Manuel Hewitt

Titanium Complexes Containing Bulky η2‐1,2,4‐Triazolato Ligands

The unusual η2-coordination of a 1,2,4-triazolato ligand to a transition metal is described. The synthesized compounds [Ti(η2-tz)4] (1), [(C5Me4CH2Ph)Ti(η2-tz)Cl2] (2), [Cp*Ti(η2-tz)Cl2] (3) and [Cp*Ti(η2-tz)3] (4) (tzH = 3,5-diisopropyl-1,2,4-triazole) were characterized by 1H and 13C NMR spectroscopy and, in the case of 1 and 2, by X-ray crystallography. Both structures confirm the η2-coordination of the ligand. In compound 1 all four ligands coordinate in an η2 fashion leading to a metal center surrounded by eight nitrogen atoms. The core of the fragment formed by the central atom and the triazolato planes exhibits a distorted D2d symmetry. A variable temperature NMR spectroscopy experiment performed on 1 confirms the occurrence of two different isopropyl groups at low temperature. The structure of compound 2 shows the geometry of the molecule in a distorted Cs symmetry, with the mirror plane perpendicular to the cyclopentadienyl and triazolato rings. The tz ligand is oriented in a transoid position relative to the benzyl substituent of the C5Me4CH2Ph group. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Automated TMS hotspot-hunting using a closed loop threshold-based algorithm

BACKGROUND Although neuronavigation is increasingly used for optimizing coil positioning, the inter-session reliability of hotspot location remains unsatisfactory, probably due to the variability of motor evoked potentials (MEPs) and residual investigator bias. PURPOSE To increase the reliability and accuracy of hotspot location we introduce a novel automated hotspot-hunting procedure (AHH). METHODS AHH is based on resting motor thresholds (RMTs) instead of MEP amplitudes. By combining robotic coil positioning with a closed loop target search algorithm AHH runs independently from the investigator. AHH first identifies all targets with an RMT below a defined intensity of stimulator output (MEP-positive) and then locates the motor hotspot of a target muscle by measuring RMTs at all identified MEP-positive targets. Results were compared to robotic MEP amplitude TMS mapping (MAM) using a 7×7 predefined target grid and suprathreshold intensities and manual hotspot search (MHS). Sequence of stimulation was randomized from pulse to pulse in AHH and MAM. Each procedure was tested in 8 subjects. RESULTS Inter-session CoG shift was significantly reduced with AHH (1.4mm (SEM: 0.4)) as compared to MAM (7.0mm (SEM: 1.8)) (p=0.018) and MHS (9.6mm (SEM: 2.2)) (p=0.007). No statistical difference was observed between MAM and MHS. RMTs were reliable between sessions. CONCLUSION Our method represents the first fully automated, i.e. investigator-independent, TMS hotspot-hunting procedure. Measuring RMTs instead of MEP amplitudes leads to significantly increased accuracy and reliability of CoG locations. Moreover, by assessing thresholds AHH is the first procedure to fulfill the original hotspot definition.

Neuroscientists do not use non-invasive brain stimulation on themselves for neural enhancement.

Self-application of non-invasive brain stimulation (NIBS) such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), or transcranial alternating current stimulation (tACS) is now a matter of debate: we can find several articles in professional journals or lay publications discussing the pros and cons. Development of safe and effective hometherapy devices for treatment of neuropsychiatric disorders also involves their possible use for the non-therapeutic purpose of neural enhancement. Moreover, promotion of do-it-yourself kits for tDCS has raised concerns among scientists [1e4]. There are several meta-analyses or reviews for therapeutic use of NIBS [5,6], but none providing a scientific rationale for self-application. To collect opinions from researchers about the self-application of NIBS on healthy subjects, including the researchers themselves, we conducted an anonymous survey. In a questionnaire, we asked researchers involved in human NIBS studies whether they thought neuroenhancement by either rTMS or tDCS/tACS is useful in normal subjects for real-life applications, and whether they used rTMS or tDCS/tACS on themselves for the purpose of neuroenhancement for real-life applications. To those who replied that they did not use NIBS on themselves, we further asked for the reason. “Benefit too small,” “takes too much time to apply,” and “safety concerns,” were presented as possible reasons, where multiple answers are allowed. We also allowed free comments under “other (please specify).” If a researcher had ever performed some type(s) of NIBS, the researcher was asked which type(s) of stimulation they used: rTMS, tDCS, tACS, or “other (please specify).”Here again, multiple answers were allowed. Finally, all responders rated pharmaceutical neuroenhancement compared to NIBS in terms of time consumption, side effects, and benefit. They rated pharmacology as being worse, slightly worse, same, slightly better, better, or “don’t know.” The main purpose of this questionnaire was to know how the researchers think about NIBS as a tool for neuroenhancement; we therefore included this last question to compare pharmacological enhancement with NIBS. We received 287 valid responses from researchers who declared that they had performed their own research in the area of brain stimulation. Before that we sent 3299 e-mails to the addresses of potentially active researchers in the field who were already being contacted regarding attendance at the 5th International Conference on Non-invasive Brain Stimulation 2013 in Leipzig (http://www. nbs-conference.de/). There were 391 responses. From these, we excluded 74 responders who were not engaged in human NIBS

5 kHz Transcranial Alternating Current Stimulation: Lack of Cortical Excitability Changes When Grouped in a Theta Burst Pattern

Background: Suprathreshold transcranial single pulse electrical stimulation (tES) is painful and not applicable in a repetitive mode to induce plastic after-effects. Objective: In order to circumvent this pain problem, we applied here a 5 kHz transcranial alternating current stimulation (tACS) theta burst protocol with a field intensity of up to 10 mA to the primary motor cortex (M1). Furthermore, we were interested in finding out whether electrical theta burst stimulation (eTBS) is able to induce lasting after-effects on cortical plasticity. Methods: Three different eTBS protocols were applied at 5 mA in a sham controlled, double blinded cross-over design on the M1 region of seventeen healthy subjects during the first part of the study. The second study part consists of three different eTBS protocols ranging from 5 mA to 10 mA and 1 ms to 5 ms sinusoidal bursts, applied to the M1 region of 14 healthy subjects. Results: We were able to apply all eTBS protocols in a safe manner, with only six subjects reporting mild side effects related to the stimulation. However, no eTBS protocol induced lasting effects on muscle- evoked potential (MEP) amplitudes when compared to sham stimulation. Significant inhibition of MEP amplitude was only seen in the lower intensity protocols as compared to baseline. Conclusion: eTBS is a safe method to apply high frequency tACS with up to 10 mA intensity. Future studies need to explore the parameter space to a larger extent in order to assure efficacy.

Steer by ear: Myoelectric auricular control of powered wheelchairs for individuals with spinal cord injury.

PURPOSE Providing mobility solutions for individuals with tetraplegia remains challenging. Existing control devices have shortcomings such as varying or poor signal quality or interference with communication. To overcome these limitations, we present a novel myoelectric auricular control system (ACS) based on bilateral activation of the posterior auricular muscles (PAMs). METHODS Ten able-bodied subjects and two individuals with tetraplegia practiced PAM activation over 4 days using visual feedback and software-based training for 1 h/day. Initially, half of these subjects were not able to voluntarily activate their PAMs. This ability was tested with regard to 8 parameters such as contraction rate, lateralized activation, wheelchair speed and path length in a virtual obstacle course. In session 5, all subjects steered an electric wheelchair with the ACS. RESULTS Performance of all subjects in controlling their PAMs improved steadily over the training period. By day 5, all subjects successfully generated basic steering commands using the ACS in a powered wheelchair, and subjects with tetraplegia completed a complex real-world obstacle course. This study demonstrates that the ability to activate PAM on both sides together or unilaterally can be learned and used intuitively to steer a wheelchair. CONCLUSIONS With the ACS we can exploit the untapped potential of the PAMs by assigning them a new, complex function. The inherent advantages of the ACS, such as not interfering with oral communication, robustness, stability over time and proportional and continuous signal generation, meet the specific needs of wheelchair users and render it a realistic alternative to currently available assistive technologies.

Towards physiological ankle movements with the ActiGait implantable drop foot stimulator in chronic stroke

Ahead of Print article withdrawn by publisher.

Cortical representation of auricular muscles in humans: A robot-controlled TMS mapping and fMRI study

Background Most humans have the ability to activate the auricular muscles. Although (intentional) control suggests an involvement of higher cortical centers underlying posterior auricular muscle (PAM) activation, the cortical representation of the auricular muscles is still unknown. Methods With the purpose of identifying a possible cortical representation area we performed automated robotic and image-guided transcranial magnetic stimulation (TMS) mapping (n = 8) and functional magnetic resonance imaging (fMRI) (n = 13). For topographical comparison, a similar experimental protocol was applied for the first dorsal interosseus muscle (FDI) of the hand. Results The calculated centers of gravity (COGs) of both muscles were located on the precentral gyrus with the PAM COGs located more laterally compared to the FDI. The distance between the mean PAM and mean FDI COG was 26.3 mm. The TMS mapping results were confirmed by fMRI, which showed a dominance of cortical activation within the precentral gyrus during the corresponding motor tasks. The correspondence of TMS and fMRI results was high. Conclusion The involvement of the primary motor cortex in PAM activation might point to an evolved function of the auricular muscles in humans and/or the ability of intentional (and selective) muscle activation.

A hybrid auricular control system: direct, simultaneous, and proportional myoelectric control of two degrees of freedom in prosthetic hands

OBJECTIVE The conventional myoelectric control scheme of hand prostheses provides a high level of robustness during continuous use. Typically, the electrical activity of an agonist/antagonist muscle pair in the forearm is detected and used to control either opening/closing or rotation of the prosthetic hand. The translation of more sophisticated control approaches (e.g. regression-based classifiers) to clinical practice is limited mainly because of their lack of robustness in real-world conditions (e.g. due to different arm positions). We therefore explore a new hybrid approach, in which a second degree of freedom (DOF) controlled by the myoelectric activity of the posterior auricular muscles is added to the conventional forearm control. With this, an independent, simultaneous and proportional control of rotation and opening/closing of the hand is possible. APPROACH In this study, we compared the hybrid auricular control system (hACS) to the two most commonly used control techniques for two DOF. Ten able-bodied subjects and one person with transradial amputation performed two standardizes tests in three different arm positions. MAIN RESULTS Subjects controlled a hand prosthesis significantly more rapidly and more accurately using the hACS. Moreover, the robustness of the system was not influenced by different arm positions. SIGNIFICANCE The hACS therefore offers an alternative solution for simultaneous and proportional myoelectric control of two degrees of freedom that avoids several robustness issues related to machine learning based approaches.

P253: Myoelectric control by auricular muscles – an alternative human-machine interface

L. Schmalfuß1, W. Duttenhoefer1, J. Meincke1, F. Klinker1, M. Hewitt1, M.R. Tuga2, A. Kogut3, M. Reischl4, R. Rupp3, D. Liebetanz1 1University Medical Center Goettingen, Department of Clinical Neurophysiologie, Goettingen, Germany; 2Karsruhe Institute of Technology, Applied Computer Science/Automation Technology, Karlsruhe, Germany; 3Heidelberg University Hospital, Spinal Cord Injury Center, Heidelberg, Germany; 4Karsruhe Institute of Technology, Applied Computer Science, Karlsruhe, Germany

A prototyping environment for evaluation of man-machine interfaces based on electromyographic activity

A man-machine interface (MMI) based on electromyographic (EMG) signals ideally records signals obtained from many sensors at high data rates, transmits them wireless and generates multiple output signals for multidimensional control of assistive devices e.g. hand prostheses. A MMI needs to be tested using sophisticated training paradigms, which can be adapted in a flexible way. Therefore, the aim of this work was to setup an integrated prototyping environment for evaluation of EMG-based MMIs.