Feasibility of high-density electric source imaging in the presurgical workflow: Effect of number of spikes and automated spike detection.

OBJECTIVE: Presurgical high-density electric source imaging (hdESI) of interictal epileptic discharges (IEDs) is only used by few epilepsy centers. One obstacle is the time-consuming workflow both for recording as well as for visual review. Therefore, we analyzed the effect of (a) an automated IED detection and (b) the number of IEDs on the accuracy of hdESI and time-effectiveness. METHODS: In 22 patients with pharmacoresistant focal epilepsy receiving epilepsy surgery (Engel 1) we retrospectively detected IEDs both visually and semi-automatically using the EEG analysis software Persyst in 256-channel EEGs. The amount of IEDs, the Euclidean distance between hdESI maximum and resection zone, and the operator time were compared. Additionally, we evaluated the intra-individual effect of IED quantity on the distance between hdESI maximum of all IEDs and hdESI maximum when only a reduced amount of IEDs were included. RESULTS: There was no significant difference in the number of IEDs between visually versus semi-automatically marked IEDs (74 ± 56 IEDs/patient vs 116 ± 115 IEDs/patient). The detection method of the IEDs had no significant effect on the mean distances between resection zone and hdESI maximum (visual: 26.07 ± 31.12 mm vs semi-automated: 33.6 ± 34.75 mm). However, the mean time needed to review the full datasets semi-automatically was shorter by 275 ± 46 min (305 ± 72 min vs 30 ± 26 min, P < 0.001). The distance between hdESI of the full versus reduced amount of IEDs of the same patient was smaller than 1 cm when at least a mean of 33 IEDs were analyzed. There was a significantly shorter intraindividual distance between resection zone and hdESI maximum when 30 IEDs were analyzed as compared to the analysis of only 10 IEDs (P < 0.001). SIGNIFICANCE: Semi-automatized processing and limiting the amount of IEDs analyzed (~30-40 IEDs per cluster) appear to be time-saving clinical tools to increase the practicability of hdESI in the presurgical work-up.

Prospective CERAD Neuropsychological Assessment in Patients With Multiple System Atrophy.

The objective of the study was to characterize the pattern of cognitive dysfunction in patients with multiple system atrophy (MSA) applying a standardized neuropsychological assessment. A total of 20 patients with the diagnosis of probable or possible MSA were enrolled for neuropsychological assessment applying the CERAD plus battery. All patients were tested at baseline and 14/20 patients received additional follow-up assessments (median follow-up of 24 months). Additionally, relationship between cortical thickness values/subcortical gray matter volumes and CERAD subitems was evaluated at baseline in a subgroup of 13/20 patients. Trail Making Test (TMT) was the most sensitive CERAD item at baseline with abnormal performance (z-score < -1.28) in one or both pathological TMT items (TMT-A, TMT-B) in 60% of patients with MSA. Additionally, there was a significant inverse correlation between the volume of the left and the right accumbens area and the TMT A item after adjusting for age (left side: p = 0.0009; right side p = 0.003). Comparing both subtypes, patients with MSA-C had significant lower values in phonemic verbal fluency (p = 0.04) and a trend for lower values in semantic verbal fluency (p = 0.06) compared to MSA-P. Additionally, patients with MSA-C showed significantly worse performance in the TMT-B task (p = 0.04) and a trend for worse performance in the TMT-A task (p = 0.06). Concerning longitudinal follow-up, a significant worsening in the TMT-B (p = 0.03) can be reported in MSA. In conclusion, frontal-executive dysfunction presents the hallmark of cognitive impairment in MSA.

Finger Sequence Learning in Adults Who Stutter.

Originary neurogenic, non-syndromatic stuttering has been linked to a dysfunctional sensorimotor system. Studies have demonstrated that adults who stutter (AWS) perform poorly at speech and finger motor tasks and learning (e.g., Smits-Bandstra et al., 2006b; Namasivayam and van Lieshout, 2008). The high relapse rate after stuttering treatment could be a further hint for deficient motor learning and, in particular, for the limited generalization of the learned technique in daily communication. In this study, we tested generalization of finger sequence skills in AWS using an effector-dependent transfer task after a 24-h retention period. Additionally, we wanted to corroborate previous motor learning results in AWS for practice and retention: 16 AWS and 16 age-, sex-, and education-matched controls performed the task during four test sessions. Our results indicate that generalization performance in AWS was not inferior to that of fluent controls. In addition, we found, contrary to previous results, that AWS showed a steeper learning progress after practice and consolidation compared with controls. We suggest that with sufficient practice and a 24-h consolidation phase, AWS are able to retain the learned performance of tapping a five-item finger sequence as well as fluent controls in terms of speed and accuracy.

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.

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.

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.

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.

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

Ahead of Print article withdrawn by publisher.

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

PURPOSE: Functional electrical stimulation represents an alternative to conventional and passive ankle foot orthosis (AFO) for the treatment of stroke-related drop foot. We evaluated the implantable 4-channel stimulator ActiGait, which selectively and directly stimulates the peroneal nerve. In addition, it bypasses the need for surface electrodes and cables. METHODS: Walking speed (10-meter gait test, [m/s]) and walking endurance (6-minute gait test [m/6min]) of 5 patients were tested prior to, as well as 6 and 12 weeks after, the implantation of the ActiGait implantable drop foot stimulator system. In addition, ankle joint angles were assessed during specific phases of the gait cycle, i.e. initiation angle (IA) at the first contact of the foot to the floor, initial plantar flexion (IPF), dorsiflexion (DF) and final plantar flexion (FPF) in [°] during stance phase. The ankle joint angles were measured at baseline and 12 weeks after ActiGait implantation. RESULTS: At the first follow-up, patients' gait speed was found to have increased (0.55; 0.77 m/s) as had walking endurance (211; 260 m). Improvement in gait speed (0.55; 0.77 m/s) and endurance (214; 248 m) was still present after 12 weeks. In addition, gait analysis after 12 weeks revealed a nearly normal physiological initiation angle (113° vs 122°) and an increase in the initial plantar flexion (7° vs. 0°). The initiation angle (IA) represents a well-suited parameter for adequate pre-positioning of the foot at the beginning of the stance phase and is necessary to prevent stumbling and falling. Furthermore, IA is identical to the maximum achieved dorsiflexion during the swing phase of gait. Thus, analysis of the IA of subjects walking with the implantable drop foot stimulator systems ActiGait is particularly useful in showing that the implantable system restores the IA towards physiological ankle movements. CONCLUSION: The ActiGait system increased gait speed, walking endurance and the physiology of important ankle joint kinematics. This is most likely a result of ankle dorsiflexion by active peroneal stimulation during the swing phase of gait and optimized prepositioning (IA) of the foot at the beginning of stance phase. The ActiGait system represents a therapeutic option for the treatment of patients suffering drop foot due to a cerebrovascular insult.

Unsymmetrical tren-based ligands: synthesis and reactivity of rhenium complexes.

Reaction of bis(2-aminoethyl)(3-aminopropyl)amine with C(6)F(6) and K(2)CO(3) in DMSO yields unsymmetrical [(C(6)F(5))HNCH(2)CH(2)](2)NCH(2)CH(2)CH(2)NH(C(6)F(5)) ([N(3)N]H(3)). The tetraamine acts as a tridentate ligand in complexes of the type H[N(3)N]Re(O)X (X = Cl 1, Br 2) prepared by reacting Re(O)X(3)(PPh(3))(2) with [N(3)N]H(3) and an excess of NEt(3) in THF. Addition of 1 equiv of TaCH(CMe(2)Ph)Br(3)(THF)(2) to 1 gives the dimeric compound H[N(3)N]ClReOReBrCl[N(3)N]H (3) in quantitative yield that contains a Re(V)[double bond]O[bond]Re(IV) core with uncoordinated aminopropyl groups in each ligand. Addition of 2 equiv of TaCH(CMe(2)Ph)Cl(3)(THF)(2) to 1 leads to the chloro complex [N(3)N]ReCl (4) with all three amido groups coordinated to the metal, whereas by addition of 2 equiv of TaCH(CMe(2)Ph)Br(3)(THF)(2) to 2 the dibromo species H[N(3)N]ReBr(2) (5) with one uncoordinated amino group is isolated. Reduction of 4 under an atmosphere of dinitrogen with sodium amalgam gives the dinitrogen complex [N(3)N]Re(N(2)) (6). Single-crystal X-ray structure determinations have been carried out on complexes 1, 3, 5, and 6.