oscillations. These results suggest that alpha and beta oscillations during reinforcement learning reflect patients' observed reinforcement magnitudes, rather than their reinforcement prediction errors or their tendencies to repeat versus adapt their responses, arguing both against an involvement of phasic dopamine and against applicability of the status-quo theory

Thalamic stimulation for tremor. Subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect

The aim of this study was to investigate the impact of unilateral deep brain stimulation (DBS) of the ventrointermediate (Vim) thalamic nucleus on neuropsychological functioning comparing stimulation-on with stimulation-off conditions. Nine patients [five patients with Parkinson's Disease (PD), two patients with essential tremor (ET) and 2 patients with multiple sclerosis (MS)] underwent comprehensive neuropsychological testing for cognitive functions, including general mental impairment, aphasia, agnosia, executive and constructional abilities, learning, memory, cognitive processing speed and attention as well as depression. The neuropsychological assessments were performed at least 6 months postoperatively (mean 9 months). Testing in the stimulation-on and stimulation-off condition was obtained within a period of 3 to 4 weeks. Unilateral DBS resulted in improvement of tremor in all patients. There were no significant differences between the stimulation-on and the stimulation-off condition with the exception of a decrement of word-recall in the short delay free-recall subtest of the Rey Auditory-Verbal Learning Test (RAVLT). Subgroup analysis indicated that the impairment in word-recall was related to left-sided thalamic stimulation. Our study confirms that chronic unilateral DBS is a safe method with regard to cognitive function. The subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect

STRUCTURING OF ELECTRODE SURFACES WITH LIGAND-FREE NANOPARTICLES VIA ELECTROPHORETIC DEPOSITION- FUNDAMENTALS AND IN VIVO APPLICATIONS

Electrodes for neural stimulation and recording are highly relevant in modern medicine, e.g. for the treatment of movement disorders. As these electrodes have to be implanted directly into the patient´s brain, impaired biocompatibility as well as reduced performance due to increased impedance upon tissue contact are serious problems. Strategies to improve the efficiency of electrodes entail the implementation of defined nanoscopic structures to the electrode surface, which increase the surface area and improve the current flow by possible edge effects1. In this context electrophoretic deposition (EPD) of nanoparticles (NP) constitutes an efficient and feasible way for surface structuring as in contrast to e.g. ablative laser machining, electric field lines are naturally ordered perpendicular to the implant´s surface, so that electrophoretic deposition is well compatible to shaped implants and curved surfaces. In this work an EPD process for the structuring of Pt electrode surfaces with NP is systematically investigated. Reference NP from a modern synthesis route named pulsed laser ablation in liquids (PLAL)2 are utilized as they possess a high surface charge density in order to ease their movement in an electric field. The electrophoretic velocity of these NP was examined and found to be linearly-correlated with the electric field strength, while the slope is dictated by the NP´s surface charge density (zeta-potential).3, 4 On the other hand the PLAL-generated NP are, by design, completely free of organic ligand, which significantly affected their deposition in an EPD setup. It was found that the deposited mass linearly increased with process time, yielding a well scalable process, while on the other hand control experiments with ligands showed a saturation of the deposited mass due to electrochemical shielding of the surface by charged ligands.4 It was furthermore demonstrated that the EPD process with ligand-free NP could also be done in a continuous flow-through setup suitable for the parallel structuring of multiple electrodes.5 Interestingly, the deposition velocity was not size dependent as particle size distributions prior to and after EPD were identical.5 In consecutive experiments, the surface properties like coverage, oxidation, wettability6 and impedance of the electrode materials were evaluated and correlated with the EPD process parameters electric field strength, colloid concentration and deposition time. As a result a detailed map was obtained, which allows a defined tuning of Pt surface properties by Pt NP EPD. Finally, the impedance of electrodes coated with ligand-free Pt NP were evaluated in long term stimulation experiments with rats. The NP coating could stabilize the impedance of the electrodes in vivo, while it continuously increased in non-coated controls.7 Furthermore, the coated electrodes exhibited excellent biocompatibility similar to the controls7 while no significant NP desorption from the surface was found upon mechanical tear. 1. X. F. F. Wei and W. M. Grill, J. Neural Eng., 2005, 2, 139-147. 2. V. Amendola and M. Meneghetti, Phys. Chem. Chem. Phys., 2013, 15, 3027-3046. 3. A. Menendez-Manjon, J. Jakobi, K. Schwabe, J. K. Krauss and S. Barcikowski, J. Laser Micro Nanoeng., 2009, 4, 95-99. 4. C. Streich, S. Koenen, M. Lelle, K. Peneva and S. Barcikowski, Appl. Surf. Sci., 2015, 348, 92-99. 5. S. Koenen, R. Streubel, J. Jakobi, K. Schwabe, J. K. Krauss and S. Barcikowski, J. Electrochem. Soc., 2015, 162, D174-D179. 6. A. Heinemann, S. Koenen, K. Schwabe, C. Rehbock and S. Barcikowski, Key engineering materials, 2015, 654, 218-223. 7. S. D. Angelov, S. Koenen, J. Jakobi, H. E. Heissler, M. Alam, K. Schwabe, S. Barcikowski and J. K. Krauss, J. Nanobiotechnol., 2016, 14

Position-Dependent Dysfunction of Deep Brain Stimulation in Tourette Syndrome: Diagnostic Clues

Background: Detection of defective deep brain stimulation (DBS) contacts/electrodes is sometimes challenging. Case Report: We report a patient with Tourette syndrome (TS), who presented with abrupt tic increase and mild generalized headache 9 years after DBS implantation. On the suspicion of a hardware defect, a fracture of the DBS electrode and extension lead was ruled out by radiography and standard implantable pulse generator readouts. Further investigation revealed position-dependent modifiable therapeutic impedances, suggesting an impaired contact of the extension lead/adaptor. After replacement normal impedances were recorded, and the patient fully recovered. Discussion: In DBS dysfunction with inconspicuous hardware check, position-dependent defects might be suspected

Responses of freshwater microbial decomposers to copper oxide nanoparticles

Intensive use of nano metals increases the chance of their release into natural watercourses and may pose at risk aquatic biota and their ecological functions. In streams, microbial decomposers, predominantly aquatic fungi, play a crucial role in organic matter turnover. We investigated the impact of nano CuO on stream-dwelling microbial decomposers of leaf litter by examining i) structure and functions of fungal and bacterial communities retrieved from a non-polluted stream, and ii) the physiological and cellular responses of fungal populations isolated from metal-polluted and non-polluted streams. Results were compared to those obtained after exposure to Cu2+. The exposure to nano CuO (≤500 ppm, 4 levels) and Cu2+ (≤30 ppm, 4 levels) significantly reduced leaf decomposition, bacterial and fungal biomass, fungal reproduction and diversity. Cluster analysis of DGGE based on DNA fingerprints showed that both forms of copper induced shifts in community structure. However, impacts were stronger for bacteria than fungi. At the cellular level, increased nano CuO concentrations (≤200 ppm, 5 levels) induced activity of laccase by single fungal populations. Fungal populations from non-polluted streams were more affected by nano CuO than those from polluted streams, as shown by stronger inhibition of biomass production, accumulation of reactive oxygen species (ROS), plasma membrane disruption and DNA strand breaks. Results showed that nano forms are less toxic than ionic forms, and further suggest that the toxicity of nano CuO to freshwater microbial decomposers may occur due to induction of oxidative stress.FEDER-POFC-COMPETE and FCT supported this study (PEst-C/BIA/UI4050/2011, PTDC/AAC- AMB/121650/2010 and FCT-DAAD: 2010-2011) and AP (SFRH/BD/45614/2008)

Copper oxide nanoparticles induce oxidative stress, DNA strand breaks and laccase activity in aquatic fungi

This work was supported by the DAAD-FCT-2010-2011 project (Micro)analysis of nanoparticles on aquatic fungi and A. Pradhan received the FCT grant SFRH/BD/45614/2008